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Medicine & Pharmacology, Oncology & Oncogenics; 99mTc-MIBI, 99mTc-tetrofosmin, Adenosine triphosphate-binding cassette transporters, Multidrug resistance, Multidrug resistance-associated protein
Online: 15 August 2018 (10:47:56 CEST)
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Objectives: Little is known about the affinity of 99mTc-labeled 2-methoxyisobutylisonitrile (99mTc-MIBI) and tetrofosmin (99mTc-TF) for multiple drug resistance in cancer cells. Additionally, if 99mTc-labeled compounds are metabolized immediately after injection, imaging with these compounds may not allow monitoring of multiple drug resistance in cancer cells. We examined the affinity of 99mTc-labeled compounds for these transporters and their stability in vivo. Methods: 99mTc-MIBI or 99mTc-TF was incubated in vesicles expressing P-glycoprotein (MDR1), multidrug resistance-associated protein (MRP)1-4, or breast cancer resistance protein with and without verapamil (MDR1 inhibitor) or MK-571 (MRP inhibitor). Time activity curves of 99mTc-labeled compounds were established using SK-N-SH neuroblastoma, SK-MEL-28 melanoma, and PC-3 prostate adenocarcinoma cell lines, and transporter expression of multiple drug resistance was measured in these cells. The stability of 99mTc-labeled compounds was evaluated in mice and human liver S9 fractions. Results: In vesicles, 99mTc-labeled compounds had affinity for MDR1 and MRP1. 99mTc-TF had additional affinity for MRP2 and MRP3. In SK-N-SH cells expressing MDR1 and MRP1, MK-571 produced the highest uptake of both 99mTc-labeled compounds. 99mTc-MIBI uptake with inhibitors was higher than 99mTc-TF uptake with inhibitors. 99mTc-TF was taken up more in SK-MEL-28 cells expressing MRP1 and MRP2 than PC-3 cells expressing MRP1 and MRP3. 99mTc-MIBI was metabolized after a 30-min incubation in SK-N-SH cells, mouse liver, human liver S9 fractions, and plasma. 99mTc-TF had high stability. Conclusion: 99mTc-MIBI is exported via MDR1 and MRP1 (MRP1 > MDR1) at greater levels and more quickly compared to 99mTc-TF, which is exported via MDR1 and MRP1-3 (MRP1 > MDR1; MRP1, 2 > MRP3). Although 99mTc-MIBI is metabolized, clinical imaging for monitoring MDR and shorter examination times may be possible with an earlier scanning time on late phase imaging. 99mTc-TF has high stability and accurately reflects the function of MDR1 and MRP1-3.
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Fabian V. Filipp,
Stanca Birlea,
Marcus W. Bosenberg,
Douglas Brash,
Pamela B. Cassidy,
Suzie Chen,
John August D'orazio,
Mayumi Fujita,
Boon-Kee Goh,
Meenhard Herlyn,
Arup K. Indra,
Lionel Larue,
Sancy A. Leachman,
Caroline Le Poole,
Feng Liu-Smith,
Prashiela Manga,
Lluis Montoliu,
David A. Norris,
Yiqun Shellman,
Keiran S. M. Smalley,
Richard A. Spritz,
Richard A. Sturm,
Susan M. Swetter,
Tamara Terzian,
Kazumasa Wakamatsu,
Jeffrey S. Weber,
Neil F. Box
Medicine & Pharmacology, Oncology & Oncogenics; melanocyte; melanoma; oncology; precision medicine; immunotherapy; pigmentation; vitiligo; albinism; melasma; melanin; dermatology; skin; UV; cancer prevention; IFPCS; PASPCR; SMR; IPCC
Online: 13 August 2018 (11:04:12 CEST)
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In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology.
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Medicine & Pharmacology, Oncology & Oncogenics; Resveratrol; TRAIL; apoptosis; lung cancer cells; NF-κB; Cytochrome c
Online: 13 August 2018 (06:18:03 CEST)
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Aims TRAIL is a promising anticancer agent that has the potential to sensitize a wide variety of cancer or transformed cells by inducing apoptosis. However, resistance to TRAIL is a growing concern. Current manuscript aimed to employing combination treatment to investigate resveratrol induced TRAIL sensitization in NSCLC. Method A549 and HCC-15 cells were used in experimental design. Cell viability was determined by morphological image, crystal violet staining and MTT assay. Apoptosis was evaluated by LDH assay, Annexin V and DAPI staining. Autophagy and apoptosis indicator protein were examined by western blotting. TEM and puncta assay were carried out to evaluate the autophagy. MTP and ROS activity were evaluated by JC-1 and H2DCFDA staining. Findings Resveratrol is a polyphenolic compound capable of activation of tumor suppressor p53 and its pro-apoptotic modulator PUMA. Herein, we showed the p53-independent apoptosis by decrease the expression of phosphorylated Akt-mediated suppression of NF-κB that is also substantiated with the downregulation of anti-apoptotic factors Bcl-2 and Bcl-xl in NSCLC, resulting in an attenuation of TRAIL resistance in combined treatment. Furthermore, apoptosis was induced in TRAIL-resistant lung cancer cells with a co-treatment of resveratrol and TRAIL assessed by the loss of MMP, ROS generations which resulting the translocation of cytochrome c from the mitochondria into the cytosol due to mitochondrial dysfunction. Moreover, autophagy flux was not affected by resveratrol-induced TRAIL-mediated apoptosis in NSCLC. Significance Overall, targeting the NF-κB (p65) pathway via resveratrol attenuates TRAIL resistance and induces TRAIL-mediated apoptosis which could be the effective TRAIL-based cancer therapy regimen.
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Herve Lawin,
Lucie Ayi Fanou,
Antoine Vikkey Hinson,
Marie Stolbrink,
Parfait Houngbegnon,
Marius Kedote,
Benjamin Fayomi,
Jacqueline Kagima,
Patrick Katoto,
Edgard Marius Dona Ouendo,
Kevin Mortimer
Medicine & Pharmacology, General Medical Research; Air pollution; Health risk; Driving; Automobile; Bus; Motorcycle
Online: 12 August 2018 (19:35:44 CEST)
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Introduction: Ambient air pollution is major global health problem and commercial drivers are particularly exposed to it. No systematic assessment of the health risks associated with occupational exposure to ambient air pollution in this population has been carried out. Methods: We conducted a systematic review using a protocol-driven strategy. Papers published from inception to 20th April 2018 in MEDLINE, EMBASE, CINAHL, African journals online, Cochrane library, ISRCTN and WHO ICTRP databases were screened for inclusion by two independent reviewers. Original articles with at least an available abstract in English or French were included. Results: The initial search retrieved 1454 published articles of which 20 articles were included. 3 Studies reported a significant difference in white blood cells (106/L) among commercial motorcyclists compared to rural inhabitants (5.041±1.209 vs 5.900±1.213,p=0.001), an increased risk of lung cancer (RR=1.6, 95%CI 1.5-1.8) in bus drivers and an increased standardized mortality ratio (SMR) in bus drivers from Hodgkin’s lymphoma (SMR 2.17, 95%CI 1.19-3.87) compared to white collar workers. Other studies also found that drivers had more oxidative DNA damage and chromosome breaks. 4 papers failed to demonstrate that the drivers were more exposed to air pollution than the controls. 3 other studies also reported no significant difference in lung function parameters and respiratory symptoms. The genetic polymorphisms of detoxifying enzymes were not also homogeneously distributed compared to the controls. Conclusion: There is some evidence that occupational exposure to ambient air pollution among commercial drivers is associated with adverse health outcomes but the existing literature is limited with few studies of small sample size, methodological weaknesses and contradictory findings. Further research is recommended.
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Medicine & Pharmacology, Nursing & Health Studies; Telehealth, mHealth, wellness, preventative medicine
Online: 10 August 2018 (14:30:16 CEST)
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Objective: Health/wellness applications on mobile devices (Apps) may positively affect the health of seniors (persons age 65+). But for an App to promote health in its target audience, it must achieve meaningful use. Method: For one and a half years, residents at a Life Plan Community (mean age 86) used a wellness App running on iPad. In a digital survey, residents rated their overall satisfaction with the App on a scale from 1 (strongly dislike) to 10 (strongly enjoy). Results: User satisfaction (96 respondents of 252; 38% response rate) was distributed with maximum 8, median 7, mean 6.6, and standard deviation 2.3. Discussion: The results suggest that it is feasible to inspire seniors to pursue whole-person wellness using an App: technology may promote “active aging.”
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Medicine & Pharmacology, Other; cardiovascular variability; heart-rate variability; peripheral arterial disease; photoplethysmography; pulse
Online: 10 August 2018 (13:43:45 CEST)
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Photoplethysmography (PPG) is a simple-to-perform vascular optics measurement technique that can detect changes in blood volume in the microvascular tissue bed. Beat-to-beat analysis of the PPG waveform enables the study of the variability of pulse features such as amplitude and pulse arrival time (PAT), and when quantified in the time and frequency domains, has considerable potential to shed light on perfusion changes associated with peripheral arterial disease (PAD). In this pilot study innovative multi-site bilateral finger and toe PPG recordings from 43 healthy control subjects and 31 PAD subjects were compared (recordings each at least 5 minutes, collected in a warm temperature-controlled room). Beat-to-beat normalized amplitude and PAT variability was then quantified in the time-domain using SD and IQR measures and in the frequency-domain bilaterally using Magnitude Squared Coherence (MSC). Significantly reduced normalized amplitude variability (healthy control 0.0384 (IQR 0.0217-0.0744) vs PAD 0.0160 (0.0080-0.0338) (p<0.001) and significantly increased PAT variability (healthy control 0.0063 (0.0052-0.0086) vs PAD 0.0093 (0.0078-0.0144) (p<0.001) was demonstrated in PAD using the time-domain analysis. Frequency-domain analysis demonstrated significantly lower MSC values across a range of frequency bands for PAD patients. These changes suggest a loss of right-to-left body side coherence and cardiovascular control in PAD. This study has also demonstrated the feasibility of using these measurement and analysis methods in studies investigating multi-site PPG variability for a wide range of cardiac and vascular patient groups.
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Medicine & Pharmacology, Veterinary Medicine; Porcine rotavirus H; Porcine rotavirus C; Full genome; Classification; Genotype; Non-structural protein 3; Gene rearrangement
Online: 9 August 2018 (11:38:44 CEST)
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Rotavirus species H (RVH) has been detected in pigs, humans and bats. Moreover, porcine RVHs have been recently identified in several swine-producing countries. Despite their zoonotic impact, genome information of RVHs is still limited. This study aimed to establish a tentative complete genome-based genotyping system for RVHs, by appending genomic sequences from 12 porcine RVHs identified in Japan between 2013 and 2015 to those from human and other porcine RVHs reported in previous studies. Phylogenetic analysis of 11 RNA segments indicated that porcine RVHs could be classified into multiple genotypes. Consequently, the genotype classification for RVHs revealed the existence of genotypes 10G, 6P, 6I, 3R, 4C, 7M, 6A, 2N, 4T, 6E, 3H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Surprisingly, two distinctive types in NSP1 and NSP3 genes were identified from among the twelve porcine RVHs. Our data suggest a potentially novel gene rearrangement event between porcine RVH and rotavirus species C in the NSP3 gene. These findings would provide a new insight in understanding for evolution of RV.
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Ricardo Lopez Santi,
Sohaib Haseeb,
Bryce Alexander,
Adrian D’Ovidio,
Sergio Gimenez,
Carlos Secotaro,
Diego Martinez Demaria,
Luis Maria Pupi,
Sonia Costantini,
Daniel Piskorz,
Alejandro Amarilla,
Alberto Lorenzatti,
Narcisa Gutierrez,
Wilma Hopman,
Adrian Baranchuk
Medicine & Pharmacology, Cardiology; alcohol drinking; health knowledge; physician attitudes; standard drink; wine
Online: 9 August 2018 (08:07:39 CEST)
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Despite epidemiological findings of improvements in cardiovascular risk factors with a light-to-moderate intake of alcohol, many misconceptions remain regarding alcohol intake and the risks and benefits of consumption. We sought to examine physician attitudes and recommendations regarding alcohol intake in a cohort of Argentine physicians and to establish their sources of knowledge. An online national survey was distributed through the Argentine Federation of Cardiology (FAC) to cardiologists, internal medicine specialists, general and other subspecialty physicians in Argentina. The survey was completed by 745 physicians, of whom 671 (90%) were cardiologists. In total, 35% of physicians viewed moderate alcohol intake to be beneficial for cardiovascular health, 36% believed only wine offered such benefits, 24% viewed any intake to be harmful, and 5% had other opinions. More than half (57%) self-reported their knowledge to come from academic sources. Regarding knowledge of drinking guidelines, only 41% of physicians were aware of the concept of ‘standard drink’. Physicians were generally not comfortable converting ‘standard drinks’ into other metric units, however men tended to be more comfortable than women (p=0.052). Physicians were not satisfied with their knowledge of drinking guidelines (3.01 ± 2.73, on a 0-10 scale). Physicians were generally comfortable in counselling patients regarding safe-limits of consumption (6.22 ± 3.20, on a 0-10 scale). Argentine physicians were not satisfied with their knowledge of alcohol consumption guidelines or their understanding of the reported metrics. Only one-third of study participants viewed moderate alcohol intake as beneficial for cardiovascular health. This study shows the necessity to optimize the sources of knowledge.
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Medicine & Pharmacology, Nutrition; metabolic syndrome; diabetes mellitus; obesity, lactobacilli; bifidobacteria; glucose; macrophages; inflammation; mouse model
Online: 8 August 2018 (14:27:20 CEST)
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Introduction. The use of probiotics demonstrate efficacy against obesity and metabolic syndrome (MetS). Detection effective probiotic strains for hyperglycemia and immunity associated with is important task. The aim of the study was to evaluate an influence of Lactobacillus casei IMV B-7280 separately and composition L. casei IMV B-7280 / Bifidobacterium animalis VKB / B. animalis VKL on the levels of blood glucose and immunity in obese mice. Meterials and methods. Obesity was induced by fat-enriched diet (FED) in male BALB/c mice. Obese mice were transferred to standard diet and received per os probiotic strains daily during 10 days. We measured tumor necrosis factor-a (TNF-a) in blood serum using enzyme-linked immunosorbent assay and functional activity of peritoneal exudate macrophages (PEMs). Glucose levels in blood was defined with glucometer. Results. We ascertained that all probiotic strains induced reducing mice weight and visceral fat, normalization of TNF-a production and functional activity of PEMs. Treatment with L. casei IMV B-7280 was associated with decreasing blood glucose levels. No normalization of glucose and TNF-a levels in obese mice, transferred to standard diet without probiotic treatment, although we revealed decreasing their weight and visceral fat and partial recover of functional activity of PEMs. Conclusions. Probiotic strain L. casei IMV B-7280 (separately) and composition L. casei IMV B-7280 / B. animalis VKB / B. animalis VKL can re-equilibrate metabolic and inflammation indices in mouse obesity model. L. casei IMV B-7280 alone was more efficient in decreasing glucose levels than composition of strains.
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Medicine & Pharmacology, Nursing & Health Studies; Training; competence; incentives; management; performance.
