DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF IVERMECTIN AND CLORSULON IN IVERCAM INJECTION

A precise, simple, accurate and selective method was developed and validate for estimation of Ivermectin and Clorsulon in Ivercam injection, Reversed phase high performance liquid chromatographic (RP-HPLC) method was developed for routine quantification of Ivermectin and Clorsulon in laboratory prepared mixtures as well as in combined dosage form. Chromatographic separation was achieved on a BDS hypersil C18 (5μ, 250 x 4.6 mm) utilizing mobile phase of filtered and degassed mixture of 60 phosphate buffer (pH 5.5 adjusted with 1% O-phosphoric acid) and Methanol (60:40 v/v) at a flow rate of 1 mL/min with UV detection at 234 nm. The method has been validated for linearity, accuracy and precision. In RP-HPLC method, the calibration graphs were linear in the concentration range of 2.5-7.5 μg/ml for Ivermectin and 25-75 μg/ml for Clorsulon with percentage recoveries of 100.34 % and 99.76% for Ivermectin and Clorsulon respectively. Conclusion: The results obtained by RP-HPLC methods are rapid, accurate and precise. Therefore proposed method can be used for routine analysis of Clorsulon and Ivermectin in injection

EFFECTS OF LENGTH OF PROXIMAL FEMORAL NAIL ON INTRAOPERATIVE AND POST-OPERATIVE OUTCOMES OF INTERTROCHANTERIC FRACTURES

Background: Trochanteric femoral fractures are often seen in patients aged they can be caused by high-energy or low energy trauma or may be pathological. Particularly in the elderly, hip fractures are a major cause of increased mortality and morbidity. Because of the decreased physical capacity, concomitant systemic diseases, and increased vulnerability to environmental dangers, even low-energy trauma can cause unstable femoral trochanteric fractures in this age group. Compare the functional outcome of the short proximal femoral nail with a long proximal femoral nail in intertrochanteric fractures. Methods: This randomized control trial was conducted in the Department of Orthopedics, Surat Municipal Institute of Medical Science, Surat. Results: The mean duration of surgery in the long PFN group was 79.84 +7.09 minutes and the short PFN group was 50.72 +7.96 minutes. The two-tailed P value<0.001this difference is considered to be extremely statistically significant. The mean intra operative blood loss in the long PFN group was 330.8+ 31.74 ml and the short PFN group was 170 + 23.10 ml. The two-tailed P value < 0.001, this difference is considered to be statistically significant. The number of cases with limb shortening were more in the Short PFN group than the patients in whom long PFN was use. Conclusion: Both the long and short intramedullary nails are the optional internal fixation choices for femoral intertrochanteric fracture. But the long nail could avoided the refracture of femur and reduced postoperative hip pain whereas the short nail has the advantage of reduced surgical time, blood loss and fluoroscopic time

Identification and Characterization of Six Spectroscopically Confirmed Massive Protostructures at 2.5<z<4.52.5<z<4.5

We present six spectroscopically confirmed massive protostructures, spanning a redshift range of $2.5<z<4.5$ in the Extended Chandra Deep Field South (ECDFS) field discovered as part of the Charting Cluster Construction in VUDS and ORELSE (C3VO) survey. We identify and characterize these remarkable systems by applying an overdensity measurement technique on an extensive data compilation of public and proprietary spectroscopic and photometric observations in this highly studied extragalactic field. Each of these six protostructures, i.e., a large scale overdensity (volume $>9000$\thinspace cMpc$^3$) of more than $2.5\sigma_{\delta}$ above the field density levels at these redshifts, have a total mass $M_{tot}\ge10^{14.8}M_\odot$ and one or more highly overdense (overdensity$\thinspace>5\sigma_{\delta}$) peaks. One of the most complex protostructures discovered is a massive ($M_{tot}=10^{15.1}M_\odot$) system at $z\sim3.47$ that contains six peaks and 55 spectroscopic members. We also discover protostructures at $z\sim3.30$ and $z\sim3.70$ that appear to at least partially overlap on sky with the protostructure at $z\sim3.47$, suggesting a possible connection. We additionally report on the discovery of three massive protostructures at $z=2.67$, 2.80, and 4.14 and discuss their properties. Finally, we discuss the relationship between star formation rate and environment in the richest of these protostructures, finding an enhancement of star formation activity in the densest regions. The diversity of the protostructures reported here provide an opportunity to study the complex effects of dense environments on galaxy evolution over a large redshift range in the early universe.Comment: 10 pages, 4 figures, 1 tabl

