Intensification mechanisms and moisture dynamics of super cyclonic storm 'Amphan' over the Bay of Bengal: Implications for aerosol re-distribution.

The present research investigates the dynamics and underlying causes contributing to the exceptional intensity of Super Cyclonic Storm (SuCS) Amphan (16th to 21st May 2020) over the Bay of Bengal (BoB), as well as its impact on aerosol redistribution along the four cities of eastern coast and north-eastern India. Notably, the SuCS was formed during the first phase of the COVID-19 lockdown in India, giving it a unique aspect of study and analysis. Our analysis based on 30 years of climatology data from Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2) reanalysis reveals 'positive' monthly anomalous winds (0.8 to 1.6 m/s) prevailed over the central BoB for May 2020. The present study further found the evolution of 'barrier layer thickness'(BLT) leading up to landfall, noting a thickening trend from 8 to 3 days before landfall, contributing to maintaining warmer sea surface temperatures near the coast. Additionally, utilizing European Centre for Medium-Range Weather Forecasts (ECMWF), reanalysis version-5 (ERA-5) data, a mean positive sea surface temperature (SST) anomaly of 0.8 to 1 °C was observed 'before' cyclone period (10-15 May 2020) near the cyclogenesis point. A detailed examination of Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) vertical cross-section plots during the cyclone's intensification stage reveals the presence of high-altitude clouds composed primarily of ice crystals. Further, analysis also indicates that the cyclone transported Sea-salt PM2.5 aerosols from the ocean, dispersing them in the landfall region.The aerosol optical Depth (AOD) data obtained from the National Aeronautics and Space Administration's (NASA) 'Clouds and the Earth's Radiant Energy System (CERES)' mission and MERRA-2 were also analysed, revealing that the cyclone redistributed aerosols over the Bengal basin region (mainly over 'Kolkata') and three other nearby cities along the track of the cyclone (i.e., Bhubaneswar (Odisha) Agartala (Tripura) and Shillong (Meghalaya) respectively).

Photoresponse of Carbon Nanofiber-Based Photodetector and Its Enhancement on CuNi Nanoparticle Adsorption.

We explore the photodetection properties of a carbon nanofiber (CNF)-based p-CNF/n-Si heterojunction device in the 400-800 nm wavelength range and investigate the changes brought in by adsorption of CuNi (CN) nanoparticles on the CNFs. The nanoparticles and CN-CNF nanocomposites were synthesized by using chemical hydrothermal routes. The p-type semiconducting nature of the CNFs and nanocomposites was determined using X-ray photoelectron (XPS) and UV-vis spectroscopies. The p-CNF/n-Si device is found to be better than many carbon-nanotube-based devices in terms of its peak responsivity (0.6 A/W) and gain (1.6), with an acceptably moderate peak detectivity (1.3 × 109 Jones) at 450 nm and a -5 V bias. The p-CN-CNF/n-Si device displays an appreciable enhancement in the photoresponse with respect to the p-CNF/n-Si device, with a peak responsivity of 2.8 A/W, peak detectivity of 9.4 × 109 Jones, and gain of 8. With the aid of valence band XPS and Raman spectra, the enhancement is explainable in terms of a CN to CNF charge transfer and the resulting increase in the built-in potential at the heterojunction.

Novel Small-Molecule ROCK2 Inhibitor GNS-3595 Attenuates Pulmonary Fibrosis in Preclinical Studies.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that leads to respiratory decline caused by scarring and thickening of lung tissues. Multiple pathways contribute to the fibrotic process in this disease, such as inflammation, epithelial-to-mesenchymal transition, and oxidative stress. The Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway is a key regulator of profibrotic signaling, as it affects the organization of actin-myosin and the remodeling of the extracellular matrix. ROCK1/2, a downstream effector of RhoA, is overexpressed in patients with IPF and is a promising target for IPF therapy. However, because of the hypotensive side effects of ROCK1/2 inhibitors, selective ROCK2 compounds are being explored. In this study, we report the discovery of GNS-3595, a potent and selective ROCK2 inhibitor that has ∼80-fold selectivity over ROCK1 at physiological concentrations of ATP. GNS-3595 effectively inhibited ROCK2-mediated phosphorylation of myosin light chain and reduced the expression of fibrosis-related proteins (e.g., collagen, fibronectin, and α-smooth muscle actin) in various in vitro cellular models. GNS-3595 also prevented transforming growth factor ß-induced fibroblast-to-myofibroblast transition. In addition, in a bleomycin-induced mouse model of pulmonary fibrosis, therapeutic exposure to GNS-3595, suppressed lung fibrosis, stabilized body weight loss, and prevented fibrosis-induced lung weight gain. Transcriptome and protein expression analysis from lung tissues showed that GNS-3595 can revert the fibrosis-related gene expression induced by bleomycin. These results indicate that GNS-3595 is a highly potent, selective, and orally active ROCK2 inhibitor with promising therapeutic efficacy against pulmonary fibrosis.

