Larvicidal Activity of Methanol and Chloroform Extract of Swertia celiata against Three Mosquito Vectors

Background: Mosquitoes are an important public health concern as they spread life-threatening diseases such as malaria, filaria, Japanese encephalitis, dengue fever, chikungunya, and yellow fever. In the last decades, synthetic insecticides were extensively used for the control of these vector-borne diseases but it also reported the detrimental side-effects in human beings and pet animals. To overcome the side effects, plants-derived secondary metabolites were screened and tested for insecticidal properties. The present study deals with the insecticidal activity of chloroform and methanol extracts of Swertia celiata leaves against Culex quenquifasciatus, Aedes aegypti, and Anopheles stephensi larvae.Method: The S. celiata leaves were subjected to chloroform and methanol with 1:3 (Weight/ Volume) ratio and the extracted solvent was dried using rotary vacuum evaporator. The larvicidal activity of the extract was tested using WHO method and LC50 and LC90 were evaluated by probit analysis.Results: The LC50 value of chloroform extract of S. celiata was found to be 65.288, 67.406 and 71.608 ppm whereas LC90 was 184.721, 186.582 and 192.497 ppm against C. quinquefasciatus, Ae. aegypti and A. stephensi, respectively. The methanolic extract was also found potent; LC50 was 91.503, 101.574 and 99.104 ppm whereas LC90 was 230.823, 271.927 and 234.257 ppm against C. quinquefasciatus, Ae. aegypti and A. stephensi, respectively. Both chloroform and methanol extract were found significantly lethal tothe tested mosquito vectors.Conclusion: Taken results together, chloroform extract showed higher toxicity as compared to methanolic extract against all the tested species. The study clearly revealed that S. ciliata extract or bioactive compounds can be used as an alternative to synthetic insecticides

Prompt emission polarimetry of Gamma Ray Bursts with ASTROSAT CZT-Imager

X-ray and Gamma-ray polarization measurements of the prompt emission of Gamma-ray bursts (GRBs) are believed to be extremely important for testing various models of GRBs. So far, the available measurements of hard X-ray polarization of GRB prompt emission have not significantly constrained the GRB models, particularly because of the difficulty of measuring polarization in these bands. The CZT Imager (CZTI) onboard {\em AstroSat} is primarily an X-ray spectroscopic instrument that also works as a wide angle GRB monitor due to the transparency of its support structure above 100 keV. It also has experimentally verified polarization measurement capability in the 100 $-$ 300 keV energy range and thus provides a unique opportunity to attempt spectro-polarimetric studies of GRBs. Here we present the polarization data for the brightest 11 GRBs detected by CZTI during its first year of operation. Among these, 5 GRBs show polarization signatures with $\gtrapprox$3$\sigma$, and 1 GRB shows $\>$2$\sigma$ detection significance. We place upper limits for the remaining 5 GRBs. We provide details of the various tests performed to validate our polarization measurements. While it is difficult yet to discriminate between various emission models with the current sample alone, the large number of polarization measurements CZTI expects to gather in its minimum lifetime of five years should help to significantly improve our understanding of the prompt emission.Comment: Accepted for Publication in ApJ ; a figure has been update

Organizational metrics of interchromatin speckle factor domains: integrative classifier for stem cell adhesion & lineage signaling.

Stem cell fates on biomaterials are influenced by the complex confluence of microenvironmental cues emanating from soluble growth factors, cell-to-cell contacts, and biomaterial properties. Cell-microenvironment interactions influence the cell fate by initiating a series of outside-in signaling events that traverse from the focal adhesions to the nucleus via the cytoskeleton and modulate the sub-nuclear protein organization and gene expression. Here, we report a novel imaging-based framework that highlights the spatial organization of sub-nuclear proteins, specifically the splicing factor SC-35 in the nucleoplasm, as an integrative marker to distinguish between minute differences of stem cell lineage pathways in response to stimulatory soluble factors, surface topologies, and microscale topographies. This framework involves the high resolution image acquisition of SC-35 domains and imaging-based feature extraction to obtain quantitative nuclear metrics in tandem with machine learning approaches to generate a predictive cell state classification model. The acquired SC-35 metrics led to \u3e 90% correct classification of emergent human mesenchymal stem cell (hMSC) phenotypes in populations of hMSCs exposed for merely 3 days to basal, adipogenic, or osteogenic soluble cues, as well as varying levels of dexamethasone-induced alkaline phosphatase (ALP) expression. Early osteogenic cellular responses across a series of surface patterns, fibrous scaffolds, and micropillars were also detected and classified using this imaging-based methodology. Complex cell states resulting from inhibition of RhoGTPase, β-catenin, and FAK could be classified with \u3e 90% sensitivity on the basis of differences in the SC-35 organizational metrics. This indicates that SC-35 organization is sensitively impacted by adhesion-related signaling molecules that regulate osteogenic differentiation. Our results show that diverse microenvironment cues affect different attributes of the SC-35 organizational metrics and lead to distinct emergent organizational patterns. Taken together, these studies demonstrate that the early organization of SC-35 domains could serve as a “fingerprint” of the intracellular mechanotransductive signaling that governs growth factor- and topography-responsive stem cell states

