Efficacy of Ropivacaine for Sub-Arachnoid Block in Patients with Recent History of Scorpion Sting: A case series

Failure of sub-arachnoid block (SAB), due to resistance to bupivacaine after a recent scorpion sting can lead to multiple block attempts and subsequent conversion to general anaesthesia. We report this case series of 10 patients with successful SAB with newly launched 0.75% hyperbaric ropivacaine, in patients with recent scorpion sting. Thus, intrathecal hyperbaric ropivacaine may be considered as the local anaesthetic agent of choice in patients with scorpion sting to prevent failure of SAB. Keywords: Bupivacaine; Ropivacaine; Scorpion sting; Spinal anaesthesia

Automated Delineation of Supraglacial Debris Cover Using Deep Learning and Multisource Remote Sensing Data

Funding: S.K. acknowledges funding from the DST-India via INSPIRE fellowship scheme (DST/INSPIRE Fellowship/2017/IF170680). S.K. acknowledges funding from Deutscher Akademischer Austauschdienst (DAAD) funding ID 2021/22 (57552338).Peer reviewedPublisher PD

Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains

The ISWI family of ATP-dependent chromatin remodelers represses transcription by changing nucleosome positioning. The interactions with extranucleosomal DNA and the requirement of a minimal length of extranucleosomal DNA by ISWI mediate the spacing of nucleosomes. ISW2 from Saccharomyces cerevisiae, a member of the ISWI family, has a conserved domain called SLIDE (SANT-like ISWI domain), whose binding to extranucleosomal DNA ~19 bp from the edge of nucleosomes is required for efficiently pushing DNA into nucleosomes and maintaining the unidirectional movement of nucleosomes, as reported here. Loss of SLIDE binding does not perturb ATPase domain binding to the SHL2 site of nucleosomes or its initial movement of DNA inside of nucleosomes. ISW2 has therefore two distinct roles in mobilizing nucleosomes, with the ATPase domain translocating and moving DNA inside nucleosomes, and the SLIDE domain facilitating the entry of linker DNA into nucleosomes

Global, regional, and national sex differences in the global burden of tuberculosis by HIV status, 1990–2019: results from the Global Burden of Disease Study 2019

