ARTICLE Download: 79| View: 986| Comments: 1 | doi:10.20944/preprints201905.0213.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Poor prognosis; medically non-beneficial care; futility; breaking bad news; withdrawal of care; miracle; hope; goals of care; communication; health disparities; racial discrimination; ethnocultural discrimination
Online: 16 May 2019 (12:38:38 CEST)
Objective: To recommend how physicians can best respond to families whose hopes for a miracle via divine intervention influence their medical decisions, like, for example, making them not want to withdraw ventilatory support in cases of poor neurologic prognosis because they are still hoping for God to intervene. Methods: Auto-ethnographic analysis of chaplaincy experience in this clinical context yields a nuanced 90-second, point-of-care spiritual intervention physicians can use to address the religious aspect of families who base medical decisions on their hopes for a miracle via divine intervention. Explanation of how spiritual intervention dovetails with existing physician communication protocol for responding to families hoping for a miracle. Results: Spiritual intervention for religious aspect of miracle-hoping families is integrated into existing physician communication protocol for responding to families hoping for a miracle with recommendations for utilization of existing communication technology when necessary. Conclusion: Properly addressing the religious dimension of families hoping for a miracle may be helpful for physicians interested in decreasing their own stress levels, improving outcomes for this clinical context, and ensuring that unintentional discrimination does not perpetuate racial disparities in end-of-life care.
Wed, 15 May 2019
ARTICLE Download: 50| View: 192| Comments: 0 | doi:10.20944/preprints201905.0188.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: smartphone dependency; aggression; ego-resilience; parenting behavior; peer attachment
Online: 15 May 2019 (10:45:15 CEST)
This study was conducted to examine the moderating and mediating effect of ego - resilience, parenting attitude, and peer attachment in the relation between smartphone dependency and aggression. Participants were 1,863 youths using a smartphone among the first middle school students responded in the 7th Korean Children and Youth Panel Survey (KCYPS) conducted by the National Youth Policy Institute in Korea. The data were analyzed by descriptive statistics, a correlation, and a hierarchical regression analysis. First, ego-resilience showed a partial mediating effect on the relationship between smartphone dependency, aggression and significant moderating effects were revealed. Second, parenting behavior showed a partial mediating effect on the relationship between smartphone dependency and aggression, with no moderating effects seen. Third, peer attachment had a partial mediating effect on the relationship between smartphone dependency and aggression, with no moderating effects seen. The research suggested the mental health and growth of students could be improved by applying various nursing and health care programs to improve ego-resilience, parenting behavior and peer attachment as they grow into adulthood.
ARTICLE Download: 41| View: 158| Comments: 0
Subject: Medicine & Pharmacology, Nutrition Keywords: ontology; nutritional epidemiology; minimal data information; data quality descriptors; study reporting guidelines; Semantic Web
Online: 15 May 2019 (05:51:53 CEST)
1) Background: The use of linked data in Semantic Web are promising approaches to add value to nutrition research. An ontology, which defines the logical relationships between well-defined taxonomic terms, enables linking and harmonizing research output. To enable the description of domain-specific output in nutritional epidemiology, we propose the Ontology for Nutritional Epidemiology (ONE) according to authoritative guidance for nutritional epidemiologic research; 2) Methods: First, a scoping review was conducted to identify existing ontology terms for reuse in ONE. Second, existing data standards and manuscript reporting guidelines for nutritional epidemiology were converted into ontology, and the terms used in the standards were summarized and listed separately in a taxonomic hierarchy. Third, the ontologies of the nutritional epidemiologic standards, reporting guidelines and the core concepts were gathered in ONE. Three case studies were illustrated for its potential applications. (i) annotation of existing manuscripts and data, (ii) ontology-based inference, and (iii) estimation of reporting completeness in a sample of nine manuscripts; 3) Results: Ontologies for “food and nutrition” (n=33), “disease and special population” (n=86), “data description” (n=21), “research description” (n=32) and “supplementary (meta) data description” (n=44) were reviewed and listed. ONE consists of 339 classes (79 new classes to describe nutrition data and 24 new classes to describe the content of nutrition manuscripts). The case studies demonstrated the application of ONE. 4) Conclusion: ONE is a resource to automate data integration, searching and browsing, and can be used to assess reporting completeness in nutritional epidemiology.
Tue, 14 May 2019
REVIEW Download: 52| View: 128| Comments: 0 | doi:10.20944/preprints201905.0177.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: Cataract surgery, acute endophthalmitis, chronic endophthalmitis
Online: 14 May 2019 (15:28:30 CEST)
Background: The assessment of the incidence and characteristic of acute and chronic post-operative endophthalmitis (POE) after cataract surgery in Poland during 2010 - 2015. Patients and methods: All hospitalizations of patients, in the National Database of Hospitalizations, who underwent cataract surgery alone or in combined procedures in Poland between January 2010 and December 2015, with a billing code of endophthalmitis, were selected. Acute endophthalmitis was identified if symptoms occurred within 1 - 42 days from the cataract surgery and chronic endophthalmitis if symptoms occurred ≥ 43 days after cataract surgery, respectively. Results: In total, 1331 cases of POE after 1,218,777 cataract extractions were identified. The overall incidence of POE decreased from 0.125% in 2010 to 0.066% in 2015. In multiple logistic regression analyses, increasing age was significantly associated with acute POE, while type II diabetes mellitus, extracapsular cataract extraction and one-day surgery were significantly associated with chronic POE. The combined cataract surgery and male sex were significant risk factors for both acute and chronic POE. A total of 62.51% of all eyes affected by POE received antibiotic treatment and 37.49% had vitrectomy treatment. Conclusions: During the study period, the total incidence of post-operative endophthalmitis after cataract surgery decreased significantly.
CASE REPORT Download: 68| View: 131| Comments: 0 | doi:10.20944/preprints201905.0173.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Pancreatic ductal adenocarcinoma; non small cell lung cancer; double primary cancers; B7-H3; gefitinib; chemotherapy
Online: 14 May 2019 (13:04:44 CEST)
Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.
ARTICLE Download: 36| View: 102| Comments: 0 | doi:10.20944/preprints201905.0109.v2
Subject: Medicine & Pharmacology, Pediatrics Keywords: child; diarrhea; water sanitation and hygiene; rehydration solution; zinc; case management; antibacterial agents; drug utilization; community participation; India
Online: 14 May 2019 (11:46:53 CEST)
Childhood diarrhea continues to be a major cause of under-five (U-5) mortality globally and in India. In this study, 1571 U-5 children residing in nine rural villages and four urban slums in Ujjain, India were included with the objective to use community participation and drug utilization research to improve diarrheal case management. The mean age was 2.08 years, with 297 (19%), children living in high diarrheal index households. Most mothers (70%) considered stale food, teething (62%), and hot weather (55%) as causes of diarrhea. Water, sanitation, and hygiene (WASH)-related characteristics revealed that most (93%) households had toilets, but only 23% of the children used them. The study identified ineffective household water treatment by filtration through cloth by most (93%) households and dumping of household waste on the streets (89%). The results revealed low community awareness of correct causes of diarrhea (poor hand hygiene, 21%; littering around the household, 15%) and of correct diarrhea treatment (oral rehydration solution (ORS) and zinc use, 29% and 11%, respectively) and a high antibiotic prescription rate by healthcare providers (83%). Based on the results of the present study, context-specific house-to-house interventions will be designed and implemented.
CASE REPORT Download: 21| View: 90| Comments: 0 | doi:10.20944/preprints201904.0017.v2
Subject: Medicine & Pharmacology, Other Keywords: marginal ridge staining; enamel crack; detecting cracks in teeth; PTR-LUM
Online: 14 May 2019 (07:37:04 CEST)
Detecting cracks in teeth is a clinical challenge. Patients may complain of diffuse pain on chewing, pain, at times, on temperature change and pain that occurs episodically. Common diagnostic tools such as radiographs and visual examination may not detect cracks. This case report shows how PTR-LUM in The Canary System can detect cracks in teeth not seen with other devices. In this clinical situation, the crack involved a portion of the mesial and distal surfaces of a mandibular second molar.
Mon, 13 May 2019
ARTICLE Download: 45| View: 175| Comments: 0 | doi:10.20944/preprints201905.0165.v1
Online: 13 May 2019 (14:36:07 CEST)
Background: As the opioid epidemic continues, understanding the geospatial, temporal and demand patterns is important for policymakers to assign resources and interdict individual, organization, and country-level bad actors. Methods: GIS geospatial-temporal analysis, k-means cluster analysis, and extreme-gradient boosted random forests are used to evaluated ICD-10 F11 opioid-related admissions. The period of analysis was January 2016 through September 2018. Results: The analysis shows existing high-intensity areas in Chicago and New Jersey with emerging areas in Atlanta, Salt Lake City, Phoenix, and Las Vegas. Further, cluster analysis supports the current inflow from China through Mexico and Canada with another cluster in the Northeast likely associated with the Dominican flow. Explanatory models suggest that hospital overall workload and financial variables may be used for allocating opioid-related funds effectively, as the gradient-boosted random forest models accounted for 88% of the variability on a blinded test data set. Conclusions: Based on GIS analysis, the opioid epidemic is likely to spread or diffuse through the country, and interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement.
ARTICLE Download: 26| View: 82| Comments: 0 | doi:10.20944/preprints201905.0153.v1
Online: 13 May 2019 (10:16:48 CEST)
A recent systematic review for 19 selected articles after searching through to 30 September 2017 showed vitamin D deficiency was associated with ischemic stroke (IS), not hemorrhagic stroke (HS). But a heterogeneity would be introduced with comparing the lowest and highest category of vitamin D. The aim of this article was to conduct an updated meta-analysis (UMA) with searching through to 31 March 2019. An interval collapsing method as information extraction was applied in order to decrease a heterogeneity among studies. Additional articles were selected from cited lists from 19 selected articles using citation discovery tools. Random effect model was applied if I-squared value was over 50%. A funnel plot and Egger’s test were used to detect a publication bias. After 5 new studies were added, the summary RRs [and their 95% confidence intervals] (I-squared value) were 1.52 [1.33–1.74] (0.0%) in IS, and 2.44 [1.34–4.46] (69.7%) in HS. This UMA supported the hypothesis that serum vitamin D deficiency was associated with an increased risk of HS as well as IS. Diverse public health programs against vitamin D deficiency status would be needed for higher risk group, especially elderly people.
Fri, 10 May 2019
ARTICLE Download: 28| View: 153| Comments: 0 | doi:10.20944/preprints201905.0117.v1
Online: 10 May 2019 (10:30:14 CEST)
Dental scaling has high importance in oral health due to its effect on preventing the teeth root destruction. Moreover, it can influence other health aspects such as reducing the risk factor of infective endocarditis. There are various devices applicable to dental scaling. It is essential to select the most appropriate type of instrument to achieve more efficient scaling. Multi-Attribute Decision Making (MADM) is a mathematical approach widely applied in for selecting the best alternative based on essential criteria. In the present research, several criteria including cost, ease of use and sterilization, durability and effectiveness considered as criteria for device selection. The experts in the related field were asked to score the criteria and corresponded alternative. According to the results, obtained by applying the TOPSIS method, Piezon Master is the most option which is mainly due to its durability and effectiveness. The second rank belongs to Cavitron due to its ease of use and sterilization in addition to affordable cost.
Thu, 9 May 2019
ARTICLE Download: 39| View: 158| Comments: 0 | doi:10.20944/preprints201905.0109.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: child; diarrhea; water sanitation and hygiene; rehydration solution; zinc; case management; antibacterial agents; drug utilization; community participation; India
Online: 9 May 2019 (12:39:13 CEST)
Childhood diarrhea continues to be a major cause of under-five (U-5) mortality globally and in India. In this study, 1571 U-5 children residing in nine rural villages and four urban slums in Ujjain, India were included with the objective to use community participation and drug utilization research to improve diarrheal case management. The mean age was 2.08 years, with 297 (19%), children living in high diarrheal index households. Most mothers (70%) considered stale food, teething (62%) and hot weather (55%) as causes of diarrhea. Water, sanitation, and hygiene (WASH)-related characteristics revealed that most (93%) households had toilets, but only 23% children used them. The study identified ineffective household water treatment by filtration through cloth by most (93%) households and dumping of household waste on streets (89%). The results revealed low community awareness of correct causes of diarrhea (poor hand hygiene, 21%; littering around the household, 15%) and of correct diarrhea treatment (oral rehydration solution [ORS] and zinc use, 29% and 11%, respectively) and a high antibiotic prescription rate by health care providers (83%). Based on the results of the present study, context-specific house-to-house interventions will be designed and implemented.
Wed, 8 May 2019
ARTICLE Download: 71| View: 379| Comments: 0 | doi:10.20944/preprints201905.0091.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Iranian traditional medicine; alternative and complementary medicine; database; natural products; Mizaj; temperament
Online: 8 May 2019 (10:08:54 CEST)
As a holistic medical school, Iranian traditional medicine (ITM) considers the human body as a dynamic and intricate network of interconnecting processes. Currently, systems biology and more precisely systems medicine and pharmacology can be an aid in providing rationalizations for many traditional medications and treatments and elucidating a great deal of knowledge they can offer to guide future research in medicine. Therefore, re-organization and standardization of traditional medicine data are requested more than ever before. To address this issue, we have constructed UNaProd, a Universal Natural Product database for materia medica of ITM. Primarily based on Makhzan al-Advieh, which is the most recent encyclopedia of materia medica in ITM with the largest number of monographs, this database was created using both text mining methods and manual editing. UNaProd is currently hosting to 2696 monographs from herbal to animal to mineral compounds in 16 diverse attributes such as origin and scientific name. In the current version, UNaProd is hyperlinked to IrGO and CMAUP databases for Mizaj and molecular features respectively and it is freely available at http://jafarilab.com/unaprod/.
Tue, 7 May 2019
ARTICLE Download: 50| View: 142| Comments: 0 | doi:10.20944/preprints201905.0075.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: Consumers' consciousness for health; companies’ health-friendly activities; health-friendly products and services; health status
Online: 7 May 2019 (11:14:55 CEST)
Although health policy resides mainly with the government, industry can play an important role in building a health ecosystem. From March to May, we administered questionnaires to 1,200 individuals from the general Korean population asking about their perception of health-friendly labels, and if they would purchase such labeled products (foods, pharmaceuticals, etc.) and services (purifying water, preventing air pollution, etc.) at extra cost. The participants placed a high value on the importance of mental, social, spiritual, and physical health factors in terms of company’s products and services with a score of about 8 out of 10 (range, 7.74-8.33). Most respondents (72.4%) said they were interested in adopting health-friendly labels. When a health-friendly label is introduced (such as one by the Business for Social Responsiveness), 65.1% of the respondents said they intended to purchase the product or service, while 6.8% said they did not, and 75.0% said they were willing to pay extra for the health-friendly product or service. Multivariate logistic regression models showed urban residence, high education level, and good social health to be significantly associated with positive attitudes toward health-friendly labels. People with high income, no religion, or normal weight were more likely to say they intend to purchase products and services with health-friendly labels. They also had a more positive attitude toward paying more for such products and services, as did people with good spiritual health. This study provides data that illustrate the importance of health-friendly products and services to the general population and companies.
Mon, 6 May 2019
BRIEF REPORT Download: 48| View: 148| Comments: 0 | doi:10.20944/preprints201905.0062.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: SCAN zinc-finger; SCAND1; CDC37; MZF1; prostate cancer
Online: 6 May 2019 (12:10:22 CEST)
Cell division control 37 (CDC37) increases the stability of HSP90 client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SCAN transcription factor family- MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1 / ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc-fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in CDC37 gene, negatively regulated CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1.
