REVIEW Download: 2631| View: 438| Comments: 0 | doi:10.20944/preprints201711.0081.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Marfan; connective tissue disease; irritable bowel syndrome; hernia
Online: 14 November 2017 (04:08:45 CET)
Symptoms attributed to the gastrointestinal manifestations of multi-system disorders play an important role in the long-term management of these conditions. Gastrointestinal complications of a variety of connective tissue disorders have been studied and there is an increased interest in the incidence and prevalence of these symptoms. Descriptions of the occurrence of gastrointestinal complications in Marfan syndrome have appeared infrequently in the medical literature. In this review article we focus on both structural and functional gastrointestinal pathology that may occur in patients with Marfan syndrome.
Mon, 10 July 2017
ARTICLE Download: 2601| View: 691| Comments: 0 | doi:10.20944/preprints201707.0014.v1
Subject: Medicine & Pharmacology, Behavioral Neuroscience Keywords: network; topology; integration; segregation; fMRI
Online: 10 July 2017 (05:48:41 CEST)
Recent methodological advances have enabled researchers to track the network structure of the human brain over time. Together, these studies provide novel insights into effective brain function, highlighting the importance of the systems-level perspective in understanding the manner in which the human brain organizes its activity to facilitate behavior. Here, we review a range of recent fMRI and electrophysiological studies that have mapped the relationship between inter-regional communication and network structure across a diverse range of brain states. In doing so, we identify both behavioral and biological axes that may underlie the tendency for network reconfiguration. We conclude our review by providing suggestions for future research endeavors that may help to refine our understanding of the functioning of the human brain.
Mon, 24 April 2017
ARTICLE Download: 2373| View: 580| Comments: 0 | doi:10.20944/preprints201704.0145.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: emotion and will; music therapy; five phases; five phases music therapy; psychology
Online: 24 April 2017 (05:37:45 CEST)
Music therapy has served as complementary and alternative medicine for various neurological disorders. Five Phases Music Therapy (FPMT) employs the theory of five phases and five music scales or tones (Gong (do), Shang (ri), Jue (mi), Zhi (so) and Yu (la)) to analyze and treat mind-body illness. In Chinese Medicine (CM) the five music scales are used to connect the human body and the universe, summarize personalities and constitution and analyze the influences of climatic changes on health. FPMT has a self-contained theory and routine of practice application. Large amount of clinical and fundamental reports has been available and clinical benefits have been obtained. However more systemic clinic research esp. Evidence-based and random controlled trials must be performed to validate and optimize it’s routines and biological and neurological mechanism must be further explored. It’s reasonable to believe that the introduction of FPMT to the world outside China may attract more attentions to use this effective music therapy.
Mon, 5 September 2016
ARTICLE Download: 2230| View: 1014| Comments: 0 | doi:10.20944/preprints201609.0018.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: polyphenols, flavonoids, seaweeds, antioxidant activity, anticancer activity
Online: 5 September 2016 (14:23:52 CEST)
Seaweeds are considered as one of the largest biomass producers in marine environment that is rich in bioactive metabolites and a source of natural ingredients for functional foods. The potential antioxidant activity and the potential inhibition of Caco2 cell proliferation, of crude extracts of: Chlorophyta (Ulva lactuca, and Codium tomentosum), Phaeophyta (Cystoseira crinita, Cystoseira stricta, and Sargassum vulgare), and Rhodophyta (Gelidium latifolium, Hypnea musciformis, and Jania rubens) collected from western Libyan coast were evaluated in vitro. The antioxidant activity was determined by reducing power and DPPH assays while cell proliferation, morphological changes and the cell cycle arrest were assessed by MTT, inverted light microscope and flow cytometry methods respectively. The polyphenols and flavonoids rich extracts showed remarkable reducing power and antiradical properties. After exposure of Caco2 cells to; various concentrations of extracts (50, 100,150 and 200 µg/mL) especially from brown algae for 72 h, significantly reduced cell proliferation. The antiproliferative effect of algae extracts was correlated with their polyphenol and flavonoid contents. Cell cycle analysis further showed that cells were arrested in G phases along with an increment in sub-diploidal cell population (sub-G) after extract application. These results imply that seaweeds which are rich in bioactive compounds may be in anticancer drug research programs. However, further investigations are essential to reveal the molecular mechanisms of the anticancer activities of these algae.
Tue, 4 June 2019
ARTICLE Download: 2217| View: 3538| Comments: 5 | doi:10.20944/preprints201906.0030.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: autism; autistic spectrum disorder; children; behavior; ultrasonography; prenatal; pregnancy
Online: 4 June 2019 (12:56:37 CEST)
For the past several decades, abdominal prenatal ultrasonography has been the most significant technology in obstetrics with a long-established application. However, the frequency, exposure time, thermal and cavitation exposure indices, and increased acoustic output of the ultrasonic waves may be harmful to the embryo/fetus and might increase susceptibility to Autism Spectrum Disorder (ASD). The increase in the prevalence of ASD is associated with an affluent ethnicity, high socioeconomic status, and high parental education where prenatal ultrasonography is readily available and affordable. Enhanced biophysical adverse effects may link the analogous increase in prenatal ultrasonography and autism, and prenatal ultrasonography may emerge as a risk factor for autism. Radiography usage provides historical evidence for this fact: the predominant past opinion was that exposure to X-rays during pregnancy caused no significant risk to a fetus. However, the association between X-ray exposure and childhood leukemia was only established 40 years after X-ray use began. This review focuses on excessive PUS usage and ASD development. Public Abstract Advancements in medical technology over the past several decades have made prenatal ultrasound more frequently accessible to expecting mothers during their pregnancy, especially for the affluent. A parallel development in health care is the increase in autism diagnoses (Autism Spectrum Disorder, or ASD) in children of affluent families. There is a general lack of studies of the impact of prenatal ultrasound on fetuses, especially around varying attributes such as frequency, duration of exposure, and thermal and cavitation indices. There is also a historical precedent set, where exposing fetuses to X-rays was not found to be harmful until it was linked to the development of childhood leukemia decades later. This paper seeks to establish a need to further study these attributes of prenatal ultrasound overuse and their possible impact on a developing fetus, with a special focus on the occurrence of Autism.
Mon, 5 September 2016
REVIEW Download: 2085| View: 1117| Comments: 0 | doi:10.20944/preprints201609.0013.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Camellia sinensis; tea ploysaccharides; chemical composition; antioxidant; antitumors; antihyperglycemia; anti-inflammation
Online: 5 September 2016 (10:19:33 CEST)
Tea (Camellia sinenesis) is a health beneficial beverage and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of hetero-polysaccharides bounded with proteins. There were tests showing that TPS had various bioactivities, such as antioxidant, antitumors, antihyperglycemia, anti-inflammation and improving immunity. However, inconsistent results concerning chemical composition and bioactivity of TPS were published in recent years. The advances in chemical composition and bioactivities of TPS were reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS were also discussed.
Fri, 23 December 2016
REVIEW Download: 2062| View: 1195| Comments: 0 | doi:10.20944/preprints201612.0119.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: antibiotic; bacteroidetes; dietary emulsifier; firmicutes; food additive; gut microbiota; non-nutritive sweetener; proteobacteria
Online: 23 December 2016 (11:21:40 CET)
Gut bacteria play an important role in several metabolic processes and human diseases, such as obesity and its co-morbidities, like fatty liver disease, insulin resistance/diabetes and cardiovascular events. Among several factors, dietary patterns, probiotics, prebiotics, synbiotics, antimicrobials and non-dietary factors, such as stress, age, exercise and climatic conditions, can dramatically impact the human gut microbiota diversity and equilibrium. However, the effect of minor food constituents, including food additives and trace contaminants, on human gut microbiota has received less attention. Consequently, the present review aimed to provide an objective perspective of the current knowledge regarding the impacts of minor food constituents on human gut microbiota and consequently, on human health.
Sun, 22 January 2017
REVIEW Download: 1925| View: 1410| Comments: 0 | doi:10.20944/preprints201701.0094.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: theranostics; nuclear medicine; personalized medicine
Online: 22 January 2017 (04:29:27 CET)
The importance of personalized medicine is growing, since there is an urged need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for a specific molecular targeting in means of diagnostics and therapy. The visualisation of potential targets can help to predict if a patient would benefit from a particular treatment or not. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents is constantly rising. In this article important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with the well-known radioiodine therapy in patients with thyroid cancer and then guides through different approaches for the treatment of advanced cancer with targeted therapies. The aim of this review is to provide a summary of background knowledge, current applications and advantages of targeted therapies and imaging in nuclear medicine practice.
Tue, 6 December 2016
REVIEW Download: 1760| View: 2297| Comments: 1 | doi:10.20944/preprints201612.0027.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: chatbot technology; ontology-based systems; expert systems; diagnosis; conversational agents; robotics; human-robot interaction; physician-patient relationship; intelligent agents
Online: 6 December 2016 (04:46:32 CET)
Access to medical care is a global issue. Technology-aided approaches have been applied in addressing this. Interventions have however not focused on medical diagnosis as a fully automated procedure and available applications employ mainly text-based inputs rather than conversation in natural language. We explored the utility of ontology-based chatbot technology for the design of intelligent agents for medical diagnosis through a systematic review of the most recent related literature. English articles published in 2011-2016 returned 233 hits which yielded 11 relevant articles after a 3-stage screening. Findings showed that the creation of expert systems had been the focus of many the studies which utilize the physician-system-patient framework with system training based mostly on expert knowledge for designing web- or mobile phone-based applications that serve assistive purposes. Findings further indicated gaps in the design and evaluation of more effective systems deployable as standalone applications, for example, on an embodied robotic system. The need for technology supporting the physical examination part of diagnosis, connection to data sources on patients’ vitals and medical history are also indicated in addition to the need for more qualitative work on natural language-based interaction. The system should be one that is continuously learning. Future works should also be directed towards the building of more robust knowledge base as well as evaluation of theory-based diagnostic methodological options
Tue, 9 August 2016
REVIEW Download: 1596| View: 1083| Comments: 0 | doi:10.20944/preprints201608.0090.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: intestinal organoids; dog; practical applications
Online: 9 August 2016 (11:38:04 CEST)
Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from various species, organs and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we report on intestinal stem cells, organoid culture, organoid disease modeling, transplantation, current and future uses of this exciting new insight model to veterinary medicine field.
Thu, 27 September 2018
ARTICLE Download: 1596| View: 400| Comments: 0 | doi:10.20944/preprints201809.0544.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Bodybuilding; Drug Free; Competing; Peaking; Carbohydrate Loading; Water Loading; Sodium Loading; Fat Loading: Vitamin C; Fibre Restriction
Online: 27 September 2018 (12:58:34 CEST)
Bodybuilders utilize peaking strategies in a bid to fine-tune their aesthetics for competition day. The most prevalent peaking strategies utilized by natural bodybuilders are unreported in the current literature. Eighty-one (M - 59, F - 22) natural bodybuilders were recruited from competitions during the 2016 and 2017 British Natural Bodybuilder Federation seasons. Competitors completed a 34-item questionnaire designed to investigate peaking and contest day strategies. The questionnaire listed commonly utilized peaking strategies and provided additional space for qualitative information. Analysis of the data indicated that carbohydrate (CHO), water and sodium manipulation were the most commonly utilized peak week strategies. The consumption of high glycemic index CHO was the most common competition day strategy. Only 6.2 % of competitors reported following their regular diet the week prior to competition. The CHO manipulation strategies were similar to classical CHO loading, whereby bodybuilders attempt to maximize muscle glycogen concentrations. Furthermore, bodybuilders attempted to remove superfluous water by exploiting the diuretic/polyuria effect associated with water loading/restriction. The potentially deleterious effects of peaking on bodybuilders' health is considered and the efficacy of these strategies to enhance appearance is discussed. The findings of the present investigation are likely to be of interest to bodybuilders and their coaches.
Thu, 8 March 2018
ARTICLE Download: 1577| View: 7063| Comments: 3 | doi:10.20944/preprints201803.0062.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Lyme disease; Borrelia burgdorferi; Tickborne disease; Chronic infection; Spirochete culture
Online: 8 March 2018 (07:08:02 CET)
Introduction: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. Materials & Methods: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of 10 control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Results: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR) methods. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.
Sun, 25 December 2016
COMMUNICATION Download: 1557| View: 1712| Comments: 0 | doi:10.20944/preprints201612.0122.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: furfuryl alcohol; β- myrcene; carcinogens; occurrence
Online: 25 December 2016 (08:21:19 CET)
For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The International Agency for Research on Cancer (IARC) continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene belong to these potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages while β-myrcene occurs naturally as a constituent of essential oils of plants such as hops, lemongrass and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using data from own nuclear magnetic resonance (NMR) analysis and literature review. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg) and in some fish products (about 10 mg/kg) while among beverages, wines contained between 1–10 mg/L with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is either very old or based on single sample analysis, and currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.