Unveiling Distinctive MRI Characteristics in the Diagnosis of GFAP Astrocytopathy: A Rare Autoimmune Neuroinflammatory Disorder.

Glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune inflammatory disorder affecting the central nervous system, involving the meninges, brain parenchyma, and spinal cord. The distinctive radiologic feature observed on magnetic resonance imaging (MRI) is characterized by periventricular radial and linear contrast enhancement. This case report details a 45-year-old male who initially exhibited constitutional symptoms, followed by encephalitis, lower limb weakness, and urinary retention. The MRI findings revealed meningoencephalitis with longitudinal extensive myelitis. Notably, the cerebrospinal fluid analysis confirmed the presence of anti-GFAP antibodies.

Impact of Daily Growth Hormone Adherence on Height Velocity Among Children With Growth Hormone Deficiency (GHD).

OBJECTIVE: To describe adherence to daily somatropin treatment and impact on height velocity within 1 year of treatment start among patients with pediatric growth hormone deficiency in a real-world US population. METHODS: This retrospective cohort study included pediatric patients aged ≥3 years to <16 years with pediatric growth hormone deficiency prescribed somatropin by a pediatric endocrinologist at a US-based center of excellence between January 1, 2015 and December 31, 2020. Patient data were collected using hospital electronic health records linked to a specialty pharmacy patient prescription records. Adherence, evaluated over 12 months, was measured using the proportion of days covered metric and patients were categorized as adherent if their proportion of days covered ≥80%. Height velocity was annualized to compare across adherent and nonadherent patients. RESULTS: One hundred eighty-one patients were identified and included in this study, of which 70.2% were male,73.5% were white, and mean age (standard deviation [SD]) at index was 12.1 (2.8). In the height velocity analysis, 174 patients were included and the mean (SD) annualized change in height was 10.2 (5.7) cm/y in the adherent group (n = 108) and 9.8 (7.6) in the nonadherent group (n = 66). The difference in height velocity between the groups was not statistically significant. CONCLUSIONS: Minor improvements in average height velocity were observed in the patient group who were adherent to somatropin therapy, although not statistically significant. Lack of observed significance may be due to small sample sizes, short observation period, a likely heterogenous population in terms of growth hormone prescribing, data bias due to single-center origin, or potential patient misclassification.

Withanolides production by the endophytic fungus Penicillium oxalicum associated with Withania somnifera (L.) Dunal.

Withanolides are steroidal lactones with diverse bioactive potential and their production from plant sources varies with genotype, age, culture conditions, and geographical region. Endophytic fungi serve as an alternative source to produce withanolides, like their host plant, Withania somnifera (L.) Dunal. The present study aimed to isolate endophytic fungi capable of producing withanolides, characterization and investigation of biological activities of these molecules. The methanolic fungal crude extract of one of the fungal isolates WSE16 showed maximum withanolide production (219 mg/L). The fungal isolate WSE16 was identified as Penicillium oxalicum based on its morphological and internal transcribed spacer (ITS) sequence analysis and submitted in NCBI (accession number OR888725). The methanolic crude extract of P. oxalicum was further purified by column chromatography, and collected fractions were assessed for the presence of withanolides. Fractions F3 and F4 showed a higher content of withanolides (51.8 and 59.1 mg/L, respectively) than other fractions. Fractions F3 and F4 exhibited antibacterial activity against Staphylococcus aureus with an IC50 of 23.52 and 17.39 µg/ml, respectively. These fractions also showed antioxidant activity (DPPH assay with IC50 of 39.42 and 38.71 µg/ml, superoxide anion scavenging assay with IC50 of 41.10 and 38.84 µg/ml, and reducing power assay with IC50 of 42.61 and 41.40 µg/ml, respectively) and acetylcholinesterase inhibitory activity (IC50 of 30.34 and 22.05 µg/ml, respectively). The withanolides present in fraction 3 and fraction 4 were identified as (20S, 22R)-1a-Acetoxy-27-hydroxywitha-5, 24-dienolide-3b-(O-b-D-glucopyranoside) and withanamide A, respectively, using UV, FTIR, HRMS, and NMR analysis. These results suggest that P. oxalicum, an endophytic fungus isolated from W. somnifera, is a potential source for producing bioactive withanolides.