ARTICLE Download: 49| View: 192| Comments: 0 | doi:10.20944/preprints201905.0054.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: acute hamstring muscle complex injury; radial extracorporeal shock wave therapy; rESWT, RSWT; soccer medicine
Online: 6 May 2019 (11:08:28 CEST)
Background: Acute injuries of the hamstring muscle complex (HMC) Type 3b (interfascicle / bundle-tear) are frequently observed in various sports disciplines both in elite and recreational sport. The treatment of choice of acute HMC injuries Type 3b is a progressive physiotherapeutic exercise program. Besides this, there is currently only insufficient scientific evidence to support other treatment methods, including local infiltrations and injections of platelet-rich-plasma. Very recently it was demonstrated that extracorporeal shock wave therapy (ESWT) may accelerate regeneration after acute skeletal muscle injury. The aim of the present study is to test the hypothesis that the combination of radial ESWT (rESWT) and a specific rehabilitation program (RP) is effective and safe in treatment of acute HMC injury Type 3b in athletes, and is statistically significantly more effective than the combination of sham-rESWT and RP. Methods/Design: We will perform a double blind, randomized, sham-controlled clinical trial at the clinic KinEf Kinesiología Deportiva, Ciudad Autónoma de Buenos Aires, Argentina. Fourty patients with acute HMC injury Type 3b will be randomly allocated to receive either rESWT (nine rESWT sessions; three sessions per week; 2500 radial extracorporeal shock waves (rESWs) per session; energy density depending on what the patient tolerates) or sham-rESWT. In addition, all patients will receive a specific rehabilitation program that will last for eight weeks. The primary outcome measure will be the individual time (days) necessary to return to play. Secondary outcomes will include the presence or absence of reinjury during a time period of six months after inclusion into the study. Discussion: Because of the lack of adequate treatment options for acute HMC injury Type 3b in athletes and particularly the high reinjury rate, we hypothesize that the results of this trial will be of importance and have impact on clinical practice. Trial registration: ClinicalTrials.gov ID NCT03473899. Registered March 22, 2018.
ARTICLE Download: 41| View: 137| Comments: 0 | doi:10.20944/preprints201905.0053.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: corpus cavernosum; erectile dysfunction; reactive oxygen species; SHR
Online: 6 May 2019 (11:02:31 CEST)
Carvacrol is a monoterpene found in essential oils from various plants. Several pharmacological properties have already been described for carvacrol, including antimicrobial, anti-inflammatory, anticarcinogenic, antioxidant, vasorelaxant and hypotensive activities. The present study evaluated the effect of carvacrol on hypertensive rats with erectile dysfunction. Twelve-week-old spontaneously hypertensive rats (SHR) were treated with vehicle, carvacrol (50 or 100 mg/kg/day) or sildenafil (1.5 mg/kg/day), intragastrically, for four weeks. Wistar Kyoto (WKY) rats were used as the normotensive controls. All substances tested reduced systolic blood pressure during the treatment period. The intracavernosal pressure/mean arterial pressure ratio of the hypertensive rats was improved by carvacrol and sildenafil treatments. In isolated rat corpora cavernosa, the acetylcholine- and SNP-induced relaxation responses were significantly increased by carvacrol or sildenafil treatments. In SHR corpora cavernosa, treatment with carvacrol attenuated the hypercontractility induced by phenylephrine or electrical field stimulation. Phe-induced hypercontractility in the presence of tempol was not altered when compared to the response induced by carvacrol alone. In rat corpora cavernosa fluorescence intensity emitted by the DHE probe was significantly reduced in SHR treated (carvacrol or sildenafil) groups when compared to that emitted in the SHR-CTL. This study showed that carvacrol improves the erectile function of hypertensive rats and reduces endothelial dysfunction, smooth muscle cell hypercontractility and superoxide anion generation.
ARTICLE Download: 37| View: 98| Comments: 0 | doi:10.20944/preprints201905.0051.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: infant formulae; infant foods; minerals; toxic metals; hydroxymethylfurfural; storage conditions; safety
Online: 6 May 2019 (10:38:25 CEST)
Infant foods and formulae may contain toxic substances and elements which can be neo-formed contaminants or derived from raw materials or processing. The content of minerals, toxic elements and hydroxymethylfurfural in infant foods and formulae were evaluated. The effect of storage temperature on HMF formation in infant formulae and its potential as a quality parameter was also evaluated. Prune-based foods contained the highest HMF content. HMF significantly increased when storage temperature was elevated to 30 ℃ for 21 days. All trace elements were present in adequate amounts while the concentration of nickel was higher when compared to those of other studies. The study indicates that HMF can be used as quality indicator for product shelf-life and that the concentrations of minerals and toxic elements vary greatly due to the diverse compositions of foods and formulae. Such contaminants need to be monitored as infants represent a vulnerable group compared to adults.
REVIEW Download: 88| View: 80| Comments: 0 | doi:10.20944/preprints201905.0035.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: blood pressure, diuretics, thiazide, beta blocker, calcium channel blocker, renin angiotensin system
Online: 6 May 2019 (08:31:53 CEST)
Hypertension is a common and growing medical problem that leads to enormous cardiovascular and kidney disease worldwide. While many drugs exist to treat hypertension, there is large individual variation in how a given individual responds to different agents, which contributes to dismal rates of hypertension control. While demographic factors predict which drugs may work better in certain individuals, a great degree of this variation has a genetic basis. In recent years, genome wide association studies have begun to identify specific gene variants that predict drug response to particular agents. This review identifies the major genetic variants influencing antihypertensive response that have emerged from this growing body of work. For novel genetic variants without a previously known biologic basis in blood pressure, it is crucial to validate initial findings in subsequent studies. This information may eventually lead to a more personalized approach to hypertension management that will improve blood pressure control and patient outcomes. The integration of this large amount of data and its real world application will be highly challenging, but strategies to accomplish this are discussed.
ARTICLE Download: 40| View: 74| Comments: 0
Subject: Medicine & Pharmacology, Other Keywords: trichomonas vaginalis; compliance; treatment; STIs; HIV; cost-effectiveness
Online: 6 May 2019 (06:02:07 CEST)
Background: Trichomoniasis is the most common non-viral STI globally and yet is not a reportable disease. Trichomonas Vaginalis is an important source of reproductive morbidity and may increase risk of acquisition and transmission of HIV. WHO and CDC recommend various regimens of Nitro-Imidazoles for treatment. The common Nitro-Imidazoles used for Trichomoniasis are Metronidazole and Tinidazole, which vary in their cost, efficacy and side effect profile and it is relevant to study these factors, for better management of the patients. Objectives: This study aims to compare and study the efficacy, compliance of various treatment regimens, their outcomes and side-effects for Trichomoniasis, among STI clinic attendees in Trinidad. Methods: A clinical trial study was designed and after obtaining the informed consent a routine clinical examination was conducted and the swabs for Trichomoniasis tests were collected for diagnosis from the 692 participants. Out of 692 participants, Eighty two (82) patients with established diagnosis of Trichomonas infection were quasi-randomly treated using different regimens. Compliance to treatment, side effects and outcome were evaluated. Results: The prevalence of the Trichomoniasis in population attending our STI clinic is 11.9% and prevalence of HIV is 9%. Of the total 82 participants for the treatment, 80% were females; nearly 90% of the patients belonged to age group 15-45 years and over 60% were below 30 yrs. Among those diagnosed for Trichomonas vaginalis, 13.3% had associated HIV infection. The compliance with respect to single dose treatment was significantly better than the long duration oral regimen and has significant relation with side effects of the treatment. The outcome is generally better and comparable and shows no significant difference between different treatment regimens used in the study. Conclusions: Metronidazole and Tinidazole are commonly used drugs in various regimens. compliance is better with those treated with Tinidazole and Metronidazole stat, than with other groups. Outcome is comparable between these regimens, especially when combined with other important factors like abstinence and treatment of the partners. The treatment regimens mainly differ in the compliance and side effects profile, which suggests that to improve the compliance the drugs with less side effects, short course regimen would be a preferred choice.
Sun, 5 May 2019
ARTICLE Download: 35| View: 71| Comments: 0 | doi:10.20944/preprints201905.0015.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: laparoscopic; open surgery; non-metastatic colorectal cancer; single surgeon experience
Online: 5 May 2019 (11:25:43 CEST)
The oncologic merits of laparoscopic technique for colorectal cancer surgery remain debatable. Eligible patients with non-metastatic colorectal cancer who were scheduled for an elective resection by only one surgeon in a medical institution were randomized to either laparoscopic or open treatment. During this period, total 188 patients received laparoscopic surgery and other 163 patients to open approach. The primary endpoint was cancer-free 5-year survival after operative treatment and secondary endpoint was the tumor recurrence incidence. We found there was no statistically significant difference between open and laparoscopic groups regarding average number of lymph nodes dissected, overall mortality rate, cancer recurrence rate or cancer-free 5-year survival. Nevertheless, laparoscopic approach was more effective for colorectal cancer treatment with shorter hospital stay and less blood loss despite operation time was significantly longer. Meanwhile fewer patients receiving laparoscopic approach developed postoperative urinary tract infection, wound infection, pneumonia or anastomosis leakage, which reached statistical significance. For non-metastatic colorectal cancer patients, laparoscopic surgery resulted in better short-term outcomes whether in total complications and intra-operative blood loss. Though there was no significant statistical difference in terms of cancer-free 5-year survival and tumor recurrence, we favor patients receiving laparoscopic surgery if not contraindicated.
Tue, 30 April 2019
REVIEW Download: 411| View: 271| Comments: 0 | doi:10.20944/preprints201904.0327.v1
Subject: Medicine & Pharmacology, Dermatology Keywords: sunscreen; sunburn; UV Radiation; melanoma; photoaging
Online: 30 April 2019 (11:18:23 CEST)
The sunscreen industry is achieving remarkable worldwide prominence by responding to the growing need for skin protection with fast-paced innovation. Increased consumer awareness of the harmful effects of sunlight has fueled the demand for improved photo protection. The need for broad-spectrum protection from both UVA and UVB rays has inspired scientists worldwide to research new cosmetic formulations and delivery systems. More effective sunscreen actives, emollients and novel cosmetic and functional ingredients have been regularly added to the formulator’s repertoire. Creativity in innovation has been hindered only by regulatory agencies and patent restrictions worldwide. Familiarity with the current restrictive regulations and patent law infringements has become integral to any research effort attempting to provide improved protection to individuals affected by the sun’s damaging effects. The increasing incidence of skin cancers and photo damaging effects caused by ultraviolet radiation has increased the use of sun screening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Unlike the situation in Europe where sunscreen ingredients are considered under cosmetics guidelines, the FDA is required to define sunscreens as drugs since they are advertised to prevent sunburn and, more recently, the risk of skin cancer. In the USA, the FDA has been regulating this industry since August 25, 1978, with the publication of the Advance Notice of Proposed Rulemaking. Sunscreens are considered drugs and cosmetics and therefore must be governed by the FDA-OTC monograph. With the variety of sunscreen agents used in cosmetic and UV protection products, Australia, Canada, and the European Union (EU) have also developed regulatory protocols on safe sunscreen product use. Unlike the USA though, Australia has approved 34 active sunscreen ingredients and the EU has approved 28 of these ingredients. Current FDA regulations allow labeling of sunscreen products to a maximum of 30þ, despite the many products currently available with numbers as high as 100. From a cosmetic formulation point of view, increasing the SPF number in a product is governed by simple chemical principles.
Mon, 29 April 2019
ARTICLE Download: 130| View: 296| Comments: 0 | doi:10.20944/preprints201904.0323.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: medical education; augmented reality; virtual reality; mixed reality; extended reality
Online: 29 April 2019 (10:09:05 CEST)
Background: Since the advent of virtual reality (VR), it has been used in medical education for surgical training and anatomy teaching. Recently, other modalities of extended reality (XR) such as augmented reality (AR) and mixed reality (MR) has also made its way into medical education. Although there has been research validating XR’s use in medical education, there have been few studies on the research trends of the different XR modalities. The paper aims to compare the research trends of the XR modalities in general and in terms of the medical fields studied and outcomes measured. Methods: Web of Science was searched, and preliminary data was extracted to analyze the general trend. Inclusion and exclusion criteria were then applied, and finalized articles were analyzed and grouped based on the medical field studied and outcomes measured. Results: 31 articles on VR, eight on AR and one on MR were included in the final analysis. We found that there is increasing research in VR since 1990 and AR since 2008. The research in MR is constant. Most of the papers on VR studied endoscopic surgery and anatomy whereas AR studied mostly anatomy and endovascular procedures. Using Miller’s prism of clinical competence, the competency measured most for VR and AR is “show”. Discussion and conclusion: Advancement in computing, communication and display technologies since 1990 may contribute to the increase in research on VR whereas the ubiquity of smartphone since 2008 may explain the increase in research on AR. Although both VR and AR are used in surgical training and anatomy teaching, we found possible strengths of VR in counseling and AR in practical skills. The competency "show" was measured most as most of the papers were on surgery, and the XR simulators used can capture surgical parameters
Wed, 24 April 2019
ARTICLE Download: 157| View: 874| Comments: 2
Subject: Medicine & Pharmacology, Dentistry Keywords: allograft, resorption, sclerotic bone, exfoliation, bone failure
Online: 24 April 2019 (12:33:49 CEST)
AbstractCadaver bone is possibly the most common transplant material used today. Common types of cadaver bone transplants are freeze-dried bone allografts and xenografts. Studies have shown that mineralized freeze-dried bone allografts have the same percentage of retained bone graft particles at different time points, indicating that these materials are never resorbed. However, it is commonly accepted by clinicians that these materials are resorbed and convert the graft site into normal bone. This histologic study was undertaken to determine the fate of mineralized freeze-dried bone allograft particles grafted into human extraction sockets. Materials and Methods:This study is a photographic, radiologic, and histological analysis of mineralized freeze-dried bone allograft healing in human sockets after mineralization at different time points. The mineralized freeze-dried bone allografts used for evaluation in this study were particulate bone graft materials in maxillary or mandibular extraction sockets. Patient selection was random, based on the following time periods: 6 months, 2 years, 5 years, 7 years, 10 years and 15 years. No block bone grafts were evaluated. Results:No resorption of cadaver bone graft particles was found at any time point. No osteoclasts were found in any of the histology at any time point. At different time points from 6 months through 15 years, mineralized freeze-dried bone allograft particles were found to be exfoliated out of the alveolar crest as a result of the formation of a hypervascular zone surrounding the grafted site. The embedded graft particles remain embedded in sclerotic bone until the particles reach the alveolar crest at which time the sclerotic bone and graft particles break up and are released into the gingiva. All histologic samples from 6 months to 15 years contained residual graft particles. The sclerotic bone formed around graft particles did not integrate to the graft particles or the implant surface. Conclusions:Mineralized freeze-dried bone allograft particles are not resorbed after mineralization. A hypervascular zone forms around the grafted site and exfoliates the bone graft particles into the gingiva. The mineralization process produces sclerotic bone which never remodels into normal bone. Sclerotic bone covers but does not integrate to the retained bone graft particles or implant surface resulting in a weakened structure with an increased likelihood of bone failure and implant loss.