Sat, 6 August 2016
ARTICLE Download: 1505| View: 1118| Comments: 0 | doi:10.20944/preprints201608.0068.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: community-based health insurance; cooperative; benefit package; social inclusion; healthcare; Nepal
Online: 6 August 2016 (11:54:03 CEST)
Background: Health insurance (HI) run by government is providing health care service to large population. Due to poor accountability, participation and sustainability, cooperative health insurance is becoming more popular and effective in low and middle income and some high-income countries too. In Nepal, there are public and cooperative HI is in practice. The aim of this study is to compare the effectiveness of public (government) and cooperative HI in relation to benefit packages, population coverage, inclusiveness, health care utilization, and promptness for treatment in these two health insurance models in Nepal. Method: This is an institution based concurrent mixed study consists of qualitative and quantitative variables from public and cooperative groups. We included all public HI operated by government hospitals and cooperatives groups those purchased hospital service in contract. Two separate study tools were applied to access the effectiveness of insurance models. The key questions were asked for the representatives of government and private health insurance. The numeric information consisted of in quantitative data and subjective response was included in qualitative approach. Descriptive statistics and Mean Whitney U test was applied in numeric data and qualitative information were analyzed by inductive approach Results: The study revealed that new enrolment was not increased, health care utilization rate was increased and the benefit package was almost same in both groups. The overall inclusiveness was higher for the government HI, but enrolment from the religious minority, proportion of negotiated amount during treatment were significantly higher (p<0.05). During illness, the response time to reach hospital was significantly faster in cooperative health insurance than government health insurance. Qualitative findings showed that level of participation, accountability, transparency and recording system was better in cooperative health insurance than public. Conclusion: Cooperative HI could be more sustainable and accountable to the community for all; low, middle and high-income countries.
Sat, 13 August 2016
ARTICLE Download: 1455| View: 1137| Comments: 0 | doi:10.20944/preprints201608.0133.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: calorie restriction; PUFA; meal replacement; metabolic syndrome; middle age
Online: 13 August 2016 (03:39:38 CEST)
The increasing prevalence of obesity and sedentary lifestyles has led to an increased incidence of metabolic syndrome (MetS) worldwide. In Taiwan, middle-aged women are at a greater risk of MetS, type 2 diabetes, and cardiovascular disease than men are because they have more subcutaneous fat and larger waist circumferences compared to men with equal visceral fat levels. This study investigated the effects of calorie restriction supplemented with fish oil (CRF) in middle-aged women with MetS. For 12 weeks, 75 eligible participants were randomly assigned either calorie restriction (CR) or CRF. Both dietary intervention groups were further divided into two age groups: ≤45 and >45 years. The changes in MetS severity, inflammatory status, iron status, and red blood cell fatty acid profile were evaluated. Seventy-one participants completed the trial. Both dietary interventions significantly ameliorated MetS and improved the participants’ inflammatory status. CR significantly increased total iron binding capacity, whereas CRF increased hepcidin levels. Furthermore, CRF significantly increased the n-6/n-3 and arachidonic acid/docosahexaenoic acid ratios. In conclusion, CR and CRF improved the anthropometric and MetS characteristics of early-middle aged women, including body weight, blood glucose levels, triglyceride levels, as well as the scores for the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity cheque index. Dietary intervention was more effective in >45-year-old women than ≤45-year-old women.
Mon, 2 January 2017
ARTICLE Download: 1439| View: 967| Comments: 0 | doi:10.20944/preprints201701.0003.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: pito; beverage; bacteria; coliform; Lower Prampram; Ghana
Online: 2 January 2017 (10:55:07 CET)
Pito is a traditionally brewed alcoholic beverage in some African countries. It is gaining much prominence and the patronage among the youth. Therefore, samples of the drink were collected every week for six weeks from three different popular brewing sites at Lower Prampram in the Ningo-Prampram District of Accra, Ghana. The samples were processed and examined for bacteria and fungi using the Standard Plate Count (SPC) technique. A total of six different bacteria and a fungus were isolated. The bacteria were Escherichia coli, Klesiella pneumoniae, Shigella spp, Enterobacter aerogenes, Staphylococcus aureus and Pseudomonas aeroginosa, whiles the fungus was Saccharomyces cerevisiae. Total viable counts as well as individual isolates counts in all the pito samples were found to be less than 104 cfu/ml. It is noteworthy that, Saccharomyces cerevisiae, the only fungus isolated is known to be associated with fermentation and the microbes isolated from the pito samples were found to be within the permissible limits. However, these potentially pathogenic microbes, if found in unacceptable limits, from the fermenting samples could merit public health attention. Therefore, periodic screening of pito and their brewers, coupled with education on the maintenance of recommended guidelines concerning food and drink production is encouraged.
Thu, 3 November 2016
ARTICLE Download: 1397| View: 1032| Comments: 0 | doi:10.20944/preprints201611.0027.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: vitamin C; hyperuricemia; gout; glomerular filtration rate
Online: 3 November 2016 (10:49:06 CET)
Abstract: Hyperuricemia is commonly diagnosed in subjects with abnormal purine metabolism. Prolonged hyperuricemia often associated with gout, which is a vital risk factor for joint dysfunction. The current study was designed to determine the efficacy of vitamin C supplements for treatment of high serum uric acid (UA) among hyperuricemic and gouty patients, and finding-out the effect of supplementation on serum creatinine (Cr) level and glomerular filtration rate (GFR). This intervention study was started in April, 2013, till two months. A convenient sample of 30 adults aged between 24-75 years of both genders was assigned into two study groups: hyperuricemic (n=15) and gouty (n=15) groups. Each participant supplemented with 500 mg/day vitamin C chewable tablets for 2 months. Serum UA, Cr, and GFR were measured before and after treatment. At the end of this study, Cr and GFR enhanced insignificantly in both groups. UA increased insignificantly in gouty group after 2 months by about 0.31 mg/dl. On the other hand, hyperuricemic group showed significant (P ≤0.05) decrease in UA (-0.78 mg/dl) after 2 months duration. In conclusion, supplementation with 500 mg/day vitamin C for 2 months significantly attenuated serum UA for hyperuricemic patients and insignificantly affected serum UA in gouty patients. The uselessness of vitamin C supplements on gouty patients could be associated to a number of possible reasons.
Tue, 6 September 2016
REVIEW Download: 1393| View: 1135| Comments: 0 | doi:10.20944/preprints201609.0022.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Pervasive developmental disorder; Autism spectrum disorder (ASD); brain network; Theory of Mind (ToM); Music Therapy (MT); therapeutic effect
Online: 6 September 2016 (11:53:58 CEST)
Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.
Wed, 21 September 2016
ARTICLE Download: 1390| View: 1520| Comments: 0 | doi:10.20944/preprints201609.0074.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: hepatocellular carcinoma; hepatitis B virus X protein; Notch1 pathway; ERK; AKT
Online: 21 September 2016 (09:49:13 CEST)
Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.
Tue, 20 September 2016
ARTICLE Download: 1373| View: 757| Comments: 0 | doi:10.20944/preprints201609.0066.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: antibody titre; vaccination; dog; canine distemper virus; Jos
Online: 20 September 2016 (10:14:26 CEST)
Determination of antibody titre of dogs vaccinated against canine distemper in Jos North and South local Government Areas of Plateau State was carried out by collection of sera of vaccinated dogs and administration of well-structured questionnaires to dog owners. The samples collected were analyzed using the immune-blot ELISA Kit to determining the antibody titre (immunoglobulin G). It indicated that dogs vaccinated against the disease mounted adequate protective immunity. The result revealed that 54 (90.0%) of the sampled dogs have protective immunity, with those given more than one dose having higher level of protective antibody. Statistically, the result showed that the antibody titre did not differ significantly in relation to immunity and sex, breed, age and location but significant difference was seen in relation to number of primary vaccination. The result also revealed that those dogs that received booster doses (secondary vaccination) had more protective antibody. The study was aimed at evaluating the antibody titre of dogs vaccinated against canine distemper in Jos, Plateau State.
Mon, 26 September 2016
ARTICLE Download: 1368| View: 1034| Comments: 0 | doi:10.20944/preprints201609.0093.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: metastatic breast cancer; taxanes; eribulin; observational study
Online: 26 September 2016 (11:39:32 CEST)
Taxanes have been shown to be the most effective treatment for recurrent or metastatic breast cancer. However, for patients pretreated with taxanes, more active and possibly less toxic drugs are needed. In this retrospective study, we investigated on the effectiveness and safety of eribulin mesylate in 91 taxane-refractory subjects, extracted from the ESEMPIO database, which included 497 metastatic breast cancer patients treated with eribulin allover the Italy. This analysis included only those patients who have shown disease progression while receiving taxane therapy (primary refractory), or those who achieved a response followed by progression while still on therapy (taxane failure). Overall, 41/91 patients (45.2%) showed a clinical benefit; 1 complete response (2.2%) and 16 partial responses (17.6%) were observed. The median progression free survival was 3.1 months (95% CI: 2.8–3.5) and the median overall survival was 11.6 months (95% CI: 8.7–16.7). With regard to toxicity, 53 patients (58%) experienced asthenia/fatigue, 23 (25%) showed peripheral neurotoxicity, 18 (20%) alopecia, 12 (13%) mild constipation and 27 (30%) neutropenia. The toxicity related to the treatment led to eribulin dose reduction in 19 (21%) and discontinuation in 9 (10%) patients, respectively. In conclusion, this study suggests that eribulin is effective and well tolerated also in taxane-refractory patient.
Tue, 2 August 2016
ARTICLE Download: 1318| View: 1055| Comments: 0 | doi:10.20944/preprints201608.0011.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: curcumin; furazolidone; oxidative stress; DNA damage; mitochondrial pathway
Online: 2 August 2016 (05:59:38 CEST)
Furazolidone (FZD) is a synthetic nitrofuran with the antiprotozoal and antibacterial activity. The proper mechanism of FZD induced toxicity is still unclear. This study aimed to investigate the protective effect of curcumin on FZD induced oxidative stress, DNA injury and apoptosis in human hepatocyte L02 cells. The results showed that curcumin treatment significantly ameliorated FZD induced cytotoxicity, characterized by decreasing the production of reactive oxygen species (ROS) and malondialdehyde, as well as increasing superoxide dismutase, catalase activities and glutathione contents. Moreover, curcumin pretreatment significantly inhibited FZD induced the loss of mitochondrial membrane potential, the activation caspase-9 and -3 and apoptosis. Comet assay showed that curcumin attenuated FZD induced DNA injury in a dose-dependent manner. Correspondingly, curcumin markedly reversed the up-regulation of p53, Bax, caspase-9 and -3 mRNA expressions and the down-regulation of Bcl-2 mRNA (all p<0.05 or 0.01). These results reveal that curcumin protects against FZD induced oxidative stress, DNA injury and cell apoptosis via inhibiting oxidative stress and mitochondrial pathway, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, our study highlights that curcumin may be a potential way to prevent FZD-mediated oxidative DNA injury and apoptosis in human or animals.
Mon, 26 September 2016
ARTICLE Download: 1310| View: 924| Comments: 0 | doi:10.20944/preprints201608.0165.v2
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Pueraria mirifica; mammary gland; uterus; carcinogenesis; estrogenic activity; Donryu rat
Online: 26 September 2016 (09:25:39 CEST)
Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3% and, more pronouncedly, of 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.
Mon, 29 August 2016
ARTICLE Download: 1308| View: 968| Comments: 0 | doi:10.20944/preprints201608.0225.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: circular RNAs (circRNAs); circulating circRNA; type 2 diabetes mellitus (T2DM); pre-diabetes; microarray analysis; biomarker
Online: 29 August 2016 (13:37:38 CEST)
The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.
Mon, 28 November 2016
REVIEW Download: 1306| View: 1003| Comments: 0 | doi:10.20944/preprints201611.0138.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: computational imaging; midsagittal plane; inter-hemispheric fissure; symmetry analysis; neuroimaging
Online: 28 November 2016 (02:03:34 CET)
Brain is the most complex organ in the human body and it is divided into two hemispheres - left and right hemispheres. Left hemisphere is responsible for control of right side of our body whereas right hemisphere is responsible for control of left side of our body. Brain image segmentation from different neuroimaging modalities is one of the important parts in clinical diagnostic tools. Neuroimaging based digital imagery generally contain noise, inhomogeneity, aliasing artifacts, and orientational deviations. Therefore, accurate segmentation of brain images is a very difficult task. However, the development of accurate segmentation of brain images is very important and crucial for a correct diagnosis of any brain related diseases. One of the fundamental segmentation tasks is to identify and segment inter-hemispheric fissure/mid-sagittal plane, which separate the two hemispheres of the brain. Moreover, the symmetric/asymmetric analyses of left and right hemispheres of brain structures are important for radiologists to analyze diseases such as Alzheimer's, Autism, Schizophrenia, Lesions and Epilepsy. Therefore, in this paper we have analyzed the existing computational techniques used to find brain symmetric/asymmetric analysis in various neuroimaging techniques (MRI/CT/PET/SPECT), which are utilized for detecting various brain related disorders.
Thu, 9 March 2017
REVIEW Download: 1297| View: 766| Comments: 0 | doi:10.20944/preprints201703.0052.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: mucositis; radiotherapy; chemotherapy; pathophysiology; management; melatonin
Online: 9 March 2017 (04:46:30 CET)
The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives.
Sat, 12 November 2016
REVIEW Download: 1293| View: 1051| Comments: 0 | doi:10.20944/preprints201611.0067.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: vancomycin; broad view; veterinary use at a glance; rational use; alternatives
Online: 12 November 2016 (11:09:37 CET)
Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.
Mon, 18 September 2017
HYPOTHESIS Download: 1287| View: 1143| Comments: 0 | doi:10.20944/preprints201709.0081.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: sarcoidosis; monocytes; cancer; neoplasia; vitamin D; 25-hydroxyvitamin D3; 1,25-hydroxyvitamin D3; etiology; spontaneous remission of cancer; vitamin D side effects
Online: 18 September 2017 (14:21:11 CEST)
The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).
