Synthesis and Characterization of Drug-Loaded Poly( ε

We produced drug-loaded poly(ε-caprolactone) (PCL)/silica hybrid nanofibrous scaffolds with various silica sol contents (0 vol%, 10 vol%, 15 vol%, and 20 vol%) using electrospinning and examined their physicochemical properties, mechanical properties, drug release behavior, and in vitro biocompatibility to evaluate their potential application for guided bone regeneration (GBR). The loading efficiency of tetracycline hydrochloride (TCH) drug was remarkably enhanced by hybridizing the PCL solution with the silica sol. All produced hybrid scaffolds had a highly nanofibrous structure, in which the silica phase was homogeneously hybridized with the PCL polymer, while preserving their intrinsic characteristics. This led to considerable increases in hydrophilicity and mechanical properties (e.g., ultimate tensile strength and elastic modulus). In addition, the release rate and cumulative maximum amounts of the TCH from the hybrid scaffolds significantly increased with increasing the silica content, while all produced hybrid nanofibrous scaffolds showed good biocompatibility assessed by in vitro cell tests

Ibuprofen intercalation and release from different layered double hydroxides.

AIM: The chemical composition of layered double hydroxides (LDHs) affects their structure and properties. The method of ibuprofen (IBU) intercalation into LDHs may modify its release, reduce adverse effects and decrease the required dosing frequency. METHODOLOGY: This study investigates the effects of four different LDHs; MgAl-LDH, MgFe-LDH, NiAl-LDH and NiFe-LDH on in vitro release of IBU intercalated by coprecipitation and anionic-exchange. RESULTS: MgAl-LDH was the most crystalline and substitution of either cation decreased LDH order. Fourier-transform infrared spectra and power x-ray diffractograms confirmed the intercalation of IBU within the lamellar structure of MgAl-LDH and MgFe-LDH. Intercalation of IBU by anion-exchange resulted in slower, partial, drug release compared with coprecipitation. CONCLUSION: The chemical composition of LDHs affects their crystallinity, IBU intercalation and subsequent release

Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. METHODS: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. RESULTS: Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. CONCLUSIONS: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour

Changes in standard of candidates taking the MRCP(UK) Part 1 examination, 1985 to 2002: Analysis of marker questions

The maintenance of standards is a problem for postgraduate medical examinations, particularly if they use norm-referencing as the sole method of standard setting. In each of its diets, the MRCP(UK) Part 1 Examination includes a number of marker questions, which are unchanged from their use in a previous diet. This paper describes two complementary studies of marker questions for 52 diets of the MRCP(UK) Part 1 Examination over the years 1985 to 2001 to assess whether standards have changed

The predominant learning approaches of medical students

Background By identifying medical students’ learning approaches and the factors that influence students’ learning approaches, medical schools and health care institutions are better equipped to intervene and optimize their learning experience. The aims of our study is to determine the predominant learning approach amongst medical students on a clinical posting in a hospital in Singapore and to examine the demographic factors that affect their learning approach. Methods The Approaches and Study Skills Inventory for Students (ASSIST) questionnaire was administered to 250 medical students from various medical schools on clinical attachment to the Obstetrics and Gynaecology (O&G) department of KK Women’s and Children’s Hospital (KKH) Singapore between March 2013 and May 2015 to determine students’ predominant learning approaches. Multinomial logistic regression was used to examine the association between demographic factors (age, gender and highest education qualification) and predominant learning approach. A cut-off of p \u3c 0.05 was used for statistical significance. Results Amongst 238 students with one predominant learning approach, 96 (40.3%) and 121 students (50.8%) adopted the deep and strategic approach respectively, whilst only 21 (8.8%) adopted the surface approach. Male students appeared less likely to adopt the strategic learning approach than female students (p value = 0.06). Predominant learning approaches were not influenced by demographic characteristics such as age, gender and highest educational qualifications. Conclusions This study provided insight into the learning approaches of a heterogeneous group of medical students in Singapore. While it is encouraging that the majority of students predominantly utilised the deep and strategic learning approach, there was a significant proportion of students who utilised the surface approach. Interventions can be explored to promote deeper learning amongst these students

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Introduction Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. Methods Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile. Results Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head-to-head comparison models. Discussion Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non-demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI

Lower Left Ventricular Ejection Fraction Relates to Cerebrospinal Fluid Biomarker Evidence of Neurodegeneration in Older Adults