Tue, 23 April 2019
ARTICLE Download: 49| View: 181| Comments: 0 | doi:10.20944/preprints201904.0246.v2
Subject: Medicine & Pharmacology, Behavioral Neuroscience Keywords: Oxytocin, Oxytocin Receptor, Autism, Nepsys Scale, MAST Immune System Disease, Dendritic Spines, Magnocellular Neurons, Desensitization, Labor, Down Regulation
Online: 23 April 2019 (11:12:19 CEST)
This paper develops mathematical models examining possible roles of oxytocin and oxytocin receptors in the development of autism. This is done by demonstrating that mathematical operations on normalized data from the Stanford study (K.J. Parker, 2016), which establishes a correspondence between severity of autism in children and their oxytocin blood levels, generates a graph that is the same as the graph of mathematical operations on a normalized theoretical model for the severity of autism. This procedure establishes the validity of the theoretical model and the significance of oxytocin receptors in autism. A steady-state model follows, explaining the constant baseline concentrations of oxytocin observed in the cerebral spinal fluid and blood in terms of the neuromodulation by oxytocin of oxytocin receptors on the magnocellular neurons that produce oxytocin in nuclei in the hypothalamus. The implications of these models for possible roles of oxytocin and oxytocin receptors in autism is considered for several unrelated conditions that may be associated with autism. These are: oxytocin receptor desensitization and down-regulation as factors during labor in offspring autism development; reductions in the oxytocin receptor numbers in the fixed oxytocin receptor expression that occurs before birth; MAST Immune System disease; and the excess number of dendritic spines from lack of pruning observed in brains of autistic people. Research into the feasibility of generating magnocellular neurons and other neurons from adult stem cells is suggested as a way of doing invitro studies of oxytocin and oxytocin receptors to assess the validity of theories presented in this paper.
Mon, 22 April 2019
ARTICLE Download: 49| View: 120| Comments: 0
Subject: Medicine & Pharmacology, Nutrition Keywords: school health; child/adolescent health; health education; health promotion; school nutrition; school health; policy
Online: 22 April 2019 (11:57:43 CEST)
Supporting the implementation of school food and nutrition policies (SFNPs) is an international priority to encourage healthier eating among children and youth. Schools are an important intervention setting to promote childhood nutrition, and many jurisdictions have adopted policies, guidelines, and programs to modify the school nutrition environment and promote healthier eating. The purpose of this study was to explore the association between perceived adequacy and capacity for SFNP implementation on food availability and policy adherence in the province of Nova Scotia (NS), Canada, one of the first regions in Canada to launch a comprehensive SFNP. A cross sectional online survey was conducted in 2014-15 to provide a current-state of policy implementation and adherence. Adequacy and capacity for food policy implementation was used to assess policy adherence through the availability of prohibited ‘minimum’ nutrition foods. An exploratory factor analysis was conducted on a selected of available foods and ‘slow’ and ‘quick’ service food composition measures were dichotomized for food availability. Schools with above perceived average adequacy and capacity for policy implementation had more than three times (3.62) greater odds of adhering to a lunch policy, while schools that adhered to a snack and lunch policy had 52% and 82% lower odds of serving quick service foods, respectively. This study identified the need for appropriate adequacy and capacity for policy implementation to ensure policy adherence and improve the school food environment. These findings highlight the potential of SFNPs to have a positive impact on childhood nutrition, but adequately supporting their implementation is critical to ensure their impact.
ARTICLE Download: 45| View: 127| Comments: 0 | doi:10.20944/preprints201904.0240.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: sarcopenia; slow gait speed; cognitive impairment; older adult; aging
Online: 22 April 2019 (11:28:59 CEST)
Cognitive impairment and sarcopenia may share common risk factors and pathophysiological pathways. This study was performed to examine the association between impairments in specific cognitive domains and sarcopenia (and its defining components) in a large group of community-dwelling older adults. Cross-sectional analysis was performed on the baseline data of 3,014 adults aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study (KFACS). The final analysis included 1,887 adults underwent dual-energy X-ray absorptiometry and cognitive function assessments. Those with disability in activities of daily living, dementia, severe cognitive impairment, Parkinson’s disease, musculoskeletal complaints, neurological disorders, or who were illiterate were excluded. Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet, the Frontal Assessment Battery. For sarcopenia, we used the diagnostic criteria of the Asian Working Group for Sarcopenia. The prevalence of sarcopenia was 9.6% for men and 7.6% for women. Sarcopenia (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.04–2.99) and slow gait speed (OR 2.58, 95% CI 1.34–4.99) were associated with cognitive impairment in men. Only slow gait speed (OR 1.88, 95% CI 1.05–3.36) was associated with cognitive impairment in women. Sarcopenia is associated with cognitive impairment mainly due to slow gait speed. Our results suggested that cognitive impairment domains, such as processing speed and executive function, are associated with sarcopenia-related slow gait speed.
ARTICLE Download: 41| View: 125| Comments: 0 | doi:10.20944/preprints201904.0239.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Glucose tolerance; pharmacokineti; , Kaempferia parviflora; methoxyflavone
Online: 22 April 2019 (11:25:03 CEST)
Kaempferia parviflora Wall. ex Baker (KP), Krachaidam in Thai or Thai ginseng, is an herbal medicine that has many potential pharmacological effects. This study focused on the oral glucose tolerance test and pharmacokinetic study in healthy volunteers administered with KP extract (90 and 180 mg/day, placebo). The oral glucose tolerance tests were performed at baselines and 28-days of administration. The pharmacokinetics were determined after a single dose administration of the tested products using 3,5,7,3,4-pentamethoxyflavone (PMF) and 5,7,4-trimethoxylfavone (TMF) as markers. The results showed that glucose metabolism via oral glucose tolerance test was not affected by KP extract. The results of pharmacokinetics study revealed that only TMF and PMF, but not DMF levels could be detected in human blood. The given doses of KP extract at 90 and 180 mg/day showed a linear dose-relationship of blood PMF concentration whereas blood TMF was detected only at high given dose (180 mg/day). The half-lives of PMF and TMF were 2–3 h. The Cmax, AUC and Tmax values of PMF and TMF estimated for the 180 mg/day dose were 85.3711.31, 73.2329.93 mg/ml; 291.8948.23, 412.20203.69 mg.h/ml; and 3.890.37, 4.500.96 h, respectively. PMF was quickly eliminated with higher Ke and Cl than TMF at the dose of 180 mg/day of KP extract. In conclusion, the results demonstrated that KP extract had no effect on glucose tolerance test. In addition, this is the first demonstration of the pharmacokinetic parameters of methoxyflavones of KP extract in healthy volunteers in a phase I study in drug development. The data suggest the safety of the KP extract and will be of benefit for further clinical trials using KP extract as food and sport supplements as well as a drug in health product development.
REVIEW Download: 93| View: 137| Comments: 0
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: EGFR-mutated non-small cell lung cancer; EGFR-TKI; intrinsic resistance; resistance mechanisms
Online: 22 April 2019 (11:08:42 CEST)
Activating mutations in the Epidermal Growth Factor Receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (< 3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.
Fri, 19 April 2019
REVIEW Download: 36| View: 164| Comments: 0 | doi:10.20944/preprints201904.0224.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: homeobox; oncogenesis; EMT; immunosuppression; IL6
Online: 19 April 2019 (11:56:10 CEST)
Hepatocellular carcinoma (HCC) is the fifth most common type of cancer, and is the third leading cause of cancer-related deaths each year. It involves a multi-step progression and is strongly associated with chronic inflammation induced by the intake of environmental toxins and/or viral infections (i.e., hepatitis B and C viruses). Although several genetic dysregulations are considered to be involved in disease progression, the detailed regulatory mechanisms are not well defined. Homeobox (Hox) genes that encode transcription factors with homeodomains control cell growth, differentiation, and morphogenesis in embryonic development. Recently, more aberrant expressions of Hox genes were found in a wide variety of human cancer, including HCC. In this review, we summarize the currently available evidence related to the role of Hox genes in the development of HCC. The objective is to determine the roles of this conserved transcription factor family and its potential use as a therapeutic target in future investigations.
ARTICLE Download: 33| View: 144| Comments: 0 | doi:10.20944/preprints201904.0212.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: stroke; post-stroke dementia; anaemia
Online: 19 April 2019 (09:41:13 CEST)
Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.
Thu, 18 April 2019
REVIEW Download: 57| View: 155| Comments: 0 | doi:10.20944/preprints201904.0208.v1
Subject: Medicine & Pharmacology, Other Keywords: rhabdomyolysis; pigment nephropathy; haem; NLRP3 inflammasome; acute kidney injury
Online: 18 April 2019 (08:11:08 CEST)
Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxidative stress and inflammation. Haem is associated with inflammation in sterile and infectious conditions, contributing to the pathogenesis of many disorders such as rhabdomyolysis and haemolytic diseases. In fact, haem appears to be a signaling molecule that is able to activate the inflammasome pathway. Recent studies highlight a pathogenic function for haem in triggering inflammatory responses through the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Among the inflammasome multiprotein complexes, the NLRP3 inflammasome has been the most widely characterized as a trigger of inflammatory caspases and the maturation of interleukin-18 and -1β. In the present review, we discuss the latest evidence on the importance of inflammasome-mediated inflammation in pigment nephropathy. Finally, we highlight the potential role of inflammasome inhibitors in the prophylaxis and treatment of pigment nephropathy.
Wed, 17 April 2019
ARTICLE Download: 41| View: 175| Comments: 0 | doi:10.20944/preprints201901.0128.v2
Subject: Medicine & Pharmacology, Ophthalmology Keywords: air pollution; conjunctivitis; exposure; linear; model; case-crossover; poisson
Online: 17 April 2019 (11:58:14 CEST)
The purpose of this study is to assess the concentration-response relations between conjunctivitis and exposure to ambient ozone. This retrospective study includes emergency department (ED) visits for conjunctivitis in Edmonton, Canada, for the period April 1992–March 2002. Daily average levels of ozone (range: 1.2–50.9, ppb), of temperature, and of relative humidity were estimated and used for the period of the study. For each of the considered exposure lags, (from 0 to 9 days), six different models were fitted to estimate the concentration-response function. The goodness of fit was assessed using the Akaike information criterion. During the period of the study, 17,211 ED visits for conjunctivitis were recorded and used. For all subjects together, a positive statistically significant association was obtained for the exposure lagged by 5 days. For female subjects, lags 1, 3, and 9 had positive statistically significant associations (lag 2 had negative associations). For male subjects, only lag 5 had a positive statistically significant association. The estimated non-linear concentration-response functions for the considered groups (all, males, females) and lags, revealed the associations along the exposure levels. The fitted shapes are described by algebraic functions and may have various forms. The estimated functions are useful to determine the risk associated with exposure to ground-level ozone.
ARTICLE Download: 96| View: 226| Comments: 0 | doi:10.20944/preprints201904.0200.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: adipose-derived; bone regeneration; cartilage regeneration; clinical application; clinical studies; differentiation; hair loss; induced pluripotent stem cells; maxillary sinus augmentation; osteoarthritis; pluripotency; regenerative
Online: 17 April 2019 (11:25:14 CEST)
Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.
ARTICLE Download: 52| View: 160| Comments: 0 | doi:10.20944/preprints201904.0193.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: C. argyrosperma; corneal chemical burn; angiogenesis; corneal neovascularization (CNV); vascular endothelial growth factor (VEGF); Interleukin-1β (IL-1β); Cyclooxigenase-2 (COX-2); Nuclear Factor-kappaB (NF-κB)
Online: 17 April 2019 (06:07:15 CEST)
Cornea severe inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. The cornea can be used to study the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, Methanol (Met) and Hexane (Hex), from the seed of Cucurbita argyrosperma, in the inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. Clinical manifestation as opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological evaluation were performed. Inflammatory (COX-2, NF-κB, and IL-1β), and angiogenic (VEGF-A, VEGFR1, VEGFR2) markers were assessed by immunohistochemistry. Cox-2, Il-1β, and Vegf-a mRNA levels were also determined. After treatments, we observed slim corneal thickness with lower opacity scores and low cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased CNV area. The staining of inflammatory and angiogenic factors was significantly decreased. These effects are related to a down-expression of Cox-2, Il-1β, and Vegf. These results suggest that intake of C. argyrosperma seed can be used to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.
Tue, 16 April 2019
ARTICLE Download: 85| View: 149| Comments: 0 | doi:10.20944/preprints201904.0176.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depression; cytokines; inflammation; endogenous opioid; opioid receptor
Online: 16 April 2019 (09:49:14 CEST)
Background: There is now evidence that immune and opioid systems show functional reciprocal relationships and that both systems may participate in the pathophysiology of major depression (MDD). Objective: The present study was carried out to delineate differences between MDD patients and healthy controls in dynorphin and kappa opioid receptor (KORs) in association with levels of β-endorphins and mu opioid receptors (MORs), interleukin-6 (IL-6) and IL-10. Method: The present study recruited 60 drug-free male participants with MDD aged 24-70 year and 30 age-matched healthy males as control group and measured serum levels of dynorphin, KOR, β-endorphin, MOR, IL-6 and IL-10. Results: Serum dynorphin, KOR, β-endorphin and MOR are significantly increased in MDD as compared with controls. The increases in the dynorphin/KOR system and β-endorhin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls, whereby both opioid peptides and cytokines show a bootstrapped (n=2000) area under the receiver operating curve of 0.972. KOR and the dynorphin/KOR system are both significantly decreased in depressed subjects with comorbid nicotine dependence. Conclusion: Our findings suggest that in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorhin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by a) exerting immune regulatory activities attenuating the primary immune response; and b) modulating reward responses and mood as well as emotional and behavioral responses to stress.
Mon, 15 April 2019
ARTICLE Download: 93| View: 285| Comments: 0 | doi:10.20944/preprints201904.0170.v1
Subject: Medicine & Pharmacology, Other Keywords: topic modelling; latent dirichlet allocation; text mining; assisted reproduction; ART; IVF
Online: 15 April 2019 (12:25:12 CEST)
Study question: What are the current trends of research in Human Assisted Reproduction around the world? Summary answer: USA is the leading country, followed by the UK, China, France and Italy. The largest research area is “laboratory techniques”, although other areas such as “public health”, “quality, ethics and law” and “female factor” are gaining ground worldwide. What is known already: Scientific research, especially in health and medical sciences, aims at addressing specific needs that society (and, especially, patients) perceives as pressing. One of the main challenges for policymakers and research funders alike is therefore to align research priorities to societal needs. We can thus think of research agendas in terms of a demand side (societal needs) and a supply side (research outputs). Research output in Human Assisted Reproduction has expanded in the past years, as indicated by the increasing number of scientific publications in indexed journals in this area. Nevertheless, no map of research related to assisted reproduction has been produced so far, hindering the identification of potential areas of improvement and need. Study design, size, duration: 26,000+ scientific publications (articles, letters, and reviews) on Human Assisted Reproduction produced worldwide between 2005 and 2016 were analyzed. These publications were indexed in PubMed or obtained from reference list of indexed publications included in the analysis.Participants/materials, setting, methods: The corpus of publications was obtained by combining the MeSH terms: “Reproductive techniques”, “Reproductive medicine”, “Reproductive health”, “Fertility”, “Infertility”, and “Germ cells”. Then it was analyzed by means of text mining algorithms (Topic Modeling (TM) based on Latent Dirichlet Allocation (LDA)), in order to obtain the main topics of interest. Finally, these categories were analyzed across world regions and time. Main results and the role of chance: We identified 44 main topics, which were further grouped in 11 macro categories, form larger to smaller: “laboratory techniques”, “male factor”, “quality, ethics and law”, “female factor”, “public health and infectious diseases”, “basic research and genetics”, “pregnancy complications and risks”, “general infertility and ART”, “psychosocial aspects”, “cancer”, and “research methodology”. The USA was the leading country in number of publications, followed by the UK, China, France and Italy. Interestingly, research contents in high income countries is fairly homogeneous across macro-categories, and it is dominated by “laboratory techniques” in Western and Southern Europe, and by “quality, ethics and law” in North America, Australia and New Zealand. In middle income countries we observe that research is mainly performed on “male factor”, and noticeably less on “female factor”. Finally, research on “public health and infectious diseases” predominates in low-income countries. Regarding temporal evolution of research, “laboratory techniques” is the most abundant topic on a yearly basis, and relatively constant over time. However, since production in most of the other categories is increasing, the relative contribution of this research category is actually decreasing. Publication is especially increasing in “public health and infectious diseases” (in all world regions, but especially in low income countries), “quality, ethics and law” (high income countries), and “female factor” (middle income countries). Limitations, reasons for caution: Three main factors might limit the robustness of our work: the textual corpus analyzed is based on abstract and titles, the reproducibility of the stochastic algorithms applied, which may produce slightly differing results at each run, and the interpretation of the topics obtained. Wider implications of the findings: This study should prove beneficial in the design of research strategies and policies that foster the alignment between supply (assisted reproduction research) and demand (society). Study funding/competing interest(s): PTQ-14-06718 of the Spanish MINECO Torres Quevedo programme (FAM).