Tue, 13 September 2016
CASE REPORT Download: 1271| View: 1001| Comments: 0 | doi:10.20944/preprints201609.0045.v1
Subject: Medicine & Pharmacology, Other Keywords: eosinophilic pneumonia; lung nodules; dyspnea; eosinophils
Online: 13 September 2016 (04:04:39 CEST)
Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterized by an abnormal and marked accumulation of eosinophils in the interstitial and alveolar spaces of the lung. Idiopathic chronic eosinophilic pneumonia is reported to comprise anywhere from 0-2.5% of cases within the registries of interstitial lung disease. Diagnosis is based on the clinical constellation of symptoms, characteristic radiographic findings and peripheral blood or BAL eosinophilia, in the absence of infection or drug-induced eosinophilia. There is no consensus on the dose and duration of treatment, but most authors recommend initial doses of prednisone at 0.5–1 mg/kg/day with gradual tapering of the dose for total treatment duration of 6–12 months.
Tue, 7 February 2017
REVIEW Download: 1269| View: 894| Comments: 0 | doi:10.20944/preprints201702.0020.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: alpha-synuclein; Parkinsons disease; dementia with Lewy bodies; multiple system atrophy; tunelling nanotube; glymphatic system; cell-to-cell spread
Online: 7 February 2017 (03:24:21 CET)
Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.
Tue, 20 September 2016
ARTICLE Download: 1261| View: 926| Comments: 0 | doi:10.20944/preprints201609.0073.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: diabetes mellitus, molecular docking, thin layer chromatography, alpha amylase, ellagic acid
Online: 20 September 2016 (16:13:12 CEST)
Diabetes mellitus is the fifth deadliest disease in the developing countries. Even with all the research and new drugs available, combating diabetes is still challenging. There are successes in finding new cost effective drugs without side effects, even if not perfect. In our investigation we studied binding mechanism of secondary metabolite of T. chebula in silico. It was observed that three compounds out of 16 have a higher binding affinity for the target proteins. Ellagic acid showed highest binding affinity with alpha amylase, beta glucosidase and alpha glucosidase with lesser binding energies -4.5kcal/mol, -5.36kcal/mol and -4.48kcal/mol respectively. Arjungenin has lesser binding energy of 4.77 kcal/mol with glucokinase while luteoline has binding energy of -7.25kcal/mol for enzyme glycogen synthase kinase. These entire compounds interacted with non-covalent interaction. Petroleum ether extract showed the significant alpha amylase inhibitory activity i.e. 51.22% as compared to standard drug (65.99%).TLC analysis revealed the presence of total 9 compounds in different plant extracts one of them might be a lead compound which could be further exploited for the development of novel safer and potent antidiabetic drug.
Wed, 7 September 2016
REVIEW Download: 1255| View: 868| Comments: 0 | doi:10.20944/preprints201609.0029.v1
Subject: Medicine & Pharmacology, Other Keywords: HLA; type 1 diabetes; ethnicity; screening; haplotype
Online: 7 September 2016 (12:49:02 CEST)
Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.
Fri, 27 October 2017
ARTICLE Download: 1254| View: 1501| Comments: 0 | doi:10.20944/preprints201710.0169.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Schizophrenia; bipolar; psychosis; depression; polygenic risk score; diagnosis; RDoC
Online: 27 October 2017 (11:58:11 CEST)
In current diagnostic systems, schizophrenia and bipolar disorder are still conceptualized as distinct categorical entities. Recently, both clinical and genetic evidence have challenged this Kraepelinian dichotomy. There are only few longitudinal studies addressing the potential overlaps between these conditions. Here, we present design and first results of the PsyCourse study, an ongoing transdiagnostic study of the affective-to-psychotic continuum that combines longitudinal deep phenotyping and dimensional assessment of psychopathology with an extensive collection of biomaterial. Within the DSM-IV framework, we compare two broad diagnostic groups: one consisting of predominantly affective and one of predominantly psychotic disorders. Depressive, manic, and psychotic symptoms as well as global functioning over time were analyzed. Furthermore, we explore the effects of polygenic risk scores for schizophrenia on diagnostic group membership and address their effects on non-participation in follow-up visits. While phenotypic results show differences in both current psychotic and manic symptoms, depressive symptoms did not vary between both groups. Polygenic risk scores for schizophrenia significantly explained part of the variability of the diagnostic group. Furthermore, there was a trend that a higher polygenic loading for schizophrenia was associated with attrition. Because of its unique properties, the PsyCourse study presents a prime resource for the interrogation of complex genotype-phenotype relationships.
Wed, 11 January 2017
REVIEW Download: 1235| View: 1180| Comments: 0 | doi:10.20944/preprints201701.0057.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: osteoarthritis; rheumatoid arthritis; medicinal plants; herbs
Online: 11 January 2017 (07:56:32 CET)
Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.
Fri, 28 October 2016
REVIEW Download: 1231| View: 1041| Comments: 0 | doi:10.20944/preprints201610.0125.v1
Subject: Medicine & Pharmacology, Other Keywords: herbal medicinal products; food supplements; botanicals; normative; phytotherapy; Italian pharmaceutical market; parapharmaceuticals
Online: 28 October 2016 (08:06:07 CEST)
The Italian herbal products market is the most prosperous in Europe. The proof is represented by the use of these products in several marketing categories, ranging from medicine to nutrition and cosmetics. Market and legislation in Italy are at the same time cause and consequence of this peculiar situation. In fact, the legislation on botanical food supplements in Italy is very permissive and at the same time the market shows an overall satisfaction of users and strong feedback in terms of consumption, which brings a widening use of medicinal plants, formerly the prerogative of pharmaceuticals, to other fields such as nutrition. This review summarizes the market and normative panorama of herbal products in Italy, highlighting the blurred boundaries of health indications, marketing authorizations and quality controls between herbal medicines and non pharmaceutical products, such as food supplements, cosmetics and other herbal-based “parapharmaceuticals”.
Tue, 30 August 2016
COMMUNICATION Download: 1226| View: 1161| Comments: 1 | doi:10.20944/preprints201608.0228.v1
Online: 30 August 2016 (04:27:17 CEST)
Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient or absent activity of the enzyme alfa-galactosidase A. This defect enzyme leads to accumulation of glycolipids, primarily globotriaosylceramide (Gb3), in the vascular endothelium of several organs, including the skin, kidneys, nervous system, and heart. The characteristic early clinical features of Fabry disease include acroparaesthesia, angiokeratoma, heat intolerance, hypohidrosis, cornea verticillata and gastrointestinal symptoms. Later complications occur with the disease progression and include progressive renal failure, hypertrofic cardiomyopathy, cerebrovascular disease and reduced life expectancy. Anderson Fabry disease is therefore a disabling and systemic disease which requires a timely diagnosis. The purpose of our study is to define sweat glands morphological abnormalities in children and adolescents with Fabry disease with minimal symptoms and in patients affected by variants of Fabry disease in which biopsy is essential, to establish a baseline morphological diagnosis of the disease before to undergo to kidney or endomyocardial biopsy or when the classical approach is not possible because of some complications, with minimal discomfort for patients.
Mon, 26 September 2016
ARTICLE Download: 1210| View: 849| Comments: 0 | doi:10.20944/preprints201609.0094.v1
Subject: Medicine & Pharmacology, Other Keywords: curcumin; nanosuspension; electrolyte; particle aggregation; stabilizer; ionic surfactant
Online: 26 September 2016 (11:47:18 CEST)
We have successfully developed curcumin nanosuspension aimed for oral delivery. The main purpose is to improve bioavailability through enhancing its solubility. The nanoparticles were stabilized using various stabilizers including polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (Na-CMC), d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), and sodium dodecyl sulfate (SDS). The average diameter of particles, microscopic appearance, and sedimentation of each preparation was observed and compared. Each stabilizer demonstrated different degree of inhibition of particle aggregation under electrolyte-containing simulated gastrointestinal (GIT) fluid. Non-ionic stabilizers (PVA, PVP, and TPGS) has shown to preserve the nanosuspension stability against electrolytes. In contrast, strong ionic surfactants such as SDS were found to be very sensitive to electrolytes. The results can provide useful information for the formulators to choose the most suitable stabilizers by considering the nature of stabilizers and physiological characteristics of target site of the drug.
Fri, 23 December 2016
ARTICLE Download: 1210| View: 716| Comments: 0 | doi:10.20944/preprints201612.0121.v1
Subject: Medicine & Pharmacology, Dermatology Keywords: antibacterial activity, cinnamon, honey, checkerboards method, synergistic activity
Online: 23 December 2016 (18:37:59 CET)
Propionibacterium acnes and Staphylococcus epidermidis are the major skin bacteria that cause the formation of acne. The present study was conducted to investigate antibacterial activity of ethanolic extract of cinnamon bark, honey and their combination against acne bacteria. The antibacterial activity of extract of cinnamon bark and honey were investigated against P. acnes and S. epidermidis using disc diffusion method. Minimum Inhibitory Concentration (MIC) and minimal bactericidal concentration (MBC) were performed using Clinical and Laboratory Standard Institute (CLSI) methods. The interaction combination between extract of cinnamon bark and honey was determined by using a checkerboards method. The results showed that he MIC of extract of cinnamon bark and honey against P. acne were 256 µg/mL and 50% v/v, respectively, while against S. epidermidis were 1024 µg/mL and 50% v/v, respectively. The MBC of extract of cinnamon against P. acnes and S. epidermidis were more than 2048 µg/mL, whereas the MBC for honey against P. acnes and S. epidermidis were 100%. The combination of cinnamon bark extract and honey against against P. acnes and S. epidermidis, showed additive activity with the FICI value 0.625. Therefore, the combination of extract of cinnamon bark and honey has potential activity against acne causing bacteria.
Tue, 4 October 2016
ARTICLE Download: 1205| View: 1120| Comments: 0 | doi:10.20944/preprints201610.0005.v1
Subject: Medicine & Pharmacology, Other Keywords: Landfill, Waste, Socio-environmental impact, Hematologic diseases
Online: 4 October 2016 (09:03:17 CEST)
We are experiencing an unprecedented urbanization process that alongside with physical, social and economic developments is having a significant impact on population’s health. Due to higher apprehensions of pollution, violence and poverty, our modern cities no longer ensure a good quality of life so they become unhealthy environments. This study aims to measure the socio-environmental and hematologic profile of residents of Santo André’s landfill – “Bairro Espírito Santo” by using the contextualization of the studied area. The research method is Observational type and from Retrospective cohort and by convenience sampling in Santo André in the Greater ABC region. The study determined a socio environmental profile and the hematologic diseases screening related to a close location to the landfill. The disease manifests itself within a broad spectrum of symptoms that causes changes in blood count parameters. The full blood counts analysis was performed, indicating that the blood counts of residents living near the landfill led to positive hematological changes and diseases like Leukopenia, Anemia, Neutropenia and lymphocytosis were the most common changes. However it is considered that the proof of the relation of cause- effect to environmental exposures that may trigger chronic manifestations in humans requires specific studies that are often complicated.
Fri, 12 August 2016
ARTICLE Download: 1201| View: 1273| Comments: 0 | doi:10.20944/preprints201608.0132.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: fall risk assessment; risk of falling; force platforms; inertial sensors.
Online: 12 August 2016 (09:32:28 CEST)
Purpose: National Institute for Health and Care Excellence (NICE) has recently published quality standards for assessment of fall risk and preventing further falls. According to the standards, multifactorial fall risk assessments should include: identification of falls history; analysis of gait, balance, mobility and muscle strength, among other factors. Despite being based on subjective analysis or simple timing and not being multifactorial, physiotherapists and physicians quite often use these tests as reference scales to differentiate between lower and higher risk of falling. Instrumented TUG has been recently reported to provide important additional information to the overall score. Objective: To explore a case-based approach of fall risk assessment to identify the most relevant and informative risk factors that in combination could better define a person risk profile. Materials and Methods: A multifactorial assessment of fall risk through questionnaires, standard functional tests, tests instrumented with inertial sensors, and force platforms has been studied within a group aged 55-80 years old. Different fall risk factors and fall risk assessment methods were analyzed in a case-based descriptive study. Results & Discussion: Subjects at higher risk of falling were identified based on their detailed profiles. A set of features were obtained from the instrumented standard tests differing significantly between subjects presenting higher or lower fall risk. Therefore, instrumenting conventional tests with wearables containing inertial sensors and force platforms gives more detailed and quantitative insights. This information can be used to better define and tailor fall prevention exercises and to improve the follow-up of the evolution of the subject.