Background Tuberculosis is a major contributor to the global burden of disease, causing more than a million deaths annually. Given an emphasis on equity in access to diagnosis and treatment of tuberculosis in global health targets, evaluations of differences in tuberculosis burden by sex are crucial. We aimed to assess the levels and trends of the global burden of tuberculosis, with an emphasis on investigating differences in sex by HIV status for 204 countries and territories from 1990 to 2019. Methods We used a Bayesian hierarchical Cause of Death Ensemble model (CODEm) platform to analyse 21 505 site-years of vital registration data, 705 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, and 680 site-years of mortality surveillance data to estimate mortality due to tuberculosis among HIV-negative individuals. We used a population attributable fraction approach to estimate mortality related to HIV and tuberculosis coinfection. A compartmental meta-regression tool (DisMod-MR 2.1) was then used to synthesise all available data sources, including prevalence surveys, annual case notifications, population-based tuberculin surveys, and tuberculosis cause-specific mortality, to produce estimates of incidence, prevalence, and mortality that were internally consistent. We further estimated the fraction of tuberculosis mortality that is attributable to independent effects of risk factors, including smoking, alcohol use, and diabetes, for HIV-negative individuals. For individuals with HIV and tuberculosis coinfection, we assessed mortality attributable to HIV risk factors including unsafe sex, intimate partner violence (only estimated among females), and injection drug use. We present 95% uncertainty intervals for all estimates. Findings Globally, in 2019, among HIV-negative individuals, there were 1.18 million (95% uncertainty interval 1.08-1.29) deaths due to tuberculosis and 8.50 million (7.45-9.73) incident cases of tuberculosis. Among HIV-positive individuals, there were 217 000 (153 000-279 000) deaths due to tuberculosis and 1.15 million (1.01-1.32) incident cases in 2019. More deaths and incident cases occurred in males than in females among HIV-negative individuals globally in 2019, with 342 000 (234 000-425 000) more deaths and 1.01 million (0.82-1.23) more incident cases in males than in females. Among HIV-positive individuals, 6250 (1820-11 400) more deaths and 81 100 (63 300-100 000) more incident cases occurred among females than among males in 2019. Age-standardised mortality rates among HIV-negative males were more than two times greater in 105 countries and age-standardised incidence rates were more than 1.5 times greater in 74 countries than among HIV-negative females in 2019. The fraction of global tuberculosis deaths among HIV-negative individuals attributable to alcohol use, smoking, and diabetes was 4.27 (3.69-5.02), 6.17 (5.48-7.02), and 1.17 (1.07-1.28) times higher, respectively, among males than among females in 2019. Among individuals with HIV and tuberculosis coinfection, the fraction of mortality attributable to injection drug use was 2.23 (2.03-2.44) times greater among males than females, whereas the fraction due to unsafe sex was 1.06 (1.05-1.08) times greater among females than males. Interpretation As countries refine national tuberculosis programmes and strategies to end the tuberculosis epidemic, the excess burden experienced by males is important. Interventions are needed to actively communicate, especially to men, the importance of early diagnosis and treatment. These interventions should occur in parallel with efforts to minimise excess HIV burden among women in the highest HIV burden countries that are contributing to excess HIV and tuberculosis coinfection burden for females. Placing a focus on tuberculosis burden among HIV-negative males and HIV and tuberculosis coinfection among females might help to diminish the overall burden of tuberculosis. This strategy will be crucial in reaching both equity and burden targets outlined by global health milestone

Experimental realisation of parallel optical logic gates and combinational logic using multiple beam interference

In this paper, we report the experimental realisation of parallel optical logic gates and some combinational logic using multiple beam interference in three cascaded Michelson type interferometers. Considering light intensity at different points of 2-D interference pattern of four input laser beams as output, (i) two input AND, OR, NAND, NOR, XOR, XNOR optical logic gates in parallel, (ii) three input AND and NAND optical logic gates in parallel, and (iii) four input AND logic gate as well as some combinational logic in parallel were realised. By controlling the four input laser beams electro-optically or all-optically using nonlinear optical materials having large nonlinearity and fast response time, ultrafast photonic information processing can be performed utilizing present scheme due to parallel operation of large number of logic gates

Histone Octamer Structure Is Altered Early in ISW2 ATP-Dependent Nucleosome Remodeling.

Nucleosomes are the fundamental building blocks of chromatin that regulate DNA access and are composed of histone octamers. ATP-dependent chromatin remodelers like ISW2 regulate chromatin access by translationally moving nucleosomes to different DNA regions. We find that histone octamers are more pliable than previously assumed and distorted by ISW2 early in remodeling before DNA enters nucleosomes and the ATPase motor moves processively on nucleosomal DNA. Uncoupling the ATPase activity of ISW2 from nucleosome movement with deletion of the SANT domain from the C terminus of the Isw2 catalytic subunit traps remodeling intermediates in which the histone octamer structure is changed. We find restricting histone movement by chemical crosslinking also traps remodeling intermediates resembling those seen early in ISW2 remodeling with loss of the SANT domain. Other evidence shows histone octamers are intrinsically prone to changing their conformation and can be distorted merely by H3-H4 tetramer disulfide crosslinking

Analysis of Facility and Home Isolation Strategies in COVID 19 Pandemic: Evidences from Jodhpur, India