Validity of Montreal Cognitive Assessment to Detect Cognitive Impairment in Individuals with Type 2 Diabetes.

INTRODUCTION: Guidelines recommend screening older people (> 60-65 years) with type 2 diabetes (T2D) for cognitive impairment, as it has implications in the management of diabetes. The Montreal Cognitive Assessment (MoCA) is a sensitive test for the detection of mild cognitive impairment (MCI) in the general population, but its validity in T2D has not been established. METHODS: We administered MoCA to patients with T2D (age ≥ 60 years) and controls (no T2D), along with a culturally validated neuropsychological battery and functional activity questionnaire. MCI was defined as performance in one or more cognitive domains ≥ 1.0 SD below the control group (on two tests representing a cognitive domain), with preserved functional activities. The discriminant validity of MoCA for the diagnosis of MCI at different cut-offs was ascertained. RESULTS: We enrolled 267 patients with T2D and 120 controls; 39% of the participants with T2D met the diagnostic criteria for MCI on detailed neuropsychological testing. At the recommended cut-off on MoCA (< 26), the sensitivity (94.2%) was high, but the specificity was quite low (29.5%). The cut-off score of < 23 showed an optimal trade-off between sensitivity (69.2%), specificity (71.8%), and diagnostic accuracy (70.8%). The cut-off of < 21 exhibited the highest diagnostic accuracy (74.9%) with an excellent specificity (91.4%), a good positive and negative predictive value (78.5% and 73.7%, respectively). CONCLUSIONS: The recommended screening cut-off point on MoCA of < 26 has a suboptimal specificity and may increase the referral burden in memory clinics. A lower cut-off of < 21 on MoCA maximizes the diagnostic accuracy. Interactive Visual Abstract available for this article.

Type 2 diabetes (T2D) is a risk factor for cognitive dysfunction which potentially impacts diabetes self-management skills. Guidelines recommend screening older adults with diabetes for early detection of cognitive impairment. For screening cognitive impairment in busy endocrine clinics, we need a test that is easy and rapid to administer, sensitive enough to pick the cognitive deficits of T2D and at the same time gives less false-positive outcomes. The Montreal Cognitive Assessment (MoCA) scale is a widely available cognitive screening tool, but there are no studies evaluating its discriminant properties in people with diabetes. We evaluated the performance metrics of MoCA in this population. We found mild cognitive impairment in four out of ten participants with T2D at or above 60 years of age. At the recommended cut-off on MoCA (< 26), the sensitivity was high, but the specificity quite low. We found better diagnostic accuracy at lower cut-offs (20/21), with high specificity but a lower sensitivity. At this cut-off, approximately one out of five people screened using MoCA would require detailed neuropsychological testing, and four out of five who undergo detailed evaluation would have true cognitive impairment.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

A Systematic Review of the Statistical Methods Adopted for Analyzing Follow-Up Data in Cohort Multiple Randomized Controlled Trial.

BACKGROUND: The cohort multiple randomized controlled trial (cmRCT) can tackle some of the weaknesses of an RCT which has triggered the interest of researchers considerably over time. Several challenges persist regarding the methods of analyzing such valued data. The paucity of international recommendations concerning the statistical methods for analyzing trial data has led to a variety of strategies further complicating the result comparison. Our aim was to review the different cmRCT analysis methods since cmRCT was first proposed in 2010. METHODOLOGY: A search for full-length studies presenting statistical analysis of the data collected adopting a cmRCT design was conducted on PubMed, Cochrane Library, EMBASE, JSTOR, Scopus, MEDLINE, and ClinicalTrials.gov. RESULTS: Out of 186 studies screened, we selected 22 for the full-text screening and 11 were found eligible for data extraction. All 11 studies were conducted in high-income countries, reflecting the design being underutilized in other settings. All of the studies were found to have used intention-to-treat (ITT) analysis with four of them utilizing instrumental variables (IV) analysis or a complier average causal effect (CACE). Randomization was noted often to be interchangeably used for random selection. Sample size calculation was not clearly specified in the majority of the studies. CONCLUSION: Clarity regarding the distinction between an RCT and a cmRCT is warranted. The fundamental difference in design, which leads to certain biases that need to be taken care of by adopting IV or CACE analysis, has to be understood before taking up a cmRCT.

Video Teleconference Administration of the Addenbrooke's Cognitive Examination-III for the Assessment of Neuropsychological Status: An Experience in Indian Subjects with Cognitive Dysfunction.

