Vitamin D and the Immune System

In the past few decades, various novel actions of vitamin D have been discovered. The mechanism of action of calcitriol or vitamin D is mediated by the Vitamin D receptor (VDR), a subfamily of nuclear receptors, which acts as a transcription factor in the target cells after formation of a heterodimer with the retinoid X receptor (RXR). As the VDR has been found in virtually all cell types, vitamin D exerts multiple actions on different tissues. Vitamin D has important immunomodulatory actions, which includes enhancement of the innate immune system and inhibition of the adaptative immune responses. These actions are associated with an increase in production of interleukin (IL)-4 by T helper (Th)-2 lymphocytes and the up-regulation of regulatory T lymphocytes. Vitamin D can regulate the immune responses in secondary lymphoid organs as well as in target organs through a number of mechanisms. Vitamin D inhibits the expression of APC cytokines, such as interleukin-1 (IL-1), IL-6, IL-12, and tissue necrosis factor- α (TNF-α) and decreases the expression of a set of major histocompatibility complex (MCH) class II cell surface proteins in macrophages. Vitamin D also inhibits B cell differentiation and antibody production. These actions reflect an important role of Vitamin D in balancing the immune system

Integrity and attack-resilience of GPS-based positioning and timing: a Bayesian and measurement fusion approach

Robust Position, Velocity, and Timing (PVT) are essential for the safe operations of critical infrastructure sectors, such as transportation systems and power grids. Different transportation systems, both human-operated and autonomous vehicles, navigate using accurate position and velocity information. On the other hand, precise timing is crucial for various economic activities worldwide, such as banking, stock markets, and the power grid. GPS serves as a backbone for many state-of-the-art applications related to these crucial infrastructures. GPS provides sub-microsecond accurate timing and meter level of accurate positioning. It has global coverage and is free for all users. The GPS positioning and timing service has some limitations. The positioning accuracy degrades in urban environments due to tall structures that block and reflect satellite signals. Degraded positioning is not safe for the operation of autonomously driving vehicles. Furthermore, GPS signals are susceptible to external attacks due to their low signal power and unencrypted signal structures. Researchers have shown that GPS Spoofing Attacks (GSAs) are feasible, and GSA for timing is able to alter timing without modifying the positioning solution. Such attacks create unsafe operating conditions for the modern power grid, which will use GPS timing for monitoring the wide-area network. The contribution of this work is to develop algorithms to mitigate the above limitations. We develop Bayesian algorithms that utilize multiple sensors and receivers. For improving positioning, first, we design an adaptive filter based on Bayesian algorithms to augment GPS with the additional vision sensor. Second, we develop an integrity monitoring algorithm for Direct Positioning (DP), which is an advanced GPS receiver architecture that directly works on the position domain and is robust to signal blockage and multipath effects. To monitor integrity, we estimate vertical protection levels using a Bayesian approach. We further generate GPS datasets simulating open, semi-urban, and urban environments for validating DP with multiple receivers. For mitigating GSAs for timing, we design static and dynamic state estimators for the power grid. The static state estimator utilizes measurement residuals to correct power grid states. In the dynamic state estimator, we fuse GPS and power grid measurements to provide resiliency against GSAs. We create a virtual power grid testbed and generate datasets for a power grid network under different GSAs. These are the first datasets that contain both power grid and GPS measurements under GSAs, and we make them openly available. Our estimators are validated on various power grid networks and on the generated datasets

Revisiting Prostate Cancer in India: A Genomic View

In the recent past, there has been a rise in Prostate Cancer (PCa) in Asia, particularly India.  Although systematic reviews on PCa have dealt on the genetics, genomics and the environmental influence in causal of PCa, no predictive analytics in comparing the PCa from Caucasian, American to Asian population was attempted. In this review article, we have attempted to elaborate this aspect of PCa and deliberated on challenges related to next generation sequencing methods of PCa’s manifestation when compared to the west

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Xanthogranulomatous cholecystitis: challenges in management & feasibility of laparoscopic surgery

Objective: Xanthogranulomatous cholecystitis (XGC) is a rare, unusual and destructive form of chronic cholecystitis. It is clinically indistinguishable from other forms of cholecystitis and hence difficult to diagnose. Due to its propensity to form dense adhesions with stuctures surrounding the gall bladder and mimic malignancy of gall bladder intra-operatively, it’s difficult to manage. This retrospective study was conducted with the aim to review the clinico-pathologic presentation of XGC and the possibility of its laparoscopic management. Patient and methods: All cases of histo-pathologically diagnosed XGC from January 2008 to December 2012 at Sharda Hospital, School of Medical Sciences & Research, Greater Noida were analyzed retrospectively. Results: Sixty two cases of biopsy proved XGC were studied.The mean age at presentation was 56.4 ± 14.3 years (range 30 – 72 years), with a male: female ratio of 1.6:1. Gall bladder wall thickening on ultrasonography was seen in 91.9% cases and all (100%) had cholelithiasis. Laparoscopic cholecystectomy was possible in 18 (29%) cases, with a high conversion rate of 71% to open surgery. Two cases of carcinoma gall bladder accompanying XGC were documented. Both the mean operative time and hospital stay for laparoscopic surgery were longer for cases with XGC (105 minutes & 4.2 days respectively). No mortality occurred during the study period. Conclusion: XGC is difficult to diagnose preoperatively due to lack of distinguishing clinical features and imaging study results. Due to dense peri-cholecystic adhesions laparoscopic surgery though feasible in some cases is difficult to perform with a high conversion rate. Overall morbidity is also increased due to same reasons

Ionospheric effect of earthquakes as determined from ground based TEC measurement and satellite data