Pankaj Bhardwaj,1 Nitin Kumar Joshi,1 Manoj Kumar Gupta,1 Akhil Dhanesh Goel,1 Suman Saurabh,1 Jaykaran Charan,2 Prakash Rajpurohit,3 Suresh Ola,4 Pritam Singh,5 Sunil Bisht,5 NR Bishnoi,6 Balwant Manda,5 Kuldeep Singh,7 Sanjeev Misra8 1Community Medicine & Family Medicine and School of Public Health (SPH), All India Institute of Medical Sciences, Jodhpur, India; 2Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India; 3District Collector Office, Jodhpur, India; 4Jodhpur Municipal Corporation, Jodhpur, India; 5Medical & Health Department, Jodhpur, India; 6Administrative Office, All India Institute of Medical Sciences, Jodhpur, India; 7Department of Pediatrics, All India Institute of Medical Sciences, Jodhpur, India; 8Department of Surgical Oncology, All India Institute of Medical Sciences, Jodhpur, IndiaCorrespondence: Pankaj BhardwajDepartment of Community Medicine & Family Medicine, School of Public Health, AIIMS, Jodhpur, IndiaTel +918003996903Email [email protected]: Jodhpur administration directed its efforts to control and mitigate COVID 19 infection by implementing and monitoring facility isolation (FI) and home isolation (HI) measures. This study is conducted with a hypothesis that there is no difference in the quality of life and cost-effectiveness of mildly symptomatic or asymptomatic patients in HI and FI.Patients and Methods: A mixed-method study was conducted in Jodhpur in September 2020. The purposive sampling technique was used and data from 120 individuals admitted in HI and FI were collected. The information about the status and functioning of isolation facilities was collected from various sources. Multi-stakeholder interactions with 15 personnel engaged in managing isolation facilities were done. EQ-5D version (EQ-5D-5L) which consists of the EQ-5D descriptive system and the EQ visual analog scale (EQ-VAS) was used to assess health-related quality of life.Results: The strength of HI strategy is demonstrated by its ability to provide psychological and social support with minimal logistic requirements but the issue of sufficient household infrastructure, adequate family and societal support for implementing this strategy is of concern. The strength of FI strategy includes its ability to provide support to patients who have issues of sufficient household infrastructure, adequate family and societal support, but this strategy poses a threat of increasing human resource constraints and financial load on the health system. The respondents from HI obtained a mean EQ-5D index score of 0.90 and a mean VAS score of 85, whereas it was 0.80 and 78.5, respectively, for FI. The cost estimated for home isolation was Rs 549 (7.43 US $) per person, whereas it was Rs 2440 (33.02 US$) for facility Isolation.Conclusion: Though HI seems advantageous in terms of a better quality of life and cost-saving over FI, both the strategies are context-specific having their own trade-offs.Keywords: COVID 19, patient isolation, quality of life, public health, cost saving

CRISPR/Cas9 gene editing

Publisher Copyright: © 2021Background: Alzheimer's disease (AD) is an insidious, irreversible, and progressive neurodegenerative health condition manifesting as cognitive deficits and amyloid beta (Aβ) plaques and neurofibrillary tangles. Approximately 50 million individuals are affected by AD, and the number is rapidly increasing globally. This review explores the role of CRISPR/Cas9 gene editing in the management of AD and its clinical manifestations. Aim of Review: This review aims to provide a deep insight into the recent progress in CRISPR/Cas9-mediated genome editing and its use against neurodegenerative disorders, specifically AD. However, we have referred to its use against parkinsons's disease (PD), Huntington's disease (HD), and other human diseases, as is one of the most promising and emerging technologies for disease treatment. Key Scientific Concepts of Review: The pathophysiology of AD is known to be linked with gene mutations, that is, presenilin (PSEN) and amyloid beta precursor protein (APP). However, clinical trials focused at the genetic level could not meet the desired efficiency. The CRISPR/Cas9 genome editing tool is one of the most powerful technologies for correcting inconsistent genetic signatures and now extensively used for AD management. It has significant potential for the correction of undesired gene mutations associated with AD. This technology has allowed the development of empirical AD models, therapeutic lines, and diagnostic approaches for better understanding the nervous system, from in vitro to in vivo models.Peer reviewe