Online: 8 August 2018 (10:55:28 CEST)
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Background.Nurse gives professional nursing service to patients according to competence owned. Based on these services in the end of every year, nurses are given incentives for medical services as financial incentive. Purpose. To analyze the impact of competence training and incentives medical services’ distribution upon the achievement of nurse’s performances in General Hospital of W. Z. Johannes Kupang. Matterial and method. Observational survey research with cross sectional design. Population. Nurses in General Hospital of W. Z. Johannes Kupang. Technique. Total sampling technique with number of samples 183 respondents. Inclusive criteria of samples are willing to be interviewed, nurse’s status, permanent offices without limitation from particular working unit or poly in hospital. Independent variable: (1) competence training; (2) Incentives for medical services. Dependent variable; Nurse’s performance achievement. Variables are measured by using Lickert scale. Information are recorded through questionnaire. Analyzes using linier regression. Result. There are impacts of competence training (α=.000;ß=.489)and distribution of incentives for medical services(α=.012; ß=.152)upon nurse’s performances achievement in General Hospital of Prof.W. Z. Johannes Kupang. Conclusion.The training of nursing service status that could increase competences among nurses with affair incentives for medical services’ distribution simultaneously end up in the increasing of nurse’s performances achievement in a hospital
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Medicine & Pharmacology, Pathology & Pathobiology; amyloid diseases; biocomputing; drug design; natural antiamyloids
Online: 8 August 2018 (04:27:10 CEST)
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Amyloids result from the aggregation of several unrelated proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being put in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms, and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which make it plausible that more effective drugs will be developed in the future.
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Medicine & Pharmacology, Cardiology; atherosclerosis, mesenchymal stem cells, inflammation
Online: 7 August 2018 (23:22:20 CEST)
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Atherosclerosis is a chronic inflammatory disease which results in thickening of the vessel wall and narrowing of the lumen. It is a leading cause of death worldwide. Preventive treatment is taken into prioritized consideration since currently no effective approaches to cure atherosclerosis are available. These treatments mainly focus on lowering blood cholesterol levels, especially LDL-C, by statins. Even so, lowering lipid levels is not sufficient to reduce the risk of cardiovascular events in all patients. Recently, atherosclerosis has increasingly been recognized as a chronic inflammatory disease involving the immune system, initiating new therapeutic approaches which could alleviate or prevent atherosclerosis by modulating inflammation. Mesenchymal stem cells (MSCs) have emerged as a promising option to relieve inflammation and balance immune responses in inflammatory diseases. Several studies including our group also reported that MSCs may be a new therapeutic option for atherosclerosis. This review summarizes the updated state of our knowledge in the administration of MSCs to alleviate atherosclerosis and discusses some of the key unresolved challenges that need to be solved in future studies.
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Medicine & Pharmacology, Oncology & Oncogenics; histone deacetylase inhibitor, MHY2256, p53, apoptosis, autophagy, Ishikawa, endometrial cancer
Online: 7 August 2018 (14:37:46 CEST)
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We previously found a novel a new sirtuin (SIRT) inhibitor MHY2256 that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. Here, we investigated the anticancer activity of MHY2256 against hormone-related cancer, which is an endometrial cancer with poor prognosis. We found that MHY2256 markedly reduced cellular proliferation at low concentrations against Ishikawa endometrial cancer cells. The IC50 values of MHY2256 were much lower than that of salermide. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3 with similar effects as salermide, a well-known SIRT inhibitor. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. Detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers.
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Shinya Rai,
Hirokazu Tanaka,
Ko Fujimoto,
Takahiro Kumode,
Hiroaki Inoue,
Yasuhiro Taniguchi,
Luis Espinoza,
Yasuyoshi Morita,
Yoichi Tatsumi,
Takashi Ashida,
Ryota Matsuoka,
Yukie Kikuti,
Naoya Nakamura,
Itaru Matsumura
Medicine & Pharmacology, Oncology & Oncogenics; Lymphoproliferative diseases, Hodgkin lymphoma, Chronic Lymphocytic Leukemia, clonality, Hodgkin/Reed–Sternberg cell, Bendamustine
Online: 7 August 2018 (12:02:58 CEST)
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A 62-year-old male was diagnosed with B-CLL and treated with Fludarabine-containing regimen which maintained the disease in partial response. Nine years after diagnosis, a rapidly growing systemic lymphadenopathy was observed, and a biopsy specimen revealed the presence of typical Hodgkin/Reed–Sternberg (HRS) cells, surrounded by T-lymphocytes and CLL cells. Sequencing analysis of the germline CDR3 region of the IGH gene showed that the HRS cells were clonally unrelated to the preexisting CLL cells and the HRS cells were composed of five different clones, leading to the molecular diagnosis of de novo lymphocyte-rich classic Hodgkin LPDs with SLL. Because the initial treatment was neither effective for classic Hodgkin LPDs nor for SLL, Bendamustine, Rituximab (BR) was started and complete remission was achieved, which has continued for more than one year so far. BR may be a good therapeutic option for both entities without causing hematological toxicity.
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Andric Christopher Perez-Ortiz,
Alexandra Luna-Angulo,
Juan Carlos Zenteno,
Alvaro Rendon,
Liliana Guadalupe Cortes-Ballinas,
David Jimenez-Collado,
Bani Antonio-Aguirre,
Martha Janneth Peralta-Ildefonso,
Israel Ramirez,
Stefany Jacob-Kuttothara,
Francisco Javier Estrada-Mena
Medicine & Pharmacology, Ophthalmology; SGCD; delta-sarcoglycan; candidate-gene approach; AMD
Online: 7 August 2018 (08:04:52 CEST)
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1) Background: CFH and HTRA1 genes are traditional markers of increased risk of AMD across populations. Recent findings suggest that additional genes, for instance, in the dystrophin-associated protein complex might be promising markers for AMD. 2) Methods: Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of 134 cases with 134 unpaired controls. Cases were 60 years or older (CARMS grade 4-5, as assessed by experienced ophthalmologists following the AAO guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or RPE changes on fundus exam and negative family history of AMD. We examined SNPs in the SGCD gene: rs931798, rs140617, rs140616, and rs970476 by sequencing and RT-PCR. Genotyping quality check and univariate analyses were performed with PLINK v.1.9. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. 3) Results: After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% (1.81, 95%CI 1.06-3.14, p=0.031), especially the geographic atrophy phenotype (1.82, 95%CI 1.03-3.21, p=0.038) compared to the G/G homozygous. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (Adjusted OR 0.13, 95%CI 0.02-0.91, p=0.041). 4) Conclusions: SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted.
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Medicine & Pharmacology, Pharmacology & Toxicology; acute toxicity; intravenous lipid emulsion; propofol; rat model
Online: 7 August 2018 (07:54:12 CEST)
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Propofol is the general anesthetic used for the anesthesia induction and its continuation. Propofol is generally safe and it doesn't have an antidote. Propofol has severe side effects such as cardiovascular depression and hypotension. The aim of this study was observed the effects of intravenous lipid emulsion (ILE) treatment in the preventi̇on of depressive effects of propofol on cardiovascular and respiratory system. Twenty-eight Sprague-Dawley adult rats randomly divided into 4 groups. The saline administered group was defined as the control group. The second group administered propofol, the third group administered ILE, and the fourth administered propofol with ILE therapy. Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Median arterial blood pressure (MAP), Respiratory rate (RR), Heart rate (HR) and mortality were recorded during 60 minutes of follow-up. In the propofol group, SBP, DBP, MAP, RR and HR scores were decline steadily, after 60 minutes all rats in this group died. In the ILE group with propofol, after a while, decreased SBP, DBP, MAP, RR and HR scores was increased, and these values were observed close to the control group. The mortality ratio of the propofol group was detected as 100%, and survival ratio was found 100% in ILE + propofol group. The side effects such as hypotension, bradycardia and respiratory depression which can be seen after propofol application in rats could be recovered with ILE treatment and mortality due to these side effects were prevented.
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Medicine & Pharmacology, Pediatrics; unintentional childhood injuries; first aid; health seeking, community survey injuries; India
Online: 6 August 2018 (16:25:34 CEST)
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Background: There is lack of data on types of community first aids use and treatment given post injuries from many low-middle income countries, including India. Materials and Methods: A cross-sectional study was conducted among children up-to 18 years of age, in Ujjain district, India to understand types of first aid given and health seeking post injury. Results: A total of 1087 injuries, in 1049 children were identified in last one year, 729 (67%) received, first aid and 758 (72%) sought some healthcare. Children with burns received most (86%) first aid, while most children (84%) with road traffic accidents (RTA) sought health care. Most children (52%) sought healthcare from a private health set-up; most (65%) being transported within the golden hour; motorbikes being the most preferred (50%) mode of transport. Only 1% injured used ambulance services. Commonly reported first aid included: use of coconut oil on wounds from falls (38%) and burns (44%); antiseptic cream on wounds from RTA (31%), turmeric in falls (16%), and rubbing of metal on a bitten site (47%). Potentially harmful substances applied included lime, toothpaste, clay and mud. Conclusion: In most injuries, appropriate locally available substances, were used by the community. Our findings will help design community interventions to increase appropriate first aid in childhood injuries.
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Medicine & Pharmacology, Oncology & Oncogenics; Big Data, Systems Models, Cancer metabolism, Cancer personalized treatment, Drug Discovery.
Online: 6 August 2018 (15:09:15 CEST)
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Coordinated sets of extremely numerous digital data, on a given social or economic event, are treated by Artificial Intelligence tools to obtain reasonably accurate, valuable predictions. The same approach, applied to biomedical issues, as how to choose the right drug to completely cure a given cancer patient, does not reach satisfactory results. It is the “organized biological complexity”, which requires a different systems approach, to integrate, in an Augmented Intelligence strategy, statistical computations of digital data, network construction of “omics” findings, well-designed mathematical models and new experiments in an iterative pathway to reconstruct the “logic” beneath the “organized complexity”, as shown here for Systems Metabolomics of cancer. On this basis new diagnostic approaches, able to identify precision drug treatments, as well as new discovery strategy for more effective anti-cancer drugs are described.
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Medicine & Pharmacology, Other; sonic hedgehog; endothelial cells; endothelial progenitor cells; canonical signals; non-canonical signals; extracellular vesicles
Online: 6 August 2018 (10:13:51 CEST)
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The Hedgehog (Hh) signaling pathway plays an essential role in embryonic and postnatal vasculature development and homeostasis of organs. Under physiological condition, Hh family’s member Sonic Hedgehog (SHh) regulates endothelial cell growth, promotes cell migration, and induces the construction of blood vessels. In this review, we highlight recent topics in EPC biology, regarding current advance in SHh canonical and non-canonical signaling pathway in EPCs and EC biology in terms of homeostasis, extracellular SHh signal transmission by parental cell-derived extracellular vesicle (exosomes containing single-strand non-codding miRNA), and SHh signal impairment in cardiovascular diseases. Also, we discuss SHh signaling pathway activation of EPCs as a promising therapeutic tool against cardiovascular disease patients.
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Medicine & Pharmacology, Ophthalmology; congenital cataract; consanguineous; circadian; mutation
Online: 6 August 2018 (10:04:11 CEST)
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In mice, mutations or targeted disruptions of the core circadian gene Bmal1 have been implicated in early onset of ocular pathologies, including premature/congenital cataract development. The aim of the present study was to analyze probands of consanguineous Pakistani cataract families to identify the novel pathogenic variants in the BMAL1 gene. We have studied 21 congenital cataract families. Ophthalmic examination was performed for the probands and available family members. Genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing was performed for the entire coding region of the BMAL1 gene. Targeted Sanger sequencing of BMAL1 revealed a heterozygous variant c.41A>T; p.(Asp14Val) in one proband, but it did not co-segregate with the disease phenotype in the family. In addition, a nonsynonymous variant (rs2290037) was identified in five probands. Our study is the first one to analyze the role of BMAL1 gene mutations in humans for their association with congenital cataract. Although we were unable to find the variants associated with congenital cataract families from Pakistan, more studies from other populations will be informative to further prove the role of BMAL1 with the disease.
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Medicine & Pharmacology, General Medical Research; selenium; selenocysteine; selenoproteins; selenocysteine insertion sequence; nonsense-mediated decay
Online: 4 August 2018 (11:47:34 CEST)
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Selenium is a trace metal essential to human health, and its deficiency has been related to, for instance, cardiovascular and myodegenerative diseases, infertility and osteochondropathy Kashin-Beck disease. It is incorporated as selenocysteine to selenoproteins, which protect against reactive oxygen and nitrogen species. They also participate in the activation of thyroid hormone, and play a role in immune system functioning. The synthesis and incorporation of selenocysteine occurs via a special mechanism, which differs from the one used for standard amino acids. The codon for selenocysteine is the regular in-frame stop codon, which can be passed by specific complex machinery participating in translation elongation and termination. This includes the presence of selenocysteine insertion sequence (SECIS) in the 3’-untranslated part of the selenoprotein mRNAs. Selenium deficiency is known to control both selenoprotein and non-selenoprotein transcriptomes. Nonsense-mediated decay is involved in the regulation of selenoprotein mRNA levels, both other mechanisms are also possible.
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Medicine & Pharmacology, General Medical Research; genistein; ∆F508-CF; mouse; survival
Online: 4 August 2018 (11:24:00 CEST)
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Genistein is a naturally occurring isoflavone found in soy. Mice homozygous for the ∆F508 mutation are characterized with severe intestinal disease and require constant laxative treatment for survival. This pathology mimics the intestinal obstruction (meconium ileus) seen in some cystic fibrosis (CF) patients. We therefore tested whether dietary supplementation with genistein would reduce the dependence of the ∆F508 CF mouse model on laxatives for survival, thereby improving mortality rates. At weaning (21 days), we maintained homozygous ∆F508 mice on three diet regimens for a period of up to 65 days; normal diet, normal diet + Colyte or genistein diet. Survival rates for males were as follows: standard diet (38%), standard diet plus Colyte (83%) or genistein diet (60%). Survival rates for females were as follows: standard diet (47%), standard diet plus Colyte (71%), or genistein diet (87%). Average weight of male mice fed genistein diet increased by ~2.5 g more compared to those with Colyte treatment. Genistein diet did not change final body weight of females. Expression of SGLT-1 increased 2-fold with genistein diet in females (no change in males). Expression of GLUT2 and GLUT5 was comparable between all diet groups. Genistein diet reduced the number of goblet cells per micometer of crypt depth in female, yet was without effect in males. We conclude that supplementation of diet with genistein for ~45 days increases the survival rate of female ∆F508-CF mice precluding the requirement for laxatives, and only improves weight gain in males.
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Medicine & Pharmacology, Cardiology; Lyme disease; Lyme carditis; Atrioventricular block
Online: 3 August 2018 (20:21:23 CEST)
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Lyme carditis (LC) is a manifestation of the early disseminated stage of Lyme disease and often presents as high-degree atrioventricular (AV) block. High-degree AV block in LC can be treated with antibiotics, usually resolving with highly favourable prognosis, thus preventing the unnecessary implantation of permanent pacemakers. We present a systematic approach to the diagnosis and management of LC that implements the Suspicious Index in Lyme Carditis (SILC) risk stratification score.
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Medicine & Pharmacology, Urology; sarcopenia; prognosis; biomarker; bladder cancer; urothelial carcinoma
Online: 3 August 2018 (16:05:54 CEST)
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Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients.
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Medicine & Pharmacology, Nutrition; Asian Americans; child; diet; eating; feeding behavior; sodium, dietary
Online: 3 August 2018 (05:05:05 CEST)
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Obesity has been identified as an emerging health concern for Chinese American children; however, very little is known about diets in Asian American children. The objective of our paper was to describe the dietary intakes of urban Chinese American schoolchildren using a state-of-the-art approach for dietary assessment. Data for this analysis come from the Food Journal Project 2017, a pilot and feasibility study conducted by a multi-sector collaboration. Children aged 8-12 (n=83) completed two dietary assessments using a food diary from January-June 2017. Children were then interviewed using the food diary as a guide and dietary data were entered into the online ASA24 system by study staff. Chinese American children were identified using surname, and were compared to non-Chinese peers with respect to nutrient intake and the Healthy Eating Index 2010 (HEI-2010). Chinese American children consumed more sodium dense diets, more protein, and less sugar compared to non-Chinese children. With regards to the HEI-2010, Chinese American children had less favorable whole grains and sodium scores; and more favorable seafood protein and empty calories scores compared to non-Chinese children. Sodium reduction and increasing whole grain intakes may be warranted in this group, but should be verified with additional studies.