ARTICLE Download: 41| View: 126| Comments: 0 | doi:10.20944/preprints201904.0169.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: esthetic archwires; coating stability; backscattered electron microscopy
Online: 15 April 2019 (11:55:14 CEST)
Background/Aim: There is continuing interest in engineering esthetic labial archwires. The aim of this study was to coat nickel-titanium (NiTi) and beta-titanium (β-Ti), also known as titanium molybdenum (TMA), archwires by plasma electrolytic oxidation (PEO) and to analyze the characteristics of the PEO-surfaces. Materials and Methods: PEO-coatings were generated on 0.014-inch NiTi and 0.19x0.25-inch β-Ti archwires. The surfaces were analyzed by scanning electron microscopy and stereomicroscopy. Cytocombability testing was performed with ceramized and untreated samples according to EN ISO 10993-5 in XTT-, BrdU- and LDH-assays. The direct cell impact was analyzed using LIVE-/DEAD-staining. In addition, the archwires were inserted in an orthodontic model and photographs were taken before and after insertion. Results: The PEO coatings were 15 to 20 µm thick and esthetically pleasing. The cytocompatibility analysis revealed good cytocompatibility results for both ceramized NiTi and β-Ti archwires. In the direct cell tests, the ceramized samples showed improved compatibility as compared to those of uncoated samples. However, bending of the archwires resulted in loss of the PEO-surfaces. Nevertheless, it was possible to insert the β-Ti PEO-coated archwire in an orthodontic model without loss of the PEO-ceramic. Conclusion: PEO is a promising technique for the generation of esthetic orthodontic archwires. Since the PEO-coating does not resist bending, its clinical use seems to be limited so far to orthodontic techniques using straight or pre-bended archwires.
ARTICLE Download: 42| View: 94| Comments: 0 | doi:10.20944/preprints201904.0164.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: team-based learning; flipped classroom; team re-allocation
Online: 15 April 2019 (11:36:43 CEST)
Previously, we described the initial use of Flipped Team‐Based learning (FTBL) defined as TBL approach combined with flipped classroom learning methodology, in which students previewed online lectures and applied their knowledge in different in-class activities. The purpose of the present study is to review the progress within this approach and to investigate how constant changes in team allocation can affect student’s perception regarding this modified FTBL approach. Although students showed reluctance initially to get out of their ‘comfort zone’, our findings show that learners perceived the adoption of the continued random allocation, and became accustomed to this learning approach, which finally assisted them to enhance their team-work skills and classroom performance, to develop their reflective capabilities as well as improving their rapport building skills, learning and academic performance. Learners also believed that this learning strategy that creates critical incidents can simulate their future work environment as they might be expected to work in unfamiliar situations. Therefore, the present study indicated strong support for the modified FTBL method and was seen to work exceptionally well, despite some minor problems that students can experience working in a team and/or with different teammates in every session.
Sat, 13 April 2019
ARTICLE Download: 42| View: 117| Comments: 0 | doi:10.20944/preprints201904.0152.v1
Online: 13 April 2019 (05:08:57 CEST)
Background: Formation and rupture of cerebral aneurysms may be related to certain types of configuration of the circle of Willis. Analysis of their interdependence can be of great importance. Methods: A group of 114 patients treated operatively for the cerebral aneurysm rupture and a group of 56 autopsied subjects were involved in the study. Four basic types of the circle of Willis configurations were formed–two symmetric types A and C, and two asymmetric types B and D. Results: A statistically significantly higher presence of asymmetry of the circle of Willis in the group of surgically treated subjects (p=0.006) with a significant presence of asymmetric Type B in this group (p=0.017) were determined. The presence of changes in the A1 segment in the group of subjects with solitary aneurysms on the anterior communicating artery showed a statistically significant presence in the group of autopsied subjects (p=0.0004). Analyzing the presence of symmetry of the circle of Willis between the two groups, that is, the total presence of symmetric types A and C indicated their statistically significant presence in the group of autopsied patients (p=0.043). Conclusion: Changes such as hypoplasia or aplasia of A1 and the resulting asymmetry of the circle of Willis directly affect the possibility of the rupture of cerebral aneurysms. Detection of the corresponding types of the circle of Willis after diagnostic examination can be the basis for the development of a protocol for monitoring such patients.
Thu, 11 April 2019
ARTICLE Download: 81| View: 158| Comments: 0 | doi:10.20944/preprints201904.0142.v1
Subject: Medicine & Pharmacology, Urology Keywords: NGF/TrkA signaling; mitogenesis; invasiveness; EMT; 3D models; castrate-resistant prostate cancers
Online: 11 April 2019 (12:55:18 CEST)
Resistance to hormone therapy and disease progression is the major challenge in clinical management of prostate cancer (PC). Drugs currently used in PC therapy initially show a potent antitumor effect. Nevertheless, PC gradually develops resistance, relapses and spreads. Most patients develop, indeed, castrate-resistant PC (CRPC), which is almost incurable. The nerve growth factor (NGF) acts on a variety of non-neuronal cells by activating the NGF tyrosine-kinase receptor, TrkA. NGF signaling is deregulated in PC. In androgen-dependent PC cells, TrkA mediates the proliferative action of NGF through its cross talk with the androgen receptor (AR). Epithelial PC cells, however, acquire the ability to express NGF and TrkA, as the disease progresses, indicating a role for NGF/TrkA axis in PC progression and androgen-resistance. We here report that once activated by NGF, TrkA mediates proliferation, invasiveness and epithelial-mesenchyme transition (EMT) in various CRPC cells. NGF promotes organoid growth in 3D models of CRPC cells, and specific inhibition of TrkA impairs all these responses. Thus TrkA represents a new biomarker to target in CRPC.
Wed, 10 April 2019
ARTICLE Download: 62| View: 166| Comments: 0 | doi:10.20944/preprints201904.0130.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: retrospective hospital-based study, overweight, obesity, pregnancy pathologies, caesarean section, weight gain
Online: 10 April 2019 (12:34:37 CEST)
This study aimed to evaluate the impact of selected pregnancy pathologies statistically depending on overweight/obesity and excessive maternal weight gain during pregnancy on women who gave birth in the years 2013–2015 at the Second Department of Gynecology and Obstetrics at the University Hospital in Bratislava, Slovakia. In a retrospective study, we analyzed data gathered from the sample, which consisted of 7,122 women. Our results indicate a positive statistical dependency of the groups of women with overweight and obesity and gestational hypertension (adjusted odds ratio [AOR]=15.3; 95% CI 9.0−25.8 for obesity), preeclampsia (AOR=3.4; 95% CI 1.9−6.0 for overweight and AOR=13.2; 95% CI 7.7−22.5 for obesity), and gestational diabetes mellitus (AOR=1.9; 95% CI 1.2−2.9 for overweight and AOR=2.4; 95% CI 1.4−4.0 for obesity). A higher incidence of pregnancies terminated by cesarean section was observed in the group of obese women. Gestational weight gain above the IOM (the Institute of Medicine) recommendations was associated with a higher risk of pregnancy terminated by C-section (AOR=1.2; 95% CI 1.0−1.3), gestational hypertension (AOR=1.7; 95% CI 1.0−2.7), and infant macrosomia (AOR=1.7; 95% CI 1.3−2.1). Overweight and obesity during pregnancy significantly contribute to the development of pregnancy pathologies and increased incidence of cesarean section. Systematic efforts to reduce weight before pregnancy through pre-pregnancy dietary counseling, regular physical activity, and healthy lifestyle should be the primary goal.
REVIEW Download: 71| View: 144| Comments: 0 | doi:10.20944/preprints201904.0127.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: PTEN; PI3K; cancer predisposition syndromes; targeted therapies; mouse models of human cancer
Online: 10 April 2019 (10:37:43 CEST)
The PI3K-AKT-mTOR signal transduction pathway regulates a variety of biological processes including cell growth, cell cycle progression and proliferation, cellular metabolism and cytoskeleton reorganization. Fine-tuning of the PI3K pathway signaling output is essential for the maintenance of tissue homeostasis and uncontrolled activation of this cascade leads to a number of human pathologies including cancer. Inactivation of the tumour suppressor phosphatase PTEN and/or activating mutations in the proto-typical lipid kinase PI3K have emerged as some of the most frequent events associated with human cancer and as a result the PI3K pathway has become a highly sought-after target for cancer therapies. In this review we summarize the essential role of the PTEN-PI3K axis in controlling cellular behaviors by modulating activation of key proto-oncogenic molecular nodes and functional targets. Further, we highlight important functional redundancies and peculiarities of these two critical enzymes that over the last few decades have become a central part of the cancer research field and have instructed hundreds of pre-clinical and clinical trials to better cancer treatments.
ARTICLE Download: 54| View: 132| Comments: 0 | doi:10.20944/preprints201904.0124.v1
Subject: Medicine & Pharmacology, Other Keywords: dental care; immigrants; inequalities; health survey; economic crisis
Online: 10 April 2019 (09:44:49 CEST)
This study evaluates inequalities in the use of dental services according to place of birth before and after the economic crisis in Spain. A cross-sectional study was performed in the population aged 18 to 65 years in Spain. We used data from three Spanish National Health Surveys for years 2006 (before the crisis), 2014 and 2017 (after the crisis). Log-binomial regression was used to quantify the association between region of origin and use of dental care services before and after controlling for the selected covariates. In 2006, we found a greater probability of not using dental care services in immigrants from Asia (PR:1.36, 95% CI:1.10–1.67) and Africa (PR:1.16; 95% CI:1.05–1.28) compared to the natives. For 2014, the probability of not using dental care services was greater for all immigrants compared to the natives, with the greatest odds for those from Africa (PR:1.71; 95% CI:1.46–2.01) and Asia (PR:1.3; 95% CI:1.23–1. 47). The associations for 2017 were weaker in magnitude than the ones observed for 2014, although stronger than for 2006. This study suggests that the economic recovery did not have the same impact for natives and immigrants regardless of regions of origin, given the observed inequalities in use of dental services.
ARTICLE Download: 81| View: 164| Comments: 0 | doi:10.20944/preprints201904.0120.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: mixed reality headset; mobility assessment; wearable sensor; fall risk; aging
Online: 10 April 2019 (08:33:16 CEST)
Functional mobility assessments (i.e., Timed Up and Go) are commonly used clinical tools for mobility and fall risk screening in the aging population. In this work, we proposed a new Mixed Reality (MR)-based assessment that utilized a Microsoft HoloLensTM headset to automatically lead and track the performance of functional mobility tests, and subsequently evaluated its validity in comparison with reference inertial sensors. Twenty-two healthy adults (10 older, 12 young) participated in this study. An automated functional mobility assessment app was developed based on the HoloLens platform. Mobility performance was recorded with the headset built-in sensor and validated with reference inertial sensor (Opal, APDM) taped on the headset and lower back. Results indicate vertical kinematic measures by HoloLens was in good agreement with the reference sensor (Normalized RMSE ~ 10%). Additionally, the HoloLens-based test completion time was in perfect agreement with clinical standard stopwatch measure. Overall, our preliminary investigation indicates that it is possible to use an MR headset to automatically guide users to complete common mobility tests with good measurement accuracy, thus it has great potential to provide objective and efficient sensor-based mobility assessment.
Mon, 8 April 2019
ARTICLE Download: 96| View: 515| Comments: 0 | doi:10.20944/preprints201904.0093.v1
Subject: Medicine & Pharmacology, Other Keywords: Patients involvement; research interests; ART treatments; treatment personalization; psychological effects; healthy habits; fertility protection; infertility prevention; lifestyle; diet
Online: 8 April 2019 (12:46:17 CEST)
STUDY QUESTION: Which are the main research interests among patients of assisted reproductive technologies (ART)? SUMMARY ANSWER: Patients identified as research priorities that deserve further investigation: success rates and risks of ART, side-effects of treatments, resources to cope with infertility, effectiveness of alternative therapies, lifestyle habits to protect fertility, oocyte quality and ovarian reserve, and causes of genetic or hereditary infertility. WHAT IS KNOWN ALREADY: The involvement of patients and caregivers in setting research agendas in medicine has gathered significant momentum in the last decade. Patients’ involvement in setting research priorities offers several benefits: improved patient knowledge and awareness of their condition; greater understanding of the medical professionals of the impact of the condition on patients’ quality of life; reduced costs associated with redundant research activities. This is may be also applicable to research in infertility and ART, where patients’ interests have never been explored before. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study that consists of an anonymous online survey, which was sent up to three times to 2112 patients from 11 fertility centers in 5 countries between January-December 2018. The study design was based on the James Lind Alliance priority setting partnership model, which comprises the identification of patients groups, the exploration of the research agenda, the analysis of collected data and identification of priorities. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 2112 patients were contacted, and 945 surveys were answered (RR: 44.7%). Patients were asked to identify research questions relevant to them in the areas of infertility causes and prevention, fertility treatments (medication and ART), and the emotional aspects of infertility. Answers were categorized in topics and ranked by frequency. A long list of the top-30 research topics was extracted from the aggregate results, from which, a short list of the top-10 research topics was created. At the end, 10 research questions related to each of the 10 research topics were constructed, based on the answers given by patients. MAIN RESULTS AND THE ROLE OF CHANCE: Female (845, 89.4%) and male (100, 10.6%) patients were included. The mean age of patients was 37.8 (SD 1.74). Most of the patients did not have children at the time of the survey (523, 59%), while 51 (5.7%) were pregnant. Sixty (6.3%) patients did not start treatment, 579 (61.3%) were performing a treatment with their own gametes and 304 (32.2%) were treated through gamete donation. Patients were mainly interested in the effectiveness of ART -especially per clinical profile-, side effects of drugs, protection of fertility and prevention of infertility –especially through diet and exercise-, and psychological aspects of the infertility journey. The top-10 research questions (and weight) obtained were: 1) What are the side-effects of ART treatments? (41.6%); 2) What are the most effective methods to cope with infertility from the psychological point of view? (37.2%); 3) What effects could diet have on fertility? (25.9%); 4) What are ART success rates per clinical profile? (25.9%); 5) Are there habits and lifestyle factors that could prevent infertility? (20.0%); 6) What are the long-term risks associated to ART? (18.5%); 7) Are alternative therapies such as acupuncture, yoga, and meditation effective to treat/prevent infertility? (18.5%); 8) What is the impact of exercise on fertility? (15.4%); 9) How does oocytes quantity and quality affect fertility? (9.5%); 10) What are the genetic patterns or hereditary conditions causing/related to infertility? (9.5%). LIMITATIONS, REASONS FOR CAUTION: Although all respondents had attended a fertility center, not all of them were diagnosed as infertile (i.e. single women) and had started treatment at the time of response, while a few were pregnant; their priorities for research might have been influenced by their infertility journey. Also, all participants attended private fertility centers: areas of interest may be different in public settings. WIDER IMPLICATIONS FOR THE FINDINGS: Researchers and clinicians should keep in mind that, in addition to improvement of treatments’ success rates and side-effects, patients greatly value research on causes, prevention and emotional aspects of infertility. As their views might differ from those of medical professionals, patients’ voices should be incorporated in setting infertility research priorities.
