A rare case of renal thrombotic microangiopathy associated with Castleman’s disease

BACKGROUND: Castleman’s disease (CD) is an uncommon, heterogeneous lympho-proliferative disorder leading to high circulating levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). Renal involvement has been only described in a limited number of small studies. Herein, we report a rare case of renal thrombotic microangiopathy (TMA) associated with CD and investigate the podocyte expression of VEGF in the renal biopsy prior to initiation of treatment. CASE PRESENTATION: An 18-year-old male presented with fever, diarrhea, diffuse lymphadenopathy, ascites and acute kidney injury. Laboratory tests for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura were negative. The kidney biopsy showed TMA. An excisional lymph node biopsy was consistent with CD, plasma cell variant. Immunofluorescence staining showed suppressed podocyte VEGF expression. Chemotherapy that inhibits production of inflammatory mediators including IL-6 and VEGF led to complete recovery of renal function. CONCLUSIONS: Our case illustrates a rare renal histological feature of CD. IL-6 and VEGF are postulated to suppress glomerular VEGF expression, thereby causing renal TMA. Therapy directed against these inflammatory mediators may have important therapeutic implications

Length-scale Dependence of Stokes-Einstien Breakdown in Active Glass-forming Liquids

Stokes-Einstein (SE) relation, which relates diffusion constant with the viscosity of a liquid at high temperatures in equilibrium, is violated in the supercooled temperature regime. Whether this relation is obeyed in nonequilibrium active liquids is a question of significant current interest to the statistical physics community trying to develop the theoretical framework of nonequilibrium statistical mechanics. Via extensive computer simulations of model active glass-forming liquids in three dimensions, we show that SE is obeyed at a high temperature similar to the equilibrium behaviour, and it gets violated in the supercooled temperature regimes. The degree of violation increases systematically with the increasing activity which quantifies the amount the system is driven out of equilibrium. First passage-time (FPT) distributions helped us to gain insights into this enhanced breakdown from the increased short-time peak, depicting hoppers. Subsequently, we study the wave vector dependence of SE relation and show that it gets restored at a wave vector that decreases with increasing activity, and the cross-over wave vector is found to be proportional to the inverse of the dynamical heterogeneity length scale in the system. Our work showed how SE violation in active supercooled liquids could be rationalized using the growth of dynamic length scale, which is found to grow enormously with increasing activity in these systems

A Novel Method to Probe the Pronounced Growth of Correlation Lengths in an Active Glass-forming Liquids using Elongated Probe

The growth of correlation lengths in equilibrium glass-forming liquids near the glass transition is considered a critical finding in the quest to understand the physics of glass formation. These understandings helped us understand various dynamical phenomena observed in supercooled liquids. It is known that at least two different length scales exist - one is of thermodynamic origin, while the other is dynamical in nature. Recent observations of glassy dynamics in biological and synthetic systems where the external or internal driving source controls the dynamics, apart from the usual thermal noise, led to the emergence of the field of active matter. A question of whether the physics of glass formation in these active systems is also accompanied by growing dynamic and static lengths is indeed timely. In this article, we probe the growth of dynamic and static lengths in a model active glass system using rod-like elongated probe particles, an experimentally viable method. We show that the dynamic and static lengths in these non-equilibrium systems grow much more rapidly than their passive counterparts. We then offer an understanding of the violation of the Stokes-Einstein relation and Stokes-Einstein-Debye relation using these lengths via a scaling theory

Endogenous RGS proteins enhance acute desensitization of GABAB receptor-activated GIRK currents in HEK-293T cells

The coupling of GABAB receptors to G-protein-gated inwardly rectifying potassium (GIRK) channels constitutes an important inhibitory pathway in the brain. Here, we examined the mechanism underlying desensitization of agonist-evoked currents carried by homomeric GIRK2 channels expressed in HEK-293T cells. The canonical GABAB receptor agonist baclofen produced GIRK2 currents that decayed by 57.3±1.4% after 60s of stimulation, and then deactivated rapidly (time constant of 3.90±0.21s) upon removal of agonist. Surface labeling studies revealed that GABAB receptors, in contrast to µ opioid receptors (MOR), did not internalize with a sustained stimulation for 10 min, excluding receptor redistribution as the primary mechanism for desensitization. Furthermore, heterologous desensitization was observed between GABAB receptors and MOR, implicating downstream proteins, such G-proteins or the GIRK channel. To investigate the G-protein turnover cycle, the non-hydrolyzable GTP analogue (GTPγS) was included in the intracellular solution and found to attenuate desensitization to 38.3±2.0%. The extent of desensitization was also reduced (45.3±1.3%) by coexpressing a mutant form of the Gαq G-protein subunit that has been designed to sequester endogenous RGS proteins. Finally, reconstitution of GABAB receptors with Gαo G-proteins rendered insensitive to RGS resulted in significantly less desensitization (28.5±3.2%). Taken together, our results demonstrate that endogenous levels of RGS proteins effectively enhance GABAB receptor-dependent desensitization of GIRK current

An Adaptive Task Scheduling in Fog Computing

Internet applications generate massive amount of data. For processing the data, it is transmitted to cloud. Time-sensitive applications require faster access. However, the limitation with the cloud is the connectivity with the end devices. Fog was developed by Cisco to overcome this limitation. Fog has better connectivity with the end devices, with some limitations. Fog works as intermediate layer between the end devices and the cloud. When providing the quality of service to end users, scheduling plays an important role. Scheduling a task based on the end users requirement is a tedious thing. In this paper, we proposed a cloud-fog task scheduling model, which provides quality of service to end devices with proper security