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Antonella Di Sotto,
Silvia Di Giacomo,
Donatella Amatore,
Marcello Locatelli,
Annabella Vitalone,
Chiara Toniolo,
Giuseppe Leonardo Rotino,
Roberto Lo Scalzo,
Anna Teresa Palamara,
Maria Elena Marcocci,
Lucia Nencioni
Medicine & Pharmacology, Pharmacology & Toxicology; eggplant peel; polyphenols; HSV-1; Warburg effect; antioxidant activity; antiviral agents; vegetable waste
Online: 3 August 2018 (04:53:37 CEST)
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DR2B and DR2C extracts, from peel of commercially and physiologically ripe eggplants, were studied for the antioxidative cytoprotective properties and anti-HSV-1 activity, in line with the evidence that several antioxidants can impair viral replication by maintaining reducing conditions into the host cells. The antioxidative cytoprotective effects against tBOOH-induced damage was assessed in Caco2 cells, while the antiviral activity was studied in Vero cells; phenolic and anthocyanin fingerprint was characterized by integrated phytochemical methods. Results highlighted different compositions of the extracts, with chlorogenic acid and delphinidin-3-rutinoside as the major constituents; other peculiar phytochemicals were also identified. DR2C resulted able to partly counteract the tBOOH-induced cytotoxicity, with a remarkable lowering of lactate metabolism under both normoxia and hypoxia. DR2B and DR2C reduced ROS production, possessed scavenging and chelating properties. Interestingly, DR2C increased intracellular GSH levels. Furthermore, DR2C inhibited the HSV-1 replication when added for 24 h after viral adsorption, as also confirmed by the reduction of many viral proteins expression. Since DR2C was able to reduce NOX4 expression during HSV-1 infection, its antiviral activity may be correlated to its antioxidant properties. Although further studies are needed to better characterize DR2C activity, the results suggest this extract as a promising new anti-HSV-1 agent.
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Medicine & Pharmacology, Pediatrics; infant; premature; pain; acupuncture; skin to skin contact; sucrose; massage; musical therapy; breastfeeding
Online: 3 August 2018 (04:09:31 CEST)
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Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used but may be ineffective, have side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective is to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: ‘infant’, ‘premature’, ‘pain’, ‘acupuncture’, ‘skin to skin contact’, ‘sucrose’ ‘massage’, ‘musical therapy’ and ‘breastfeeding’. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin to skin care and musical therapy. Most non-pharmacological methods of analgesia provide some modicum of relief for preterm infants but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.
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Takahiro Yamamoto,
Motoki Fujita,
Yasutaka Oda,
Masaki Todani,
Toru Hifumi,
Yutaka Kondo,
Junya Shimazaki,
Shinichiro Shiraishi,
Kei Hayashida,
Shoji Yokobori,
Shuhei Takauji,
Masahiro Wakasugi,
Shunsuke Nakamura,
Jun Kanda,
Masaharu Yagi,
Takashi Moriya,
Takashi Kawahara,
Michihiko Tonouchi,
Hiroyuki Yokota,
Yasufumi Miyake,
Keiki Shimizu,
Ryosuke Tsuruta
Medicine & Pharmacology, General Medical Research; heat-related illness; international classification; heat cramp; syncope; heat exhaustion; heat stroke; novel classification
Online: 3 August 2018 (03:51:27 CEST)
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The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between June 1 and September 30, 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as stage III were significantly higher than those of patients classified as stage I or II. There were no deaths among the patients classified as stage I. This novel classification may avoid underestimating the severity of heat-related illness.
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Yi Yuan,
Hui Li Ang,
Xianning Lai,
Lingzhi Wang,
Vijay Pandey,
Benjamin BoJun Huang,
Tuan Zea Tan,
Hui Yi Chong,
Philip Zheng Yang Ong,
Kanchugarakoppal S. Rangappa,
Frank Arfuso,
Kevin Shyong-Wei Tan,
Basappa,
Boon Cher Goh,
Ruby Yun-Ju Huang,
Gautam Sethi,
Peter E. Lobie,
Alan Prem Kumar
Medicine & Pharmacology, Oncology & Oncogenics; breast tumor kinase (BRK); protein tyrosine kinase 6 (PTK6); breast cancer; pathways; therapeutics
Online: 2 August 2018 (09:58:55 CEST)
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The search for improved therapeutic approaches to breast cancer are still on going. Breast tumor kinase (BRK, also known as PTK6) is one of the targets, it is highly expressed in breast carcinomas while displaying low or no expression in the normal mammary gland, which hints at the oncogenic role of this enzyme in breast cancer. In these twenty years, an increasing number of studies have focused on understanding the cellular roles of BRK in breast cancers. This review outlines the advances made towards understanding the cellular and physiological role of BRK, the molecular and chemical inhibitors and its therapeutic significance in breast cancer.
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Medicine & Pharmacology, Pharmacology & Toxicology; pseudopterosin; triple negative breast cancer; glucocorticoid receptor alpha; dexamethasone; cell proliferation; 3D invasion; tumor spheroid; co-culture; interleukin 6; interleukin 8
Online: 2 August 2018 (06:08:31 CEST)
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Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.
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Medicine & Pharmacology, General Medical Research; Hedgehog; Ischemia; Heart; Brain; Skeletal muscle
Online: 1 August 2018 (16:31:01 CEST)
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Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.
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Georg Fuellen,
Ludger Jansen,
Alan A. Cohen,
Walter Luyten,
Manfred Gogol,
Andreas Simm,
Nadine Saul,
Francesca Cirulli,
Alessandra Berry,
Peter Antal,
Rüdiger Köhling,
Steffen Möller
Medicine & Pharmacology, General Medical Research; terminology, health, aging, biological age, wellbeing, biomarker
Online: 1 August 2018 (15:00:47 CEST)
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Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need: (1) to find a broadly acceptable and useful definition of health, based on a list of features (which may or may not be molecular); (2) to operationalize features of health so that it can be measured; (3) to identify predictive biomarkers and (molecular) pathways of health, and (4) to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of (a) physiological function, (b) cognitive function and (c) physical function, amended, specifically in case of humans, by (d) lack of disease, and by (e) reproductive function. Often used concepts such as lack of frailty, allostatic load, or self-reported health (in case of human), and indices such as the Healthy Aging Index can be viewed as projections or surrogates of our definition. We further define aging as the set of all processes in an individual that reduce its “wellbeing”, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other, specifically by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts that are a key to reducing the need for medical and nursing care.
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Medicine & Pharmacology, Obstetrics & Gynaecology; expanded carrier screening; prenatal diagnosis; pregnancy management; clinical utility; at-risk couple
Online: 1 August 2018 (12:07:35 CEST)
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Purpose: Expanded carrier screening (ECS) informs couples of their risk of having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes of at-risk couples (ARCs). We describe the impact of ECS on planned and actual pregnancy management in the largest sample of ARCs studied to date. Methods: Couples who elected ECS and were found to be at high risk of having a pregnancy affected by at least one of 176 genetic conditions were invited to complete a survey about their actions and pregnancy management. Results: Three hundred ninety-one ARCs completed the survey. Among those screened before becoming pregnant, 77% planned or pursued actions to avoid having affected offspring. Among those screened during pregnancy, 37% elected prenatal diagnostic testing (PNDx) for that pregnancy. In subsequent pregnancies that occurred in both the preconception and prenatal screening groups, PNDx was pursued in 29%. The decision to decline PNDx was most frequently based on the fear of procedure-related miscarriage, as well as the belief that termination would not be pursued in the event of a positive diagnosis. Conclusions: ECS results impacted couples’ reproductive decision-making and led to altered pregnancy management that effectively eliminates the risk of having affected offspring.
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Medicine & Pharmacology, General Medical Research; Cancer genomics; CNA; CGH; bioinformatics
Online: 31 July 2018 (10:21:40 CEST)
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Cancers arise from the accumulation of somatic genome mutations, with varying contributions of intrinsic (i.e. genetic predisposition) and extrinsic (i.e. environmental) factors. For the understanding of malignant clones, precise information about their genomic composition has to be correlated with morphological, clinical and individual features, in the context of the available medical knowledge. Rapid improvements in molecular profiling techniques, the accumulation of large amount of data in genomic alterations in human malignancies and the expansion of bioinformatic tools and methodologies have facilitated the understanding of the molecular changes during oncogenesis, and their correlation with clinico-pathological phenotypes. Far beyond a limited set of "driver" genes, oncogenomic profiling has identified a large variety of somatic mutations; and whole genome sequencing studies of healthy individuals have improved the knowledge of heritable genome variation. Nevertheless, main challenges arise from the skewed representation of individuals from varying population backgrounds in biomedical studies, and also through the limited extend in which some cancer entities are represented in the scientific literature. Content analyses of oncogenomic publications could provide guidance for the planning and support of future studies aiming at filling prominent knowledge gaps.
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Medicine & Pharmacology, Dermatology; onchodermatitis; onchocercal skin disease; onchocerciasis; ivermectin
Online: 31 July 2018 (09:47:34 CEST)
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Onchocerciasis causes debilitating pruritus and rashes as well as visual impairment and blindness . Prior to control measures, eye disease was particularly prominent in savanna areas of sub-Saharan Africa whilst skin disease was more common across rainforest regions of tropical Africa. Mass drug distribution with ivermectin is changing the global scene of onchocerciasis. There has been successful progressive elimination in Central and Southern American countries and the World Health Organization has set a target for elimination in Africa of 2025. This literature review was conducted to examine progress regarding onchocercal skin disease. PubMed searches were performed using keywords "onchocerciasis", "onchodermatitis" and "onchocercal skin disease" over the past eight years. Articles in English, or with an English abstract, were assessed for relevance, including any pertinent references within the articles. Recent progress in awareness of, understanding and treatment of onchocercal skin disease is reviewed with particular emphasis on publications within the past 5 years. The global burden of onchodermatitis is progressively reducing and is no longer seen in children in many formerly endemic foci.
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Medicine & Pharmacology, Nutrition; tempeh; lactic acid bacteria; short chain fatty acids; metabolic syndrome; high fat diet; feces
Online: 31 July 2018 (09:37:51 CEST)
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The increased consumption of high fat-containing foods has been linked to the prevalence of obesity and abnormal metabolic syndromes. Rhizopus oligosporus, a fungus in the family Mucoraceae, is widely used as a starter for homemade tempeh. Although R. oligosporus can prevent the growth of other microorganisms, it grows well with lactic acid bacteria (LAB). Lactobacillus plantarum can produce β-glucosidase, which catalyzes the hydrolysis of glucoside isoflavones into aglycones (with greater bioavailability). Therefore, the development of a soybean-based functional food by the co-inoculation of R. oligosporus and L. plantarum is a promising approach to increase the bioactivity of tempeh. In this study, the ameliorative effect of L. plantarum in soy tempeh on abnormal carbohydrate metabolism in high-fat diet (HFD)-induced hyperglycemic rats was evaluated. The co-incubation of L. plantarum with R. oligosporus during soy tempeh fermentation reduced the homeostatic model assessment of insulin resistance, HbA1c, serum glucose, total cholesterol, triglyceride, free fatty acid, insulin, and low-density lipoprotein contents and significantly increased the high-density lipoprotein content in HFD rats. It also increased the LAB counts as well as the bile acid, cholesterol, triglyceride, and short-chain fatty acid contents in the feces of HFD rats. Our results suggested that the modulation of serum glucose and lipid levels by LAB occurs via alterations in the internal microbiota, leading to the inhibition of cholesterol synthesis and promotion of lipolysis. Tempeh, produced with both L. plantarum and R. oligosporus, may be a beneficial dietary supplement for individuals with abnormal carbohydrate metabolism.
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Medicine & Pharmacology, General Medical Research; aging; disability; healthy aging; osteoarthritis; pain, rehabilitation, successful aging
Online: 30 July 2018 (22:20:03 CEST)
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Background: Aging is commonly accepted as a time period of declining heath. Aims: This review aimed to examine the research base concerning the use of term ‘successful aging’, a process and outcome deemed desirable, but challenging to attain. A second was to provide related information to demonstrate how health professionals as well as individuals can aim for a ‘successful aging’ process and outcome, despite the presence of disabling osteoarthritis. Methods: Information specifically focusing on ‘successful aging’ and the concept of improving opportunities for advancing ‘successful aging’ despite osteoarthritis was sought. Results: Among the many articles on ‘successful aging’, several authors highlight the need to include, a broader array of older adults into the conceptual framework. Moreover, conditions such as osteoarthritis should not necessarily preclude the individual from attaining a personally valued successful aging outcome. Conclusion: Pursuing more inclusive research and research designs, and not neglecting to include people with chronic osteoarthritis can potentially heighten the life quality of all aging individuals, while reducing pain and depression, among other adverse aging and disability correlates among those with osteoarthritis
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Medicine & Pharmacology, Nutrition; Sleep; Social Jetlag; Diet Food and Nutrition; Nutrition Surveys; Cross-sectional; Epidemiology; Adults; Public Health
Online: 30 July 2018 (14:41:06 CEST)
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Limited observational studies have described the relationship between sleep duration and overall diet. The present study investigated the association between sleep duration at weekdays and empirically derived dietary patterns in a nationally representative sample of UK adults, aged 19-64 years old, participating in the 2008-2012 UK National Diet and Nutrition Survey Rolling Programme. Survey members completed between three to four days of dietary records. Sleep duration at weekdays was categorised into tertiles to reflect short, normal and long sleep duration. Social jetlag was calculated as the difference between sleep duration at weekends and weekdays. The association between sleep duration/ social jetlag and dietary patterns, derived by principal components analysis, was assessed regressing diet on sleep whilst accounting for the complex survey design and adjusting for relevant confounders. Survey members in the highest tertile of sleep duration had on average 0.45 (95% CI -0.78, -0.12) lower healthy dietary pattern score compared to middle tertile (p =0.007). There was an inverted u-shaped association between social jetlag and a healthy dietary pattern, such that when sleep at weekends exceeded weekday sleep by 1h 45min, scores for indicating a healthy dietary pattern declined (p =0.005). In conclusion, long sleep duration at weekdays and an increased social jetlag are associated with a lower healthy dietary pattern score. Further research is required to address factors influencing dietary patterns in long sleepers.
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Medicine & Pharmacology, Sport Sciences & Therapy; Baduanjin, Qigong, COPD, rehabilitation
Online: 27 July 2018 (17:28:01 CEST)
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Baduanjin exercise is a traditional Chinese health-Qigong routine, created by an ancient physician for health promotion. Its mild-to-moderate exercise intensity is suitable for individuals with medical conditions. Recently, a large number of trials were conducted to investigate the effects of Baduanjin exercise in patients with chronic obstructive pulmonary disease (COPD). It needs to be determined whether Baduanjin exercise prescription is beneficial for the management of COPD patients. Thus, we conducted a systematic review to objectively evaluate the existing literature on this topic. We searched six databases (PubMed, Web of Science, Cochrane Library, Scopus, CNKI, and Wanfang) from its inception till early May, 2018. The adapted PEDro scale was used for study quality assessment of all randomized controlled trials (RCT). The pooled effect size (Hedge’s g) of exercise capability (6-Minute Walking Test, 6-MWT), lung function parameters (forced expiratory volume in first second, FEV1; forced volume vital capacity, FVC; FEV1/FVC ratio), and quality of life were calculated based on the random-effects model. Twenty RCTs (n = 1975 COPD patients) were included in this review, with sum scores of the adapted PEDro scale between 5 and 9. Study results of meta-analysis indicate that Baduanjin is effective in improving exercise capability (Hedge’s g = 0.69, CI 0.44 to 0.94, p < 0.001, I2 = 66%), FEV1 (Hedge’s g = 0.47, CI 0.22 to 0.73, p < 0.001, I2 = 68.01%), FEV1% (Hedge’s g = 0.38, CI 0.21 to 0.56, p < 0.001, I2 = 54.74%), FVC (Hedge’s g = 0.39, CI 0.22 to 0.56, p < 0.001, I2 = 14.57%), FEV1/FVC (Hedge’s g = 0.5, CI 0.33 to 0.68, p < 0.001, I2 = 53.49%), and the quality of life of COPD patients (Hedge’ s g = - 0.45, CI -0.77 to - 0.12, p < 0.05, I2 = 77.02%), as compared to control groups. Baduanjin exercise as an adjunctive treatment may potentially improve exercise capability and pulmonary function of COPD patients as well as quality of life. Baduanjin exercise could be tentatively prescribed for COPD in combination with the conventional rehabilitation program to quicken the process of recovery. To confirm the positive effects of Baduanjin exercise for COPD patients, future researchers need to consider our suggestions mentioned in this article.