Mon, 5 September 2016
ARTICLE Download: 1181| View: 983| Comments: 0 | doi:10.20944/preprints201609.0019.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: dietary patterns, food-frequency questionnaire, dietary, lifestyle practices, adolescents
Online: 5 September 2016 (14:46:56 CEST)
Abstract: Objective: The aim of the study was to identify dietary patterns and its association with socio-economic, dietary and lifestyle practices among adolescents in Malaysia. Methods: A validated food frequency questionnaire was used to assess dietary patterns. Results: Multivariate analyses show that age and physical activity (PA) levels were emerged as positive determinants of healthy-based food pattern in Malay (All, p<0.001), whereas higher consumption of eating-out from home (EatOut) and fast food (All, p<0.05) were negative determinants. High weekly breakfast skipping (p<0.001) and EatOut (p<0.01) were positively associated with a western-based pattern, whereas age (p<0.001) and household income (p<0.05) were negative determinants. Higher frequency of daily snacking (p<0.05) was emerged as positive determinant of local-based food pattern. For Chinese adolescents, age (p<0.001), PA levels (p<0.001) and maternal education level (p<0.05) emerged as positive determinants for the healthy-based pattern, whereas high EatOut and fast food intakes (All, p<0.01) were negative determinants. Higher weekly consumption of EatOut (p<0.01), fast food (p<0.05) and carbonated beverages (p<0.05), and daily snacking practice (p<0.01) were positively associated with higher western-based food pattern, whereas age (p<0.01) was inversely associated. Conclusion: These findings suggest that unhealthy dietary and lifestyle practices could increase the risk of adherence to unhealthy western-based food pattern that is high in fat, sugar and salt contents, and consequently increase the risk of developing obesity and metabolic-related disorders during these critical years of growth.
Sat, 6 August 2016
ARTICLE Download: 1179| View: 947| Comments: 0 | doi:10.20944/preprints201608.0070.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: dietary pattern; prostate cancer; systematic review; meta-analysis
Online: 6 August 2016 (12:30:38 CEST)
Dietary patterns were recently applied to examine the relationship between eating habits and prostate cancer (PC) risk. While the associations between PC risk with glycemic index and Mediterranean score have been reviewed, no meta-analysis is currently available on dietary patterns defined by “a posteriori” methods. Search was carried out (PubMed, Web of Science) to identify studies reporting the relationship between dietary patterns and PC risk. Relevant dietary patterns were selected and the risk estimated were calculated by a random-effect model. Multivariable-adjusted odds ratios (ORs) for a 1st-percentile increase in dietary pattern score were combined by a dose response meta-analysis. 12 observational studies were included in the meta-analysis which identified “Healthy pattern” and “Western pattern”. The Healthy pattern was not related to PC risk (OR=0.96; 95% CI: 0.88-1.04) while the Western pattern significantly increased it (OR=1.34; 95% CI: 1.08-1.65). In addition, a “Carbohydrate pattern”, identified in four articles, was positively associated with a higher PC risk (OR=1.64; 95% CI: 1.35-2.00). A significant linear trend between the Western (p=0.011) and the Carbohydrate (p=0.005) pattern and the increment of PC risk was observed. The small numbers of studies included suggest that further investigations are necessary to support these findings.
Sat, 15 October 2016
ARTICLE Download: 1171| View: 1000| Comments: 0 | doi:10.20944/preprints201610.0060.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: gingiva; bisphosphonate; soft tissue; fibroblasts; keratinocytes; bisphosphonate associated osteonecrosis of the jaws
Online: 15 October 2016 (08:03:48 CEST)
Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.
Thu, 11 August 2016
EDITORIAL Download: 1170| View: 1052| Comments: 1 | doi:10.20944/preprints201608.0130.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: carcinogenesis; cancer; age distribution of cancer
Online: 11 August 2016 (11:40:40 CEST)
Tobacco use, most people would say. Smoking tobacco increases the risk of developing many types of cancer and is responsible for approximately one-third of all cancer deaths. The association between tobacco use and lung cancer is well known; lung cancer occurs about 20 times more often in heavy smokers than in nonsmokers . However, many lung cancers are diagnosed in never smokers , and most smokers do not develop lung cancer [3,4].
Thu, 17 November 2016
ARTICLE Download: 1168| View: 949| Comments: 0 | doi:10.20944/preprints201611.0089.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: hypertension; salt intake; urinary excretion; Morocco
Online: 17 November 2016 (10:49:28 CET)
Introduction: Hypertension is a serious public health problem in Morocco. The objective of this pilot study was to estimate the salt intake of Moroccan adults by measuring 24-hour urinary sodium excretion. Methods: 132 participants were recruited from the central region of Morocco. Sodium, potassium and creatinine levels were measured using the 24-hour urine samples. Additional data included anthropometric measurements and socio-demographic questionnaire. Results: The daily sodium, potassium and creatinine excretions were 2779.1±1334.9 mg, 1350.0±642.8 mg and 820.3 ± 381.2 mg, respectively. Data analysis revealed that 71.2% of the participants had a daily sodium intake more than 2000 mg (5g of salt) recommended by the WHO. The mean of potassium excretion was 1350.0±642.8 mg /day, this average was lower than 3.51g per day recommended by the WHO. Conclusion: Public health measures to reduce sodium and increase potassium consumption in order to decrease the population’s risk of high blood pressure and heart disease are recommended.
Thu, 1 September 2016
ARTICLE Download: 1163| View: 995| Comments: 0 | doi:10.20944/preprints201609.0001.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: protein-disulfide isomerase-associated 3; osteoarthritis; extracorporeal shockwave therapy; 1α,25-Dihydroxyvitamin D3 signaling pathway; two dimensional electrophoresis
Online: 1 September 2016 (10:47:39 CEST)
Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)2D3 rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.
Fri, 2 September 2016
ARTICLE Download: 1163| View: 943| Comments: 0 | doi:10.20944/preprints201609.0006.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Vernonia mespilifolia; Artemia salina; toxicity; biological activity; hatchability; lethality
Online: 2 September 2016 (11:24:10 CEST)
Vernonia mespilifolia is widely used in folk medicine in the Eastern Cape Province, South Africa. The aim of this study was to evaluate the biological activity of the acetone, aqueous and ethanol extracts of Vernonia mespilifolia using brine shrimp hatchability and lethality assay. The result showed hatching success in this order: aqueous extract (48.6%) > acetone extract (38.2%) > ethanol extract (26.8%). The LC50 of the lethality assay were in this order: acetone extract (67.8 µg/mL) > aqueous extract (132 µg/mL) > ethanol extract (383 µg/mL). According to Meyer’s toxicity index (using brine shrimps), LC50 < 1000 µg/ mL is toxic. Therefore, the results of the three solvent extracts could be said to be toxic as do have LC50 < 1000 µg/ mL. However, the toxicity of the crude extracts could suggest or confer some antitumor properties, hence further in vitro, in vivo and antitumour assays are recommended to further substantiate these claims.
Tue, 1 November 2016
ARTICLE Download: 1159| View: 928| Comments: 0 | doi:10.20944/preprints201611.0008.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: nitrofurantoin; active pharmaceutical ingredient; 4-aminobenzoic acid; cocrystallization; intermolecular interaction; Raman spectroscopy; terahertz spectroscopy
Online: 1 November 2016 (09:54:24 CET)
Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.
Mon, 21 November 2016
ARTICLE Download: 1159| View: 958| Comments: 0 | doi:10.20944/preprints201611.0107.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: pancreatic cancer; deguelin; autophagy; doxorubicin
Online: 21 November 2016 (10:01:23 CET)
Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.
Tue, 16 August 2016
ESSAY Download: 1145| View: 983| Comments: 1 | doi:10.20944/preprints201608.0158.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: alcohol; cancer; ethanol; tobacco; carcinogenesis; oral cavity; pharynx; esophagus; stem cells; stem cell division theory of cancer
Online: 16 August 2016 (09:45:33 CEST)
Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. The risk of these cancers is increased even in people who have only one alcoholic drink per day. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect has been overlooked probably because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of endogenous and exogenous DNA-damaging agents (e.g., reactive oxygen species, acetaldehyde and tobacco carcinogens). Alcohol consumption probably increases the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Because the cytotoxic activity of ethanol is concentration-dependent, the risk of these cancers will not only increase with increasing amounts of ethanol, but also with increasing concentrations; an ounce of whisky is probably more carcinogenic when taken undiluted than when taken mixed with non-alcoholic beverages. The local cytotoxic effect of ethanol can also explain the known synergistic effect of alcohol and tobacco use on the risk of these cancers. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.
Tue, 9 August 2016
ARTICLE Download: 1143| View: 936| Comments: 0 | doi:10.20944/preprints201608.0087.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: natriuretic peptides; heart failure; congestion; outcome
Online: 9 August 2016 (11:33:03 CEST)
Background According to some authors, a single isolated measurement of serum BNP executed on hospital admission would not be a sufficiently accurate method to predict the outcome of patients with ADHF. Aims For verifying this assumption, a retrospective study was conducted on patients hospitalized for ADHF. Our main objective was to ascertain whether there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Methods Medical records were examined so as to make a partition of the ADHF patient population into two groups, the former characterized by a rise in BNP during hospitalization, and the latter exhibiting a decrease in BNP in the measurement taken at hospital discharge. Results 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge, whereas 124 (70.06%) showed decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention and persistent orthopnea at discharge. Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter [1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; p (one-way ANOVA)=0.001]. In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the six-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of six-month all-cause mortality after adjustment for age, sodium at discharge, creatinine at discharge and New York Heart Association (NYHA) class at discharge (hazard ratio 34.49; 95% confidence intervals: 4.55–261.06; P =0.001). Conclusions Among patients with history of ADHF, more elevated BNP levels at the time of discharge from the hospital compared to those detected at admission identify a patient subset with higher grade of congestion and higher six-month mortality.
Fri, 2 September 2016
ARTICLE Download: 1138| View: 1353| Comments: 0 | doi:10.20944/preprints201608.0232.v2
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: mHealth; ODK scan; mobile health application; digitizing data collection; data management processes; paper-to-digital system; technology-assisted data management; treatment adherence
Online: 2 September 2016 (03:17:38 CEST)
The present grievous situation of the tuberculosis disease can be improved by efficient case management and timely follow-up evaluations. With the advent of digital technology this can be achieved by quick summarization of the patient-centric data. The aim of our study was to assess the effectiveness of the ODK Scan paper-to-digital system during testing period of three months. A sequential, explanatory mixed-method research approach was employed to elucidate technology use. Training, smartphones, application and 3G enabled SIMs were provided to the four field workers. At the beginning, baseline measures of the data management aspects were recorded and compared with endline measures to see the impact of ODK Scan. Additionally, at the end, users’ feedback was collected regarding app usability, user interface design and workflow changes. 122 patients’ records were retrieved from the server and analysed for quality. It was found that ODK Scan recognized 99.2% of multiple choice bubble responses and 79.4% of numerical digit responses correctly. However, the overall quality of the digital data was decreased in comparison to manually entered data. Using ODK Scan, a significant time reduction is observed in data aggregation and data transfer activities, however, data verification and form filling activities took more time. Interviews revealed that field workers saw value in using ODK Scan, however, they were more concerned about the time consuming aspects of the use of ODK Scan. Therefore, it is concluded that minimal disturbance in the existing workflow, continuous feedback and value additions are the important considerations for the implementing organization to ensure technology adoption and workflow improvements.
Fri, 27 April 2018
ARTICLE Download: 1138| View: 294| Comments: 0 | doi:10.20944/preprints201804.0349.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: bacterial infections; sensitivity; specificity; immature granulocytes; Latvia; child; sepsis
Online: 27 April 2018 (06:09:47 CEST)
Background: Detection of small proportion of serious bacterial infections (SBI) with potentially life threating course in a large group of children with fever admitted to emergency department (ED) is still complicated. Measurement of immature granulocytes (IG) percentage may be used as a marker of bacterial infections. The aim of the study was to evaluate whether the IG percentage is a useful additional predictive marker of SBI. Methods: This study included 258 children with febrile infections admitted to the ED. Clinical follow-up, microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (i) infected patients with no suspicion of SBI (n = 75); (ii) patients with suspicion of SBI (n = 183). IG percentage, white blood cell count (WBC) and C-reactive protein (CRP) levels were analyzed from the first routine blood samples at hospital admission. Results: A statistically significant difference in IG percentage levels was observed in children with SBI and those without - the mean IG percentage was 1.2% for the SBI group, 0.3% for those without SBI. The cutoff level of IG percentage to predict SBI was 0.45 (84% specificity, 66% sensitivity, 90% positive predictive value). We combine variables and evaluate their additive values. The sensitivity of WBC to detected SBI improved from 74% to 85% when IG percentage was added to the prediction models. When CRP, WBC and IG percentage were combined, the sensitivity to predict SBI increased to 93%, the specificity to 86%. (95% CI 77–93%). Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.80 for IG percentage. Conclusion: Addition of IG percentage to traditionally used markers of SBI as WBC and CRP may help to identify children with serious bacterial infections. Furthermore IG percentage can be rapidly obtained from the traditional full blood count without any extra sampling and costs.
Tue, 14 March 2017
ARTICLE Download: 1137| View: 901| Comments: 0 | doi:10.20944/preprints201703.0087.v1
Online: 14 March 2017 (18:34:37 CET)
For many years marine algae has been subject of numerous researches and as a source of natural products with antiviral activity, such as terpenes, alkaloids and sulphated polysaccharides. However, the anti-Zika virus (ZIKV) potential of algae has not been studied. In this study we evaluated extracts seven species of the three major classes of seaweeds (Phaeophyceae, Chlorophyceae and Rhodophyceae) against ZIKV. All seaweeds tested are native of the Brazilian coast, except for Kappaphycus alvarezii that can be cultivated. ZIKV a mosquito-borne flavivirus, has become a public health problem. In recent years there has been an increase in the number of cases and a strong association between ZIKV outbreak and the spread of cases of Guillain-Barré Syndrome and microcephaly. All seaweed extracts tested in this work inhibits ZIKV replication in a dose-dependent manner. Caulerpa racemosa, Kappaphycus alvarezii and Osmundaria obtusiloba extracts were able to inhibit viral replication at low concentrations with EC50 values ranging from 1.38 to 1.98 µg/mL. We observed that O. obtusiloba presented a significant virucidal effect. Our results suggest that extracts of C. racemosa, K. alvarezii and O. obtusiloba presented very promising results, being excellent candidates for further studies, demonstrating that marine algae are an interesting source for the development of novel anti-ZIKV agents.