Objective: To determine the feasibility, reliability, and acceptability of video teleconference (VTC)-based neuropsychological assessment using Addenbrooke's cognitive examination-III (ACE-III). Methods: This study was performed from January 2022 to April 2022, during the third wave of the COVID-19 pandemic in India. We administered ACE-III using video-teleconferencing and compared the scores to face-to-face (FTF) testing for the eligible participants. We also conducted a participant's satisfaction survey of VTC-administered ACE-III compared to FTF-administered ACE-III, using a 7-point Likert scale. Results: We screened 37 participants and 24 (64.9%) successfully underwent ACE-III testing through VTC. We included 20 patients (mean age: 62.7 ± 10 years, mean education: 12.0 ± 4.6 years, 85% men) for final analysis, (who completed both VTC and FTF-administered ACE-III). Nine patients had major neurocognitive disorder (dementia), eight had mild neurocognitive disorder (MCI), and three had subjective cognitive decline (SCD). The two tests were administered at a median gap of 36 (18,74.5) days. The Intraclass correlation coefficients (ICC) of ACE-3 total scores (0.97) and the subdomain scores was high (>0.8). There was "very low" to "no" bias on the Bland-Altman plots, across all domains. The mean overall satisfaction score was 4.1, indicating that VTC is "as good as" FTF. Conclusions: Results support the feasibility and acceptability of remote administration of ACE-III via VTC. There is a good agreement between the ACE-III scores across VTC and in-person conditions.

Does Coherence Affect the Multielectron Oxygen Reduction Reaction?

The oxygen reduction reaction (ORR) is the key for oxygen-based respiration and the operation of fuel cells. It involves the transmission of two pairs of electrons. We probed what type of interaction between the electrons is required to enable their efficient transfer into the oxygen. We show experimentally that the transfer of the electrons is controlled by the "hidden property" and present a theoretical model suggesting that it is related to coherent phase relations between the two electrons. Using spin polarization electrochemical measurements, with electrodes coated with different thicknesses of chiral coating, we confirm the special relation between the electrons. This relation is destroyed by multiple scattering events that result in the formation of hydrogen peroxide, which indicates a reduction in the ORR efficiency. Another indication for the possible role of coherence is the fluctuations in the reaction efficiency as a function of thickness of the chiral coated electrode.

Genotyping, in silico screening and molecular dynamics simulation of SNPs of MGMT and ERCC1 gene in lung cancer patients treated with platinum-based doublet chemotherapy.

Lung cancer, the leading cause of death worldwide, arises from an intricate combination of genetic and environmental factors. Genetic variations can influence the chemotherapeutic response of lung cancer patients in DNA repair genes. This study examines the response to platinum-based drugs among lung cancer patients of North Indian descent who possess genetic variations in the MGMT and ERCC1 genes. P CR-RFLP method was used for genotypic analysis. MedCalc statistical software was used to calculate odds ratios and Median Survival Time (MST). GROMACS software was used to perform Molecular dynamic simulation. ADCC Patients revealed a significant association with MGMT in the heterozygous genotype (HR= 1.56, p=0.02) and also with ERCC1 in both mutant and combined variants (HR= 1.25, p=0.01; HR=0.78, p=0.03). SQCC subjects harbouring ERCC1 polymorphism also reported a 2-fold increase in hazard ratio and a corresponding decrease in survival time for heterozygous and combined variants (HR= 2.55, p=0.02; HR 2.33, p=0.01, respectively). MD simulation results demonstrate a lower RMSD, stable radius of gyration, and lower RMSF, indicating the mutated MGMT protein is more stable than the wild. Further, the docking score for DNA-Wild and DNA-L84F mutants are -201.6 and -131.8, respectively. MD Simulation of the complexes further validated the results. Our study concludes that MGMT and ERCC1 polymorphisms are associated with decreased overall survival. Further, computational analysis of MGMT (rs12917) polymorphism revealed that mutated MGMT cannot bind properly to the DNA and hence cannot properly repair DNA, resulting in lower overall survival.Communicated by Ramaswamy H. Sarma.

Neuropathic Tremor in Guillain-Barré Syndrome.