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Medicine & Pharmacology, Pediatrics; qualitative, mindfulness, meditation, chronic illness, adolescents, eHealth
Online: 27 July 2018 (15:34:58 CEST)
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Mindfulness-based interventions (MBIs) have been shown to improve health and well-being in adolescents with chronic illnesses. Because they are most often delivered in person in a group setting, there are several barriers that limit access to MBIs for youth with limited mobility or who cannot access in-person MBIs in their communities. The objective of this study was to determine if eHealth is a viable platform to increase accessibility to MBIs for teens with chronic illnesses. This study reports the qualitative results of a mixed method randomized trial describing the experience of the Mindful Awareness and Resilience Skills for Adolescents (MARS-A) program, an 8-week MBI, delivered either in person or via eHealth. Participants were adolescents between the ages of 13 and 18 with a chronic illness recruited at a tertiary pediatric hospital in Toronto, Canada. Individual semi-structured post-participation audio-video interviews were conducted by a research assistant. A multiple-pass inductive process was used to review interview transcripts and interpret emergent themes from the participants’ lived experiences. Fifteen participants completed post-participation interviews. Four distinct themes emerged from participants in both the in-person and eHealth groups: creation of a safe space, fostering peer support and connection, integration of mindfulness skills into daily life and improved well-being through the application of mindfulness. Results from this study suggest that eHealth may be an acceptable and feasible mode of delivery for MBIs in adolescents with chronic illnesses. EHealth should be considered in future studies as a promising avenue to increase access to MBIs in this population.
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Medicine & Pharmacology, General Medical Research; 3-hydroxy-3-methylglutaryl-coenzyme-A inhibitors; Sepsis
Online: 27 July 2018 (13:07:17 CEST)
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Background:
Most sepsis patients died during their first episode and the long-term survival post discharge was low. Major adverse cardiovascular events and repeated infections were regarded as the major causes in such conditions. No definite medications were proven to effectively improve the long-term outcome. We aimed to examine the benefit of statins on the long-term outcome of survived sepsis patients.
Methods:
Between 1999 and 2013, a total of 220,082 patients with the first episode of sepsis hospitalization were included and 134,448 ones (61.09%) survived to discharge. The survived patients who subsequently had statins use of >30 cumulative defined daily doses (cDDDs) post discharge were defined as the statin users. After propensity score matching of 1:5, a total of 7,356 and 36,780 survived patients were retrieved as the study (statin-users) and comparison cohort (non-statin users), respectively. The main outcome was the long term survival post discharge. HR with 95% CI was calculated using the Cox regression model to evaluate the effectiveness of statins with further stratification analyses according to cDDDs.
Results:
The study cohort, that is, the statin users had an adjusted HR of 0.29 (95% CI, 0.27-0.31) in long term mortality rate compared with the comparison cohort. For statin users with the cDDDs of 30–180, 180–365, and >365, the adjusted HRs were 0.32, 0.22, and 0.16, respectively, (95% CI, 0.30-0.34, 0.19-0.26, and 0.12-0.23, respectively) compared with the non-statin users (defined as statins use <30 cDDDs post discharge), and the P for trend <.0001. In the sensitivity analysis, after excluding the survived patients who died within three and six months post discharge, the adjusted HR of statins use remained significant (0.35, 95% CI 0.32-0.37 and 0.42, 95% CI 0.39-0.45, respectively).
Conclusions:
Statins decreased the long-term mortality post sepsis. Further randomized control trial deserved to be conducted to confirm this observation.
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Medicine & Pharmacology, Pharmacology & Toxicology; autophagy; huntingtin; insulin signaling; liraglutide; oxidative stress
Online: 27 July 2018 (03:35:44 CEST)
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Huntington's disease (HD) is a progressive and fatal neurodegenerative disease caused by CAG repeat expansion in the coding region of huntingtin (HTT) protein. The accumulation of mutant HTT (mHTT) contributes to neurotoxicity by causing autophagy defects and oxidative stress that ultimately lead to neuronal death. Interestingly, epidemiologic studies have demonstrated that the prevalence of type-2 diabetes, a metabolic disease mainly caused by defective insulin signaling, is higher in patients with HD than in healthy controls. Although the precise mechanisms of mHTT-mediated toxicity remain unclear, the blockade of brain insulin signaling may initiate or exacerbate mHTT-induced neurodegeneration. In this study, we used an in vitro HD model to investigate whether neuronal insulin signaling is involved in mHTT-mediated neurotoxicity. Our results demonstrated that mHTT overexpression significantly impairs insulin signaling and causes apoptosis in neuronal cells. However, treatment with liraglutide, a GLP-1 analogue, markedly restores insulin sensitivity and enhances cell viability. This neuroprotective effect may be attributed to the contribution of the upregulated expression of genes associated with endogenous antioxidant pathways to oxidative stress reduction. In addition, liraglutide stimulates autophagy through AMPK activation, which attenuates the accumulation of HTT aggregates within neuronal cells. Our findings collectively suggest that liraglutide can rescue impaired insulin signaling caused by mHTT and that GLP-1 may potentially reduce mHTT-induced neurotoxicity in the pathogenesis of HD.
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Medicine & Pharmacology, Psychiatry & Mental Health studies; psychiatry; gut microbiome; probiotics
Online: 27 July 2018 (03:22:02 CEST)
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The microbiome gut brain (MGB) axis involves bidirectional routes of communication and has emerged as a potential therapeutic target for multiple medical specialities including psychiatry. Significant numbers of preclinical trials have taken place with some transitioning to clinical studies in more recent years. Some positive results have been reported secondary to probiotic administration in both healthy populations and specific patient groups. This review aims to summarise the current understanding of the MGB axis and the preclinical and clinical findings relevant to psychiatry. The link between the gut microbiome and irritable bowel syndrome (IBS) is well established. Significant differences have been identified between the microbiome of patients with a diagnosis of depressive disorder and healthy controls. Similar findings have occurred in patients diagnosed with bipolar affective disorder. A probiotic containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum produced clinically measurable symptom improvement in patients with depressive disorder. To date some promising results have suggested that probiotics could play a role in the treatment of stress-related psychiatric disease. However, more well-controlled clinical trials are required to determine which clinical conditions are likely to benefit most significantly from this novel approach.
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Medicine & Pharmacology, Gastroenterology; 4-Hydroxynonenal; lipid peroxidation; redox balance; oxidative stress; stomach; peptic ulcer; gastritis; Helicobacter pylori; gastric cancer; non-steroid anti-inflammatory drugs-induced gastropathy
Online: 27 July 2018 (03:07:19 CEST)
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The integrity, high functional activity and sufficient regeneration rate of gastric mucosa (GM) in harsh conditions is very challenging pathophysiological demand. The health of gastric epithelium highly depends of efficiency of redox balance maintenance, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in (patho)physiological adaptive reactions, cells signaling, and are also implicated in pathogenesis of numerous gastric diseases. However, while mechanisms and consequences of HNE and its protein adducts production in response to strong stressors during acute and chronic gastric injury are well studied, many other important issues related to gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, the relevance of antioxidants for HNE-related redox homeostasis in GM and many other still need extensive studies and new comprehensive approaches. Therefore, in order to address existing issues preclinical studies and clinical intervention trials are required, which should include also determination of HNE preferably by immunohistological and specific HNE-His ELISA analyses.
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Medicine & Pharmacology, Nutrition; inflammation; coronary disease; mediterranean diet; low-fat diet; C-reactive protein; adiponectin; visceral fat; body composition
Online: 26 July 2018 (10:33:01 CEST)
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The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.
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Medicine & Pharmacology, Other; app; somatotropin; serious games; gamification; digital; mobile health
Online: 26 July 2018 (04:41:50 CEST)
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Growth hormone (GH) deficiency affects up to 1 in 4,000 children and is usually treated with daily injections of GH whilst the child is still growing. With children typically diagnosed around 5 years old, this can mean over 10 years of therapy, which can place a considerable burden on the child and parent. Over three-quarters of children are estimated to be not fully compliant with therapy, which can compromise their chances of attaining their target height. In recent years, interactive mobile health (smart phone or tablet) interventions using game-like concepts, so called ‘gamification’, have increased in popularity and have demonstrated success in promoting positive self-management behaviour in children with chronic conditions, such as diabetes. The application of gamified interventions has the potential to support adherence to therapy and positive behaviour in children with GH deficiency in a number of ways: 1) By providing education in a format that the child understands and accepts (e.g. using behavioural constructs to facilitate explaining why adherence is important); 2) By providing a mechanism to reduce the anxiety and stress associated with administering the injection (e.g. diversion with a virtual pet); and 3) By providing feedback to encourage on-going engagement (e.g. rewards, progression through levels).
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Medicine & Pharmacology, Nursing & Health Studies; southeast Europe; immigrant; healtcare
Online: 26 July 2018 (04:08:21 CEST)
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BACKGROUND: We investigated whether immigrants from Southeast Europe (SE) and Swiss patients have different reasons for visiting the emergency department (ED). METHODS: Our retrospective data analysis for the years 2013-2017 describes the pattern of ED consultations for immigrants from SE living in Switzerland (Canton Bern), in comparison with Swiss nationals, with a focus on type of referral and reason for admission. RESULTS: A total of 153,320 Swiss citizens and 12,852 immigrants from SE were included in the study. The mean age was 51.30 (SD=21.13) years for the Swiss patients and 39.70 (SD=15.87) years for the SE patients. For some countries of origin (Albania, Bosnia and Herzegovina, and Turkey), there were highly statistically significant differences in sex distribution with the predominance for male. SE immigrants had a greater proportion of patients in the lower triage level (level 3: SE: 67.3% vs. Swiss: 56.0%) and a greater proportion of patients in the high triage level than the Swiss population (level 1: SE: 3.4% vs. Swiss: 8.8%,). SE patients of working age (16-65 years) were six times more often admitted by ambulance than older (≥65 years) SE patients, whereas in the Swiss population this ratio was similar. In both groups, fast track service was primarily used for patients of working age (<65) and more than three times more often in the SE than the Swiss group (SE: 39.1%, Swiss: 12.6%). CONCLUSION: We identified some indications in access to primary care in Emergency Department for immigrants highlighting the need for attention to the role of organizational characteristics of primary health care in the Switzerland. The authors have highlighted the need for professional support to improve the quality of healthcare for immigrants. In the future, more primary care services and general practitioners will need to be provided with a migrant background.
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James Dorling,
David Broom,
Stephen Burns,
David Clayton,
Kevin Deighton,
Lewis James,
James King,
Masashi Miyashita,
Alice Thackray,
Rachel Batterham,
David Stensel
Medicine & Pharmacology, Nutrition; appetite; energy intake; appetite-related hormones; energy balance; exercise; physical activity; energy compensation; weight control
Online: 25 July 2018 (16:20:17 CEST)
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Exercise facilitates weight control, partly through effects on appetite regulation. Single bouts of exercise induce a short-term energy deficit without stimulating compensatory effects on appetite, whilst limited evidence suggests that exercise training may modify subjective and homeostatic mediators of appetite in directions associated with enhanced meal-induced satiety. However, large variability in responses exists between individuals. This article reviews the evidence relating to how adiposity, sex and habitual physical activity modulate exercise-induced appetite, energy intake and appetite-related hormone responses. The balance of evidence suggests that adiposity and sex do not modify appetite or energy intake responses to acute or chronic exercise interventions, but individuals with higher habitual physical activity levels may better adjust energy intake in response to energy balance perturbations. The effect of these individual characteristics and behaviours on appetite-related hormone responses to exercise remains equivocal. These findings support the continued promotion of exercise as a strategy for inducing short-term energy deficits irrespective of adiposity and sex, as well as the ability of exercise to positively influence energy balance over the longer term. Future well-controlled studies are required to further ascertain potential mediators of appetite responses to exercise.
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Medicine & Pharmacology, Other; mobility; hospitalization; older adults; implementation
Online: 25 July 2018 (16:03:50 CEST)
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Immobility during hospitalization is widely recognized as a contributor to deconditioning, functional loss, and increased need for institutional post-acute care. Several studies have demonstrated that inpatient walking programs can mitigate some of these negative outcomes, yet hospital mobility programs are not widely available in U.S. hospitals. STRIDE is a supervised walking program for hospitalized older adults that fills this important gap in clinical care. Herein we describe how STRIDE works and how it is being disseminated to other hospitals using the Replicating Effective Programs (REP) framework. Guided by REP, we define core components of the program and areas where the program can be tailored to better fit the needs and local conditions of its new context (hospital). We describe key adaptations made by 4 hospitals who have implemented the STRIDE program and discuss lessons learned for successful implementation of hospital mobility programs.
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Medicine & Pharmacology, Other; sepsis; dysregulation; adaptation; evolution; natural selection; medical reversal
Online: 25 July 2018 (13:19:58 CEST)
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For decades, sepsis research has been motivated by the idea of a dangerous overreaction of the immune system in sepsis. But is it true that the response to sepsis is dysregulated? This review surveys the history of sepsis trials and found that evidence for dysregulation does not exist in many of the physiologic mechanisms of sepsis. It is time to consider the alternative hypothesis, that sepsis traits are often functional, and do more harm than good. This review discusses the implications of this perspective for the future of sepsis research
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Medicine & Pharmacology, Behavioral Neuroscience; protein tau; Alzheimer’s disease; neurodegenerative disease; synaptic dysfunction; Aβ-peptides; tau-imaging
Online: 25 July 2018 (12:10:18 CEST)
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One of the most commonly known chronic neurodegenerative disorders is Alzheimer’s disease (AD) that manifests the common type of dementia in 60-80% of AD cases. From a clinical standpoint, a patent cognitive decline and a severe change in personality, as caused by a loss of neurons, is usually evident in AD with about 50 million people affected in 2016. The disease progression in patients is distinguished by a gradual plummet in cognitive functions, eliciting symptoms like memory loss, and eventually requiring full-time medical care. From a pathophysiological standpoint, the defining characteristics are intracellular aggregations of hyper-phosphorylated tau protein, known as neurofibrillary tangles (NFT) and depositions of amyloid β-peptides (Aβ) in the brain. The abnormal phosphorylation of tau protein is attributed to a wide gamut of neurological disorders known as tauopathies. In addition to the hyperphosphorylated tau lesions, neuroinflammatory processes could occur in a sustained manner through astro-glial activation, resulting in the disease progression. Recent findings have suggested a strong interplay between the mechanism of tau phosphorylation, disruption of microtubules, and synaptic loss and pathology of AD. The mechanisms underlying these interactions along with their respective consequences in Tau pathology are still ill-defined. Thus, in this review, (1) we highlight the interplays existing between Tau pathology and AD and, (2) take a closer look into its role while identifying some promising therapeutic advances including state of the art imaging techniques.