ARTICLE Download: 72| View: 138| Comments: 0 | doi:10.20944/preprints201904.0089.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: Fook intake; pizza; pasta; vegetables; pregnancy; adverse perinatal outcome
Online: 8 April 2019 (11:35:16 CEST)
Growing body of evidence endorse the hypothesis of a protective role played by the in-utero environment on a suitable fetal programming, mainly sustained by fitting maternal diet. Our purpose was to assess the linkage between maternal food intake and poor obstetric results, with a special focus on typical Italian food. A cross sectional study including delivering women was designed. A self-reported questionnaire about socio-demographic data, obstetric history, and food frequency intake during pregnancy was administrated. A composite of adverse perinatal outcomes (APO) was constructed. Statistically significant differences were found between APO and control group in smoking habit (9.7 vs. 3.2%, p=0.045) and BMI at delivery (27.9±4.9 vs. 26.9±3.9, p=0.003). Women complicated by any or more APOs reported increased rates of pasta (5.3± 3.6 vs.4.4±1.9 times per week, p<0.001) and pizza (1.9±3.4 vs. 1.1±0.6, p<0.001) intake, with lower consumption of vegetables (5.4±3.9 vs. 7.1±2.9, p<0.001). By logistic regression analysis and after adjustments for maternal age, ethnicity, SES, maternal BMI at delivery, excessive ingestion of pizza (aOR 1.676, 95%CI 1.199-2.343, p=0.033), but not pasta (aOR 1.077, 95%CI 0.950-1.211, p=0.244), was found associated with APO. Vegetable consumption showed a protective role in reducing APOs (aOR 0.897, 95%CI 0.818-0.985, p=0.022). Nutrition in pregnancy should minimalize pizza intakes.
ARTICLE Download: 59| View: 110| Comments: 0 | doi:10.20944/preprints201904.0086.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Cryptococcal meningitis; Cryptococcus; HIV; CD4 T cells; CD8 T cells; adaptive immune response; IRIS
Online: 8 April 2019 (11:02:55 CEST)
Cryptococcal meningitis remains a significant opportunistic infection among HIV-infected patients, contributing 15%-20% of HIV-related mortality. A complication of initiating Antiretroviral therapy (ART) following opportunistic infection is Immune Reconstitution Inflammatory Syndrome (IRIS). IRIS afflicts 10-30% of HIV-infected patients with cryptococcal meningitis (CM), but its immunopathogenesis is poorly understood. We compared circulating T cell memory subsets and cytokine responses among 17 HIV-infected Ugandans with CM: 11 with and 6 without CM-IRIS. At meningitis diagnosis, stimulation with cryptococcal capsule component, glucuronoxylomannan (GXM) elicited consistently lower frequencies of CD4+ and CD8+ T cell memory subsets expressing intracellular cytokines (IL-2, IFN-γ and IL-17) among subjects who subsequently developed CM-IRIS. After ART initiation, T cells evolved to show a decreased CD8+ central memory phenotype. At the onset of CM-IRIS, stimulation more frequently generated polyfunctional IL-2+/IL-17+ CD4+ T cells in patients with CM-IRIS. Moreover, CD8+ central and effector memory T cells from CM-IRIS subjects also demonstrated more robust IL-2 responses to antigenic stimulation vs. controls. Thus, ART during CM elicits distinct differences in T cell cytokine production in response to cryptococcal antigens both prior to and during the development of IRIS, suggesting an immunologic foundation for the development of this morbid complication of CM infection.
Sun, 7 April 2019
ARTICLE Download: 66| View: 116| Comments: 0 | doi:10.20944/preprints201904.0070.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: mycoplasma pneumoniae pneumonia; macrolide antibiotics; antibiotic resistance; corticosteroids; prednisolone; methylprednisolone; children
Online: 7 April 2019 (12:35:26 CEST)
Antibiotics’ effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015-2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24-36 h after admission. Initially, oral prednisolone (1 mg/kg) or intravenous methylprednisolone (IVMP) (1-2 mg/kg) was administered for mild pneumonia patients, and IVMP (5 -10 mg/kg/day) for severe pneumonia patients. If patients showed persistent fever for 36-48 hours or disease progression, additive IVMP (5 mg/kg or 10 mg/kg) was given. Eighty-five patients received only a broad-spectrum antibiotic without macrolide. The mean age and the male:female ratio were 5.6 ± 3.1 years, respectively. Seventy-four percent of patients (190/257) showed immediate defervescence within 24 h, and 95.7% (246/257) of patients showed defervescence within 72 h with improvements in clinical symptoms. Eight patients who received additive IVMP also showed clinical improvement within 48 h without adverse reactions. There were no clinical or laboratory differences between patients treated with a macrolide (n = 172) and without (n = 85). Early corticosteroid therapy might reduce disease morbidity and prevent disease progression in MP pneumonia patients without side effects, and antibiotics may have limited effects on MP infection.
Fri, 5 April 2019
ARTICLE Download: 52| View: 189| Comments: 0 | doi:10.20944/preprints201903.0207.v2
Subject: Medicine & Pharmacology, Ophthalmology Keywords: myopia,photon-electron theory,high-frequency electromagnetic radiation
Online: 5 April 2019 (12:16:15 CEST)
The exact etiology of myopia remains elusive. The author proposes the particle property of photon in living tissue and the photon-electron theory in living tissue, if the frequency of the photon exceeds the threshold, the photon has enough energy to strike the electron away and forms a hole of a diameter in photon diameter scale in living tissue include the eye. Longer time of high-frequency electromagnetic radiation will cause more holes and a larger radius of holes. The visual light which passes through the radiated hole in the eye cannot be refracted on the macula, this is myopia symptom of blurred vision, shortening the distance of the eye and the object will include more visual light into cornea and lens, this is myopia another symptom of nearsightedness. The particle property of photon causes elongation of the eye and the macular holes.
ARTICLE Download: 63| View: 173| Comments: 0 | doi:10.20944/preprints201904.0062.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: BCG; Eudragit, oral vaccine; tuberculosis; in vitro viability
Online: 5 April 2019 (11:59:53 CEST)
Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.
Thu, 4 April 2019
ARTICLE Download: 61| View: 166| Comments: 0 | doi:10.20944/preprints201904.0057.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: miscarriage; fetal loss; risk factor; ethnicity; maternal race
Online: 4 April 2019 (15:52:25 CEST)
In last decades, growing migration flows have modified the obstetric clinical care, requiring specific attention by health care systems. The aim was to describe the phenomenon focusing on miscarriage (pregnancy loss at <20 weeks). Patients admitted for care at miscarriage in a six-year period (2012-17) were revised. Miscarriage rates in all ethnic groups, dichotomized in early (within the first 12 weeks of gestation) and late (at <20 weeks) pregnancy loss. Associations between women's characteristics (age, parity, inter-pregnancy interval (IPI)) were explored to elucidate any differences. A total of 1,940 patients were included, segregated in early (n = 1769, 91.2%) and late (n = 171, 8.8%) pregnancy losses. Caucasian ethnicity was the most common (87.9%), leaving the minority groups to 12.1%. Maternal age was higher among Caucasians women than other subgroups, in contrast to Asiatic patients. Nulliparity was observed in 1045 (53.9%) patient, more widespread among Caucasian and Maghrebins. A positive obstetric history counting at least one miscarriage was frequent, ranging from 22.2% to 75%, in particular among Asiatic women, while the recurrence in Caucasians. In Afro-Carribeans the most relevant rate of late miscarriage was found. By multiple regression modelling, maternal age, nulliparity and Afro-Carribean were identified as determinants. Maternal ethnicity should be considered in the management of pregnancy losses in combination with already well-defined risk factors, including age at miscarriare and nulliparity.
ARTICLE Download: 79| View: 187| Comments: 0 | doi:10.20944/preprints201904.0054.v1
Online: 4 April 2019 (12:35:43 CEST)
Beta-thalassemia major (β-TM) is a severe form of thalassemia caused by mutations in the β-globin gene, resulting in partial or complete deficiency of β-globin chains. This deficiency results in oxidative stress, dyserythropoiesis, and chronic anemia. Cytokine dependent hematopoietic cell linker (CLNK) belongs to the adaptor protein family and has the capacity to interact with multiple signaling proteins thereby modulating signal transduction. The aim of the present study was to examine CLNK in sera of β-TM patients and examine its association with iron overload biomarkers. Sixty β-TM patients, aged 3–12 years old and undergoing blood transfusions, and 30 healthy control children were recruited and CLNK, ferritin and iron status parameters were measured. The results showed a significant increase (p < 0.001) in serum CLNK levels in β-TM patients as compared with normal controls. The increased levels of CLNK were significantly associated with increased ferritin levels. Increased CLNK levels in β-TM may be explained by reciprocal effects between immune signaling and immature erythrocytes, which, release soluble receptors and signaling molecules, including CLNK, in the blood.
COMMUNICATION Download: 58| View: 175| Comments: 0 | doi:10.20944/preprints201904.0052.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Exosomes, mass spectrometry, proteomics, biomarkers, cancer, extracellular vesicles, microvesicles, oncosomes
Online: 4 April 2019 (12:29:44 CEST)
The proteomic profile of extracellular vesicles (EVs) has been of increasing interest, particularly in understanding cancer growth, drug resistance, and metastatic behavior. Emerging data suggests that cancer-derived EVs may carry an array of oncogenic cargo, including certain integrin proteins that may, in turn, promote cell detachment, migration, and selection of future metastatic sites. We previously reported a large comparison of secreted vesicle protein cargo across sixty diverse human cancer cell lines. Here, we analyze the distinct integrin profiles of these cancer EVs. We further demonstrate the enrichment of integrin receptors in breast cancer EVs compared to vesicles secreted from benign breast epithelial cells. Total EV integrin levels, including the quantity of integrins α2, αv, β4, and β5 correlate with breast tumor stage. In particular, integrin α2 also largely reflects progenitor cell expression, highlighting the utility of this integrin protein as a potential circulating biomarker of primary tumors. This study provides preliminary evidence of the value of vesicle-associated integrin proteins in cancer diagnosis and prediction of tumor stage. Differential expression of integrins across cancer cells, and selective packaging of integrins into EVs may contribute to further understanding the development and progression of tumor growth and metastasis across a variety of cancer types.
ARTICLE Download: 44| View: 167| Comments: 0
Subject: Medicine & Pharmacology, Other Keywords: transsexuals; hysterectomy; mastectomy; reassignment surgery
Online: 4 April 2019 (12:26:30 CEST)
Mastectomy and hysterectomy with bilateral salpingo-oophorectomy are the first steps in surgical female-to-male (FtM) gender affirmation. We aimed to critically review our experience with the combined approach of hysterectomy/salpingo-oophorectomy and bilateral mastectomy and to focus on intra- and postoperative complications. In a retrospective cohort study, 108 consecutive patients were included who underwent combined hysterectomy, bilateral salpingo-oophorectomy, and bilateral mastectomy in a single operating session, between November 1998 and December 2017. Main outcome measures were operating times and intra- and postoperative courses, including major and minor adverse events. Patients were 28.9 ± 6.7 years of age and revealed a mean BMI of 24.4 ± 4.1 kg/m2. The median total operating time for patients without additional procedures was 237.6 ± 110.3 minutes. Taking all intra- and postoperative complications together, there were eight (7.4%) and 21 (19.4%) patients with major and minor complications, respectively. The most frequent complication was breast hematoma (18/108, 16.7%). There was a completely uneventful intra- and postoperative course in 82 cases (75.9%). In conclusion, for FtM reassignment surgery, the combined hysterectomy / salpingo-oophorectomy and bilateral mastectomy in a single operating session seems to be feasible and safe.
ARTICLE Download: 67| View: 201| Comments: 0 | doi:10.20944/preprints201902.0258.v2
Subject: Medicine & Pharmacology, Nutrition Keywords: alcohol; natural wine; blood alcohol content; breathalyzer; pesticides
Online: 4 April 2019 (11:23:33 CEST)
Different alcoholic beverages can have different effects on blood alcohol concentrations (BAC) and neurotoxicity even if equalized for alcohol content by volume. Anecdotal evidence suggested that natural wine is metabolized differently from conventional wines. This triple-blind study compared the BAC of 55 healthy male subjects after consuming the equivalent of 2 units of alcohol of a natural or conventional wine over 3 mins in two separate sessions one week apart. BAC was measured using a professional breathalyzer every 20 mins after consumption for 2 hrs. The BAC curves in response to the two wines diverged significantly at twenty minutes, at forty minutes and also at their maximum concentrations (peaks), with the natural wine inducing a lower BAC than the conventional wine (T20 0.40 vs. 0.46 [p<0.0002], T40 0.49 vs. 0.53 [p<0.0015], peak 0.52 vs. 0.56 [p<0.0002]). These differences are likely related to the development of different amino acids and antioxidants in the two wines during their production. This in turn may affect the kinetics of alcohol absorption and metabolism. Other contributing factors may also include pesticide residues, differences in dry extract content and the use of indigenous or selected yeasts. Further studies are needed to fully understand why natural wines are metabolized differently from conventional wines.
Wed, 3 April 2019
ARTICLE Download: 60| View: 216| Comments: 0 | doi:10.20944/preprints201904.0038.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: communication skills; standardized patients; gender; checklist; competence assessment; OSCE
Online: 3 April 2019 (10:22:49 CEST)
Background: The present study analyzes the evaluation of communication skills by standardized patients (SPs) and medical evaluators (Es) in an OSCE setting. Methods: The OSCE involved 189 sixth-year medical students, as well as 34 SPs and 63 Es. Communications skills were evaluated in 8 stations, simultaneously by SPs and Es. The SPs were actors who had been trained in the clinical case and who acted in accordance with a standardized script in a simulated clinical situation. The evaluators, also standardized, were Resident Doctors or staff Doctors from the Hospital Services involved. Results: The global scores awarded to students for communication skills were very similar in both groups, although the score awarded by Es was significantly higher, and a direct relationship was also observed between the mean scores awarded by both groups. Evaluators awarded significantly higher scores than SPs in 7 out of the 10 items on the checklist. Female medical students also scored significantly higher than their male counterparts in many items, including external appearance, listening, cordiality, optimism, interest, expression and empathy. Conclusions: Our data indicate that SPs and Es evaluated communication skills in a similar manner in an OSCE setting, a finding which suggests that health-related professionals can be used as an alternative to SPs, thus helping to lower economic costs. Our study also confirms a gender difference (in favor of women) in the evaluation of communications skills by both groups.Our data indicate that SPs and Es evaluated communication skills in a similar manner in an OSCE setting, a finding which suggests that health-related professionals can be used as an alternative to SPs, thus helping to lower economic costs. Our study also confirms a gender difference (in favor of women) in the evaluation of communications skills by both groups.