Schools as opportunity for oral health promotion: Existing status in India

Childhood is a significant stage in people’s lives where they are more receptive toward behavior shaping; thus, schools have been considered important foundation in addressing the health and social issues. School oral health education programs have produced affirmative results in improving the overall health of the child. The aim of the current review was to explore the history of school health, models of school health and existing efforts of School Oral Health Programs (SOHP) in India. The review identified five existing SOHP (Indian Dental Association - Colgate’s “Young India” Bright Smiles, Bright Futures, Chacha Nehru Sehat Yojna - School health scheme [Government of Delhi], Neev - SOHP, Intensive Dental Health Care Program - Punjab, Trinity CareFoundation - Bengaluru, National Oral Health Program, AIIMS) which is either running or proposed. It is recommended that the upcoming SOHP should be crafted on the existing evidence-based guidelines and theoretical models of school health. Prompt execution of proposed programs should be the priority to target the optimum oral health of the children.&nbsp

Cone beam computed tomography: An accurate imaging technique in comparison with orthogonal portal imaging in intensity-modulated radiotherapy for prostate cancer

Purpose: Various factors cause geometric uncertainties during prostate radiotherapy, including interfractional and intrafractional patient motions, organ motion, and daily setup errors. This may lead to increased normal tissue complications when a high dose to the prostate is administered. More-accurate treatment delivery is possible with daily imaging and localization of the prostate. This study aims to measure the shift of the prostate by using kilovoltage (kV) cone beam computed tomography (CBCT) after position verification by kV orthogonal portal imaging (OPI).Methods: Position verification in 10 patients with prostate cancer was performed by using OPI followed by CBCT before treatment delivery in 25 sessions per patient. In each session, OPI was performed by using an on-board imaging (OBI) system and pelvic bone-to-pelvic bone matching was performed. After applying the noted shift by using OPI, CBCT was performed by using the OBI system and prostate-to-prostate matching was performed. The isocenter shifts along all three translational directions in both techniques were combined into a three-dimensional (3-D) iso-displacement vector (IDV).Results: The mean (SD) IDV (in centimeters) calculated during the 250 imaging sessions was 0.931 (0.598, median 0.825) for OPI and 0.515 (336, median 0.43) for CBCT, p-value was less than 0.0001 which shows extremely statistical significant difference.Conclusion: Even after bone-to-bone matching by using OPI, a significant shift in prostate was observed on CBCT. This study concludes that imaging with CBCT provides a more accurate prostate localization than the OPI technique. Hence, CBCT should be chosen as the preferred imaging technique.</p

Cone beam computed tomography: An accurate imaging technique in comparison with orthogonal portal imaging in intensity-modulated radiotherapy for prostate cancer

Purpose: Various factors cause geometric uncertainties during prostate radiotherapy, including interfractional and intrafractional patient motions, organ motion, and daily setup errors. This may lead to increased normal tissue complications when a high dose to the prostate is administered. More-accurate treatment delivery is possible with daily imaging and localization of the prostate. This study aims to measure the shift of the prostate by using kilovoltage (kV) cone beam computed tomography (CBCT) after position verification by kV orthogonal portal imaging (OPI).Methods: Position verification in 10 patients with prostate cancer was performed by using OPI followed by CBCT before treatment delivery in 25 sessions per patient. In each session, OPI was performed by using an on-board imaging (OBI) system and pelvic bone-to-pelvic bone matching was performed. After applying the noted shift by using OPI, CBCT was performed by using the OBI system and prostate-to-prostate matching was performed. The isocenter shifts along all three translational directions in both techniques were combined into a three-dimensional (3-D) iso-displacement vector (IDV).Results: The mean (SD) IDV (in centimeters) calculated during the 250 imaging sessions was 0.931 (0.598, median 0.825) for OPI and 0.515 (336, median 0.43) for CBCT, p-value was less than 0.0001 which shows extremely statistical significant difference.Conclusion: Even after bone-to-bone matching by using OPI, a significant shift in prostate was observed on CBCT. This study concludes that imaging with CBCT provides a more accurate prostate localization than the OPI technique. Hence, CBCT should be chosen as the preferred imaging technique

Using nasal povidone-iodine to prevent bloodstream infections and transmission of Staphylococcus aureus among haemodialysis patients: A stepped-wedge cluster randomised control trial protocol

INTRODUCTION: Approximately 38% of haemodialysis patients carry METHODS AND ANALYSIS: We will perform an open-label, stepped-wedge cluster randomised trial to assess the effectiveness of nasal PVI compared with standard care. Sixteen outpatient haemodialysis units will participate in the study. The 3-year trial period will be divided into a 4-month baseline period and eight additional 4-month time blocks. The primary outcome of the study will be ETHICS AND DISSEMINATION: This study has received IRB approval from all study sites. A Data Safety and Monitoring Board will monitor this multicentre clinical trial. We will present our results at international meetings. The study team will publish findings in peer-reviewed journals and make each accepted peer-reviewed manuscript publicly available. TRIAL REGISTRATION NUMBER: NCT04210505