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Medicine & Pharmacology, Pathology & Pathobiology; pheochromocytoma; paraganglioma; GAPP; metastasis; prognosis; catecholamine; gene mutation; immunohistochemistry; pathology; diagnosis
Online: 25 July 2018 (11:41:52 CEST)
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Pheochromocytoma and sympathetic paraganglioma (PPGL) are rare neuroendocrine tumors characterized by catecholamine production in the adrenal medulla and extra-adrenal paraganglia. PPGL with metastasis was termed malignant PPGL. However, the distinction between “benign” and “malignant” PPGLs has been debated. Currently, all PPGLs are believed to have some metastatic potential and are assigned malignant tumors (ICD-O/3) by the WHO Classification of Endocrine Organs (2017, 4th edition). Therefore, the previous categories benign and malignant PPGL have been eliminated in favor of a risk stratification approach. The Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) is a tool for risk stratification for predicting metastasis and the prognosis of patients. At least 30% of PPGLs are hereditary, with 20 genes identified and genotype-phenotype correlations clarified. Of these, VHL, RET, and NF1 have been well investigated and are the primary cause of bilateral PCC. In addition, succinate dehydrogenase gene subunits SDHB and SDHD are strongly correlated with extra-adrenal location, younger age, multiple tumors, metastasis, and poor prognosis. Disease stratification by catecholamine phenotype and molecular profiling correlates with histological grading by GAPP. PPGLs should be understood comprehensively based on clinical, biochemical, molecular, and pathological data for patient care. A flow chart for pathological diagnosis is included.
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Medicine & Pharmacology, Oncology & Oncogenics; BRCA1, BRCA2, Hereditary Breast and Ovarian Cancer, Lynch Syndrome, Hereditary cancer, Family history screening. Risk assessment, Digital tool, Health information technology
Online: 25 July 2018 (09:59:26 CEST)
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The number of individuals meeting criteria for genetic counseling and testing for hereditary cancer syndromes (HCS) is far less than the number that actually receive it. To facilitate identification of patients at risk for HCS, Counsyl developed a digital identification tool (digital ID tool) to match personal and family cancer history to National Comprehensive Cancer Network (NCCN) BRCA-related Hereditary Breast and Ovarian Cancer (HBOC), Lynch syndrome, and polyposis testing criteria in one-to-one, automated fashion. The purpose of this study was to validate the ability of the digital ID tool to accurately identify histories that do and do not meet NCCN testing criteria. Methods: Third-party recorded three-generation pedigrees were retrospectively reviewed by a certified genetic counselor (CGC) to determine if independent events included in pedigree histories met NCCN guidelines, and were then sorted into groups: high risk events (meets criteria) and low risk events (does not meet criteria). Events were entered into the digital ID tool to determine the extent of its concordance with events sorted by CGC review. Statistical tests of accuracy were calculated at a 95% confidence interval (CI). Results: 197 pedigrees were reviewed consecutively representing 765 independent events for analysis across groups. 382/382 (100%) high risk events identified by the digital ID tool and 381/383 (99.47%) low risk events identified by the digital ID tool were concordant with CGC sorting. The digital ID tool had a sensitivity of 100% (99.04-100% CI) and specificity of 99.48% (98.13-99.94% CI). The overall accuracy of the digital ID tool was estimated to be 99.74% (99.06-99.97% CI), reflecting the rate at which the digital ID tool reached the same conclusion as that of CGC review of pedigree events for the recommendation of genetic testing for individuals at risk for HCS. Conclusions: The digital ID tool accurately matches NCCN criteria in one-to-one fashion to identify at-risk individuals for HCS and may be useful in clinical practice, specifically for BRCA-related HBOC and Lynch Syndrome.
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Medicine & Pharmacology, Obstetrics & Gynaecology; caffeine; coffee; epidemiology; recall bias; misclassification; residual confounding; reverse causation; publication bias
Online: 25 July 2018 (05:57:48 CEST)
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Consumption of coffee by women early in their pregnancy has been viewed as potentially increasing the risk of miscarriage, low birth weight, and childhood leukemias. Many of these reports of epidemiologic studies have not acknowledged the potential biases inherent in studying the relationship between early-pregnancy-coffee consumption and subsequent events. I discuss five of these biases, recall bias, misclassification, residual confounding, reverse causation, and publication bias. Each might account for claims that attribute adversities to early-pregnancy-coffee consumption. To what extent these biases can be avoided remains to be determined. At a minimum, they need to be acknowledged wherever they might account for what is reported.
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Medicine & Pharmacology, Sport Sciences & Therapy; secretory IgA; human alpha defensin; aerobic training
Online: 25 July 2018 (05:50:35 CEST)
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Exercise is a stressor that is known to in some cases suppress antimicrobial protein levels, particularly secretory immunoglobulin type A (IgA). Athletes in the midst of in-season training often demonstrate declining levels of sIgA as well as increased risk for ailments such as upper respiratory tract infections. Therefore, it is important to investigate natural supplements that may enhance post exercise mucosal immune function. Methods: Twenty healthy college-aged males volunteered to participate in the present single blind, repeated measures study. Three treatments were administered (botanical spray, botanical drops, placebo) at the onset of 30 minutes of 80% VO2 max cycle ergometer exercise. Secretory IgA and Human Alpha Defensin were quantified in saliva samples 30 minutes and 90 minutes post exercise. Results: Analysis via repeated measures Anova revealed a significant treatment effect at 30 min (p=0.030) with post hoc testing revealing a difference between the botanical spray and placebo (p=0.027), but by 90 minutes there was no differences by treatment (p=0.758). There was no difference by treatment observed at either 30 or 90 minutes for human alpha defensin concentrations. Conclusions: Based upon these preliminary data, it appears that a single dose of the tested botanical blend delivered via mouth spray can increase sIgA, one of the primary anti-microbial proteins in the oral cavity, for a short time post exercise.
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Medicine & Pharmacology, Oncology & Oncogenics; stereotactic radiosurgery (SRS); stereotactic radiotherapy (SRT); brain metastasis; immunotherapy; whole brain radiotherapy (WBRT)
Online: 24 July 2018 (11:47:15 CEST)
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Stereotactic radiosurgery (SRS) has become increasingly important in the management of brain metastases due to improving systemic disease control and rising incidence. Initial trials demonstrated SRS with whole brain radiotherapy (WBRT) improved local control rates versus WBRT alone. Concerns with WBRT associated neurocognitive toxicity have contributed to greater use of SRS alone, including for patients with multiple metastases and following surgical resection. Molecular information, targeted agents and immunotherapy have also altered the landscape for the management of brain metastases. This review summarises current and emerging data on the role of SRS in the management of brain metastases.
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Medicine & Pharmacology, Dentistry; genetic factors; dental implants; bone quality; bone regeneration; success rate
Online: 24 July 2018 (06:01:10 CEST)
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Dental implants provide a predictable treatment option for partial and complete edentulism via the placement of fixed permanent artificial root to support prosthetic dental crowns. Despite the high survival rates, long-term implant failures are still reported leading to implant removal and additional financial and health burdens. While extrinsic factors that improve survival rate of implants have been well explored, the impact of genetic factors on this matter is poorly understood. A systematic review and meta-analysis study was conducted to determine whether genetic factors contribute to increase the risk of dental implant failure. A comprehensive search for peer-reviewed articles on dental implants and genetics was performed using various literature database libraries. The study design was conducted according to PRISMA guidelines, and the obtained records were registered in PROSPERO database. According to the exclusion/inclusion criteria, 11 studies were eligible for this study out of 808 articles. The meta-analysis of the combined association studies of DNA variations and dental implants did not indicate an increase risk for implant failure due to DNA variations in IL-1B, IL-10 and TNF-α. This study emphasizes the need for larger randomized controlled clinical trails to inform clinicians and patients about the role of genetic factors on dental implant survival and success rate in healthy and compromised patients.
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János Sándor,
Anita Pálinkás,
Ferenc Vincze,
Nóra Kovács,
Sipos Valéria,
László Kőrösi,
Zsófia Falusi,
László Pál,
Gergely Fürjes,
Magor Papp,
Róza Ádány
Medicine & Pharmacology, Other; Roma minority, legal constrains, health care utilization, health status, geographical inequality
Online: 23 July 2018 (14:27:34 CEST)
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Roma is the largest ethnic minority of Europe with poor health status, which is poorly explored due to legal constrains of ethnicity assessment. We aimed to elaborate health-indicators for adults living in segregated Roma settlements (SRS) representing the most vulnerable Roma subpopulation. SRSs were mapped in a study area populated by 54682 adults. Records of all adults living in the study area were processed in the National Institute of Health Insurance Fund Management. Aggregated, age-sex standardized SRS-specific and non-SRS-specific indicators on healthcare utilization and premature death along with the ratio of them (RR) were computed with 95% confidence intervals. The rate of GP appointments was significantly higher among SRS inhabitants (RR=1.152, 95%CI: 1.136–1.167). The proportion of subjects hospitalized (RR=1.286, 1.177–1.405), and the reimbursement for inpatient care (RR=1.060, 1.057–1.064) were elevated for SRS. Premature mortality was significantly higher in SRSs (RR=1.711, 1.085-2.696). Our study demonstrated that it is possible to compute the SRS-specific version of the routine healthcare indicators without violating the protection of personal data by converting a sensitive ethical issue to a non-sensitive small area geographical analysis; there is an SRS-specific healthcare utilization pattern, which is associated with elevated costs and increased risk of premature death.
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Medicine & Pharmacology, Nutrition; Ginsenoside Rh2; Lipopolysaccharide; Acute lung injury; MEK; Nrf-2;
Online: 23 July 2018 (13:05:06 CEST)
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The anti-inflammatory effect of ginsenoside Rh2 (GRh2) is one of the most important ginsenosides. The purpose of this study is to identify the anti-inflammatory and antioxidant effects of GRh2 after LPS challenge lung injury animal model. GRh2 reduced LPS-induced NO, TNF-α, IL-1, IL-4, IL-6 and IL-10 productions in lung tissues. GRh2 treatment decreased the histological alterations in the lung tissues and BALF protein content and total cells number also diminished in LPS-induced lung injury mice. Moreover, GRh2 blocked iNOS, COX-2, the phosphorylation of IκB-α, ERK, JNK, p38, Raf-1 and MEK protein expression which is corresponded to the growth of HO-1, Nrf-2, catalase, SOD and GPx expressions in LPS-induce lung injury. An experimental study has suggested that GRh2 has provided with anti-inflammatory effects in vivo, and its potential therapeutic efficacy in major anterior segment lung diseases.
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Medicine & Pharmacology, Dermatology; hyperpigmentation; palpebral region; geographic skin differences; ethnic predisposition; skin disorder;
Online: 23 July 2018 (12:56:47 CEST)
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POH (Peri Orbital Hyperpigmentation) represents a minor clinical entity that attracts immense aesthetic damages and it generates social integration difficulties. This review focuses on the etiopathogenic causes of this entity, differentiating and reclassifying this defect as having, on the one hand, genetic causes of melanic hyperproduction – for Fitzpatrick cutaneous phototypes IV and V – and, on the other hand, both genetic and acquired vascular causes, in individuals with light-coloured skin phototypes. Hence, there is a big difference in the field of pathogenic treatment, for the two entities. In addition, this study notes the direct relationship between skin aging and POH, especially for aquired vascular causes. In this reasoning, other aesthetic deficiencies of the skin in the palpebral area should be also considered, like: blepharochalasis, wrinkles, the anatomical causes of the lower eyelid shading, symmetrical or asymmetric suborbital oedema. All of these issues will complicate the therapeutic decision and subsidiary, the pharmaceutical advice. In this context, the review shows the guidelines for a honest councelling of the patients, pointing the efficiency limit for the topical pharmaceutical medication (depigmentants, exfoliants) versus the necessity of minimally invasive or/ and surgical treatments (in blefarochalasis).
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Medicine & Pharmacology, Urology; neurogenic bladder, botulinum toxin, bladder overactivity, urodynamics, child
Online: 23 July 2018 (12:48:56 CEST)
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The aim of this study was to evaluate the usefulness of cystoscopic injection of Botulinum-A toxin (BTX) in the detrusor wall in the treatment of children with decreased bladder capacity due to neurogenic bladder.
The prospective, randomized non placebo controlled trial is conducted in our institution since year 2006 with the approval of the local Ethics Committee.
556 cystoscopic injections of BTX were performed in 141 children with neurogenic bladder in age 1 to 18 years.
In all cases decreased bladder capacity and bladder overactivity with urine incontinence were estimated.
The pre-and post-treatment evaluations included determination of urinary continence status, bladder function in frequency/volume chart of catheterized urine and in urodynamic studies. Parameters measured in urodynamic investigations included maximal cystometric capacity, detrusor reflex volume, maximal detrusor pressure.
Parameters were analyzed before the cystoscopy and during the follow-up examinations in 5 age groups.
Values of all measured parameters improved significantly and equally after therapy in every from 5 age groups.
The results obtained from the study confirmed that endoscopic administration of BTX improves function of urinary bladder in children with neurogenic bladder, and the method represents an alternative approach to conservative treatment and surgical augmentation.
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Medicine & Pharmacology, Dentistry; air-polishing; titanium; erythritol; chlorhexidine; biofilm; implants;
Online: 23 July 2018 (12:41:42 CEST)
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Abstract: Air-polishing with low abrasiveness powders is fats arising as a valid and mini-invasive instrument for the management of biofilm colonizing dental implants. The reported advantage is the efficient removal of plaque with respect of the titanium integrity. In the present study, we evaluated the in-situ plaque-removal and continual the post-treatment anti-bacterial efficacy of an innovative erythritol/chlorhexidine air-polishing powder and compared it with sodium bicarbonate. Two peri-implantitis-linked biofilm formers strains Staphylococcus aureus and Aggregatibacter actinomycetemcomitans were selected and used to infect titanium disks before and after the air-polishing treatment. Cells number and viability were assayed by colonies forming units (CFUs) count and metabolic-colorimetric (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) (XTT) assay. Air-polishing performed with either sodium bicarbonate or erythritol/chlorhexidine was effective in reducing bacteria biofilm viability and number onto pre-infected specimens, while erythritol/ chlorhexidine showed a higher post-treatment biofilm re-growth inhibition. Surface analysis via mechanical profilometry failed to show an increase in titanium roughness, regardless of the powder selected.
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Medicine & Pharmacology, General Medical Research; iron deficiency anemia; obestatin; ghrelin
Online: 23 July 2018 (12:34:21 CEST)
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Ghrelin and obestatin, two antagonist peptide hormones, are purportedly involved in stimulating appetite and controlling energy balance in humans. Serum ghrelin level is also associated with iron deficiency anemia (IDA), but no study has yet been made of the obestatin level in patients with IDA, even though both hormones are a single gene product. Therefore, the purpose of this investigation is to see whether there is a link between IDA and these two hormones among other hematological parameters in patients with IDA. To measure ghrelin and obestatin, human saliva and serum were collected from 30 women with IDA, aged 31.7 ± 10.7 years, and 30 control women, aged 30.2 ± 8.0 years, with repeated collection of samples over a period of 1 week and 1 month. Saliva and serum ghrelin levels were measured by ELISA. Serum hemoglobin, ferritin, hematocrit and total iron-binding capacity (TIBC) values were determined with an Olympus AU2700. Saliva and serum ghrelin and obestatin levels were significantly lower in the IDA group compared with controls; these levels increased slightly above baseline with iron treatment, but remained below the control values. Furthermore, and as expected, serum hemoglobin, ferritin, and hematocrit levels were significantly increased with iron treatment, while total iron-binding capacity decreased compared to baseline concentrations. The findings suggest that IDA might be linked to imbalance of circulating (serum) and non-circulating (saliva) ghrelin and obestatin levels. Decreased ghrelin and obestatin might destroy iron homeostasis through its effect on intestinal absorption. Measuring these hormone levels might be useful for monitoring the response to iron treatment. Also, serum and saliva levels for both hormones were well correlated. Thus, using saliva in place of serum for monitoring the two hormones should minimize inconvenience and patient discomfort.