REVIEW Download: 119| View: 360| Comments: 0 | doi:10.20944/preprints201904.0037.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: second-hand smoke; cardiovascular disease; third-hand smoke; passive vaping; electronic cigarettes; heated tobacco; water pipe; myocardial infarction; stroke; diabetes
Online: 3 April 2019 (10:07:13 CEST)
In deaths and diseases attributed to tobacco smoke cardiovascular events exceed cancer and respiratory diseases. Second hand smoke (SHS) promotes the development of arteriosclerosis and can also trigger acute changes of endothelial function and of blood coagulability. Indoor smoking bans reduced coronary syndrome and myocardial infarction 10-20% within one year and were followed by sustainable decreases of stroke and diabetes. With a smoke-free hospitality industry people recognized tobacco smoke as an air pollutant, smoking in public was denormalized and social acceptance of smoking in front of children and pregnant women decreased also in homes and in cars. Combined effects with ambient air pollution are proven for active smoking and suspected for SHS. Contamination with third hand smoke (THS, “cold smoke”) persists for months in homes and cars, creating secondary pollutants that in some cases are more toxic (e.g., tobacco-specific nitrosamines). Remnants found in air, dust, and on surfaces (carpets, wallpapers, upholstery, soft toys) were associated with their metabolites in saliva and urine of children and with elevated levels of nicotine on hands and cotinine in urine of nonsmokers residing in homes previously occupied by smokers. In animal experiments effects of THS were found on thrombogenesis, insulin resistance through oxidative stress, on the developing immune system, lipid metabolism and alterations in liver, lung, skin and behavior. Much less is known about health effects for bystanders from the aerosols exhaled during “vaping” of e-cigarettes, but nicotine and other toxins from e-cigarettes are certainly a hazard, which should be prevented by the use of dermal and oral nicotine products, which are safer for nicotine replacement and without risk for bystanders.
Tue, 2 April 2019
REVIEW Download: 45| View: 218| Comments: 0
Subject: Medicine & Pharmacology, General Medical Research Keywords: consumer health informatics; E-health; mobile Apps; outpatient follow-up; patient portal; patient-reported outcomes
Online: 2 April 2019 (12:32:10 CEST)
Replacement of fee-for-service with capitation arrangements, forces physicians and institutions to minimize health care costs, while maintaining high-quality care. In this report we describe how patients, their families (and caregivers) can work with members of the medical care team to achieve these twin goals of maintaining (and perhaps improving) high-quality care and minimizing costs. We describe how increased self-management enables patients and their families/caregivers to provide electronic patient-reported outcomes (i.e., symptoms, events) (ePROs) as frequently as the patient or the medical care team consider appropriate. These capabilities also allow greater reliance on the use of mobile technologies (mHealth) to provide ongoing assessments of physiologic measurements/phenomena. Remote surveillance of these communications allows longer intervals between (fewer) visits of patients to the medical-care team when this is appropriate and earlier interventions when that is appropriate. Systems are now available that alert medical care providers to situations when interventions might be needed.
ARTICLE Download: 71| View: 225| Comments: 0 | doi:10.20944/preprints201904.0030.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: Brody effect; electrocardiographic variation; R-wave amplitude; hemodynamic monitoring; pulse pressure variation
Online: 2 April 2019 (12:19:31 CEST)
The aim of this study was to analyze whether the respiratory variation in ECG standard lead II R-wave amplitude (ΔRDII) could be used to assess intravascular volume status following inferior vena cava (IVC) clamping. This clamping causes an acute decrease in cardiac output during liver transplantation (LT). We retrospectively compared ΔRDII and related variables before and after IVC clamping in 34 recipients. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were used to derive a cutoff value of ΔRDII for predicting pulse pressure variation (PPV). After IVC clamping, cardiac output significantly decreased while ΔRDII significantly increased (P = 0.002). The cutoff value of ΔRDII for predicting a PPV >13% was 16.9% (AUC: 0.685) with a sensitivity of 57.9% and specificity of 77.6% (95% confidence interval 0.561 – 0.793, P = 0.015). Frequency analysis of ECG also significantly increased in the respiratory frequency band (P = 0.016). Although significant changes in ΔRDII during vena cava clamping were found at norepinephrine doses < 0.1 μg/kg/min (P = 0.014), such changes were not significant at norepinephrine doses > 0.1 μg/kg/minP = 0.093). ΔRDII could be a noninvasive dynamic parameter in LT recipients presenting with hemodynamic fluctuation. Based on our data, we recommended cautious interpretation of ΔRDII may be requisite according to vasopressor administration status.
ARTICLE Download: 82| View: 218| Comments: 0 | doi:10.20944/preprints201809.0028.v2
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: photovoice; chronic illness; physical activity; barriers; facilitator
Online: 2 April 2019 (07:48:28 CEST)
Aims: A community-based multi-component intervention (increasing awareness of the importance of physical activity in chronic illness management through reading comic books, training regarding warm-up stretching exercises, identifying facilitators and barriers to exercise through photosharing, supporting self-reflection and development of action plans) was developed to promote physical activity (PA) among patients with diabetes and hypertension. This study aimed to evaluate the efficacy of this intervention on health behaviour (walking) and health outcomes. Design: A non-randomized controlled trial with waitlisted control and pre- and post-measures. Setting: Community centres for the elderly. Participants: A total of 204 older adults with diabetes and/or hypertension were recruited. They were assigned to either the intervention group (IG) or waitlisted to the control group (CG). Intervention: Under the supervision of a nurse, six weekly group meetings were arranged in community centres for the elderly in which the participants freely exchanged their views regarding the barriers and facilitators of regular physical activity. Participants were encouraged to take photos in their neighbourhood or at home and brought these photos to share at the group meetings. The photos showed both the barriers and the facilitators to PA. In the last meeting, each participant worked out a plan to perform PA in the coming four weeks. Measures: PA referred to the number of steps taken per day and it was measured by a Garmin Accelerometer at baseline, Week 6 and Week 10. Other measures included the nine-item Self-Efficacy Scale for Exercise - Chinese version (SEE-C), the 23-item Chinese Barriers to Exercise Scale and Senior Fitness Tests. Generalised Estimating Equations (GEE) models compared the outcomes over time between IG and CG. Results: A statistically significant difference in the changes in the average number of steps taken daily between the two groups at Week 10 (mean difference = 965.4; 95% confidence interval: 92.2, 1838.6, p = 0.030) was observed, although the difference at Week 6 was non-significant (mean difference = 777.6; 95% confidence interval: −35.3, 1590.5, p = 0.061). IG participants also showed significant improvements in lower body strength (mean difference = 0.967; 95% confidence interval: 0.029, 1.904, p = 0.043) and lower limb flexibility (mean difference = 2.068; 95% confidence interval: 0.404, 3.731, p = 0.015) at Week 10 compared to CG participants. Conclusion: This multi-component intervention improved the participants’ physical activity level and physical fitness, particularly in lower limb flexibility and body strength.
Mon, 1 April 2019
ARTICLE Download: 67| View: 152| Comments: 0 | doi:10.20944/preprints201904.0019.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Castor oil; Ascorbic acid; Bowel preparation; Polyethylene glycol
Online: 1 April 2019 (13:42:38 CEST)
Our aim was to evaluate efficacy and safety of 30mL CaO alone or plus Asc in bowel preparation before colonoscopy. Two hundred and forty six patients were allocated randomly to ingest 2L PEG with 30mL CaO, 1L PEG with 30mL CaO plus 5g Asc, or 3L PEG. We used Boston Bowel Preparation Scale (BBPS) to evaluate bowel preparation efficacy. We also determined other outcomes such as procedure time, polyp or adenoma detection rate and adverse events (AEs). Of 282 patients recruited, 36 were excluded. Groups were matched for baseline characteristics except weight (P = 0.020) and body mass index (BMI) (P = 0.003). Patient’s satisfaction were higher in 2L PEG-CaO (P = 0.016) and 1L PEG-CaO-Asc groups (P = 0·017). Patients’ compliance was 67.5%, 71.4% and 80.5% in 3L PEG, 2L PEG-CaO and 1L PEG-CaO-Asc groups (P = 0.014). Adequate bowel preparation rate was 75%, 78.57% and 53.66% in 3L PEG, 2L PEG-CaO and 1L PEG-CaO-Asc groups (P = 0.021). There were no differences in terms of remaining outcomes. Despite an increase in patients’ satisfaction and compliance, 1L PEG-CaO-Asc significantly decreased adequate bowel preparation rate. However, 2L PEG-CaO improved the patients' satisfaction and compliance and increased adequate bowel preparation rate.
CASE REPORT Download: 58| View: 148| Comments: 0 | doi:10.20944/preprints201904.0017.v1
Subject: Medicine & Pharmacology, Other Keywords: marginal ridge staining; enamel crack; detecting cracks in teeth; PTR-LUM
Online: 1 April 2019 (13:38:50 CEST)
Detecting cracks in teeth is a clinical challenge. Patients may complain of diffuse pain on chewing, no pain on temperature change and pain that occurs episodically. Common diagnostic tools such as radiographs and visual examination may not detect cracks. This case study shows how PTR-LUM in The Canary System can detect cracks in teeth not seen with other devices. In this clinical situation, the crack involved a large part of the mesial and distal surfaces of a mandibular second molar.
ARTICLE Download: 69| View: 183| Comments: 0 | doi:10.20944/preprints201904.0015.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: dysphagia; FEES; Parkinson’s disease; swallowing speed; screening; water test
Online: 1 April 2019 (13:32:41 CEST)
There is still a lack of a clinical test to reliably identify patients with Parkinson’s disease (PD) being at risk for aspiration. In this prospective, controlled, cross-sectional study we assessed if swallowing speed for water is a useful clinical test to predict aspiration proven by flexible endoscopic evaluation of swallowing (FEES). Due to this we measured the swallowing speed for 90 ml water in 115 consecutive and unselected PD outpatients of all clinical stages and 32 healthy controls. Average swallowing speed was lower in patients compared with controls (6.5 ± 3.9 ml/s vs. 8.5 ± 3.2 ml/s; p < 0.01). The disease-independent widely used threshold of < 10 ml/s showed insufficient sensitivity of 88% and specificity of 19% with unacceptable false-positive rates of 63% for patients and 69% for controls. Receiver operating characteristic (ROC) analysis was carried out to define a suitable cut-off value for detection of aspiration of water (area under the curve 0.72, p < 0.001) in PD patients. The optimized cut-off value was 5.5 ml/s with a sensitivity of 69% and a specificity of 64%. Overall, measuring swallowing speed is prone to methodological errors and not suitable as a screening instrument to predict aspiration in PD patients.
Sat, 30 March 2019
REVIEW Download: 106| View: 311| Comments: 0 | doi:10.20944/preprints201903.0288.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Enhancers; BET inhibitors; CDK7 inhibitors; HDAC inhibitors; Transcription factors; eRNAs; cancer
Online: 30 March 2019 (08:33:07 CET)
Tight regulation of gene transcription is essential for normal development, tissue homeostasis and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation. Interestingly, a number of approved therapeutic agents such as cyclosporine, steroid hormones, and thiazolidinediones actually function by affecting enhancer landscapes by directly targeting very specific transcription factor programs. More recently, a broader approach to targeting deregulated enhancer programs has been achieved via Bromodomain and Extraterminal (BET) inhibition or perturbation of transcription-related cyclin-dependent kinases (CDK). One challenge to enhancer-targeted therapy is proper patient stratification. We suggest that monitoring of enhancer RNA (eRNA) expression may serve as a unique biomarker of enhancer activity that can help to predict and monitor responsiveness to enhancer-targeted therapies. A more thorough investigation of cancer-specific enhancers and the underlying mechanisms of deregulation will pave the road for an effective utilization of enhancer modulators in a precision oncology approach to cancer treatment.
ARTICLE Download: 62| View: 182| Comments: 0 | doi:10.20944/preprints201903.0287.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: resistant; microRNA-21; doxorubicin; PTEN; MCF-7/Dox cell line
Online: 30 March 2019 (06:46:35 CET)
Background: Breast cancer is the leading cause of cancer mortality and morbidity among Indonesian women. Identification of biological pathways leading into therapeutic resistance through in vitro model is an important step to develop alternative effective therapy in breast cancer. Loss of PTEN expression has been associated with resistance to chemotherapy by involving PI3K/PTEN- dependent apoptosis pathway. We conducted in vitro experiment to investigate the association of hsa-miR-21 and PTEN expression in Doxorubicin-resistant MCF-7 cell line. Methods: Parental MCF-7 cells were periodically incubated with Doxorubicin to obtain specific Dox-resistant variant determined by IC50 using MTT assay. PTEN protein expression was analyzed using immunocytochemistry. Expression of mature has-miR-21 was measured using qRT-PCR. Results: The IC50 of Doxorubicin in parental MCF-7 and Doxorubicin-resistant MCF-7 cells (MCF-7/Dox) was 0.68 and 5.78 µg/ml, respectively. Hsa-miR-21 was significantly overexpressed in MCF-7/Dox cells compared to parental MCF cells (7.94 fold changes). Conclusion: PTEN and hsa-miR-21 expression levels were negatively correlated in Doxorubicin resistant-MCF cells. Further study to confirm the causal relationship of miR-21 overexpression and PTEN downregulation in MCF-7/Dox is required.
Fri, 29 March 2019
REVIEW Download: 94| View: 216| Comments: 0 | doi:10.20944/preprints201903.0282.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: pancreatitis; epidemiology; diagnosis; complications; treatment; prognosis.
Online: 29 March 2019 (12:13:17 CET)
Acute pancreatitis (AP) is an inflammatory condition of the pancreas and is one of the most common ailments of the gastrointestinal system that results in significant morbidity and mortality. The main etiologic causes of AP are alcohol consumption, gallstones, hypertriglyceridemia, and biliary stones. The clinical signs and symptoms, and diagnostic criteria of AP are well established in the literature and multiple studies. Multiple scoring systems have been used to predict the severity, prognosis, and mortality associated with AP. The present review of the literature brings to light the significant and recent contributions in the etiology, risk factors, epidemiology, diagnosis, complications, prognosis and newest modalities in treatment that could be beneficial in the management of AP.
Thu, 28 March 2019
ARTICLE Download: 127| View: 344| Comments: 0 | doi:10.20944/preprints201903.0271.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: glucocorticoid receptor; 11HSD; mitochondria; NFκB; inflammation; ovary; uterus; polycystic ovary syndrome
Online: 28 March 2019 (14:05:40 CET)
Hyperandrogenism and insulin resistance are co-pathologies of polycystic ovary syndrome (PCOS). Recent evidence has suggested that elevated local cortisol levels are associated with ovarian and endometrial insulin resistance in hyperandrogenic PCOS patients, but the molecular mechanisms underlying these clinical findings remain unclear. We and others have used chronic treatment with human chorionic gonadotropin (hCG) and insulin to create an in vivo rodent model for the onset and development of PCOS-like phenotypes. Here, we aimed to determine whether the molecular mechanisms of glucocorticoid receptor (GR) signaling, mitochondrial function, and local inflammation in the ovary and uterus are intrinsically different in PCOS-like rats compared to controls. In both the ovary and the uterus, decreased expression of two GR protein isoforms was concurrent with increased expression of Fkbp51 but not Fkbp52 mRNA in PCOS-like rats compared to controls. However, PCOS-like rats exhibited an opposite regulation of Hsd11b1 or Hsd11b2 mRNAs in the two tissues. Further, the expression of several oxidative phosphorylation-related protein components was decreased in the PCOS-like ovary and uterus, but surprisingly the expression of many genes involved in mitochondrial function and homeostasis was increased in the same tissues and animals. Additionally, PCOS-like rats showed the increased expression of ovarian and uterine NFκB signaling proteins and Tnfaip3 mRNA. In PCOS-like rats, while similar decreased expression of Il1b, Il6, and Mmp2 mRNAs was seen in the ovary and uterus, the opposite regulation of Tnfa, Ccl2, Ccl5, and Mmp3 mRNA expression was observed in the two tissues. Both ovaries and uteri from PCOS-like animals showed increased collagen deposition compared to controls. Collectively, our observations suggest that hyperandrogenism and insulin resistance disrupt ovarian and uterine GR activation and trigger compensatory or adaptive effects for mitochondrial homeostasis, allowing tissue-level maintenance of mitochondrial function in order to limit ovarian and uterine dysfunction. Our study also suggests that hyperandrogenism and insulin resistance-induced activation of NFκB signaling resulting in aberrant regulation of inflammation-related gene expression might be tissue specific in female reproductive tissues.