BACKGROUND: Subclinical cardiac dysfunction is associated with decreased cerebral blood flow, placing the aging brain at risk for Alzheimer's disease (AD) pathology and neurodegeneration. OBJECTIVE: This study investigates the association between subclinical cardiac dysfunction, measured by left ventricular ejection fraction (LVEF), and cerebrospinal fluid (CSF) biomarkers of AD and neurodegeneration. METHODS: Vanderbilt Memory & Aging Project participants free of dementia, stroke, and heart failure (n = 152, 72±6 years, 68% male) underwent echocardiogram to quantify LVEF and lumbar puncture to measure CSF levels of amyloid-β42 (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau). Linear regressions related LVEF to CSF biomarkers, adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E ɛ4 status. Secondary models tested an LVEF x cognitive diagnosis interaction and then stratified by diagnosis (normal cognitive (NC), mild cognitive impairment (MCI)). RESULTS: Higher LVEF related to decreased CSF Aβ42 levels (β= -6.50, p = 0.04) reflecting greater cerebral amyloid accumulation, but this counterintuitive result was attenuated after excluding participants with cardiovascular disease and atrial fibrillation (p = 0.07). We observed an interaction between LVEF and cognitive diagnosis on CSF t-tau (p = 0.004) and p-tau levels (p = 0.002), whereas lower LVEF was associated with increased CSF t-tau (β= -9.74, p = 0.01) and p-tau in the NC (β= -1.41, p = 0.003) but not MCI participants (p-values>0.13). CONCLUSIONS: Among cognitively normal older adults, subclinically lower LVEF relates to greater molecular evidence of tau phosphorylation and neurodegeneration. Modest age-related changes in cardiovascular function may have implications for pathophysiological changes in the brain later in life

Mine, Yours, Ours? Sharing Data on Human Genetic Variation

The achievement of a robust, effective and responsible form of data sharing is currently regarded as a priority for biological and bio-medical research. Empirical evaluations of data sharing may be regarded as an indispensable first step in the identification of critical aspects and the development of strategies aimed at increasing availability of research data for the scientific community as a whole. Research concerning human genetic variation represents a potential forerunner in the establishment of widespread sharing of primary datasets. However, no specific analysis has been conducted to date in order to ascertain whether the sharing of primary datasets is common-practice in this research field. To this aim, we analyzed a total of 543 mitochondrial and Y chromosomal datasets reported in 508 papers indexed in the Pubmed database from 2008 to 2011. A substantial portion of datasets (21.9%) was found to have been withheld, while neither strong editorial policies nor high impact factor proved to be effective in increasing the sharing rate beyond the current figure of 80.5%. Disaggregating datasets for research fields, we could observe a substantially lower sharing in medical than evolutionary and forensic genetics, more evident for whole mtDNA sequences (15.0% vs 99.6%). The low rate of positive responses to e-mail requests sent to corresponding authors of withheld datasets (28.6%) suggests that sharing should be regarded as a prerequisite for final paper acceptance, while making authors deposit their results in open online databases which provide data quality control seems to provide the best-practice standard. Finally, we estimated that 29.8% to 32.9% of total resources are used to generate withheld datasets, implying that an important portion of research funding does not produce shared knowledge. By making the scientific community and the public aware of this important aspect, we may help popularize a more effective culture of data sharing

Massive stars as thermonuclear reactors and their explosions following core collapse

Nuclear reactions transform atomic nuclei inside stars. This is the process of stellar nucleosynthesis. The basic concepts of determining nuclear reaction rates inside stars are reviewed. How stars manage to burn their fuel so slowly most of the time are also considered. Stellar thermonuclear reactions involving protons in hydrostatic burning are discussed first. Then I discuss triple alpha reactions in the helium burning stage. Carbon and oxygen survive in red giant stars because of the nuclear structure of oxygen and neon. Further nuclear burning of carbon, neon, oxygen and silicon in quiescent conditions are discussed next. In the subsequent core-collapse phase, neutronization due to electron capture from the top of the Fermi sea in a degenerate core takes place. The expected signal of neutrinos from a nearby supernova is calculated. The supernova often explodes inside a dense circumstellar medium, which is established due to the progenitor star losing its outermost envelope in a stellar wind or mass transfer in a binary system. The nature of the circumstellar medium and the ejecta of the supernova and their dynamics are revealed by observations in the optical, IR, radio, and X-ray bands, and I discuss some of these observations and their interpretations.Comment: To be published in " Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars; ed. by Aruna Goswami & Eswar Reddy, Springer Verlag, 2009. Contains 21 figure