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Y. Vandenplas,
B. Berger,
V.P. Carnielli,
J. Ksiazyk,
H. Lagström,
M. Sanchez Luna,
N. Migacheva,
J.M.M. Mosselmans,
J.C. Picaud,
M. Possner,
A. Singhal,
M. Wabitsch
Medicine & Pharmacology, Pediatrics; breast feeding; formula feeding; human milk oligosaccharide; 2’-fucosyllactose; Lacto-N-neotetraose; microbiota; bifidobacteria
Online: 23 July 2018 (11:34:09 CEST)
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Introduction The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies, as well as to evaluate published data on the addition of some of HMOs to infant formula. Method PubMed was searched from inception to April 2018 Results The presence of HMOs is a dynamic process, determined by many factors such as duration of lactation, environmental and genetic factors. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. Only a few of the many HMOs can be made industrially, and are added to infant formula. They have been shown to be safe and well tolerated, including normal growth and a trend towards health benefit. Conclusions HMOs are one of the major differences between cow’s milk and human milk , and evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk.
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Medicine & Pharmacology, Psychiatry & Mental Health studies; HPA axis, Bipolar II disorder, perturbation, cortisol
Online: 23 July 2018 (11:28:30 CEST)
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Using analytic approach we study the effect of HPA axis secretions to the emotional variation of bipolar II disorder patient. Modified Duffing – Van der Pol oscillator was used to model the emotional variation, that was solved analytically using multiple scale perturbation to obtain an asymptotic solution. The solution was graphed to understand the effect of the variation of the cortisol to the oscillator. It was observed that the increase or decrease of the HPA hormone from the basal level in the body system, affects the mood variation of bipolar II disorder patients.
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Medicine & Pharmacology, Nutrition; lycopene; carotene; retinoic acid; retinoid; vitamin A; RAR; RXR
Online: 23 July 2018 (11:08:13 CEST)
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In the human organism various carotenoids are present of which, some are retinoid precursors. The bioactive derivatives of these retinoids are the retinoic acids, which can potently activate nuclear hormone receptors like the retinoic acid receptor and the retinoid X receptor. In our study using an HPLC analytical approach we aimed to assess how plasma carotenoid and retinoid concentrations along with the ratio of their isomers are altered in atopic dermatitis (AD) patients (n=20) compared to healthy volunteers (HV, n=20). We found that plasma levels of the carotenoids lutein (HV 198 ± 68 ng/ml, AD 158 ± 57 ng/ml), zeaxanthin (HV 350 ± 142 ng/ml, AD 236 ± 85) as well as the retinoids retinol (HV 216 ± 89 ng/ml, AD 167 ± 76 ng/ml) and all-trans-retinoic acid (HV 1.1 ± 0.6 ng/ml, AD 0.7 ± 0.5 ng/ml) were significantly lower in AD-patients, while lycopene, α-carotene and β-carotene levels were comparable. In addition the ratios of 13-cis vs. all-trans lycopene as well as 13-cis vs. all-trans retinoic acid were increased in the plasma of AD-patients indicating an AD-specific 13C-isomerisation. A positive correlation with SCORRAD was calculated with 13-cis vs. all-trans lycopene ratio, while a negative correlation was observed with zeaxanthin plasma levels. Based on our results we conclude that in the plasma of AD-patients various carotenoids and retinoids are at lower levels, while the ratio of lycopene isomers was also altered. The higher rate of lycopene and retinoic acid isomerisation products might be a consequence of AD or might result in an altered activation of nuclear hormone receptor signaling pathways and thus maybe partly be responsible for the AD-phenotype and additionally may represent a good plasma marker for AD.
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Medicine & Pharmacology, Other; quality of work life; organizational culture; organizational support; self-efficacy; maritime workers; culture-work-health model
Online: 23 July 2018 (10:00:06 CEST)
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Using the culture-work-health model, this study investigates the factors influencing the quality of life of maritime workers. This study conducted a survey of 320 maritime workers who have experience living and working on a ship for more than six months. This self-administered questionnaire included questions on organizational culture and support, self-efficacy, perceived fatigue, as well as the quality of work life. Organizational culture and self-efficacy were identified as factors affecting the quality of work life, while organizational support was found to have an indirect effect after passing through self-efficacy and perceived fatigue. The final model accounts for 63.1% of the variance in maritime workers’ quality of life. As such, this study shows that self-efficacy is important for the quality of life of maritime workers, having both direct and indirect effects. Moreover, organizational support may prove the primary intervention point for relieving perceived fatigue and enhancing self-efficacy, thus improving the quality of work life.
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Medicine & Pharmacology, Oncology & Oncogenics; lung cancer; environment; EE2; NP; estrogen receptor; EGFR
Online: 22 July 2018 (11:23:02 CEST)
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Lung cancer has been the leading cause of cancer death in the world. In addition to smoking, estrogen is supposed to play an important role in the lung cancer development because women have a higher proportion of adenocarcinoma than men. In the environment, there are many metabolites and wastes that mimic human estrogen structurally and functionally. As an oral contraceptive, 17α-ethynylestradiol (EE2) is released to wastewater after being utilized. Moreover, 4-nonylphenol (NP) exiting in the petrochemical products and air pollutants has estrogenic activity. In our study, 17β-estradiol (E2), EE2, and NP are administered to stimulate A549 male lung adenocarcinoma cells and H1435 female lung adenocarcinoma cells. The results demonstrate that EE2 and NP stimulate A549 and H1435 cells proliferation in a dose- and time-dependent trend. Both estrogen receptor α and β are activated simultaneously during these processes. Up-regulation of epidermal growth factor receptor (EGFR) and ERK expression is involved in response to estrogens. In conclusion, we first time report that EE2 and NP exert biotoxic effect to stimulate the proliferation of both male and female lung cancer cells in a dose- and time- response manner. New challenges from environmental hormones to lung cancer deserved further investigation.
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Medicine & Pharmacology, Nutrition; flavonoids; dark chocolate; genotoxicity; lipid metabolism; glucose metabolism
Online: 22 July 2018 (11:05:27 CEST)
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In recent years, Atherosclerotic Cardiovascular Disease (ACVD), Obesity and Diabetes, have increase exponentially worldwide. In the present work, we evaluate the genoprotective effect of consuming a flavonoids-rich chocolate and the improvement in the biochemical parameters related to the prevention and treatment of cardiovascular risk and metabolic syndrome in young Mexican adults. A randomized, placebo-controlled, double-blind study was undertaken in the Autonomous University of Baja California. The treatments were a daily intake of 2 grams of dark chocolate containing 70% cooca or milk chocolate. Total phenolic compounds and flavonoids were evaluated in both chocolates. Anthropometrical and Biochemical parameters were measured in the 84 participants before and after the study. Buccal epithelial genotoxicity was also evaluated from the beginning to the end of the experiment in the participants. Result suggested that flavonoids of cocoa intake have protective effects against DNA damage, and Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were also improved after six months of daily intake of 2 grams of dark chocolate with a 70% of cocoa.
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Medicine & Pharmacology, Other; diabetes mellitus; sepsis; diabetes complication severity index score
Online: 22 July 2018 (10:54:29 CEST)
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Background Diabetic patients have an increased risk of infections; however, the association between type 2 diabetes and hospital outcomes of sepsis remains controversial when the diabetes severity is not considered. We examined this association using nationwide and hospital-based databases concomitantly. Methods The first part of this study was conducted using 2 nationwide databases: the Longitudinal Cohort of Diabetes Patients and the Longitudinal Health Insurance Database 2000. The diabetic complication burden was evaluated using the adapted Diabetes Complications Severity Index score (aDCSI score). In the second part, we used the hospital-based database with laboratory data, such as initial blood glucose and HbA1c levels, to make comparisons between surviving and dead patients with type 2 diabetes and sepsis. Results The nationwide study included 19,719 type 2 diabetic sepsis patients and an equal number of non-diabetic patients. The diabetic sepsis patients had an increased odds ratio (OR) of 1.14 (95% CI 1.1-1.19) for hospital mortality. The OR for mortality increased as the complication burden increased (diabetic sepsis patients with aDCSI scores of 0, 1, 2, 3, 4, and ≥5 had ORs of 0.91, 0.87, 1.14, 1.25, 1.56, and 1.77 for mortality, respectively (all P<0.001 and P for trend <0.001)). A total of 1,054 diabetic sepsis patients were included from the hospital-based database. Initial blood glucose levels in the surviving and dead diabetic sepsis patients did not differ significantly: 273.9 ± 180.3 versus 266.1 ± 200.2 (mg/dL) (P=0.095). Moreover, the surviving diabetic sepsis patients did not have a lower HbA1c (%): 8.4 ± 2.6 versus 8.0 ± 2.5 (P=0.078). Conclusions In the case of type 2 diabetic sepsis patients, the diabetes-related complication burden is the major determinant of hospital mortality rather than the diabetes itself. Contrary to popular belief, initial blood glucose and HbA1c levels may not be as important as previously thought.
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Medicine & Pharmacology, General Medical Research; Flavonoids, nitric oxide, heart, kidney, sodium balance, phenylephrine, acetylcholine
Online: 20 July 2018 (12:57:00 CEST)
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We have evaluated the antihypertensive effect of several flavonoid extracts in the spontaneous hypertensive rat model (SHR). Treatments were carried out for 6 and 12 weeks in two groups of SHR rats which received Apigenin, Lemon Extract, Grapefruit + Bitter Orange (GBO) extracts and Cocoa extract. Captopril was used as a positive control in the SHR group treated for 6 weeks (SHR6) and Diosmin was used as the industry reference in the SHR group treated for 12 weeks (SHR12). Captopril and GBO extracts significantly reduced the elevated blood pressure of the SHR6 animals, but none of the extracts was effective in the SHR12 group. Apigenin, LE, GBO and captopril also ameliorated nitric oxide-dependent and independent aortic vascular relaxation and elevated plasma and urinary excretion of nitrites, only in the SHR6 group. Kidney and urinary TBARS were also significantly reduced by GBO in the SHR6 rats. Apigenin also improved vascular relaxation in the SHR12 group and all the flavonoids studied reduced urinary TBARS excretion and proteinuria. Vascular abnormalities such as lumen/wall ratio in coronary arteries and thoracic aorta were moderately improved by these treatments in the SHR6 group. In conclusion, the flavonoids included in this study, especially apigenin, LE and GBO improved vascular vasodilatory function of young adult SHRs but only the GBO-treated rats benefited from a reduction in BP. These extracts may be used as functional food ingredients with a moderate therapeutic benefit, especially in the early phases of arterial hypertension.
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Medicine & Pharmacology, Nutrition; LPS; microbiota; inflammation; intestinal permeability; obesity
Online: 20 July 2018 (04:56:08 CEST)
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Obesity and chronic low-grade inflammation are becoming global epidemics. The dysbiosis has a specific role in the metabolism and energy stocks of the host. The discovery that a low-grade of inflammation could be directly connected to the intestinal microbiota metabolic endotoxemia (elevated levels of plasma lipopolysaccharides) has allowed the identification of novel mechanisms involved in the control of the intestinal barrier. In this review, it will analyze the latest news to explain how human symbiotic microorganisms participate in the growth of the fat reserves and promote insulin resistance as a low-grade inflammation. Besides, it will discuss new treatments with probiotics and prebiotics as a promising therapeutic approach to reverse the host's metabolic changes linked to dysbiosis observed in obesity.
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Medicine & Pharmacology, Sport Sciences & Therapy; table tennis; hue-saturation-value (HSV) image segmentation; low light source; automatic tracking
Online: 20 July 2018 (04:36:28 CEST)
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In table tennis competitions the rule violation judgment with the greatest controversy is the height of the ball serve. This is because inaccuracy in the ball height judgment, which results in erroneous judgment, is unavoidable. Thus, we designed an automatic image judgment auxiliary system for table tennis ball height during service in this study. We used a high-speed camera to record the ball toss in the table tennis service. The designed algorithm architecture can automatically search for the ball and the position of the hand action under low light source conditions. The algorithm is mainly divided into hue-saturation-value color space processing and morphology processing using Hough transform to search for the circular ball. Experiment result shows that color segmentation can successfully and accurately determine the ball position under low light conditions. The morphology method can find the position of the hand and help determine the moment when the ball leaves the hand during the service ball toss. Finally, the actual size of the target is used to estimate the actual distance unit represented by the image pixel.
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Aline de Sousa Barbosa Freitas Pereira,
Gerly Anne de Castro Brito,
Maria Laura de Souza Lima,
Arnóbio Antônio da Silva Júnior,
Emanuell dos Santos Silva,
Adriana Augusto de Rezende,
Raul Hernandes Bortolin,
Maria Galvan,
Flavia Q. Pirih,
Raimundo Fernandes de Araújo Júnior,
Caroline Addison Carvalho Xavier de Medeiros,
Gerlane Coelho Bernando Guerra,
Aurigena Antunes de Araújo
Medicine & Pharmacology, Dentistry; nanoparticles; poly lactic-co-glycolic acid; metformin; periodontal disease; inflammation
Online: 20 July 2018 (03:40:29 CEST)
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The aim of this study was synthesize and evaluate the effects of Poly (D, L-Lactide-co-glycolide) (PLGA) Nanoparticles (NPs) of metformin (PLGA+ Met) on inflammation, and bone loss in a ligature-induced periodontitis rat model. The prepared NPs were characterized by mean diameter, size particle, polydispensity index and encapsulation efficiency by Atomic force microscopy (AFM). Male albino Wistar rats were randomly divided into four groups of 20 rats in each group, and given the following treatments for 10 days to evaluate in vivo activity: (1) Sham: no ligature + water; (2) Positive control: ligature + water (with Periodontal disease and Diabetes); (3) ligature + PLGA+ 10 mg/kg Met (With Periodontal disease and Diabetes); and (4) ligature + PLGA+ 100 mg/kg Met (with Periodontal disease and Diabetes). Water or PLGA + Met was administered orally by gavage. Maxillae were fixed and scanned using Micro-computed Tomography (μCT) to quantify linear of bone loss. Histopathological characteristics were assessed through immunohistochemical staining for Osteocalcin, Cathepsyn K, RANKL/RANK/OPG pathway. IL-1β and TNF-α from gingival tissues were analysed by Elisa immunoassay. Quantitative RT-PCR reaction was used to evaluate gene expression of AMPK, NF-κB p-65, Hmgb1 and TAK-1 from gingival tissues. Statistical analysis was performed using one-way ANOVA at 5% significance. The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm with a polydispersity index of 0.285, zeta potential: 8.16 ± 1.1 mV and entrapment efficiency (EE) was 70%. The results suggest that the addition of MET in the core slightly affected the particle sizes. Treatment with PLGA+ 10 mg/kg Met showed low inflammatory cells, decreased bone loss and integrity cement and levels of IL-1β, and TNF-α (p < 0.05) were significantly reduced. Additionally, weak staining was shown by RANKL, Cathepsyn K, OPG, and osteocalcin. Radiographically, linear measurements showed a statistically significant reduction in bone loss after treatment with PLGA+ 10 mg/kg Met compared to the positive control (p < 0.05). RT-PCR showed increased AMPK expression (p < 0.05) and decreased expression of NF-κB P65, HMGB1 and TAK-1 after PLGA+ 10 mg/kg Met (p < 0.05). The PLGA nanoparticle + 10 mg/kg Met decreased glucose levels and also decreased the inflammatory response, and bone loss in ligature-induced periodontitis in rats.