REVIEW Download: 65| View: 183| Comments: 0 | doi:10.20944/preprints201903.0267.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: hepatocellular carcinoma, gut microbiota, gut-liver axis, intestinal dysbiosis
Online: 28 March 2019 (13:43:07 CET)
Hepatocellular carcinoma (HCC), one of the leading causes of death worldwide, has a causal nexus with liver injury, inflammation, and regeneration that accumulate over decades. Observations from recent studies have accounted for the involvement of the gut-liver axis in the pathophysiological mechanism responsible for HCC. The human intestine nurtures a diversified colony of microorganisms residing in the host ecosystem. The intestinal barrier is critical for conserving the normal physiology of the gut microbiome. Therefore, a rupture of this barrier or dysbiosis cause the intestinal microbiome to serve as the main source of portal-vein endotoxins such as lipopolysaccharide, in the progression of hepatic diseases. Indeed, increased bacterial translocation is a key sign of HCC. Considering the limited number of clinical studies on HCC with respect to the microbiome, we focus on the clinical as well as animal studies involving the gut microbiota with the current understandings of the mechanism by which the intestinal dysbiosis promotes hepatocarcinogenesis. Future research might offer mechanistic insights into the specific phyla targeting the leaky gut, as well as microbial dysbiosis, and their metabolites, as key pathways that drive HCC-promoting microbiome-mediated liver inflammation and fibrosis, thereby restoring the gut barrier function.
ARTICLE Download: 51| View: 176| Comments: 0 | doi:10.20944/preprints201903.0266.v1
Subject: Medicine & Pharmacology, Other Keywords: Chronic hepatitis B; Risk Factors; Prevalence; Iran
Online: 28 March 2019 (11:35:53 CET)
Background: Hepatitis B virus infection and its complications are major health problems. The aim of this study were to investigate risk factors in patients with chronic hepatitis B. Methods: This cross-sectional study was performed on 174 patients with chronic hepatitis B who referred to the Shahid Mohammadi hospital in the city of Bandar Abbas, Iran. Information was collected through a questionnaire. Results: 174 persons (97 males, 77 females) with a mean age of 42.96 years. There was no significant relationship between the risk of having disease with gender, age, weight, height, waist circumference, hip circumference, BMI and WHR (P> 0.05). The frequency of exposure to risk factors are as follows: such as history of hairdressers, vaccination, contact with suspected HBV persons, Family history of HBV positive in patients had higher prevalence than other groups. Conclusion: It seems to be more important to pay attention to lifestyles, jobs, and cultural themes of Iranian people that predispose people to risk factors so as to implement measures to control HBV spread. Also, awareness and social-health education in order to avoid unprotected sexual contact with an infected partner can be highly effective according to the high levels of hepatitis B infection among married persons. Despite existence of a long list of risk factors, various epidemiological studies with alternative methodologies along with meta-analysis of risk factors in each separate area seems to be helpful in collecting information about transmission.
ARTICLE Download: 57| View: 191| Comments: 0 | doi:10.20944/preprints201903.0265.v1
Subject: Medicine & Pharmacology, Other Keywords: Chronic hepatitis B; Epidemiology; Heoatocellular Carcinoma (HCC); cirrhosis; microRNA , HBV, Treatment
Online: 28 March 2019 (11:30:39 CET)
Introduction: Due to lack of unique method with high accurate and repeatable, assessment and even treatment of HBV infection and it,s complications such as cirrhosis and HCC has been with limitations. MicroRNAs (miRNAs) are small 19-24 nucleotide-long molecules with up-regulated and down-regulated Expression.The present research provides a narrative review expression profiling biomarkers miRNAs in diagnosis, treatment and differnciated CHB from cirrhosis or HCC.Methods: We search database google scholar, pubmed, scopus, SID on English Languish article and also assess EASL and AASLD (2002-2016).Results: Some of miRNAs are specifically more abundant in specific tissues, such as miR-122 in the liver. MiRNAs such as miRNA125a, miRNA141, miRNA1, miRNA197, miRNA122 and miRNA372, 373 have a major role in CBH and miRNA29a/b/c, miRNA200, miRNA199, miRNA133a, miRNA214 andmiRNA181b have a major role in fibrosis/cirrhosis. miR-106b and miR-181b, have a significant clinical diagnostic value in liver cirrhosis, especially at its early stages. miR-122, miR-192, miR-92, miR-223, miR-26a, miR-27a and miR-801, has a highly accurate diagnostic power that can differentiate HCC from CHB and cirrhosis and from healthy people as well as.Conclusion: In the future, the miRNAs biomarkers provide researchers with a golden opportunity and can be used as early diagnostic and miRNAs based-therapeutic panels and current knowledge between miRNAs profiling biomarkers and progressive stage of HBV related diseases. Panels of miRNAs will play a significant role in decision-making about their proper course in both of treatment and diagnosis of diseases such as hepatitis B virus infection.
ARTICLE Download: 45| View: 174| Comments: 0
Subject: Medicine & Pharmacology, Dentistry Keywords: hyaluronic acid; biphasic bone substitute; biocompatibility; tissue reaction; inflammation; macrophage; M1; M2; multinucleated giant cells
Online: 28 March 2019 (06:54:57 CET)
Biphasic bone substitutes (BBS) are nowadays established biomaterials. Through their constant development even natural components like hyaluronic acid (HY) are added to improve both their handling and also their regenerative properties. However, low knowledge exists regarding the consequences of the HY addition for their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY) combined with a BBS on the in vitro biocompatibility and the in vivo tissue reaction. Established in vitro procedures using L929 cells were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo study part, calvarial defects were created in 20 Wistar rats and subsequently filled with the BBS and the BBS combined with two different HMWHY amounts, i.e., BBS+HY(L) and BBS+HY(H). As controls empty defects were used. Established histological, immunohistochemical and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damages to the L929 cells and can considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of proinflammatory macrophages (* p < 0.05) comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to the BBS while improving the material handling properties.
REVIEW Download: 125| View: 213| Comments: 0 | doi:10.20944/preprints201903.0256.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: immunocheckpoint inhibitors; chemotherapy; tirosin kinase inhibitors; angiogenesis
Online: 28 March 2019 (06:48:37 CET)
Despite the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitor-urinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response as PD-L1 expression, tumor mutational burden, and clinical features. In addition to the identification of the patients with a high sensibility to immune checkpoint inhibitors, another approach currently under intensive investigation is the use of therapeutics in a combinatory manner with immune checkpoint inhibitors to obtain an enhancement of efficacy through the modification of the tumor immune microenvironment. In addition to the abscopal effect induced by radiotherapy, a lot of studies are evaluating several drugs able to improve response rate to immune checkpoint inhibitors, including microbiota modifiers, drugs targeting co-inhibitors receptors, anti-angiogenic therapeutics, small molecules, and oncolytic viruses. In view of the rapid and extensive development of this research field, we conducted a systematic review of the literature identifying which of these drugs are closer to achieving validation in the clinical practice.
Wed, 27 March 2019
ARTICLE Download: 40| View: 193| Comments: 0 | doi:10.20944/preprints201903.0249.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: N3, head and neck cancer, radiation, upfront neck dissection, concurrent chemoradiotherapy
Online: 27 March 2019 (08:46:58 CET)
Currently, data regarding optimal treatment modality, response, and outcome specifically for N3 head and neck cancer are lacking. This study aimed to compare the treatment outcomes between definitive concurrent chemoradiotherapy (CCRT) to the neck and upfront neck dissection followed by adjuvant CCRT. 93 N3 squamous cell carcinoma head and neck cancer patients were included. Primary tumor treatment was divided to definitive CCRT (CCRT group) or curative surgery followed by adjuvant CCRT (surgery group). Neck treatment was also classified into two treatment modalities: definitive CCRT to the neck (CCRT group) or curative neck dissection followed by adjuvant CCRT (neck dissection group). Overall, the 2-year overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 51.8%, 47.3%, 45.6%, and 43.6%, respectively. In both oropharyngeal cancer and nonoropharyngeal cancer patients, in terms of OS, LRFS, RRFS or DMFS no difference was noted regarding primary tumor treatment (CCRT vs. surgery) or neck treatment (CCRT vs. neck dissection). In summary, N3 neck patients treated with definitive CCRT can achieve similar outcomes to those treated with upfront neck dissection followed by adjuvant CCRT. Cautions should be made to avoid overtreatment for this group of patients.
Tue, 26 March 2019
REVIEW Download: 85| View: 158| Comments: 0
Subject: Medicine & Pharmacology, Nutrition Keywords: Colon; high-sulfur foods; inflammation; metagenomics; microbiota; sulfur reducing bacteria.
Online: 26 March 2019 (10:45:11 CET)
The biogeography of inflammation in ulcerative colitis (UC) suggests a proximal to distal concentration gradient of a toxin. Hydrogen sulfide (H2S) has long been considered one such toxin candidate, and dietary sulfur along with the abundance of sulfate reducing bacteria (SRB) were considered the primary determinants of H2S production and clinical course of UC. The metabolic milieu in the lumen of the colon, however, is the result of a multitude of factors beyond dietary sulfur intake and SRB abundance. Here we present an updated formulation of the H2S toxin hypothesis for UC pathogenesis, which strives to incorporate the interdependency of diet composition and the metabolic activity of the entire colon microbial community. Specifically, we suggest that the increasing severity of inflammation along the proximal-to-distal axis in UC is due to dilution of beneficial factors, concentration of toxic factors, and changing detoxification capacity of the host, all of which are intimately linked to the nutrient flow from the diet.
Mon, 25 March 2019
ARTICLE Download: 46| View: 126| Comments: 0
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: physical activity; depression; elderly people living alone; Patient Health Questionnaire-10; flexibility exercise; muscular strength exercise; complex sample logistic regression
Online: 25 March 2019 (11:10:17 CET)
Background and objectives: Only a few studies analyzed the physical activity level of elderly people living alone in local communities and evaluated the relationship between it and mental health. The purpose of this study was to investigate the relationship between physical activity and depression in the elderly living alone and to provide basic data for the prevention of depression in the elderly. Materials and Methods: We analyzed 256 elderly people living alone aged 65 years or older who completed the 2014 Korea National Health and Nutrition Examination Survey. Depression was defined as a score of 10 or higher using Patient Health Questionnaire-10(PHQ-9). This study investigated walking per week, days of muscular strength exercise performance in the past one week, days of flexibility exercise in the past one week, mean hours in a sitting position per day, the numbers of days and hours conducting a high intensity physical activity in the past one week, and numbers of days and hours conducting a medium intensity physical activity in the past one week to define physical activity. Our study presented prevalence odds ratios (pOR) and 95% confidence interval (CI) by using complex sample logistic regression analysis in order to identify the relationship between physical activity and depression. Results: The results of complex sample logistic regression analysis showed that flexibility exercise was significantly related to depression (p <0.05). On the other hand, the mean hours in a sitting position per day, aerobic physical activity, walking, and muscular strength exercise were not significantly related to geriatric depression. Conclusions: The results of our study implied that persistent flexibility exercise might be more effective to maintain a healthy mental status than muscular strength exercise. A longitudinal study is required to prove the causal relationship between physical activity and depression in the old age.
ARTICLE Download: 65| View: 136| Comments: 0
Subject: Medicine & Pharmacology, Other Keywords: Validation; communication; questionnaire; healthcare attention; patient satisfaction; nursing.
Online: 25 March 2019 (10:40:45 CET)
Background: Healthcare attention is sometimes considered purely technical, but communication has proven to be closely related to clinical results and patient satisfaction. Therefore, evaluation of communication in the scope of healthcare is a priority. The purpose of this study was to validate and adapt, if necessary, the Spanish version of the Communication Styles Inventory (CSI) in a sample of nursing professionals. (2) Methods: The sample was made up of 2313 nursing professionals selected at random from various medical centers in Spain, and is therefore a sample actively employed at the time data were acquired. We started out from the Communication Style Inventory, a questionnaire for evaluating the predominance of certain individual communication behaviors on six scales (expressiveness, preciseness, verbal aggressiveness, questioningness, emotionality and impression manipulativeness). (3) Results: Confirmatory Factor Analysis of the model proposed showed god fit indices. The reliability of the model shown by the Cronbach’s alpha of α=.81 was adequate, and so was single-level and aggregate consistency. Finally, in the analysis of variance by type of contract, configural, metric and scalar invariance was acceptable, but not strict invariance. (4) Conclusions: This instrument progresses in measuring non-technical attributes, such as communication styles, in nursing personnel.
ARTICLE Download: 86| View: 148| Comments: 0
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: supervised learning, major depression, cytokines, inflammation, neuro-immune, opioids
Online: 25 March 2019 (10:14:02 CET)
Rationale: Major depressive disorder (MDD) is characterized by signaling aberrations in interleukin (IL)-6, IL-10, beta-endorphins as well as mu (MOR) and kappa (KOR) opioid receptors. Here we examined whether these biomarkers may aid in the classification of unknown subjects into the target class MDD.Methods: The aforementioned biomarkers were assayed in 60 first-episode, drug-naïve depressed patients and 30 controls. We analyzed the data using joint principal component analysis (PCA) performed on all subjects to check whether subjects cluster by classes; support vector machine (SVM) with 10-fold validation; and linear discriminant analysis (LDA) and SIMCA performed on calibration and validation sets and we computed the figures of merit and learnt from the data. Results: PCA shows that both groups were well separated using the first three PCs, while correlation loadings show that all 5 biomarkers have discriminatory value. SVM and LDA yielded an accuracy of 100% in validation samples. Using SIMCA there was a highly significant discrimination of both groups (model-to-model distance=87.5); all biomarkers showed a significant discrimination and modeling power, while 10% of the patients were identified as outsiders and no aliens could be identified.Discussion: We have delineated that MDD is a distinct class with respect to neuro-immune and opioid biomarkers and that future unknown subjects can be authenticated as having MDD using this SIMCA fingerprint. Precision psychiatry should employ SIMCA a) to authenticate patients as belonging to the claimed target class and identify other subjects as outsiders, members of another class or aliens; and b) to acquire knowledge through learning from the data by constructing a biomarker fingerprint of the target class.
Fri, 22 March 2019
ARTICLE Download: 58| View: 80| Comments: 0
Subject: Medicine & Pharmacology, Other Keywords: Disability, function, knee osteoarthritis, physical therapy.
Online: 22 March 2019 (10:10:19 CET)
BACKGROUND: Knee osteoarthritis (OA) commonly causes increase in the patients’ disability and reduce their function because it causes pain, limitation in knee range of motion and decrease in muscle power.AIM: This study investigated the effect of three different physical therapy programs on knee range of motion , pain level, muscle strength and functional condition in patients with knee OA. DESIGN: Randomized comparative study.SETTING: Outpatient Rehabilitation clinic of Tongji Hospital (Wuhan, China).POPULATION: Seventy-two patients of Knee OA (aged 40-70) enrolled and randomly allocated into three groups. Group A (n=24) received physical agents and isometric quadriceps exercises, group B (n=24) received same physical agents as group A in addition to open kinetic chain exercises and group C (n=24) received physical agents as group A in addition to closed kinetic chain exercises.METHODS: knee range of motion (by electro goniometer), knee pain level (by VAS), quadriceps muscle strength (by isokinetic dynamometer) and functional condition (by WOMAC) were assessed before and after 5 weeks of treatment.RESULTS: In between group analysis, there were significant differences (P<0.05) between the three groups for all outcome measure. In within-group analysis, group C was the only group that showed significant differences (P<0.05) in all the outcomes. Group A and B showed significant differences (P<0.05) in quadriceps muscle strength and knee pain and no significant differences (P>0.05) in knee ROM and functional condition.CONCLUSIONS: After the study, our solid conclusion is that in physical therapy programs or protocols, closed kinematic chain exercise is very effective, it improves knee ROM, and help in reducing knee pain, muscle strength, function and disability for patients with knee osteoarthritis.CLINICAL REHABILITATION IMPACT: Comparison between different physical therapy programs provides the rehabilitation team with the best treatment intervention that is more effective in treating the problems associated with knee osteoarthritis.