Fri, 7 October 2016
COMMUNICATION Download: 1125| View: 1268| Comments: 0 | doi:10.20944/preprints201610.0015.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Blackberry juice; Thermoultrasound; Antioxidant Compounds; Fatty Acids
Online: 7 October 2016 (10:12:21 CEST)
Blackberry (Rubus fruticosus spp) is a fruit that has a significant antioxidant activity, due to its content in anthocyanins and antioxidant compounds. Emerging technologies are required as the thermoultrasound technique that ensures microbial reduction and release of compounds with antioxidant properties. The objective of this study was to evaluate changes in the antioxidant content and fatty acid profile of blackberry juice when it is subjected to conservation treatment (pasteurization and thermoultrasound). The blackberry juice and the extracted oil of blackberry juice with n-hexane (control, pasteurized and thermoultrasonicated) were evaluated in antioxidant activity, fatty acid profile and antioxidant content. The thermoultrasound juice had the highest (p < 0.05) amount of total phenols (1011 mg GAE/L), anthocyanins (118 mg Cy-3-GlE/L); antioxidant activity by ABTS (44 mg VCEAC/L) and DPPH (2665 µmol TE/L) compared to the control and pasteurized samples, as well as, as well as, oil extract of obtained of the thermoultrasound juice presented high antioxidant activity (177.54 mg VCEAC/L to ABTS and 1802.60 µmol TE/L to DPPH). The fatty acid composition of the oil extract showed the presence of myristic, linolenic, stearic, oleic, and linoleic acid, the fatty acid profile was similar in the different samples with the exception of stearic acid where this was higher in control sample. The thermoultrasound treatment can be an alternative to pasteurization treatments because keeps and releases antioxidant bioavailable compounds, preserving their fatty acids.
Wed, 17 August 2016
ARTICLE Download: 1123| View: 929| Comments: 0 | doi:10.20944/preprints201608.0164.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: vitamin B12; coronary tortuosity; coronary angiography
Online: 17 August 2016 (10:51:56 CEST)
Background: Vitamin B 12 deficiency has been implicated in endothelial dysfunction and cardiovascular disease via hyperhomocysteinemia. Coronary tortuosity (CorT) is a common coronary angiography finding. The etiology, clinical implication and long term prognosis are still not well clarified. This study was conducted with the aim to evaluate the relationship between CorT and vitamin B12. Subjects and Method: The medical records of consecutive patients, who underwent coronary angiography, were retrospectively reviewed. The study group consisted of 1624 patients. Taking into consideration the inclusion criteria, 212 patients with CorT and 210 patients with normal coronary angiographies (control group) were included in the study. Vitamin B12, other biochemical parameters, clinical and echocardiographic parameters, and CorT score were evaluated in all patients. CorT is defined as fixed 3 bends during both systole and diastole, with each bend ≥45 °. Results: Patients with CorT had higher prevalence of older, female gender, hypertension, current smoking. Vitamin B12 was significantly decreased in patient with CorT (134.7±47.8 vs 239.6±53.8 p<0.001). On multivariate analysis age, female gender, hypertension, diabetes mellitus and vitamin B12 were independent predictors for CorT (OR 1.56; 95% CI: 1.247–1.962; p < 0.001, OR 1.628; 95% CI: 1.376-2.048; p<0.001, OR 1.865; 95% CI: 1.387-2.695; p<0.001, OR 1.362; 95% CI: 1.184-1.726; p<0.001, OR 1.862; 95% CI: 1.486-2.674; p<0.001, respectively). Conclusion: In our study, we have founded a significant relationship between vitamin B12 deficiency and CorT.
Wed, 7 December 2016
ARTICLE Download: 1111| View: 920| Comments: 0 | doi:10.20944/preprints201612.0042.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: acute lung injury; mycelium of Sanghuangporus sanghuang; lipopolysaccharide; KAP1/Nrf2 pathway; PI3K/Akt/mTOR pathways; HO-1; HNGB1
Online: 7 December 2016 (11:15:30 CET)
Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases
Tue, 27 September 2016
ARTICLE Download: 1109| View: 1123| Comments: 0 | doi:10.20944/preprints201609.0102.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: salidroside; inflammation; alcoholic liver injury; TLR4; TAK1
Online: 27 September 2016 (10:45:06 CEST)
The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion of interleukin (IL)-1β. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury.
Fri, 23 September 2016
ARTICLE Download: 1102| View: 821| Comments: 0 | doi:10.20944/preprints201609.0078.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: thin film nitinol; electrostatic cell seeding; biocompatibility; endovascular devices
Online: 23 September 2016 (03:45:59 CEST)
Electrostatic endothelial cell seeding has evolved as an exceptional technique to improve the efficiency of cell seeding in terms of frequency of attached cells and the amount of cell adhesion for the treatment of vascular diseases. In the recent times, both untreated and superhydrophilic thin film nitinol (TFN) have exhibited strong prospect as substrates for creation of small-diameter endovascular grafts due to their hallmark properties of superelasticity, ultra low-profile character, grown hemocompatible oxide layer with the presence of a uniform endothelial layer on the surface. The purpose of the current study is to understand the effects of endothelial cell seeding parameters (i.e., applied voltage, incubation time, substrate chemistry and cell suspension solution) to investigate the cell seeding phenomenon and to improve the cell adhesion and growth on the TFN surface under electrostatic transplantation. Both parallel plate and cylindrical capacitor models were used along with the Taguchi Design of Experiment (DOE) methods to design in vitro test parameters. A novel in vitro system for cylindrical capacitor model was created using a micro flow pump, micro incubation system, and silicone tubings. The augmented endothelialization on thin film nitinol was developed to determine the effect of cell seeding and deployed in a 6 Fr intravascular catheter setup. Cell viability along with morphology and proliferation of adhered cells were evaluated using fluorescent and scanning electron microscopy. Our results demonstrated that the maximum number of cells attached on STFN in the catheter was observed in 5V with the 2 hr exposure of in the cell culture medium (CCM) solution. The condition showed 5V voltage with 0.68×10-6 µC electrostatic charge and 5.11 V·mm-1 electric field. Our findings have first demonstrated that the electrostatic endothelialization on the superhydrophilic thin film nitinol endograft within the catheter prior to the endovascular procedure could enhance the biocompatibility for low-profile endovascular applications.
Mon, 22 August 2016
ARTICLE Download: 1099| View: 1881| Comments: 0 | doi:10.20944/preprints201608.0188.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: oleandrin; osteosarcoma; apoptosis; caspases
Online: 22 August 2016 (05:35:06 CEST)
Our previous study has found the anti-tumor activity of oleandrin in osteosarcoma cells in vitro, but the signal transduction process of cell apoptosis induced by oleandrin is uncertain, which is explored in this study. Fluorescence staining and flow cytometry (FCM) was performed to detect the cell apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). Caspase-3 activity was detected using a commercial kit. The protein expression of cytoplasmic cytochrome c, mitochondrial cytochrome c, bcl-2, bax, caspase-9, Fas, FasL, caspase-8 and caspase-3 was detected using western blot. A pan-caspase inhibitor, z-VAD-fmk, was applied to block the apoptotic pathway and the apoptosis status were re-tested. We found that oleandrin significantly induced the increased apoptosis of U2OS cells. Meanwhile, the intracellular ROS was elevated, but the MMP decreased. The cytochrome c in mitochondria was notably decreased but increased in cytoplasm. The caspase-3 activity was also enhanced with the increase of drug concentration and treatment time. Oleandrin also down-regulated the level of bcl-2, but remarkably up-regulated the expression of bax, cleaved caspase-9, Fas, FasL, cleaved caspase-8 and cleaved caspase-3. Furthermore, the pre-treatment with z-VAD-fmk almost completely reverted the oleandrin-induced apoptosis. The results suggested that oleandrin induces the apoptosis of osteosarcoma cells via mitochondrial- and death receptor-dependent pathways.
Thu, 29 September 2016
ARTICLE Download: 1099| View: 878| Comments: 0 | doi:10.20944/preprints201609.0116.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: Neonate; qualitative research; Southeast Asia
Online: 29 September 2016 (11:17:06 CEST)
Global coverage and scale up of interventions to reduce newborn mortality remains low, though progress has been achieved in improving newborn survival in many low-income settings. An important factor in the success of newborn health interventions, and moving to scale, is appropriate design of community-based programs and strategies for local implementation. We report the results of formative research undertaken to inform the design of a newborn health intervention in Cambodia. Information was gathered on newborn care practices over a period of three months using multiple qualitative methods of data collection in the primary health facility and home setting. Analysis of the data indicated important gaps, both at home and facility level, between recommended newborn care practices and those typical in the study area. The results of this formative research have informed strategies for behavior change and improving referral of sick infants in the subsequent implementation study. Collection and dissemination of data on newborn care practices from settings such as these can contribute to efforts to advance survival, growth and development of newborns for intervention research, and for future newborn health programming.
Fri, 7 October 2016
ARTICLE Download: 1091| View: 1152| Comments: 0 | doi:10.20944/preprints201610.0016.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: molecular dynamics simulation; virtual screening; molecular docking; prostate cancer; caveolin-1
Online: 7 October 2016 (12:09:06 CEST)
Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.
Thu, 5 January 2017
REVIEW Download: 1077| View: 816| Comments: 0 | doi:10.20944/preprints201701.0027.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: iPad; tablet computers; Stroke; neuro-rehabilitation
Online: 5 January 2017 (09:56:53 CET)
Neuro-rehabilitation services are essential in reducing post-stroke impairments, enhancing independence, and improving recovery in hospital and post-discharge. However these services are therapist-dependent and resource intensive. Patients’ disengagement and boredom in stroke units are common which adversely affect functional and psychological outcomes. Novel techniques such as use of iPads™ are increasingly researched to overcome such challenges. The aim of this review is to determine the feasibility, effectiveness, acceptability, and barriers to the use of iPads™ in stroke neuro-rehabilitation. Four databases and manual literature search were used to identify published studies using the terms “iPad”, “Stroke”, and “neuro-rehabilitation”. Studies were included in accordance with the review selection criteria. A total of 16 articles were included in the review. The majority of the studies focused on iPads use in speech and language therapy. Although of small scale, the studies highlighted that iPads are feasible, have the potential to improve rehabilitation outcomes, and can improve patient’s social isolation. Patients’ stroke severity and financial limitations are some of the barriers highlighted in this review. This review presents preliminary data supportive for the use of iPad technology in stroke neuro-rehabilitation. However, further research is needed to determine impact on rehabilitation goals acquisition, clinical efficacy, and cost-efficiency.
Mon, 9 January 2017
ARTICLE Download: 1075| View: 990| Comments: 0 | doi:10.20944/preprints201701.0044.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Aflatoxins; Peanuts; Aspergillus species
Online: 9 January 2017 (09:40:46 CET)
Aflatoxin contaminates foods including peanuts. Aflatoxin is a carcinogenic toxin mainly produced bty Aspergillus flavus. Other Aspergillus species that rarely produce aflatoxins are A. nomius and A. niger. Aflatoxin is associated with liver failure, hepatocellular carcinoma (HCC) and death. Recent studies have shown that peanuts in Kenya are highly contaminated with aflatoxins but information gaps exist on the characterization of the Aspergillus species that produce aflatoxins in peanuts in Kenya. Therefore, this gap necessitated the determination of the Aspergillus species producing aflatoxins in peanuts from the main growing districts of Busia and Kisii Central districts. One hundred and two (102) peanuts samples were collected from farmers’ in each district Aspergillus species were isolated from the peanut samples by using the dilution plate technique on modified Rose Bengal agar. Phenotypical characterization of the identified Aspergillus section flavus isolates from the peanuts samples was determined using the procedure of Mellon and Cotty. This study identified five (5) Aspergillus species as contaminants in peanuts analyzed in this study. They were Aspergillus flavus L-strain, Aspergillus flavus S-strain, Aspergillus parasiticus, Aspergillus niger and Aspergillus tamari. Overall, the occurrence of Aspergillus flavus L- strain and A. flavus S- strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species identified in the study with a mean occurrence of 45.1%. Aspergillus flavus L- strain was the most common isolate (58.8%) in peanuts from Busia district while A. flavus S- strain was the most common strain (60.2%) in peanuts from Kisii Central district. Overall, the occurrence of Aspergillus flavus L strain and A. flavus S strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species (F=3.15, df =25, P=0.031) with an overall mean occurrence of 45.1%. The confirmation of occurrence of other species that produce toxins such as A. niger and A. tamarii which also produces cyclopiazonic acid suggests the need to screen peanuts for other carcinogenic mycotoxins.
Mon, 24 October 2016
REVIEW Download: 1069| View: 878| Comments: 0 | doi:10.20944/preprints201610.0100.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: BET; bromodomain; histone acetylation; gene transcription; BET inhibitor
Online: 24 October 2016 (05:06:56 CEST)
The BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises Brd2, Brd3, Brd4, and Brdt, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-Myc. These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.