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Medicine & Pharmacology, Nursing & Health Studies; alcoholism, health professionals’ attitudes, social perception, drugs-adictions
Online: 19 July 2018 (15:18:09 CEST)
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Knowing professionals’ attitudes is the basis for the development of skills for dealing with drug dependence. These attitudes may affect patients’ clinical safety and the cost-benefit ratio of the interventions. The goal of this study was to assess emergency and mental health nurses’ attitudes and perceptions towards alcoholics. A multicenter prospective descriptive study was conducted in six hospitals with 167 emergency and mental health nurses. Nurses classified alcoholics as sick individuals, although there was a tendency to feel comfortable working with them. Results indicated that these professionals had a rejecting attitude towards moderate alcohol consumption. We found a significant association between the attitude of the nurse and gender, with the degree of rejection towards the alcoholic being higher in men than in women and with less punitive attitudes in professionals from 0 to 11 years of professional experience.
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Medicine & Pharmacology, Cardiology; cardiopulmonary lesions, endocrine disruptors, ID3, vascular dysfunction, vascular remodeling
Online: 19 July 2018 (12:57:32 CEST)
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Cardiopulmonary lesions, which manifest from various types of diseases such as pulmonary arterial hypertension, atherosclerosis, pulmonary arteriovenous malformations, lymphangioleiomyomatosis, and peripheral arterial disease, pose a public health problem. Vascular remodeling, which refers to alternations to the structure of the vessel is an important pathophysiological feature of these diseases. The Inhibitor of DNA-binding/Differentiation-3 (ID3), which is part of the ID family of transcriptional regulators, has been demonstrated to contribute to an essential role in the vasculature and therefore may influence the alterations of these lesions. This review will cover the existing understanding of how ID3 may contribute to cardiopulmonary lesion perturbations via involvement in vascular remodeling. Furthermore, based on the accumulative quantity of reports that indicate oxidative stress plays a essential function in the pathophysiology of vascular remodeling, we will also consider the impact of exposure to estrogenic endocrine disruptors (EEDs) such as polychlorinated biphenyls (PCBs) and bisphenol A (BPA) on ID3 & cardiopulmonary disease. Improved understanding of how ID3 pathways contributes to these molecular mechanisms in the lesion will prospectively deliver beneficial information in the mediation of vascular remodeling associated with ID3 & EED exposure, which may play an essential role in cardiopulmonary disease prevalence.
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Medicine & Pharmacology, Pharmacology & Toxicology; annonacin; antitumor-promotion; gene and protein expressions; two-stage mouse skin tumorigenesis; histopathological examination
Online: 19 July 2018 (06:29:40 CEST)
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Annonacin, an annonaceous acetogenin isolated from Annona muricata has been reported to be strongly cytotoxic against various cell lines, in vitro. Nevertheless, its effect against in vivo tumor promoting activity has not been reported yet. Therefore, this study was aimed to investigate antitumor-promoting activity of annonacin via in vivo two-stage mouse skin tumorigenesis model and its molecular pathways involved. Annonacin 85 nM was topically applied to DMBA/TPA-induced ICR mice for 22 weeks of treatment. Histopathological examination of skin, liver and kidney as well as genes and proteins expression analysis were conducted. Annonacin significantly increased the tumor latency period and also reduced the tumor incidence, tumor burden and tumor volume, respectively. In addition, it also suppressed tumorigenesis manifested by significant reduction of hyperkeratosis, dermal papillae and number of keratin pearls on skin tissues. Annonacin also appeared to be non-toxic to liver and kidney. Significant modulation of both AKT, ERK, MTOR, p38, PTEN and Src genes and proteins were also observed in annonacin-targeted signaling pathway(s) against tumorigenesis. Collectively, results of this study indicate that annonacin is a potential therapeutic compound targeting tumor promoting stage in skin tumorigenesis by modulating multiple gene and protein in cancer signaling pathways without apparent toxicity.
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Medicine & Pharmacology, Ophthalmology; choroidal neovascularization; neovascular age-related macular degeneration; calreticulin anti-angiogenic domain
Online: 19 July 2018 (06:20:54 CEST)
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Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.
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Medicine & Pharmacology, Ophthalmology; retinal pigment epithelium (RPE); oxidative stress; mitochondria; apoptosis; 2-oxoglutarate carrier (OGC); dicarboxylate carrier (DIC); glutathione (GSH); mitochondrial GSH (mGSH)
Online: 19 July 2018 (06:15:58 CEST)
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Mitochondrial dysfunction and oxidative stress are thought to be relevant to the pathogenesis of age-related macular degeneration (AMD). Glutathione (GSH) homeostasis fulfills a number of important roles in mitochondria, such as maintenance of mitochondrial DNA and respiratory competency of cells. Although the transport of mitochondrial GSH (mGSH) is not fully understood, increasing evidence from non-ocular tissues suggests that OGC (2-oxoglutarate carrier, SLC25A11) and DIC (dicarboxylate carrier, SLC25A10) are involved in mGSH transport. However, whether OGC and DIC mediate the transfer of GSH into the mitochondria of retinal pigment epithelial cells (RPE) remains unknown. Thus, we investigated the expression, localization, and function of OGC and DIC in human RPE (hRPE) in relation to oxidative stress and GSH. Both OGC and DIC are expressed in hRPE and are localized in mitochondria. We also found a dose and time-dependent decrease of OGC and DIC expression under oxidative stress and increased expression in polarized RPE. Our data show that the downregulation of OGC and DIC resulted in increased apoptosis and mGSH depletion which can be overcome by co-treatment with GSH-MEE. These findings suggest that overexpression of OGC and DIC may be an effective strategy to decrease susceptibility to mitochondrial toxicants by elevation of mGSH.
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Medicine & Pharmacology, Psychiatry & Mental Health studies; suicide; non-suicidal self-harm; adolescents; predictors
Online: 19 July 2018 (04:05:44 CEST)
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Suicide and self-harm are very common among adolescents, especially females in western and Asian countries. The Psychosocial predictors, along with hopelessness and non-suicidal harm, have not been studied properly before. Therefore, there is a need to address these issues. The objective of the study was to ascertain the psychosocial and clinical features predicting suicide attempts and non-suicidal self-injury (NSSI) in adolescents with major depression in Pakistan. The Methodology comprised of Adolescent patients (n = 121) with major depressive disorder who were hospitalized in the LRH (Lady Reading Hospital), Peshawar. The patient’s clinical symptoms, family role (family responsibilities), quality of life, physical health and relationship with friends and family members were evaluated. Participants’ suicidal thoughts and behaviors and NSSI (self-inflicted, deliberate self-harm with no intent of suicide) were analyzed and assessed during hospitalization and followed up for 28 weeks. Poor family functions, as well as family problems and social problems, were the causative agents for adolescent’s high suicidality and non-suicidal self-harm. A history of Non-suicidal self-harm treatment is a clinical marker for suicidality. The previous suicidal attempts should be evaluated in depressed juvenile patients as indicators of future suicidal intent and behavior. Both suicidal and NSSI during the therapy and after treatment persisted in depressed adolescents who participated in the study. Major causes of suicide among our study participants were lost friend(s), drug abuse, living alone or not living with the family, disturbed parental marriage, sexual abuse, and other domestic problems.
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Medicine & Pharmacology, Other; Fibromyalgia; CFS/ME; manual therapy; integrative medicine; physiotherapy
Online: 18 July 2018 (12:26:20 CEST)
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Application of protocols without parameter standardization and rigorous controls has led manual therapy (MT) and other physiotherapy approaches to controversial outcomes. Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands. One way this can be achieved is by studying gene expression and additional physiological changes that associate to particular, parameter-controlled, treatments in animal models and translating this knowledge to properly design objective, quantitatively-monitored clinical trials. Here, we propose a Molecular Physiotherapy Approach (MPTA), requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports of MT that historically attribute benefits to these treatments. The review focuses in the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and CFS/ME. The systemic effect associated to mechanical-load responses is considered of particular relevance as it suggests that defined, low-pain areas could be selected for treatments with overall benefits, an aspect that might result essential to treat FM. Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, detrimental for CFS/ME patients, placing MT as a real option for integrative medicine programs to treat FM and CFS/ME.
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Medicine & Pharmacology, Other; health policy, VHA, VA, CMS TRICARE, Scandal
Online: 18 July 2018 (11:28:15 CEST)
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In 2014, a whistleblower reported that many U.S. veterans died while waiting for care at the Phoenix VHA. Problems with veteran’s care through 2018 reveal ongoing and systematic problem. In March 2018, the VA Inspector General identified critical deficiencies at the Washington, DC VA Medical Center including failures to track patient safety events accurately, ineffective sterile processing, and more than 10 thousand open or pending prosthetic / sensory aid consults. The VHA clearly has problems with access and quality in a budget-constrained environment. In this policy analysis, four separate interventions that address the gap between the magnitude as well as the use of the VHA’s fixed budget versus access and cost expectations are explored. These policy interventions include maintaining the status quo, returning to a “VHA-only” option, transitioning to a CMS central payer system, and consolidating care under the DoD TRICARE insurance plans. An objective evaluation suggests that extending TRICARE to veterans while phasing out the VHA’s care responsibilities, while politically unpalatable, would likely provide the best of four possible solutions under various criterion weighting schemes. A central payer solution under the CMS would also be viable consideration. A Friedman’s test with Wilcoxon rank sum post-hoc tests suggests that TRICARE patient perceptions of quality are superior to VHA and non-VHA / non-DoD (p<.001), that access provided by the TRICARE program is ranked second in terms of venue acceptance only to the CMS solution set based on primary provider acceptance, and that the cost per beneficiary of a TRICARE solution ($6.5K / beneficiary) is far better than a VHA-only solution ($14.0 K / beneficiary), the CMS central payer solution ($12.2K / beneficiary), or the status quo (between $12.2K and $14.0K / beneficiary). The intent of this paper is to provoke thoughtful consideration of solutions for providing access to high-quality healthcare for veterans within our outside of the VHA. In this policy analysis, separate interventions that address the gaps between cost, quality, and access are explored. These policy interventions include maintaining the status quo, returning to a VHA-only option, transitioning to a CMS central payer system, and consolidating care under TRICARE.
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Medicine & Pharmacology, Dentistry; ental fear; MDAS; oral health; bachelor of dental surgery (BDS) students
Online: 18 July 2018 (09:47:57 CEST)
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Objective The study aims to investigate dental fear in first and final year undergraduate dental students in India. Design Questionnaire survey. Setting BDS Students in four University dental colleges in India carried-out during 2013 and 2014. Subjects (materials) and methods: The students (n=614) were assessed using a pre-tested questionnaire. We estimated the level of dental fear by using the Modified-Dental-Anxiety-Scale (MDAS). Statistical tests were used: Fisher’s, Chi square and Mann Whitney U tests, Cluster analysis and multivariate regression analysis. Students had similar demographic and life-style patterns. Interventions: Assessed the level of dental fear among undergraduate dental students. Main outcome measures: The MDAS score (mean ± SD) for the first year BDS students was 12.96 ± 4.0 compared to 10.52 ± 3.40 for the final year group. Results: Six hundred and fourteen (n= 614) students from four dental colleges were included in this study.Seventy seven per cent were female (n= 478) and 23% were male (n=136). The mean age of the first year students was 18.31 years, and 21.54 years for the final year. First year BDS students had an increased level of dental fear (12.96 ± 4.0) compared to the final year (10.52 ± 3.40) which was highly significant (p<0.001). Conclusion(s): Dental fear was significantly higher amongst first year BDS students.
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Medicine & Pharmacology, Other; vitamin D; vitamin D deficiency; chronic kidney disease; proteinuria
Online: 18 July 2018 (08:39:27 CEST)
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Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)2-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.
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Medicine & Pharmacology, Nutrition; 24-methylenecycloartanyl ferulate, angiogenesis, PPAR-γ2, PPRE, Akt/mTOR, HoxA7, VEGF, LIF, HUVEC
Online: 17 July 2018 (09:10:14 CEST)
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We investigated the effect and molecular mechanism of 24-MCF-induced PPAR-γ2 on angiogenesis-related genes in MCF7 cells. cDNA microarray, semi-quantitative reverse transcription (RT)-PCR, and western blotting revealed that 24-MCF mediated the expression of genes related to angiogenesis in MCF-7 cells. Luciferase reporter assay demonstrated that promoter activation of the LIF gene, an anti-angiogenesis factor, was increased upon PPAR-γ2 overexpression and 24-MCF treatment, whereas activation of HoxA7 and VEGF promoters, known pro-angiogenesis factors, decreased upon PPAR-γ2 overexpression and 24-MCF treatment. We identified PPAR-response elements (PPRE) located in the VEGF (-913 to +1), HoxA7 (-1107 to +1), and LIF promoter regions (-9032 to -8403). VEGF promoter activity was abolished by mutation of the PPRE motif. Treatment with 24-MCF inhibited expression of VEGF and inhibited the Akt/mTOR pathway. Treatment with 24-MCF also decreased VEGF secretion in MCF7 cells and PMA-stimulated tube formation in HUVECs. Our findings suggest that 24-MCF induces PPAR-γ2-mediated regulation of anti-angiogenesis via PPRE motifs in VEGF, HoxA7, and LIF promoters or upstream regions. Furthermore, 24-MCF treatment inhibits angiogenesis by blocking VEGF secretion.
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Carla Gianfrancesco,
Zoe Darwin,
Salwa Albar,
Nisreen Alwan,
Michelle Carter,
Roz Haddrill,
Linda McGowan,
Michelle Morris,
Eleanor Scott,
Debbie Smith,
Janet Cade
Medicine & Pharmacology, Nutrition; 24-hour recall; nutrition assessment; technology assisted dietary assessment; gestational diabetes
Online: 16 July 2018 (12:12:42 CEST)
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myfood24 is a comprehensive self-completed online 24-hour dietary recall tool currently used for nutritional assessments in epidemiological research. However, its clinical application has been unexplored. This mixed methods prospective observational study explores the acceptability and usability of myfood24 in a clinical population, women with gestational diabetes (GDM). Women were recruited at their first diabetes antenatal clinic appointment. To assess acceptability and usability, they were asked to complete five 24-hour dietary recalls using myfood24 over two weeks and a user experience questionnaire; with a subset invited to participate in a one-to-one semi-structured interview. Of the 199 participants, mean maternal age was 33 years, mean booking BMI 29.7kg/m2, 36% primiparous, 57% White, 33% Asian. Of these 121 (61%) completed myfood24 at least once and 73 (37%) completed the user questionnaire; 15 were interviewed. Usability of myfood24 was measured using the System Usability Scale (SUS) and found to be good (mean 70.9, 95%CI 67.1, 74.6). Interviews identified several areas for improvement, including optimising its use for mobile devices. myfood24 appears to be acceptable and have potential to support self-management and behaviour change for women with GDM but requires adaptation to record blood glucose results alongside real-time tracking of diet.
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Medicine & Pharmacology, Other; dietary intervention; multilevel intervention; diet & exercise; health outcomes
Online: 16 July 2018 (09:59:19 CEST)
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There is a growing need to utilize community interventions to address modifiable behaviors that lead to poor health outcomes like obesity, diabetes, and heart disease. Poor health outcomes can be tied to community-level factors such as food deserts (identified areas with low access to fresh fruit, vegetables, and other healthful whole foods) and individual behaviors like sedentary lifestyles, consuming large portion sizes, and eating high-calorie fast food and processed foods. Through a social ecological approach with family, organization and community, the Faithful Families Cooking and Eating Smart (FFCES) intervention was created to address these concerns in a rural South Carolina community. FFCES used gatekeepers to identify 18 churches and 4 apartment complexes in low-income areas. 176 participants completed both pre- and post- survey measures. Student’s t-test measures found statistically significant change in participant perception of food security (0.39, p-value=0.005), self-efficacy with physical activity and healthy eating (0.26, p-value=000), and cooking confidence (0.17, p-value=.01). There was not significant change in cooking behaviors as assessed through the Cooking Behaviors Scale. FFCES shows that a social ecological approach can be effective at increasing and improving individual healthy behaviors and addressing community-level factors in low-income rural communities.