Role of Posterior Ligamentous Reinforcement in Proximal Junctional Kyphosis: A Cadaveric Biomechanical Study

Study Design Cadaveric biomechanical study. Purpose The purpose of this study was to biomechanically evaluate the effect of preserving or augmenting the interspinous ligament (ISL) and supraspinous ligament (SSL; ISL/SSL) complex between the upper instrumented vertebra (UIV) and UIV+1 using a cadaveric model. Overview of Literature Adult spinal deformity is becoming an increasingly prevalent disorder, and proximal junctional kyphosis (PJK) is a well-known postoperative complication following long spinal fusion. Methods Pure moments of 4 and 8 Nm were applied to the native and instrumented spine, respectively (n=8). The test conditions included the following: native spine (T7–L2), fused spine (T10–L2), fused spine with a hand-tied suture loop through the spinous processes at T9–T10, and fused spine with severed T9–T10 ISL/SSL complex. Results The flexion range of motion (ROM) at T9–T10 of the fused spine loaded at 8 Nm increased by 62% compared to that of the native spine loaded at 4 Nm. The average flexion ROM at T9–T10 for the suture loop and severed ISL/SSL spines were 141% (p=0.13) and 177% (p=0.66) of the native spine at 4 Nm, respectively (p-values vs. fused). Conclusions Transection of the ISL/SSL complex did not significantly change flexion ROM at the proximal junctional segment following instrumented spinal fusion. Furthermore, augmentation of the posterior ligamentous tension band with a polyester fiber suture loop did not mitigate excessive flexion loads on the proximal junctional segment. We postulate that the role of the posterior ligamentous tension band in mitigating PJK is secondary to the anterior column support provided by the vertebral body and intervertebral disc

Hypoalbuminemia as an independent risk factor for perioperative complications following surgical decompression of spinal metastases

Malnutrition has been shown to be a risk factor for poor perioperative outcomes in multiple surgical subspecialties, but few studies have specifically investigated the effect of hypoalbuminemia in patients undergoing operative treatment of metastatic spinal tumors. The aim of this study was to assess the role of hypoalbuminemia as an independent risk factor for 30-day perioperative mortality and morbidity after surgical decompression of metastatic spinal tumors using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2011 to 2014. We identified 1498 adult patients in the ACS-NSQIP database who underwent laminectomy and excision of metastatic extradural spinal tumors. Patients were categorized into normoalbuminemic and hypoalbuminemic (ie, albumin level <3.5 g/dL) groups. Univariate and multivariate regression analyses were performed to examine the association between preoperative hypoalbuminemia and 30-day perioperative mortality and morbidity. Subgroup analysis was performed in the hypoalbuminemic group to assess the dose-dependent effect of albumin depletion. Hypoalbuminemia was associated with increased risk of perioperative mortality, any complication, sepsis, intra- or postoperative transfusion, prolonged hospitalization, and non-home discharge. However, albumin depletion was also associated with decreased risk of readmission. There was an albumin level–dependent effect of increasing mortality and complication rates with worsening albumin depletion. Hypoalbuminemia is an independent risk factor for perioperative mortality and morbidity following surgical decompression of metastatic spinal tumors with a dose-dependent effect on mortality and complication rates. Therefore, it is important to address malnutrition and optimize nutritional status prior to surgery9332133

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation