399 research outputs found

    Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway : an overview

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    In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.RL thanks the funding support from Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme (NMRC/TCR/008-SERI/2013) and administered by the Singapore Ministry of Health’s National Medical Research Council and Co-operative Basic Research Grant from the Singapore National Medical Research Council (Project No. NMRC/CBRG/0048/2013).info:eu-repo/semantics/publishedVersio

    Cardiovascular Outcomes in Acute Coronary Syndrome and Malnutrition: A Meta-Analysis of Nutritional Assessment Tools

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    Background: There is emerging evidence that malnutrition is associated with poor prognosis among patients with acute coronary syndrome (ACS). // Objectives: This study seeks to elucidate the prognostic impact of malnutrition in patients with ACS and provide a quantitative review of most commonly used nutritional assessment tools. // Methods: Medline and Embase were searched for studies reporting outcomes in patients with malnutrition and ACS. Nutritional screening tools of interest included the Prognostic Nutrition Index, Geriatric Nutritional Risk Index, and Controlling Nutritional Status. A comparative meta-analysis was used to estimate the risk of all-cause mortality and cardiovascular events based on the presence of malnutrition and stratified according to ACS type, ACS intervention, ethnicity, and income. // Results: Thirty studies comprising 37,303 patients with ACS were included, of whom 33.5% had malnutrition. In the population with malnutrition, the pooled mortality rate was 20.59% (95% CI: 14.95%-27.67%). Malnutrition was significantly associated with all-cause mortality risk after adjusting for confounders including age and left ventricular ejection fraction (adjusted HR: 2.66, 95% CI: 1.78-3.96, P = 0.004). There was excess mortality in the group with malnutrition regardless of ACS type (P = 0.132), ethnicity (P = 0.245), and income status (P = 0.058). Subgroup analysis demonstrated no statistically significant difference in mortality risk between individuals with and without malnutrition (P = 0.499) when using Controlling Nutritional Status (OR: 7.80, 95% CI: 2.17-28.07, P = 0.011), Geriatric Nutritional Risk Index (OR: 4.30, 95% CI: 2.78-6.66, P < 0.001), and Prognostic Nutrition Index (OR: 4.67, 95% CI: 2.38-9.17, P = 0.023). // Conclusions: Malnutrition was significantly associated with all-cause mortality risk following ACS, regardless of ACS type, ethnicity, and income status, underscoring the importance of screening and interventional strategies for patients with malnutrition

    α-cell glucokinase suppresses glucose-regulated glucagon secretion

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    Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of K javax.xml.bind.JAXBElement@dee6e8 channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. αGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an α-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype

    Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

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    BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

    China’s private institutions for the education of health professionals: a time-series analysis from 1998 to 2012

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    Abstract Background Public institutions have been the major provider of education for health professionals in China for most of the twentieth century. In the 1990s, the Chinese government began to encourage the establishment of private education institutions, which have been steadily increasing in numbers over the past decade. However, there is a lack of authoritative data on these institutions and little has been published in international journals on the current status of private education of health professionals in China. In light of this knowledge gap, we performed a quantitative analysis of private institutions in China that offer higher education of health professionals. Methods Using previously unreleased national data provided by the Ministry of Education of China, we conducted time-series and descriptive analyses to study the scale, structure and educational resources from 1998 to 2012 of private institutions for health professional education. Results The number of private institutions that educate health professionals increased from two in 1999 to 123 in 2012. Private institutions displayed an average annual growth rate of 44.2% for enrolment, 59.0% for the number of students and 53.3% for the number of graduates. In 2012, nursing, clinical medicine and traditional Chinese medicine had the most students (37.2%, 32.8% and 8.9% respectively), representing 78.9% of all students in these institutions. Ninety-seven private institutions located in the more economically advantaged eastern and central China and only 26 ones were in the less economically advantaged western China, respectively turning out 85.2% and 14.8% of health professional graduates. There were less educational resources, such as the number of faculty members, physical space and assets, at private institutions than at public institutions. Conclusions Private institutions for the education of health professionals have emerged quickly in China, contributing to the demand for health professionals that exceeds what public institutions are able to offer. At the same time, the imbalance of geographical distribution and poor educational resources of private institutions are of concern. It may be of utmost importance to enhance administration and supervision to better regulate private institutions and their development plans. Future studies may be needed to better examine the effects of private institutions on the production and allocation of health workers.https://deepblue.lib.umich.edu/bitstream/2027.42/145446/1/12960_2018_Article_308.pd