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Medicine & Pharmacology, Dentistry; chronic periodontitis; bacterial load; oral biofilm; red complex
Online: 16 July 2018 (08:30:06 CEST)
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The indication for using chemical devices as an adjunct of domestic oral hygiene has become increasly used in last decades, usually following mechanical instrumentation. The efficacy of chemical devices for oral biofilm control is proven by evidence from clinical studies. The purpose of this study was to assess the effect of a new oral gel named ADC to reduce oral bacterial loading investigated by means of Polymerase Chain Reaction (PCR). Materials and methods: A total of 10 patients with a diagnosis of chronic periodontitis in the age group >25 years, were selected. None of these patients had received any surgical or non-surgical periodontal therapy and demonstrated radiographic evidence of moderate bone loss. Four sites in separate quadrants were selected in each patient for testing the efficacy of the new medical device. Microbial analysis (MA) was performed at baseline and at day 15. Paired T-Test was used to detect statistical significant reduction of total bacterial loading and specific bacteria. The results showed statistically significant reduction of the overall bacterial loading from baseline to day 15. Results: Specimens of subgingival plaque from a total of patients were investigated for the presence of “red complex” bacterial species by quantitative PCR. The total amount of bacteria detected a statistically significant difference was detected between total bacterial loading pre and post treatment. Total bacteria loading was significant statistically reduced of about 87%, (p = 0.029). Conclusion: In this study, a strong reduction of total bacterial loading using ADC gel as an adjunct to oral home care was observed.
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Medicine & Pharmacology, General Medical Research; Geriatric Evaluation and Management, Acute Care for Elders, Geriatric Rehabilitation
Online: 14 July 2018 (23:52:54 CEST)
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Comprehensive geriatric assessment, defined as an interdisciplinary assessment and development of an overall plan of treatment and follow-up, has become a fundamental part of clinical geriatric care. Since the 1970s, the Veterans Administration has encouraged the development of geriatric evaluation and management programs. Evolution of geriatric evaluation and management has occurred over time and many VA medical centers have transferred inpatient geriatric evaluation programs to long-term care Community Living Centers (CLC) and outpatient settings. Availability of resources and trained personnel across the continuum of care as well as administrative facilitation of collaboration between care components are critical to the efficient utilization of geriatric services. Facilities may need to prioritize their resources and utilize the most effective and relevant elements of geriatric evaluation and management according to patient population needs, available space, resources, and institutional priorities.
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Medicine & Pharmacology, Gastroenterology; vitamin D receptor, cytokines, miR-346, primary sclerosing cholangitis, colorectal cancer
Online: 13 July 2018 (17:36:38 CEST)
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Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder frequently associated with ulcerative colitis (UC). Patients with PSC and UC have higher risk of colorectal neoplasia than patients with UC without PSC. Oncogenic properties of micro RNA 346 (miR-346) have been recently reported. In this study we investigated expressions of miR-346 and its two target genes i.e. the receptor of vitamin D (VDR) and the tumor necrosis factor α (TNF-α), which are known to modulate carcinogenesis. Biopsies from ascending and sigmoid colon were obtained from patients with PSC with and without UC, patients with UC and healthy controls. MiR-346 expression was increased in ascending but not sigmoid colon of patients with PSC and UC when compared to other analyzed groups (p<0.001 for all). In patients with UC an exceptionally low colonic expression of miRNA-346 was accompanied by the increase in VDR expression, and the extensive upregulation of TNF-α gene which protein product is known to be cytotoxic to tumor cells at high concentration. In summary, a substantial upregulation of miRNA-346 in ascending colon of patients with PSC and UC may be responsible for the inhibition of VDR and TNF-α signaling -pathway which may result in an inadequate suppression of neoplasia.
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Medicine & Pharmacology, Nutrition; Non-alcoholic fatty liver disease; NAFLD; omega-3 fatty acid; EPA; DHA; PUFA;
Online: 13 July 2018 (14:47:22 CEST)
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Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.
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Medicine & Pharmacology, General Medical Research; TRPM7, kinase, inflammation, lymphocytes, calcium signalling, SMAD, TH17, hypersensitivity, regulatory T cells, thrombosis, graft versus host disease, T cells, innate immunity
Online: 13 July 2018 (14:14:56 CEST)
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The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in mast cell, neutrophil and macrophage function and highlight the potential of TRPM7 to regulate immune system homeostasis. Further, we shed light on how the cellular signalling cascades involving TRPM7 channel and/or kinase activity culminate in pathologies as diverse as allergic hypersensitivity, arterial thrombosis, and graft versus host disease (GVHD), stressing the need for TRPM7 specific pharmacological modulators.
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Medicine & Pharmacology, Other; cervical cancer; HPV vaccination; sub-Saharan Africa
Online: 12 July 2018 (14:32:40 CEST)
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In sub-Saharan Africa (SSA), cervical cancer is a critical public health issue; it is the second leading cause of cancer among women and the leading cause of female cancer deaths. Incidence and mortality rates are substantially higher than in high-income countries with population-based screening programs, yet implementing screening programs in SSA has so far proven to be challenging due to financial, logistical and sociocultural factors. Human Papillomavirus (HPV) vaccination is an effective approach for primary prevention of cervical cancer and presents an opportunity to reduce the burden from cervical cancer in SSA. With a number of SSA countries now eligible for GAVI support for vaccine introduction, it is timely to consider the factors that impede and facilitate implementation of vaccine programs in SSA. This article reviews the epidemiological and clinical features of cervical cancer in SSA and describes the current status of HPV vaccine implementation in SSA countries. The review considers the challenges that will need to be addressed, and effective approaches to the design and implementation of HPV vaccination programs, using Rwanda as a case study. The review aims to provide suggestions and guidance to those involved in the development and implementation of HPV vaccination programs in SSA.
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Medicine & Pharmacology, General Medical Research; Na/K – ATPase; Markov chain; master equation; Src; oxidant stress; reactive oxygen species; aging
Online: 12 July 2018 (05:26:21 CEST)
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Although the signaling function of Na/K ATPase is been studied for decades, the chasm between the pumping function and the signaling function of Na/K – ATPase is still an open issue. This article explores the relationship between ion pumping and signaling with attention to the amplification of oxidants through this signaling function. Starting with some experimental observations published by our laboratories and others, we develop some predictions regarding cellular oxidant stress.
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Medicine & Pharmacology, Clinical Neurology; brain-derived neurotrophic factor; frailty; inflammasome proteins; interleukin-1β; peri-infarct area
Online: 11 July 2018 (08:59:15 CEST)
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A risk of ischemic stroke increases exponentially after menopause. Even a mild-ischemic stroke can result in increased frailty. Frailty is a state of increased vulnerability to adverse outcomes, which subsequently increases risk of cerebrovascular events and severe cognitive decline, particularly after menopause. Several interventions to reduce frailty and subsequent risk of stroke and cognitive decline have been proposed in laboratory animals and patients. One of them is whole body vibration (WBV). WBV improves brain hemodynamics and lessens frailty-related functional and cognitive deterioration. The goal of current study is to test the efficacy of WBV in reducing post-ischemic stroke frailty and brain damage in reproductively senescent female rats. Reproductively senescent Sprague–Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO) and randomly assigned to either WBV or control groups. Animals placed in the WBV group underwent 30 days of WBV (40 Hz) treatment performed twice daily for 15 min each session for 5 days each week. The motor functions of animals belonging to both groups were tested intermittently and at the end of treatment period. Brains were then harvested for inflammatory markers and histopathological analysis. The results demonstrate a significant reduction in inflammatory markers, infarct volume, and significant increases in brain-derived neurotrophic factor and improvement in functional activity after tMCAO in middle-aged female rats that were treated with WBV as compared to the control group. Our results may help faster translation of the WBV intervention for improved outcome after stroke, particularly among frail women.
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Varvara A. Mouchtouri,
Diederik Van Reusel,
Nikolaos Bitsolas,
Antonis Katsioulis,
Raf Van den Bogaert,
Björn Helewaut,
Inge Steenhout,
Dion Damman,
Miguel Dávila Cornejo,
Christos Hadjichristodoulou,
EU SHIPSAN ACT joint action partnership
Medicine & Pharmacology, Other; international health regulations; ship sanitation certificates; inspection; ship, travel; maritime health; sanitation
Online: 10 July 2018 (12:23:09 CEST)
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The purpose of this study was to report data analysis results from the International Health Regulations (2005) Ship Sanitation Certificates (SSC), recorded in the European Information System (EIS). International sea trade and population movements by ships can contribute to the global spread of diseases. SSC are issued to ensure the implementation of control measures if public health risk exists on board. EIS designed according to the World Health Organization (WHO) “Handbook for Inspection of Ships and Issuance of SSC”. Inspection data were recorded and SSC issued by inspectors working at European ports were analysed. From July 2011-February 2017, 107 inspectors working at 54 ports in 11 countries inspected 5579 ships. Of these, there were 29 types under 85 flags (including 19 EU flags). As per IHR (2005) 10,281 Ship Sanitation Control Exception Certificates (SSCEC) and 296 Ship Sanitation Control Certificates (SSCC) were issued, 74 extensions to existing SSC were given, 7565 inspection findings were recorded, and 47 inspections were recorded without issuing an SSC. The most frequent inspection findings were the lack of potable water quality monitoring reports (23%). Ships aged ≥12 years (Odds Ratio, OR = 1.77, 95%Confidence Intervals, CI = 1.37–2.29) with an absence of cargo at time of inspection (OR = 3.36, 95%CI = 2.51–4.50) had a higher probability of receiving an SSCC, while ships under the EU flag had a lower probability of having inspection findings (OR = 0.72, 95%CI = 0.66–0.79). Risk factors to prioritise the inspections according to IHR were identified by using the EIS. A global information system, or connection of national or regional information systems and data exchange, could help to better implement SSC using common standards and procedures.
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Medicine & Pharmacology, Sport Sciences & Therapy; Static; Stretching; Post-Match; Soccer; Recovery; DOMS; Injury; Performance
Online: 10 July 2018 (11:53:41 CEST)
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Soccer is the most played sport worldwide, with over 265 million participants. It is an incredibly demanding sport, with many different technical skills and physical loads placed on the body. This makes post-match recovery strategies amongst high level soccer players of great importance. The aim of this review is to summarize the existing literature on stretching for post-match recovery, examining its relation to injury prevention, Delayed Onset Muscle Soreness (DOMS), and performance. Scientific evidence of the highest quality and relevance was extracted and reviewed. Despite its common practice, evidence does not support static stretching as a modality to improve recovery post-match amongst soccer players. Larger trials with important outcome measures are needed to determine if a post-match stretching regimen to facilitate recovery exists.
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Medicine & Pharmacology, Other; Acyclovir;Carbapol; Ethocel
Online: 10 July 2018 (10:15:00 CEST)
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This study was carried out to formulate and evaluate controlled release (CR) matrix tablets of Acyclovir using combination of hydrophilic and hydrophobic polymers. Acyclovir is a guanine derivative and is its half-life is short hence administered five times a day using immediate release tablets. Six formulations (F1-F6) were developed using Ethocel and Carbopol in equal combinations at drug-polymer (D:P) ratio of 10:5, 10:6, 10:7, 10:8, 10:9 and 10:10. Solubility study was performed using six different solvents. The compatibility studies were carried out using FTIR and DSC. According to USP, Quality Control and dimensional tests (hardness, friability, disintegration and thickness) were executed. In-vitro drug release studies of Acyclovir was carried out in dissolution apparatus using using 0.1 N HCl medium at constant temperature of 37 ± 0.5 ºC. In order to analyze the drug release kinetics, five different mathematical models were applied to the release data. The results showed that there was no incompatibility between drug and polymers. Physical QC tests were found within limits of USP. The release was retarded upto 24 hrs and non-fickian in-vitro drug release mechanism was found. A formulation developed using blend of polymers, showed excellent retention and desired release profiles thus providing absolute control for 24 hrs.
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Medicine & Pharmacology, Oncology & Oncogenics; smoking; pathologic stage; pathologic grade; low risk
Online: 10 July 2018 (10:00:46 CEST)
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Introduction: We investigated the potential effect of smoking on pathological staging in clinically low-risk patients. Material-Methods: Data of 59 patients who were diagnosed with a bladder tumor for the first time and had a single lesion radiologically and endoscopically smaller than 3 cm were investigated, retrospectively. A total of 33 patients who currently smoke or smoked were classified as ever smokers group and 26 patients who did not ever smoke were classified as never smokers group. Pathological diagnoses of the patients in both groups were compared. Results: A total of 9 patients (27.3%) in ever smokers group and 18 patients (69.2%) in never smokers group had Ta disease (p<0.05). Morover, 19 patients (57.6%) in ever smokers group and 5 patients (19.2%) in never smokers group had T1 disease (p<0.05). The number of patients with low grade (LG) tumor were 8 (24.2%) and 19 (73.1%) in ever smoking and never smoking groups, respectively (p<0.05). The number of patients with high grade (HG) tumor were 25 (75.8%) and 7 (26.9%) in ever smoking and never smoking groups, respectively (p<0.05). Ta HG was detected in 9 (27.3%) patients in ever smoking group. In contrast, no patients in never smoking group had Ta HG disease (p<0.05). The number of patients with T1 HG was 17 (51.5%) in ever smoking group and 2 (7.69%) in never smoking group (p<0.05). Conclusion:Smoking seems to associate with pathologically worse stage and grade in patients with primary, single, < 3cm bladder cancer.
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Mohammad A. Hossain,
Ami Amin,
Anju Paul,
Huzaif Qaisar,
Monika Akula,
Alireza Amirpour,
Shreya Gor,
Sofi Giglio,
Jennifer Cheng,
Roy Mathew,
Tushar Vachharajani,
Mohamed Bakr,
Arif Asif
Medicine & Pharmacology, General Medical Research; obesity; documentation; comorbidities
Online: 9 July 2018 (13:17:30 CEST)
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While obesity is a serious chronic condition, its prevalence and documentation as a diagnosis has not been extensively studied in hospitalized patients. We conducted a retrospective chart review to investigate the prevalence and documentation of obesity as a diagnosis among patients admitted to our medical center. IRB approval was obtained for this retrospective study. Body mass index as per CDC, admission and discharge diagnosis of obesity and common comorbidities including hypertension, diabetes, hyperlipidemia and others, were recorded. Length of hospital stay was calculated. We also investigated whether counselling for weight loss was provided to obese patients. A total of 540 consecutive patients with mean age of 66 ± 6 years, were investigated, of which 182(34%) had normal weight, 188(35%) patients were overweight and 170(31%) patients were obese. Obese group included 55% female and 45% male. 100 (59%) had class I obesity, 43(25%) had class II obesity and 27(16%) class III obesity. Of the obese patients 40/170(23.5%) patients had obesity documented on the admission problem list and only 21(12%) had obesity documented as a discharge diagnosis. Only 3(2%) patients received appropriate counseling and referral for obesity management during the hospitalization. Comorbidities included hypertension (68%), diabetes (35%), hyperlipidemia (36%), coronary artery disease (18%), chronic kidney disease (17%), congestive heart failure (18%) and COPD (24%). The average length of stay in normal weight, overweight and obese patients was similar (4.5 ± 0.5 days). An overwhelming percentage never had weight status documented despite significant prevalence of obesity. Hospitalization offers health care providers a window of opportunity to identify obesity, communicate risks and initiate weight management interventions.