Mon, 22 August 2016
COMMENTARY Download: 1064| View: 1033| Comments: 0 | doi:10.20944/preprints201608.0187.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: magnetic fields; power lines; cancer; carcinogenesis; stem cell division theory of cancer
Online: 22 August 2016 (05:15:53 CEST)
Extremely low-frequency electromagnetic fields (ELF-EMFs) are non-ionizing radiations typically emitted by power lines, electrical wiring and electrical appliances. Epidemiological studies have repeatedly shown a positive association between ELF-EMFs and childhood leukemia. Exposures greater than 0.3-0.4 µT increase the risk by approximately 1.5-2 fold, and estimates indicate that up to 2% of childhood leukemia cases in Europe may be attributable to ELF-EMFs. However, it is considered unlikely that ELF-EMFs can cause cancer, because carcinogenesis requires the accumulation of DNA alterations and ELF-EMFs do not have enough energy to damage the DNA. Lack of biological plausibility is a barrier to accept the evidence of carcinogenicity in human studies and to take measures to protect pregnant women and children from ELF-EMFs. Recent evidence indicates that non-mutagenic agents can cause DNA alterations and increase the risk of cancer by promoting the accumulation of cell divisions in stem cells. Cell division generates DNA alterations (e.g., mutations arising during DNA replication), which occur even in the absence of DNA-damaging agents. Importantly, ELF-EMFs can trigger the division of stem cells; this effect is under development in the field of regenerative medicine. A possible mechanism by which ELF-EMFs induce the malignant transformation of hematopoietic stem cells is discussed.
Thu, 11 August 2016
ARTICLE Download: 1054| View: 1218| Comments: 0 | doi:10.20944/preprints201608.0093.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: depression; anxiety; emotional distress; HADS; GDS; Health Centre
Online: 11 August 2016 (11:05:44 CEST)
Objective: The main purpose of this study was to investigate the mental health of Cypriot citizens, living in the current difficult period of economic recession. Specific objective was to investigate the different factors (gender, age, socio-economic factors, etc.) that may affect the levels of emotional distress, anxiety and depression in visitors of the Rural Health Centre of Kofinou. Materials and Methods: The sample consisted of total 300 Cypriots who visited Kofinou Health Centre in the period between August and September 2015. For the middle-aged citizens the Greek version of the HADS scale (Hospital Anxiety Depression Scale) was administered to 150 persons (Michopoulos I., 2007), while for the visiting senior citizens (aged over 65 years) the Greek version of the GDS scale (Geriatric Depression Scale) was used (Fountoulakis K., et al., 1999). All analyses were performed with the social science analysis package SPSS (version 21). Results: HADS: A total of 150 people of average age 47±11,5 years (23-64), were 56% women, while the 77.3% stated they had drastic reduction of income as well as 46.7% suffered from chronic disease. The 36.6% and 28.7% of the visitors showed moderate and severe forms of anxiety and depression, accordingly. Higher emotional distress is associated with lower educational level (p<0,001). Moreover, patients with low income have higher levels of anxiety (p=0,003), depression (p=0,036) and total emotional distress (p=0,007), while those with chronic disease have a higher stress (p<0,001), depression (p<0,001) and total emotional distress symptoms (p<0,001) compared to non - patients. GDS: 150 patients out of which 77 were women (51.3%). The average age of participants was 72±5,5 years. 93(62%) participants declared a drastic reduction of income due to the financial crisis while 139 (92.7%) stated they had chronic disease. 53 participants (35.3%) think they have symptoms of depression after the economic crisis. The women showed higher level of geriatric depression symptoms than men (p<0.001). Higher levels of depression is associated with lower income (p=0.001). Conclusions: The study shows that stress levels, depression and emotional distress are increased in specific population groups. The main factors affecting the mental health of the participants are the presence of chronic disease, income and level of education.
Wed, 17 August 2016
ARTICLE Download: 1042| View: 884| Comments: 1 | doi:10.20944/preprints201608.0165.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Pueraria mirifica; mammary gland; uterus; carcinogenesis; estrogenic activity; Donryu rat
Online: 17 August 2016 (11:57:56 CEST)
Pueraria mirifica (PM) is a plant which dried and powdered tuberous root is now widely used as a rejuvenating herb to promote youthfulness in both men and women. In this study, we investigated the modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized Donryu rats at doses of 0.03, 0.3 and 3% in phytoestrogen-low diet for 2 weeks induced the significant increases of uterus weight. Secondly, 4-week PM application to non-operated rats at a dose of 3% after the 7,12-dimethylbenz[a]anthracene (DMBA) initiation, resulted in significant elevation of cell proliferation in the mammary glands. In the third experiment, postpubertal administration of 0.3% (200 mg/kg b.w./day) PM to 5-week-old non-operated animals for 36 weeks following the initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, caused significant increases of mammary adenocarcinoma incidence and multiplicity. A trend for increase of uterine adenocarcinomas and a significant increase of endometrial atypical hyperplasia multiplicity was observed at 0.3% PM. Furthermore, PM at doses of 0.3 and mostly 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, the postpubertal long-term PM administration to Donryu rats exerted estrogenic effect in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day promoted carcinogenesis initiated by DMBA and ENNG.
Tue, 23 August 2016
ARTICLE Download: 1039| View: 941| Comments: 0 | doi:10.20944/preprints201608.0199.v1
Subject: Medicine & Pharmacology, Other Keywords: active ageing; social participation; mobility; assistive technologies; service delivery
Online: 23 August 2016 (14:53:52 CEST)
Active ageing is defined as the process of optimizing opportunities for physical, social and mental health to enable older people to take an active part in society without discrimination and to enjoy an independent and good quality of life. The World Health Organization assumed this as a process for increasing and maintaining an individual’s participation in activities to enhance his/her quality of life. In this survey, the authors addressed the following question: “Is assistive technology (AT) for mobility contributing to enhancement of lifelong capacity and performance?”. From June 2015 until February 2016, 96 community dwelling adults, AT users for mobility (powered wheelchairs, manual wheelchairs, lower limb prostheses, walkers, crutches and canes), aged 45-97, mean 67.02 +/- 14.24 years old, 56.3% female, were interviewed using the Psychosocial Impact of Assistive Devices Scale (P-PIADS), the Activities and Participation Profile related to Mobility (APPM) and demographics, clinical and questions about AT use and training. The participants’ profiles revealed moderate limitation and restrictions in participation, measured by the APPM (2.03). Most participants showed positive impact of AT; average scores obtained from the P-PIADS subscales were: Self-esteem 0.62, Competency 1.11 and Adaptability 1.10. P-PIADS total was 0.96, with the powered wheelchair users scoring the highest (1.53) and the walker users scoring the lowest (0.73). All subscales and P-PIADS total were positively correlated with the activities and participation profile. There was no relation between age and the psychosocial impact of AT or activities and participation profile. These results encourage the authors to follow these participants up for a lifelong intervention. To accomplish that aim, currently, the protocol is implemented at the AT prescribing centers in Coimbra, Portugal in order to assess the impact of AT on participation in society, one of the domains of the Active Ageing Index, a new analytical tool to help policy makers in developing policies for active and healthy ageing.
Thu, 8 December 2016
REVIEW Download: 1036| View: 899| Comments: 0 | doi:10.20944/preprints201612.0048.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Cortex Periplocae; traditional Chinese medicines; periplocin; phytochemistry; biological activities
Online: 8 December 2016 (10:24:43 CET)
Cortex Periplocae, as a traditional Chinese herbal medicine, has been widely used for autoimmune diseases, especially rheumatoid arthritis. Due to its potential pharmaceutical values, more studies about the biological activities of Cortex Periplocae have been conducted recently. Meanwhile, the adverse reaction of Cortex Periplocae is not a negligible problem in clinic. In this article, we reviewed a series of articles and summarized the recent studies of Cortex Periplocae in the areas of phytochemistry and pharmacology. More than 100 constituents have been isolated and identified from Cortex Periplocae, including steroids, cardiac glycosides, terpenoids, and fatty acid compounds. The crude extracts of Cortex Periplocae and its active compounds exhibit various biological activities, such as cardiotonic effect, anticancer action, and anti-inflammatory effect. This paper aims to provide an overall review on the bioactive ingredients, pharmacological effect, and toxicity of this plant. Furthermore, this review suggests investigating and developing new clinical usages according to the above pharmacological effects.
Tue, 13 February 2018
ARTICLE Download: 1033| View: 376| Comments: 0 | doi:10.20944/preprints201802.0091.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: cancer; lung cancer; leukemia; Daphne; Thapsia; daphnane diterpenes
Online: 13 February 2018 (07:08:47 CET)
Although several plant-derived drug groups (vinca alkaloids, taxanes, podophyllotoxin derivatives and camptothecins) continue to be widely used in cancer therapy, the anticancer potential of the Plant Kingdom remains largely unexplored. In this work, we have carried out a random screening for selective anticancer activity of 57 extracts from 45 plants collected in Grazalema Natural Park, an area in the South of Spain of high plant diversity and endemism. Using lung cancer cells (A549) and lung non-malignant cells (MRC-5), we found that several extracts were more cytotoxic and selective against the cancer cell line than the standard anticancer agent cisplatin. Five active extracts were further tested in cancer and normal cell lines from other tissues, including three skin cell lines with increasing degree of malignancy. An extract from the leaves of Daphne laureola L. (Thymelaeaceae) showed a striking potency and selectivity on lung cancer cells and leukemia cells; the IC50 values against these cancer cells were approximately 10000-fold lower than against the normal cells. Daphnane-type diterpene orthoesters may be responsible for this highly selective anticancer activity.
Tue, 9 August 2016
ARTICLE Download: 1030| View: 913| Comments: 0 | doi:10.20944/preprints201608.0100.v1
Online: 9 August 2016 (14:31:47 CEST)
Background and objectives: The correlation of cardiac troponin I with early in-hospital outcomes in acute myocardial infarction is not well established. This study aims to assess the role of troponin I in predicting in-hospital outcomes and early left ventricular systolic dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). Patients and methods: In a prospective study, 116 patients (74males and 42 females), with STEMI who had been admitted to the Coronary CareUnit from March 2015 to September 2015 were enrolled. Patients were divided according to the level of troponin I on admission into 3 groups (low, medium and high elevation). Results: The mean age (+ SD) of the patients was 60+11.4 years. The troponin level of 66.2% of males was high compared with 52.4% of females (p=0.002). The incidence of acute pulmonary edema (21.1%), cardiogenic shock (7%) and early left ventricular systolic dysfunction (49.3%) was significantly higher among patients with high troponin level compared with (0%, 0% and 16%, respectively) among patients with low troponin level. All deaths and cardiac arrest were of high troponin level. Conclusions: High admission troponin I in STEMI permits early identification of patients at increased risk of major cardiac complications and death.
Fri, 7 April 2017
ARTICLE Download: 1029| View: 695| Comments: 0 | doi:10.20944/preprints201704.0041.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: adolescents; depression; insomnia; mobile phone; Japanese
Online: 7 April 2017 (04:33:14 CEST)
Adolescents spend an increasing amount of time on mobile phones. The aim of this study was to assess the relationship between duration of mobile phone use and insomnia and depression in senior high school students. The cross-sectional study was conducted on 295 senior high school students in Japan. Mobile phones were owned by 98.6% of students; 58.6% of students used mobile phones for more than 2 h daily and 10.5% used them for 5 h daily. The risk of insomnia was significantly high in students who used mobile phones for 5 h or more (OR: 3.89 [95% CI: 1.21-12.49]). There was no significant association between depression and duration of mobile phone use. However, individuals who spent 120 min or more using mobile phones for social network services (OR: 3.63 [1.20-10.98]) and online chats (OR: 3.14 [1.42-6.95]) were at risk for depression. Excessive mobile phone use is associated with unhealthy sleep habits and insomnia. Moreover, the excessive use of the social network services and online chats are related to depression rather than duration of mobile phone use. Adolescents should use mobile phones appropriately to avoid sleep disturbances and the impairment of mental health.
Tue, 20 September 2016
ARTICLE Download: 1029| View: 789| Comments: 0 | doi:10.20944/preprints201609.0070.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: asian sand dust; in utero exposure; secondary sex ratio; male reproduction; daily sperm production
Online: 20 September 2016 (11:39:47 CEST)
In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.
Fri, 30 December 2016
ARTICLE Download: 1029| View: 773| Comments: 1 | doi:10.20944/preprints201612.0149.v1
Subject: Medicine & Pharmacology, Other Keywords: acute pharyngitis; rational use of drugs; incidence; prevalence
Online: 30 December 2016 (07:37:07 CET)
According to Indonesia’s result of Basic Health Research of 2013, prevalence of acute respiratory infection in 2007 and 2013 were not different (25.5% and 25.0%, respectively). Identifying the cause of acute pharyngitis is a key point in determining the optimal treatment. The main purpose is to evaluate the rational use of drugs and its irrational impact as well as the correlation of the drug use with the incidence and prevalence of acute pharyngitis. This study was a descriptive and observational study, carried out retrospectively and concurrently at two community health centers located in Bandung and Cimahi, Indonesia. There were 80.01% over prescription of antibiotics, with a total of 8.98% is non-treatment option, and 62.43% irrational used of corticosteroids. The incidence and prevalence of acute pharyngitis at one health center in Bandung were 2.45% and 2.31%, respectively, with irrationality rate of 83.82%. Those recorded at one health center in Cimahi were 2.11% of incidence and 2.00% of prevalence with irrational rate of 91.29%. It can be concluded that there were still irrational use of medicines in the treatment of acute pharyngitis in community health center. The higher incidence and prevalence might indicate the declining health services quality.
