A comparative phase 1 clinical trial to identify anti-infective mechanisms of vitamin D in people with HIV infection

Objectives:To determine if there is a biological mechanism that explains the association between HIV disease progression and increased mortality with low circulating vitamin D levels; specifically, to determine if restoring vitamin D levels induced T-cell functional changes important for antiviral immunity.Design:This was a pilot, open-label, three-arm prospective phase 1 study.Methods:We recruited 28 patients with low plasma vitamin D (<50nmol/l 25-hydroxyvitamin D3), comprising 17 HIV+ patients (11 on HAART, six treatment-naive) and 11 healthy controls, who received a single dose of 200000IU oral cholecalciferol. Advanced T-cell flow cytometry methods measured CD4(+) T-cell function associated with viral control in blood samples at baseline and 1-month after vitamin D supplementation.Results:One month of vitamin D supplementation restored plasma levels to sufficiency (>75nmol/l) in 27 of 28 patients, with no safety issues. The most striking change was in HIV+ HAART+ patients, where increased frequencies of antigen-specific T cells expressing macrophage inflammatory protein (MIP)-1 - an important anti-HIV blocking chemokine - were observed, with a concomitant increase in plasma MIP-1, both of which correlated significantly with vitamin D levels. In addition, plasma cathelicidin - a vitamin D response gene with broad antimicrobial activity - was enhanced.Conclusion:Vitamin D supplementation modulates disease-relevant T-cell functions in HIV-infected patients, and may represent a useful adjunct to HAART therapy. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

A delphi study on health in future India

PIP: A delphi study was conducted to identify or envision health scenarios in India by the year 2000. Questionnaires consisting of 48 questions on 5 areas (diagnosis and therapy; family planning; pharmaceuticals and drugs; biochemical and biomedical research; health services) were mailed to 250 experts in India. 36 responded. Results were compiled and mailed back to the respondents for changes and comments. 17 people responded. Results of the delphi study shows that policy decisions with respect to compulsory family planning as well as health education at secondary school level will precede further breakthroughs in birth control technology. Non operation reversible sterilization procedures, immunological birth control, Ayurvedic medicines for contraception and abortion, and selection of baby's sex are all possible by 2000 thereafter. Complete eradication of infectious diseases, malnutrition and associated diseases is considered unlikely before 2000, as are advances in biomedical research. Changes in health services (e.g., significant increases in hospital beds and doctors, cheap bulk drugs), particularly in rural areas, are imminent, leading to prolonging of life expectancy to 70 years. Genetic engineering may provide significant breakthroughs in the prevention of malignancies and cardiac disorders. The India delphi study is patterned after a similar delphi study conducted in the U.S. by Smith, Kline and French (SKF) Laboratories in 1968. The SKF study was able to predict some breakthroughs with basic research which have been realized.

Time reversal technique for health monitoring of metallic structure using Lamb waves

Time reversal active sensing using Lamb waves is investigated for health monitoring of a metallic structure. Experiments were conducted on an aluminum plate to study the time reversal behavior of A(0) and S-0 Lamb wave modes under narrow band and broad band pulse excitation. Damage in the form of a notch was introduced in the plate to study the changes in the characteristics of the time reversed Lamb wave modes experimentally. Time-frequency analysis of the time reversed signal was carried out to extract the damage information. A measure of damage based on wavelet transform was derived to quantify the hidden damage information in the time reversed signal. It has been shown that time reversal can be used to achieve temporal recompression of Lamb waves under broadband signal excitation. Further, the broad band excitation can also improve the resolution of the technique in detecting closely located defects. This is demonstrated by picking up the reflection of waves from the edge of the plate, from a defect close to the edge of the plate and from defects located near to each other. This study shows the effectiveness of Lamb wave time reversal for temporal recompression of dispersive Lamb waves for damage detection in health monitoring applications. (C) 2009 Elsevier B.V. All rights reserved.

Filter design using radial basis function neural network and genetic algorithm for improved operational health monitoring

The problem of denoising damage indicator signals for improved operational health monitoring of systems is addressed by applying soft computing methods to design filters. Since measured data in operational settings is contaminated with noise and outliers, pattern recognition algorithms for fault detection and isolation can give false alarms. A direct approach to improving the fault detection and isolation is to remove noise and outliers from time series of measured data or damage indicators before performing fault detection and isolation. Many popular signal-processing approaches do not work well with damage indicator signals, which can contain sudden changes due to abrupt faults and non-Gaussian outliers. Signal-processing algorithms based on radial basis function (RBF) neural network and weighted recursive median (WRM) filters are explored for denoising simulated time series. The RBF neural network filter is developed using a K-means clustering algorithm and is much less computationally expensive to develop than feedforward neural networks trained using backpropagation. The nonlinear multimodal integer-programming problem of selecting optimal integer weights of the WRM filter is solved using genetic algorithm. Numerical results are obtained for helicopter rotor structural damage indicators based on simulated frequencies. Test signals consider low order polynomial growth of damage indicators with time to simulate gradual or incipient faults and step changes in the signal to simulate abrupt faults. Noise and outliers are added to the test signals. The WRM and RBF filters result in a noise reduction of 54 - 71 and 59 - 73% for the test signals considered in this study, respectively. Their performance is much better than the moving average FIR filter, which causes significant feature distortion and has poor outlier removal capabilities and shows the potential of soft computing methods for specific signal-processing applications. (C) 2005 Elsevier B. V. All rights reserved.

Reproductive behavior and health in consanguineous marriages

In many regions of Asia and Africa, consanguineous marriages currently account for approximately 20 to 50% of all unions, and preliminary observations indicate that migrants from these areas continue to contract marriages with close relatives when resident in North America and Western Europe. Consanguinity is associated with increased gross fertility, due at least in part to younger maternal age at first livebirth. Morbidity and mortality also may be elevated, resulting in comparable numbers of surviving offspring in consanguineous and nonconsanguineous families. With advances in medicine and public health, genetic disorders will account for an increased proportion of disease worldwide. Predictably, this burden will fall more heavily on countries and communities in which consanguinity is strongly favored, as the result of the expression of deleterious recessive genes. However, studies conducted in such populations indicate that the adverse effects associated with inbreeding are experienced by a minority of families.

Differential dynamics of the serotonin(1A) receptor in membrane bilayers of varying cholesterol content revealed by all atom molecular dynamics simulation

The serotonin(1A) receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target in neuropsychiatric disorders. The receptor has been shown to require membrane cholesterol for its organization, dynamics and function. Although recent work suggests a close interaction of cholesterol with the receptor, the structural integrity of the serotonin(1A) receptor in the presence of cholesterol has not been explored. In this work, we have carried out all atom molecular dynamics simulations, totaling to 3s, to analyze the effect of cholesterol on the structure and dynamics of the serotonin(1A) receptor. Our results show that the presence of physiologically relevant concentration of membrane cholesterol alters conformational dynamics of the serotonin(1A) receptor and, on an average lowers conformational fluctuations. Our results show that, in general, transmembrane helix VII is most affected by the absence of membrane cholesterol. These results are in overall agreement with experimental data showing enhancement of GPCR stability in the presence of membrane cholesterol. Our results constitute a molecular level understanding of GPCR-cholesterol interaction, and represent an important step in our overall understanding of GPCR function in health and disease.