    Accurate Prediction of Protein Structural Class

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    Because of the increasing gap between the data from sequencing and structural genomics, the accurate prediction of the structural class of a protein domain solely from the primary sequence has remained a challenging problem in structural biology. Traditional sequence-based predictors generally select several sequence features and then feed them directly into a classification program to identify the structural class. The current best sequence-based predictor achieved an overall accuracy of 74.1% when tested on a widely used, non-homologous benchmark dataset 25PDB. In the present work, we built a multiple linear regression (MLR) model to convert the 440-dimensional (440D) sequence feature vector extracted from the Position Specific Scoring Matrix (PSSM) of a protein domain to a 4-dimensinal (4D) structural feature vector, which could then be used to predict the four major structural classes. We performed 10-fold cross-validation and jackknife tests of the method on a large non-homologous dataset containing 8,244 domains distributed among the four major classes. The performance of our approach outperformed all of the existing sequence-based methods and had an overall accuracy of 83.1%, which is even higher than the results of those predicted secondary structure-based methods

    Mangrove trees affect the community structure and distribution of anammox bacteria at an anthropogenic-polluted mangrove in the Pearl River Delta reflected by 16S rRNA and hydrazine oxidoreductase (HZO) encoding gene analyses

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    Anaerobic ammonium oxidizing (anammox) bacterial community structures were investigated in surface (1–2 cm) and lower (20–21 cm) layers of mangrove sediments at sites located immediately to the mangrove trees (S0), 10 m (S1) and 1000 m (S2) away from mangrove trees in a polluted area of the Pearl River Delta. At S0, both 16S rRNA and hydrazine oxidoreductase (HZO) encoding genes of anammox bacteria showed high diversity in lower layer sediments, but they were not detectable in lower layer sediments in mangrove forest. S1 and S2 shared similar anammox bacteria communities in both surface and lower layers, which were quite different from that of S0. At all three locations, higher richness of anammox bacteria was detected in the surface layer than the lower layer; 16S rRNA genes revealed anammox bacteria were composed by four phylogenetic clusters affiliated with the “Scalindua” genus, and one group related to the potential anammox bacteria; while the hzo genes showed that in addition to sequences related to the “Scalindua”, sequences affiliated with genera of “Kuenenia”, “Brocadia”, and “Jettenia” were also detected in mangrove sediments. Furthermore, hzo gene abundances decreased from 36.5 × 104 to 11.0 × 104 copies/gram dry sediment in lower layer sediments while increased from below detection limit to 31.5 × 104 copies/gram dry sediment in lower layer sediments from S0 to S2. The results indicated that anammox bacteria communities might be strongly influenced by mangrove trees. In addition, the correlation analysis showed the redox potential and the molar ratio of ammonium to nitrite in sediments might be important factors affecting the diversity and distribution of anammox bacteria in mangrove sediments

    Lack of Wdr13 Gene in Mice Leads to Enhanced Pancreatic Beta Cell Proliferation, Hyperinsulinemia and Mild Obesity

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    WD-repeat proteins are very diverse, yet these are structurally related proteins that participate in a wide range of cellular functions. WDR13, a member of this family, is conserved from fishes to humans and localizes into the nucleus. To understand the in vivo function(s) of Wdr13 gene, we have created and characterized a mutant mouse strain lacking this gene. The mutant mice had higher serum insulin levels and increased pancreatic islet mass as a result of enhanced beta cell proliferation. While a known cell cycle inhibitor, p21, was downregulated in the mutant islets, over expression of WDR13 in the pancreatic beta cell line (MIN6) resulted in upregulation of p21, accompanied by retardation of cell proliferation. We suggest that WDR13 is a novel negative regulator of the pancreatic beta cell proliferation. Given the higher insulin levels and better glucose clearance in Wdr13 gene deficient mice, we propose that this protein may be a potential candidate drug target for ameliorating impaired glucose metabolism in diabetes
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