Background: Neuropathic Tremor (NT) is a postural/kinetic tremor of the upper extremity, often encountered in patients with chronic neuropathies such as paraprotein-associated and hereditary neuropathies. Objectives: To describe the clinical and electrophysiological features of NT in a previously underrecognized setting- during recovery from Guillain-Barré Syndrome (GBS). Methods: Patients with a documented diagnosis of GBS in the past, presenting with tremor were identified from review of clinical records. Participants underwent structured, videotaped neurological examination, and electrophysiological analysis using tri-axial accelerometry-surface electromyography. Tremor severity was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale. Results: We describe the clinical and electrophysiological features of 5 patients with GBS associated NT. Our cohort had a fine, fast, and slightly jerky postural tremor of frequency ranging from 8 to 10 Hz. Dystonic posturing and overflow movements were noted in 4/5 patients. Tremor appeared 3 months-5 years after the onset of GBS, when patients had regained near normal muscle strength and deep tendon jerks were well elicitable. Electrophysiological analysis of tremor strongly suggested the presence of a central oscillator in all patients. Conclusion: NT is not limited to chronic inflammatory or hereditary neuropathies and may occur in the recovery phase of GBS. The tremor is characterized by a high frequency, jerky postural tremor with dystonic posturing. Electrophysiological evaluation suggests the presence of a central oscillator, hypothetically the cerebellum driven by impaired sensorimotor feedback.

Escalate: Linezolid as an add on treatment in the intensive phase of tubercular meningitis. A randomized controlled pilot trial.

Most drugs used in the treatment of Tuberculous Meningitis have limited CNS penetration thereby limiting efficacy. CSF penetration of linezolid is 80-100%.The study was a prospective, randomized, open label with blinded outcome assessment pilot trial carried out in patients with TBM. Patients were randomized in a 1:1 ratio into two treatment groups either to receive standard ATT alone or add on oral 600 mg BD Linezolid for 4 weeks along with standard four drug ATT [HRZE/S]. Primary outcome was safety and mortality at the end of one and three months measured by intention to treat analysis. 29 patients were recruited and 27 completed three months of follow up. There was no significant difference in terms of mortality with Odds ratio (95% CI) of 2 (0.161-24.87; p = 1) at one month and 0.385 (0.058-2.538; p = 0.39) at three months. There was a significant improvement in GCS in Linezolid group at one month and mRS within the Linezolid group at one and three months. No major safety concerns were observed. The sample size is underpowered to draw any definitive conclusions but improvement in mRS and GCS as well as mortality change make a case for a large sample size trial.

Goodbye materialism: exploring antecedents of minimalism and its impact on millennials well-being.

The purpose of the study is to explore the antecedents of minimalism and, further, to study the impact of minimalism on millennials' well-being via a sense of fulfilment. To understand the origins of minimalism and its following effects on well-being, a theoretical framework is created. An online survey with a structured questionnaire was created to collect the necessary data from respondents. SMART PLS was used to analyse the suggested framework. This research establishes the mediating role of a sense of fulfilment in the interactions between minimalism and well-being and shows how environmental awareness, contemporary aesthetics, voluntary simplicity, normative influence, and resource sharing positively lead to minimalism. A minimalist lifestyle will help to preserve precious resources, reduce waste, and lower carbon emissions, all of which will have a significant positive influence on the environment. Additionally, clearing up clutter will give them more room and time, which will improve their well-being because they will have more time for their family and interests. The study suggests a thorough model to comprehend the origins of minimalism. Additionally, it established a connection between well-being and minimalism.

Evaluation of structural brain changes and their correlation with cognitive functions in adults with type 1 diabetes stratified by the age of diabetes onset: A cross-sectional study.

BACKGROUND AND AIM: T1DM has a significant effect on brain structure and function. Age of onset of diabetes may be a critical factor mediating this impairment. We evaluated young adults with T1DM, stratified by the age of onset, for structural brain changes, hypothesizing that there may be a spectrum of white matter damage in these participants, compared to controls. METHODS: We recruited adult patients (20-50 years of age at the time of study enrolment) with onset of T1DM before 18 years of age and at least ten years of schooling, along with controls having normoglycaemia. We compared the Diffusion Tensor Imaging parameters between patients and controls and evaluated their correlations with cognitive z scores, and glycemic measures. RESULTS: We evaluated 93 individuals, 69 [age: 24.1 (±4.5) years, gender: 47.8% men, education: 14.7 ± 1.6 years] with T1DM and 24 [age: 27.8 (±5.4) years, gender: 58.3% men, education: 14.6 ± 1.9 years] without T1DM (controls). We did not find any significant correlation of fractional anisotropy (FA) with age at T1D diagnosis, duration of diabetes, current glycemic status, or domain-wise cognitive z scores. The FA was lower (but not statistically significant) in participants with T1DM when evaluated for the whole brain, individual lobes, hippocampi and amygdala. CONCLUSION: Participants with T1DM do not show a significant difference in the brain white matter integrity when evaluated in a cohort of young adults with relatively few microvascular complications compared to controls.