Wed, 7 September 2016
ARTICLE Download: 1027| View: 1159| Comments: 0 | doi:10.20944/preprints201609.0024.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: neurofibromatosis type 1; congenital pseudarthrosis of the tibia; whole-exome sequencing; targeted sequencing; BCOR
Online: 7 September 2016 (11:19:00 CEST)
Neurofibromatosis type1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1gene. Although congenital pseudarthrosis of the tibia (CPT) has frequently been associated with NF1, the underlying molecular mechanism of CPT in these NF1 patients is yet ill-understood. The aim of the present study was to detect NF1 mutations from genomic DNA and to harbor variants associated with CPT in NF1 patients. Whole-exome sequencing was first carried out with samples from two patients with CPT in one NF1 family, and a novel mutation c.2324A>G (p.E775G) in NF1 gene was identified. Additionally, a missense variant c.455C>T (p.P152L) in BCOR gene completely co-segregated with the CPT phenotype within this family. Subsequently, NF1 and NF2 genes in four other unrelated patients with both NF1 and CPT were screened using targeted sequencing. Four mutations in NF1 gene, including two known mutations (c.2288T>C/p.L763P, c.574 C>T/p.R192*) and two novel mutations (c.768delT/p.F256Lfs*25, c.2229_2230delTG/ p.V744Qfs*23) were detected. Further study confirmed that CPT was present in NF1 families, and NF1 mutations were closely associated with these complex phenotypes. Moreover, the data from the current study indicated that male gender might be a susceptibility factor for CPT in NF1. Therefore, we speculated that BCOR variants might be related to CPT phenotype among male NF1 patients.
Fri, 19 August 2016
ARTICLE Download: 1025| View: 1080| Comments: 0 | doi:10.20944/preprints201608.0175.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: Synergistic effect; Flos Lonicerae; Trimethoprim
Online: 19 August 2016 (09:22:06 CEST)
Observe the synergistic effect and dose-effect relationship of Trimethoprim (TMP) on bactericidal activity with Flos Lonicerae in vitro. Microamount chessboard dilution method was conducted to determine the minimal inhibitory concentration (MIC) of Trimethoprim, Flos Lonicerae, as well as the combination of Trimethoprim and Flos Lonicerae separately against Staphylococcus aureus, Escherichia coli in vitro and Salmonella. The pour plate count method was used to determine the combined bactericidal activity of Flos Lonicerae combined with Different concentrations TMP. The results showed that the MIC values of the combination of Flos Lonicerae with TMP was much less than the MIC values of the independent use of Flos Lonicerae or TMP, The FIC values of the combination of Flos Lonicerae with TMP were between 0.5 and 1, there was additive effect between them. The bactericidal rates were fitted with least square method, the 95% confidence intervals of the optimal blending quantity about the combination of Flos Lonicerae with TMP on the test organisms were 231μg·mL-1-249μg·mL-1, 237μg·mL-1-259μg·mL-1, and 235 -259μg·mL-1
Fri, 31 March 2017
REVIEW Download: 1001| View: 874| Comments: 0 | doi:10.20944/preprints201703.0235.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: social determinants; epigenetics; exposome; public health policy; resilience; allostatic load; adaptation
Online: 31 March 2017 (11:35:57 CEST)
Globally, humans are struggling with the double threat of communicable and non-communicable diseases, which are presenting new challenges to public health. Public health problems are generally studied and addressed at primary, secondary and tertiary levels. Most effective results are seen with primary interventions. Public health is becoming more aware of the importance of environment-gene interactions in the ontology of health and disease using epigenetics. Epigenetics is the study of altered gene expression without change in base pairs. Be it physical, social, behavioral, or economic factors; they all influence quality of life and health of individuals and populations. That environments are changing the human health phenotype and these changed phenotypes are heritable is of concern for the future of the human race. Knowing the causes of non-communicable human diseases using epigenetics will contribute to the development of new policies to encourage prevention using primary public health initiatives. Research and application of epigenetics shows great promise for improving population health. Continued advances in epigenetics will enhance how we understand and address the way environments are affecting the human health phenotype. For some time, health systems have been and continue to be tertiary in nature. Epigenetic changes can provide information necessary to better understand how social determinants of health can be used to build societies focused on equitable health for all people, rather than continuing to focus on treatment of diseases in the tertiary phase that leads to health disparities. Understanding mechanisms of social determinants of disease, will allow society to evolve in a health-oriented rather than a disease-oriented world. For this reason, we must enhance and apply epigenetics (physical, social, behavioral, economic) research to policy development. We will discuss how bringing social determinants together with biology can be used as new tools for public health policy.
Thu, 27 October 2016
ARTICLE Download: 986| View: 863| Comments: 0 | doi:10.20944/preprints201610.0122.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: isoflavones; menopause management; endometrial thickness; mammary density; liver function; plant extracts
Online: 27 October 2016 (12:21:59 CEST)
Long-term safety of a nutraceutical combination based on agnus castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli, and effectiveness on vasomotor symptoms and sleep disorders in postmenopausal women, were assessed. A controlled study was carried-out in menopausal women comparing this nutraceutical combination (ESP group) with formulation containing isoflavones alone (C group), at the dosage recommended. Kuppermann index, PSQI, and SF-36 were determined at baseline, 3, 6 and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. 180 women (100 in ESP group and 80 in C group, mean age 55.5 years, in menopause for about 36 months) were enrolled in the study. At the treatment end, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. Kuppermann index, and particularly hot flushes, were progressively and significantly decreased in frequency and severity during ESP versus C treatment. No adverse events were observed. Agnus castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. Endometrium, mammary glands and liver function, were unaffected after 12 months treatment.
Thu, 3 November 2016
ARTICLE Download: 985| View: 996| Comments: 0 | doi:10.20944/preprints201611.0028.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: random survival forests; ependymoma; predictors; valproic acid
Online: 3 November 2016 (11:02:12 CET)
Ependymoma is responsible for 8–10% of all pediatric brain tumors and constitutes the third most common brain tumor in children. No robust molecular markers are yet in routine clinical use. Surgical resection and adjuvant radiotherapy cure approximately 40-70% of pediatric patients with ependymoma. In our centre, we have been using prophylactic valproic acid treatment for brain tumor patients. Initial observations indicated that valproate could have a beneficial effect in the survival of patients. Recent observations by other authors have shown that patients with glioblastoma benefited from the treatment with valproic acid, a histone deacetylase inhibitor. We have used random survival forest, a novel ensemble survival modelling method to study a single- center, small number cohort of pediatric patients with ependymoma. This analysis has confirmed surgery resection extent and treatment with radiotherapy as independent predictors of overall survival. Treatment with valproic acid was also a predictor of higher survival in this cohort. These results highlight the potential usefullness of the random survival forest model in gathering information from retrospective data. More data is needed about the possible influence of histone deacetylase inhibition by valproic acid in the survival of patients with ependymoma.
Tue, 9 August 2016
CASE REPORT Download: 981| View: 929| Comments: 0 | doi:10.20944/preprints201608.0094.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: urea cycle disorder; ornithine transcarbamylase deficiency; magnetic resonance imaging; magnetic resonance spectroscopy
Online: 9 August 2016 (12:03:57 CEST)
Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.
Tue, 31 January 2017
ARTICLE Download: 974| View: 1090| Comments: 0 | doi:10.20944/preprints201701.0138.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Danggui-Shaoyao-San, chronic restraint stress, learning and memory, anxiety/depression, structural plasticity
Online: 31 January 2017 (15:30:41 CET)
Background: Clinical trails have revealed that patients with depression generally accompanied with learning and memory impairment, which critically impact on individual’s health and development. Danggui-Shaoyao-San (DSS), a famous Chinese complex prescription, significantly overcame depression and relieved cognitive disorder based on previous research and publication. However, its effectsand potential mechanism against chronic restraint stress (CRS) remained unknown. Methods: CRS animal model was established and mice were divided to six groups while they were oral administrated with Danggui-Shaoyao-San at doses of 1.25, 2.5 and 5 g/kg for 14 days. Emotional and cognitive performances were detected by behavior tests, meanwhile neural plasticity and its molecular mechanism were examined by Dil staining, western blot and immunofluorescence. Results: DSS treatment dose-dependently improved locomotion ability in open filed test, overcame depression behavior in forced swimming test and elevated plus maze test, enhanced learning and memory ability in Morris water maze test. CRS decreased number of total spines and mushroom spines, while DSS treatment dose-dependently restored these by Dil staining. Expression of BDNF and GluR1 were significantly down-regulated in CRS group, which were significantly normalized by DSS. Conclusions: DSS treatment dose-dependently reversed CRS-induced cognitive impairments by inducing structural remodeling of neurons.
Wed, 10 August 2016
ARTICLE Download: 974| View: 1058| Comments: 0 | doi:10.20944/preprints201608.0113.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: Growing pains; genu valgum; perinatal factors; bone metabolism
Online: 10 August 2016 (15:20:53 CEST)
The most prevalent musculoskeletal disorder of childhood with unclear aetiology is Growing Pains (GPs). Anatomic deformities and factors that change bone turnover are implicated in GPs pathophysiology. Perinatal risk factors alter the bone metabolism affecting the bone mineral density and content. The aim of our study was to analyze the relationship between GPs, knock knees and perinatal factors. The examined population consisted of 276 children aged 3-7 years. Among them 10 pairs of dizygotic twins were evaluated. The data were collected by using a combination of semi-structured questionnaires, clinical examinations and medical charts of the children and the obstetric history of the mothers. 78 children presented GPs meeting Peterson’s criteria. Genu valgum severity was a significant factor for GPs manifestation and for their increased frequency and intensity. Subsequently, perinatal factors regarding gestational age, Apgar score, head circumference (lower than 33cm) and birth length or weight (smaller than 50 cm and 3000gr, respectively) made a remarkable contribution to the development of GPs. Conversely, antenatal corticosteroid treatment, increased maternal age and maternal smoking during pregnancy were not predictive for the disorder. Our data are potentially supportive for the “bone strength” theory and for the contribution of anatomical disturbances in GPs appearance.
Sun, 9 October 2016
ARTICLE Download: 971| View: 1357| Comments: 0 | doi:10.20944/preprints201610.0025.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: drug repurposing; translational bioinformatics; transcriptomics; transcriptome analysis; drug discovery; protocol; gene expression
Online: 9 October 2016 (08:42:23 CEST)
Traditional methods for discovery and development of new drugs can be a very time-consuming and expensive process because it includes several stages such as compound identification, pre-clinical and clinical trials before the drug is approved by the US Food and Drug Administration (FDA). Therefore, drug repurposing, namely using currently FDA-approved drugs as therapeutics for other diseases than what they are originally prescribed for, is emerging to be a faster and more cost-effective alternative to current drug discovery methods. In this paper, we have described a three-step in silico protocol for analyzing transcriptomics data using online databases and bioinformatics tools for identifying potentially repurposable drugs. The efficacy of this protocol was evaluated by comparing its predictions with the findings of two case studies of recently reported repurposed drugs: HIV treating drug Zidovudine for the treatment of Dry Age-Related Macular Degeneration and the antidepressant Imipramine for Small-Cell Lung Carcinoma. The proposed protocol successfully identified the published findings, thus demonstrating the efficacy of this method. In addition, it also yielded several novel predictions that have not yet been published, including the finding that Imipramine could potentially treat Severe Acute Respiratory Syndrome (SARS), a disease that currently does not have any treatment or vaccine. Since this in-silico protocol is simple to use and does not require advanced computer skills, we believe any motivated participant with access to these databases and tools would be able to apply it to large datasets to identify other potentially repurposable drugs in the future.
Fri, 30 December 2016
ARTICLE Download: 963| View: 729| Comments: 0 | doi:10.20944/preprints201612.0146.v1
Subject: Medicine & Pharmacology, Other Keywords: pharmacy graduates; preparedness; patient care; Indonesia
Online: 30 December 2016 (06:12:04 CET)
Pharmacists’ roles in providing patient care remain limited in Indonesia, hence this study aimed to determine the preparedness of pharmacy graduates from one university in Indonesia to deliver patient care. Pharmacy graduates (both registered pharmacists  and recent graduates eligible for registration ) were sent a validated self-administered survey. The survey sought their perceptions about whether they had acquired 16 patient care related attributes. Further, it sought their opinion on the desirability of having those attributes. Data were analysed using SPSS version 22.0. Sixteen of 104 (15.4%) registered pharmacists and 40 of 45 (88.9%) recent pharmacy graduates participated in the study. More than 50% of participants in both groups were female and most participants were aged in their 20s. Of the recent pharmacy graduates the majority perceived they had at least partially acquired four of 16 list attributes. Male and female recent graduates had significantly different beliefs about their leadership ability (p=0.004). In comparison, most registered pharmacists perceived they had 10 out of the 16 listed attributes. The findings of this study suggested that pharmacy graduates should be better prepared to deliver patient care, and that curriculum redesign with expansion of experiential learning is required.
Wed, 14 September 2016
REVIEW Download: 945| View: 914| Comments: 0 | doi:10.20944/preprints201608.0115.v2
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: oncogenes; oncogene addiction; carcinogenesis; transcription factor; cancer genome; gene fusion; cancer genetics; cancer stem cell; targeted cancer therapy; personalized medicine
Online: 14 September 2016 (08:30:41 CEST)
It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.