63-70Total electron content (TEC) measurements have been carried out at Agra (geographic lattitude 27°N, longitude 78°E), India using a dual frequency GPS receiver since 24 June 2006. Similarly, DEMETER satellite data of electron density and VLF/ULF electromagnetic emission data are available since its launch on 29 June 2004. The effect of earthquake on GPS-TEC and electron density (Ne) data, obtained from DEMETER satellite, has been investigated in the present paper. GPS-TEC and Ne data for seven months, during 01 December 2006-30 June 2007, has been investigated. Two large magnitude earthquakes occurred during this period: one on 08 January 2007 (M=6.0, depth=16 km) and other on 05 May 2007 (M=6.2, depth=09 km) at a distance of 1587 and 887 km, respectively from the observation station at Agra. The results show anomalous enhancements in TEC and Ne 1-4 days before and 1-2 days after the occurrence of these earthquakes. The calculated percentage deviations of TEC and Ne from their monthly mean values are found to vary between 40 and 80% during anomalous enhancements. The observed effect is interpreted in terms of generation of electric fields between the ionosphere and quasi-neutral ion clusters which are formed at troposphere heights by radon gas emanation from seismic region and followed by triggering of these clusters by green house gases. The electric fields so generated penetrate the ionosphere and bring out structural and dynamical changes in ionospheric parameters

Heme polymerization by malarial parasite: a potential target for antimalarial drug development

Fast spreading drug resistance to commonly used antimalarial drugs like chloroquine and pyrimethamine has posed urgent requirement for newer drugs. Identification of critical biochemical processes necessary for parasite survival and their characterization is necessary for targeted drug design. Despite prolonged research, biochemistry of malaria parasite is poorly understood. Many common biochemical pathways, well characterized in other organisms, are yet to be looked at in malaria parasite. Polymerization of heme to form hemozoin pigment is a process unique to Plasmodia. This has attracted much attention in the recent years as a potential target for antimalarial chemotherapy, as specific inhibitors designed against such a process have the chance of high selectivity in interaction with metabolism of the host harbouring the parasite. Although the last word has yet to be said on mechanism of heme polymerization by malaria parasite, a consensus is evolving between various research groups working in this area, about its potential as a target for antimalarial design. In this review we have discussed the problem of heme polymerization and its possible use as a target for drug design as well as provide an account of the work being done in this direction by us as well as other research groups

Can post-operative antibiotic prophylaxis following elective laparoscopic cholecystectomy be completely done away with in the Indian setting? A prospective randomised study

Premise and Objective: Elective laparoscopic cholecystectomy (LC) has low risk for post-operative infectious complications; still most clinicians use persistent post-operative prophylactic antibiotics out of habit, tradition, or simply as defensive practice due to evolving medicolegal implications of a large number of surgeries being showcased as daycare or next day discharge procedures. This randomised prospective trial was done to test the need for such prophylaxis in cases of elective LC in a rural/semi-urban setting. Materials and Methods: Two hundred and ten successive patients undergoing elective LC were randomised into groups receiving single dose of injection ceftriaxone at the time of induction of anaesthesia, (Group A = 112 cases) and those who in addition to above received injection ceftriaxone twice daily for 2 days postoperatively (Group B = 98 cases). Post-operative infectious complications between two groups were compared for variables such as age, sex, body mass index and bile/stone spillage. Results: There was no significant difference in surgical site infection rates between the groups for variables such as age, sex, body mass index, duration of symptoms, American Society of Anesthesiologists grade, duration of surgery and hospital stay. Intraoperative spillage of stones (9.8% [A]: 5.1% [B]) did not increase infectious complications even in the presence of positive bile culture (Group A, N = 7 vs. Group B, N = 3). An operative time of greater than 60 min was found to be associated with increased surgical site infection (P = 0. 0006). Conclusion: Single dose of ceftriaxone at the time of induction is adequate prophylaxis following elective LC even in the rural/semi-urban Indian setting and routine continued administration of antibiotic should be abandoned as it contributes to adverse reactions, drug resistance and unnecessary financial burden

The efficacy and safety of intralesional immunotherapy with measles, mumps, rubella virus vaccine for the treatment of common warts in adults

Background: Most therapeutic modalities for common warts remain unsatisfactory. Objectives: To evaluate efficacy and safety of intralesional MMR (measles, mumps, rubella virus) vaccine in the treatment of common warts in adults. Patients and Methods: There were 110 (M:F = 61:49) patients aged 19–62 years having 1–211 warts over dorsal hands, feet, palms, soles, and periungual skin for 1–252 months. MMR vaccine 0.25 mL was injected intralesionally in the largest wart and repeated at 2-week interval until complete clearance or maximum of five doses. The outcome was evaluated as complete clearance, excellent, good, or unsatisfactory response on visual analog scale at every visit and at 4 and 8 weeks, thereafter by comparing baseline clinical photograph. Likert scale was used for patient satisfaction level assessment similarly. Results: Only 51 patients completed the study and 42 (82.4%) of them showed complete clearance of warts and 9 (17.6%) patients showed good or unsatisfactory response. In 4 (7.8%) patients, the warts subsided completely after one dose itself. The four patients showing excellent response after five doses initially also continued to improve during follow-up period of 8 weeks. Except for injection site pain, no adverse effects were noted. There was no recurrence of warts among cured who were also very much satisfied from treatment. Conclusion: Despite variable results, intralesional MMR vaccine immunotherapy appears another possible safe and effective treatment option for common warts in a set of adult patients with advantages of regression of distant warts, no significant adverse effects and low recurrence. However, well-designed, controlled studies for minimum effective dose and treatment schedule are highly desirable to make any recommendation