ARTICLE Download: 50| View: 236| Comments: 0 | doi:10.20944/preprints201903.0207.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: myopia,photon-electron theory,high-frequency electromagnetic radiation
Online: 22 March 2019 (09:51:48 CET)
The exact etiology of myopia remains elusive. The author proposes the particle property of photon in living tissue and the photon-electron theory in living tissue, if the frequency of the photon beyond the threshold, the photon has enough energy to strike the electron away and forms a hole of a diameter in photon diameter scale in living tissue include the eye.The visual light which passes through the radiation hole in the eye cannot be refracted on the macula. Longer time of high-frequency electromagnetic radiation will cause more holes and a larger radius of holes, which lead to high myopia, this is in accordance with the investigation results that high myopic eyes have macular holes (micron scale). According to the particle property of the photon model, the eye elongated by the striking of high-frequency photons.
Thu, 21 March 2019
ARTICLE Download: 74| View: 233| Comments: 0
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: premenstrual syndrome; depression; anxiety; fatigue; neuro-immune; progesterone
Online: 21 March 2019 (04:13:21 CET)
Objective: To examine associations between IgA responses to Gram-negative gut-commensal bacteria and peri-menstrual symptoms and sex hormone levels during the menstrual cycle in women with and without premenstrual symptoms. Methods: Forty women aged 18-45 years completed the Daily Record of Severity of Problems (DRSP) during all 28 consecutive days of the menstrual cycle. We assayed, in plasma,, IgA responses to 6 Gram-negative bacteria, i.e. Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii, Klebsiella pneumoniae, Pseudomonas putida and Citrobacter pylori, progesterone and oestradiol at days 7, 14, 21 and 28 of the menstrual cycle. Results: Significant changes in Δ (actual minus one week earlier) IgA to LPS of the 6 Gram-negative bacteria during the menstrual cycle were observed with peak IgA levels at T4 (day 28) and lows at T1 or T2 (day 7 or 14). The Δ IgA changes in H. alvei, M. Morganii, P. putida during the menstrual cycle were significantly and positively associated with changes in the total DRSP score, and severity of physio-somatic, anxiety and breast-craving, but not depressive, symptoms. The changes in IgA responses to LPS were largely predicted by changes in progesterone and steady-state levels of progesterone averaged over the luteal phase. Discussion: Menstrual cycle-associated changes in IgA directed against LPS and by inference bacterial translocation may be driven by effects of progesterone on transcellular, paracellular and vascular pathways thereby contributing to the severity of physio-somatic and anxiety symptoms as well as fatigue, breast swelling and food cravings.
Wed, 20 March 2019
ARTICLE Download: 59| View: 274| Comments: 0
Subject: Medicine & Pharmacology, General Medical Research Keywords: KIT assay; chronic kidney disease; biomarker; non-invasive; urine; eGFR; cfDNA
Online: 20 March 2019 (02:12:19 CET)
The standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information of early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cfDNA, methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (High versus Low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6%–99.3%) and 94.1% (95% CI: 82.3%–100%). In addition, in patients with normal renal function [eGFR ≥ 90], the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be picked up by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function.
Tue, 19 March 2019
ARTICLE Download: 66| View: 255| Comments: 0
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Oral cancer; Oropharyngeal cancer; Tumor-suppressor genes; Promoter hypermethylation
Online: 19 March 2019 (12:56:24 CET)
Silencing of tumor suppressor genes (TSGs) by DNA promoter hypermethylation is an earlyevent in carcinogenesis; Hence TSGs may serve as early tumor biomarkers. We determinedthe promoter methylation levels of p16INK4a, RASSF1A, TIMP3 and PCQAP/MED15 TSGs in salivary DNA from oral cancer (OC), and oropharyngeal cancer (OPC) patients, using methylation specific PCR coupled with densitometry analysis. We assessed the association between DNA methylation of individual TSGs with OC and OPC risk factors. We evaluated the performance and the clinical validity of this quadruple methylation marker panel in discriminating OC and OPC patients from healthy controls using CombiROC web tool. Our study reported that RASSF1A, TIMP3 and PCQAP/MED15 TSGs were significantly hypermethylated in OC and OPC cases compared to healthy controls. We found that DNA methylation levels of TSGs were significantly augmented by smoking, alcohol use and betel quid chewing by indicating that the fact that frequent exposure to risk factors may drive oral and oropharyngeal carcinogenesis through TSG promoter hypermethylation. Also, this quadruple-methylation marker panel of p16INK4a, RASSF1A, TIMP3 and PCQAP/MED15 TSGs demonstrated excellent diagnostic accuracy in the early detection of OC at 91.7% sensitivity and 92.3% specificity, and OPC at 99.8% sensitivity and 92.1% specificity, from healthy controls.
ARTICLE Download: 76| View: 246| Comments: 0
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: necroptosis; cisplatin; ototoxicity; organ of corti; spiral ganglion neuron
Online: 19 March 2019 (10:40:20 CET)
Cisplatin induces early-onset ototoxicity, resulting in hearing loss. The exact mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase(RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in animal models. Sprague–Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were was measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H-E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. H-E stains outlined necroptotic changes in the organ of Cortis (OCs) and spiral ganglion neurons (SGNs). Additionally, immunohistochemistry and western blot analysis showed overexpression of RIP3 in the OCs and SGNs that were treated with cisplatin. These results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity; inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.
Mon, 18 March 2019
ARTICLE Download: 64| View: 271| Comments: 0
Subject: Medicine & Pharmacology, Nutrition Keywords: Dietary diversity; nutrient adequacy; metabolic syndrome; aging; PREDIMED-Plus study
Online: 18 March 2019 (09:25:48 CET)
Dietary guidelines emphasizes the importance of a varied diet to provide an adequate nutrient intake. However, the aging is often associated with consumption of monotonous diets that can be nutritionally inadequate, increasing the risk for the development or progression of diet-related chronic diseases such as the metabolic syndrome (MetS). To assess the relationship between dietary diversity (DD) and nutrient adequacy and to identify associated demographic variables related with DD. We analysed cross-sectional baseline data from the PREDIMED-Plus study: 6587 Spanish adults, aged 55–75 years, with overweight/obesity and MetS. Using a 143-item validated semi-quantitative food frequency questionnaire (FFQ), we calculated an energy-adjusted score of DD (DDS). Nutrient inadequacy was defined as an intake below 2/3 of the recommended dietary intake at least of ≥4 of 17 nutrients. Logistic regression models were used to evaluate the relationship between nutritional inadequate intakes and DDS. In the higher DDS quartile there were more women and less current smokers. Compared with subjects in the highest DDS quartile, those in the lowest DDS quartile had a higher risk of inadequate nutrient intake OR=28.56 (95% C.I. 20.80-39.21). When we estimated diversity for each one of the food groups, participants in the first quartile of diversity had a higher risk of nutrient deficiency: for vegetables, OR= 14.03 (IC 95% 10.55-18.65), fruits OR=11.62 (IC 95% 6.81-19.81), dairy products OR= 6.54 (IC 95% 4.64-9.22) and protein foods OR=6.60 (IC 95% 1.96-22.24). As DDS decreases, the risk of inadequate nutrients intake rises. Given the impact of nutrient intake adequacy on the prevention of non-communicable diseases, health policies should focus on the promotion of a healthy varied diet, specifically promoting the intake of vegetables and fruit among population groups with lower DDS such as men, smokers or widow people.
ARTICLE Download: 84| View: 258| Comments: 0
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: training loads; monitoring; illness; fatigue; training intensity distribution; threshold training; polarized training;
Online: 18 March 2019 (09:22:29 CET)
Despite the continued growth of the sport, particularly among recreational athletes, very little is known about how triathletes prepare for an event. The aim of this study was to identify the training characteristics of recreational-level triathletes and assess how their preparation for a triathlon influences their health and fatigue. During the 6 weeks prior to an Olympic distance triathlon, and the 2 weeks after the event, ten (5 males, 5 females) recreational athletes completed a daily training log to provide information on every training session. In addition, participants answered the Daily Analysis of Life Demands Questionnaire (DALDA), the Training Distress Scale (TDS), and the Alberta Swim Health Questionnaire weekly. Training loads were calculated using session-based rating of perceived exertion (sRPE) and training impulse (TRIMP). Every week of training was compared to week 1 to determine how athletes’ training and health changed throughout the study. In the 6 weeks leading up to the event, training loads, total minutes trained, and time spent in each training zone did not differ significantly. Significant reductions in training duration (Z=2.39, p=0.017, ES = 0.90), training strain (Z=2.59, p=0.009, 0.98), and number of sessions (Z=2.49, p=0.012, ES = 0.94) were seen on week 6. Training intensity distribution favored a threshold approach with athletes spending 56% of their training time at zone 1, 40% at zone 2, and 4% at zone 3. No significant changes were seen in the DALDA or TDS questionnaires. The results show that while the training intensity distribution of recreational-level triathletes does not follow a polarized model, these athletes were able to maintain their health while preparing for an Olympic distance triathlon.
Fri, 15 March 2019
ARTICLE Download: 63| View: 248| Comments: 0 | doi:10.20944/preprints201903.0165.v1
Subject: Medicine & Pharmacology, Other Keywords: Environmental Tobacco Smoke (ETS); pregnant women; questionnaire; urinary cotinine; oxidative stress parameters
Online: 15 March 2019 (14:03:35 CET)
Abstract: Background: Exposure to ETS (Environmental Tobacco Smoke) is one of the most toxic environmental exposures. Objective: To investigate the impact of ETS on physiological, biochemical, psychological indicators, on the urine antioxidant capacity (AC) and oxidative damage to lipids in a pilot sample of healthy pregnant women. Methods: The exposure to ETS was investigated by a validated questionnaire, urine cotinine and the marker of oxidative damage to lipids - 8-isoprostane concentrations using an ELISA kit. Urine AC was determined by the spectrophotometric TEAC method. From the sample of pregnant women (n=319, average age 30.84 ± 5.09 years) in 80 the levels of cotinine and oxidative stress markers were analyzed. Results: From our sample, 5 % individuals (7.4 % objectified by cotinine) were current smokers and 25 % reported passive smoking in the household (18.8 % objectified by cotinine). The Kappa was 0.78 for smokers and 0.22 for ETS exposed non-smokers. Smokers as well as non-smokers had significantly higher (p<0.05) urine AC than ETS exposed non-smokers. Non-smokers had significantly lower levels of 8-isoprostane than smokers (p<0.01) and ETS-exposed non-smokers (p<0.05). Correlations between urine levels of cotinine and AC were positive in ETS exposed non-smokers. Conclusion: The harmful effect of active and passive smoking on oxidative stress parameters has been indicated.
Thu, 14 March 2019
ARTICLE Download: 127| View: 370| Comments: 0 | doi:10.20944/preprints201903.0146.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: antimicrobial stewardship; resistance; infections; antibiotic utilization; peer-reviewed literature
Online: 14 March 2019 (06:57:30 CET)
Antimicrobial stewardship efforts are an emphasis among many institutions around the world to combat inappropriate antimicrobial utilization, rising healthcare costs and emerging antimicrobial resistance. Implementation of new innovative strategies may be challenging for many institutions with limited or constrained resources. Using proven effective methods as evidenced by other institutions in the peer-reviewed literature may offer an opportunity to evaluate institution-specific practices, which may be implemented locally. A structured examination and survey of the peer-reviewed, stewardship literature by an expert group of clinicians, scholars and educators determined the most influential publications from 2016. Herein, the top thirteen manuscripts are reviewed to aid clinicians identify potential stewardship opportunities and serve as an educational tool for trainees and others.
Tue, 12 March 2019
CASE REPORT Download: 83| View: 244| Comments: 0 | doi:10.20944/preprints201903.0136.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: cricket glycosaminoglycan; N-glycan; homo db mice; anti-oxidant enzyme
Online: 12 March 2019 (10:28:47 CET)
Field cricket (Gryllus bimaculatus) is newly emerged as an edible insect in several countries. Anti-inflammatory effect of glycosaminoglycan derived this cricket was not fully investigated on chronic disease animal model such as diabetic mouse. For potential therapeutic agents, anti-diabetic activities of field cricket glycosaminoglycan (GbG) was evaluated in diabetic mice based on their abilities to reduce glucose, ALT, AST, LDL-cholesterol, and BUN levels, compared with dung beetle (Catharsius molossus) glycosaminoglycan (CaG) as a positive control glycosaminoglycan. Db mice were orally administered for one month according to their groups: Db Hetero (normal), Db Homo (type-2 diabetic), CaG (5 mg/kg), GbG (5 mg/kg), and metformin (10 mg/kg). Blood glucose level was decreased after 1st week treatment with GbG. It also inhibited LDL-cholesterol and alkaline phosphatase levels. Regarding oxidative damage of diabetic state, levels of hepatocellular biomarkers levels and protein carbonyl content were reduced in db mice treated with GbG. Especially anti-oxidative activities of catalase, superoxide dismutase, and glutathione peroxidase were significantly increased in GbG treated group compared to those in the control. GbG was composed of heparin disaccharides and main N-glycan was identified as Hex9GlcNAc2 (m/z 1905.7) of with neutral mono-sugar mainly comprising of hexose, L (+) rhamnose by mass spectroscopy. These results from sero-biochemical, hepatocellular anti-oxidant assay in db mice data suggest cricket (G. bimaculatus) glycosaminoglycan might play a role in its anti-diabetic action.
REVIEW Download: 73| View: 245| Comments: 0 | doi:10.20944/preprints201903.0133.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Pancreatic cancer; PDAC (Pancreatic Ductal Adenocarcinoma); immune microenvironment; immune biomarkers; personalized cancer care; inflammation; PD1; CTLA-4
Online: 12 March 2019 (03:15:16 CET)
It is estimated that pancreatic cancer will be the 2nd leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options in this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are incompletely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, poor antigenicity, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored.
Mon, 11 March 2019
ARTICLE Download: 111| View: 269| Comments: 0 | doi:10.20944/preprints201903.0128.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Liver cirrhosis; epidemiology; etiology; risk factors; pathophysiology; diagnosis.
Online: 11 March 2019 (09:44:18 CET)
Liver cirrhosis is a chronic disease that is characterized by the presence of fibrosis and regeneration of nodules in the liver whose consequences are the development of portal hypertension and liver failure. Cirrhosis arises from a wide variety of chronic diseases, which progresses slowly after years or decades. Liver cirrhosis is a public health problem. It is usually associated with viral hepatitis, consumption of alcohol, metabolic syndrome, autoimmune processes, storage diseases, toxic substances, and medications. Cirrhosis is the fourteenth most common cause of death in adults throughout the world, the fourth in Europe and the ninth in the United States. The prevalence of this disease is underestimated because it is symptomatic it is not diagnosed in initial stages, and it usually goes to the decompensated stage at a rate of 5 to 7% per year. We review here the epidemiology, pathophysiology, etiology, and diagnosis of liver cirrhosis.
REVIEW Download: 121| View: 229| Comments: 0 | doi:10.20944/preprints201903.0116.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: beetroot; betanins; cancer chemoprevention; anti-oxidant; inflammation; apoptosis
Online: 11 March 2019 (08:00:34 CET)