Fri, 31 March 2017
ARTICLE Download: 929| View: 665| Comments: 0 | doi:10.20944/preprints201703.0225.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: acute lung injury; fasudil, Rho kinase; endothelial function; inflammation
Online: 31 March 2017 (08:30:54 CEST)
Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS. Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary microvascular endothelial cells (PMECs). The results showed that fasudil reduced LPS-induced lung inflammation, pulmonary hyperpermeability, and endothelial apoptosis in mice. In cultured human PMECs, fasudil inhibited LPS-induced caspse-3 cleavage and cell apoptosis. It also decreased LPS-induced hyperpermeability of human PMECs monolayer by reversing the down-regulation of intercellular junctions. Moreover, fasudil inhibited LPS-induced overexpression of chemokines and intercellular adhesion molecule (ICAM)-1 in human PMECs, which in turn suppressed neutrophil chemotaxis and neutrophil-endothelial adhesion. Further molecular researches showed fasudil inhibited LPS-induced activation of ROCK, NF-κB, and p38 in human PMECs. Our findings demonstrated that fasudil alleviated LPS-induced ALI by protecting endothelial function via inhibiting endothelial apoptosis, maintaining endothelial barrier integrity, and reducing endothelial inflammation. These effects of fasudil could be attributed to the inhibition of ROCK and its downstream NF-κB and p38 signaling pathways.
Mon, 5 December 2016
ARTICLE Download: 928| View: 1154| Comments: 7 | doi:10.20944/preprints201612.0026.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: cytomegalovirus; alanine transaminase; aspartate transaminase alkaline phosphatase; γ-glutamyltranspeptidase; liver function
Online: 5 December 2016 (11:08:57 CET)
Background Cytomegalovirus (CMV) is a major pathogen that cause remarkable rate of morbidity and mortality, especially in immunocompromised patients. It is important to find risk factors associated with CMV viremia. We studied the differences in CMV seropositivity in relation to liver function biomarkers in male and female Saudi population in an attempt to understand the variation in the CMV seroprevalence with sex and find the risk factor to develop liver dysfunction or hepatocellular carcinoma. Material and subjects: The CMV- IgG and IgM were screened in serum samples of 150 non- A-G hepatities patients with elevation of liver profiles (ALT, AST, ALP and GGT) and categorized as males and females. Samples were collected from different general hospitals and polyclinic in KSA from March 2014 to June 2015. A correlation between CMV seropositivity measured with both antibodies and liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were done for the obtained data. Results: Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females. Conclusion:he data discussed above This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections with the concomitant risk of developing liver dysfunction or hepatocellular carcinoma. Keywords: Cytomegalovirus, Alanine transaminase, Aspartate transaminase Alkaline phosphatase, γ-Glutamyltranspeptidase, liver function.
Mon, 17 April 2017
ARTICLE Download: 927| View: 677| Comments: 0 | doi:10.20944/preprints201704.0092.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Parboiled rice, medium-grain white rice, cold stored, reheating, blood glucose concentration chewing time, satiety, palatability.
Online: 17 April 2017 (05:35:10 CEST)
Background: Globally, hot cooked refined rice is consumed in large quantities and is a major contributor to dietary glycaemic load. This study aimed to compare the glycaemic potency of hot and cold stored parboiled rice to widely available medium grain white rice. Method: Twenty-eight healthy volunteers participated in a three treatment experiment where postprandial blood glucose was measured over 120 minutes after consumption of 140g of rice. Three rice samples were freshly cooked medium-grain white rice, freshly cooked parboiled rice, and parboiled rice stored overnight at 4 ºC. All rice was served warm at 65 ºC. Chewing time was recorded. Results: The 24-hours cold-stored and reheated parboiled rice resulted in a 42% and 12% lower blood glucose concentration trajectory than freshly cooked medium-grain white rice and freshly cooked parboiled rice. Chewing time for 10g cold stored parboiled rice was 6 seconds (25%) longer and was considered more palatable, visually appealing and better tasting than freshly cooked medium grain (all P<0.05). Conclusions:. For regular consumers of rice reheating cooked rice after cold storage would lower the dietary glycaemic load and long term may reduce risk for type 2 and gestational diabetes. More trials are needed to identify the significance.
Tue, 17 October 2017
REVIEW Download: 927| View: 754| Comments: 0 | doi:10.20944/preprints201710.0117.v1
Subject: Medicine & Pharmacology, Other Keywords: computer-aided diagnosis; CAD algorithms; deep neural networks; medical diagnosis; review
Online: 17 October 2017 (11:57:17 CEST)
With recent focus on deep neural network architectures for development of algorithms for computer-aided diagnosis (CAD), we provide a review of studies within the last 3 years (2015-2017) reported in selected top journals and conferences. 29 studies that met our inclusion criteria were reviewed to identify trends in this field and to inform future development. Studies have focused mostly on cancer-related diseases within internal medicine while diseases within gender-/age-focused fields like gynaecology/pediatrics have not received much focus. All reviewed studies employed image datasets, mostly sourced from publicly available databases (55.2%) and few based on data from human subjects (31%) and non-medical datasets (13.8%), while CNN architecture was employed in most (70%) of the studies. Confirmation of the effect of data manipulation on quality of output and adoption of multi-class rather than binary classification also require more focus. Future studies should leverage collaborations with medical experts to aid future with actual clinical testing with reporting based on some generally applicable index to enable comparison. Our next steps on plans for CAD development for osteoarthritis (OA), with plans to consider multi-class classification and comparison across deep learning approaches and unsupervised architectures were also highlighted.
Thu, 18 August 2016
REVIEW Download: 926| View: 886| Comments: 0 | doi:10.20944/preprints201608.0160.v2
Subject: Medicine & Pharmacology, Nutrition Keywords: cranberry; cancer; proanthocyanidin; quercetin; ursolic acid
Online: 18 August 2016 (07:44:23 CEST)
Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques; whereas, in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy will be considered
Mon, 6 March 2017
ARTICLE Download: 924| View: 810| Comments: 0 | doi:10.20944/preprints201703.0030.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: bacteria; bacteriome; carcinoma; microbiome; mouth; smokeless; snuff; tobacco
Online: 6 March 2017 (07:18:27 CET)
Smokeless tobacco (ST) products vary significantly in their oral carcinogenicity. Much is known about the differences in chemical, but not bacterial, constituents of these products. In this study, we explore the composition and function of the bacteriome in ST products from 4 countries using q-PCR and 16S rRNA-based next generation sequencing. The bacterial load (16S rRNA copies/gram) was lowest in Swedish snus (3.4E+6) and highest in Yemeni shammah (6.6E+11). A total of 491 species-level taxa, many of which are potentially novel, belonging to 178 genera and 11 phyla were identified. Species richness and diversity were highest for Swedish snus and lowest for Yemeni shammah. Bacillus, Paenibacillus, and Oceanobacillus spp. were the most abundant in American snuff; species of Pseudomonas, Massilia, Propionibacterium, Puniceispirillum and Gloeothece predominated in Swedish snus. In Sudanese toombak, Facklamia, Desemzia, Atopostipes and Lysinibacillus spp. accounted for the majority of the bacteriome. Yemeni shammah exclusively contained Bacillus spp. PICRUSt functional prediction showed that genes encoding cadmium/zinc and nickel transport systems were enriched in the presumptively “high carcinogenicity” products. The bacteriome of ST products thus differed qualitatively, quantitatively and functionally. The relevance of these differences, particularly with respect to nickel and cadmium, to oral carcinogenesis warrants further investigation.
Thu, 10 November 2016
ARTICLE Download: 923| View: 865| Comments: 0 | doi:10.20944/preprints201611.0056.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: long-acting injectable; antipsychotic; decision-making; guidelines; schizophrenia
Online: 10 November 2016 (07:00:52 CET)
The purposes of this study were to identify clinician’s characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the information sources influencing medical decision-making about treatment of schizophrenia. We surveyed 202 psychiatrists during 6 regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic and information sources about their clinical decisions were collected. Most of psychiatrists used second-generation antipsychotic (SGA), and preferentially an oral formulation, in the treatment of schizophrenia. SGA LAI was prescribed to 30.4% of schizophrenic patients. The duration and the type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with the higher use of LAI antipsychotics and the lower use of oral SGA. Personal experience, government regulatory approval and guidelines for the treatment of schizophrenia were the 3 main contributing factors guiding the clinical decision-making of clinicians about treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotic. The development of specialised programmes with top specialists should lead to better use of LAI in the treatment of schizophrenia.
Mon, 24 April 2017
ARTICLE Download: 917| View: 642| Comments: 0 | doi:10.20944/preprints201704.0144.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: alcoholic fatty liver disease; PARP; PJ34; triglyceride
Online: 24 April 2017 (05:30:53 CEST)
The specific role of nicotinamide adenine dinucleotide (NAD) in hepatic triglyceride (TG) accumulation in alcoholic fatty liver disease (AFLD) were unclear. Poly ADP ribose polymerase (PARP) is a NAD-consuming enzyme and its specific role in the pathogenesis of AFLD is still elusive. In current investigation, we found that chronic alcohol exposure enhanced hepatic PARP expression and activity and lowered hepatic NAD+ level. PARP activity inhibitor PJ34 decreased the intracellular TG content in hepatocyte. Moreover, PJ34 suppressed the gene expression of DGAT1 and DGAT2 and elevated the intracellular NAD+ level in hepatocyte. These mechanistic observation was validated in alcohol-fed mice injected with PJ34 intraperitoneally. PJ34 injection attenuated hepatic TG accumulation in alcohol-fed mice. Further, the gene expression of hepatic SERBP-1c, DGAT1 and DGAT2 were lowered by PJ34 injection, while the hepatic NAD+ level was augmented by PJ34 injection in alcohol-fed mice. At last, the nicotinamide riboside supplementation alleviated hepatic TG accumulation in alcohol-fed mice. These data indicate that applying PARP specific inhibitor PJ34 by intraperitoneal injection attenuated hepatic NAD+ depletion and TG accumulation in alcohol-fed mice, which might be a potential candidate for AFLD therapy.
Mon, 5 September 2016
ARTICLE Download: 912| View: 1257| Comments: 2 | doi:10.20944/preprints201609.0014.v1
Subject: Medicine & Pharmacology, Other Keywords: HIV/AIDS; testing; trends; Behavioral Risk Factor Surveillance System; socio-demographic; Georgia
Online: 5 September 2016 (11:21:36 CEST)
Georgia is ranked fifth highest among states for rates of HIV diagnosis. About 4% of persons living with HIV infection in the United States reside in Georgia, and almost 19% of these people do not know their HIV status. The present study examined the trends and associated factors of HIV testing among adults in Georgia between 2010 and 2014 by analyzing data of the Behavioral Risk Factor Surveillance System (BRFSS). A total of 30,791 persons aged ≥18 years were identified who responded to the question “Have you ever been tested for HIV?” Overall, there were 11,543 respondents who had been tested for HIV, with a decrease in percentage from 49.4% in 2010 to 43.7% in 2014 (p<0.001). Factors associated with HIV testing were being black (p<0.001), being younger than 55 years (p<0.001), single (p=0.02), attaining education level above high school (P<0.001), engaging in HIV high-risk behaviors (p<0.001), and not having healthcare coverage (p=0.03). Overall in Georgia, there has been a decline in the temporal trend of HIV testing, and more than half of adults have never been tested for HIV. For reducing HIV transmission in Georgia, enhancing access and utilization of HIV testing should be a public health priority.
Sat, 13 August 2016
ARTICLE Download: 909| View: 850| Comments: 0 | doi:10.20944/preprints201608.0122.v1
Subject: Medicine & Pharmacology, Other Keywords: oral health; quality of life; postmenopausal women
Online: 13 August 2016 (03:14:09 CEST)
Interrelationships between traditional dental variables are becoming more evident in far reaching aspects of life such as psychosocial interaction, self-esteem, overall health and even occupational performance. This study compares quality of life (QoL) in postmenopausal women (PMW) with poor oral health (POH) with QoL in PMW with good oral health. 200 randomly recruited PMW received a dental evaluation and completed Utian Quality of Life Survey. The participants were divided into POH and healthy groups based on dental exam. Mean scores were calculated for each QoL item, domain and the overall summary score. For each of the four parameters for periodontitis diagnosis, periodontitis patients’ QoL outcomes were compared to those of healthy patients using T-test with threshold of significance at p<0.05. QoL in all fields measured were significantly poorer in the POH compared to the healthy patients, occupational (19.95±5.35vs. 27.56±6.13), health (18.02±8.23 vs. 26.59 ±6.45), emotional (15.68±10.22vs. 21.15±9.15), sexual (6.2±5.98vs. 10.02±5.35), and total score (60.21±25.85 vs. 84.26±22.35). This study finds that PMW with POH, report significantly poorer quality of life. Clinicians caring for PMW should be aware of that oral health impacts QoL and make appropriate referral decisions for patients’ dental care. Keywords: Quality of Life, Oral Health, Post-menopause, Women
Mon, 19 December 2016
REVIEW Download: 907| View: 962| Comments: 0 | doi:10.20944/preprints201612.0099.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: aging; bioactive nutrients; dietary; nutrigenomics; Oxiinflammaging
Online: 19 December 2016 (09:37:23 CET)