Investigating the Effect of Galaxy Interactions on Star Formation at 0.5<z<3.0

Observations and simulations of interacting galaxies and mergers in the local universe have shown that interactions can significantly enhance the star formation rates (SFR) and fueling of Active Galactic Nuclei (AGN). However, at higher redshift, some simulations suggest that the level of star formation enhancement induced by interactions is lower due to the higher gas fractions and already increased SFRs in these galaxies. To test this, we measure the SFR enhancement in a total of 2351 (1327) massive ($M_*>10^{10}M_\odot$) major ($1<M_1/M_2<4$) spectroscopic galaxy pairs at 0.5<z<3.0 with $\Delta V <5000$ km s$^{-1}$ (1000 km s$^{-1}$) and projected separation <150 kpc selected from the extensive spectroscopic coverage in the COSMOS and CANDELS fields. We find that the highest level of SFR enhancement is a factor of 1.23$^{+0.08}_{-0.09}$ in the closest projected separation bin (<25 kpc) relative to a stellar mass-, redshift-, and environment-matched control sample of isolated galaxies. We find that the level of SFR enhancement is a factor of $\sim1.5$ higher at 0.5<z<1 than at 1<z<3 in the closest projected separation bin. Among a sample of visually identified mergers, we find an enhancement of a factor of 1.86$^{+0.29}_{-0.18}$ for coalesced systems. For this visually identified sample, we see a clear trend of increased SFR enhancement with decreasing projected separation (2.40$^{+0.62}_{-0.37}$ vs.\ 1.58$^{+0.29}_{-0.20}$ for 0.5<z<1.6 and 1.6<z<3.0, respectively). The SFR enhancement seen in our interactions and mergers are all lower than the level seen in local samples at the same separation, suggesting that the level of interaction-induced star formation evolves significantly over this time period.Comment: 23 pages, 13 figures, Accepted for publication in Ap

Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity

Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by ß-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to ß-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by ß-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.Netherlands Organization for Scientific Research (NWO). B.N. is supported by an NHMRC (Australia) CJ Martin Early Career Fellowship. N.P.R. Netherlands Heart Foundation (2012T051). N.P.R. and M.G.N. received a H2020 grant (H2020-PHC-2015-667873-2) from the European Union (grant agreement 667837). Fundação para a Ciência e Tecnologia, FCT (IF/00735/2014 to A.C., IF/00021/2014 to R.S., RECI/BBB-BQB/0230/2012 to L.G.G., and SFRH/BPD/96176/2013 to C. Cunha). The NMR spectrometers are part of the National NMR Facility supported by FCT (RECI/BBB-BQB/0230/2012). The research leading to these results received funding from the Fundação para a Ciência e Tecnologia (FCT), cofunded by Programa Operacional Regional do Norte (ON.2—O Novo Norte); from the Quadro de Referência Estratégico Nacional (QREN) through the Fundo Europeu de Desenvolvimento Regional (FEDER) and from the Projeto Estratégico – LA 26 – 2013–2014 (PEst-C/SAU/LA0026/2013). NIH (DK43351 and DK097485) and Helmsley Trust. D.L.W. is supported, in part, by the NIH (GM53522, GM083016, GM119197, and C06RR0306551

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Outcome of Acute Viral Hepatitis in Children admitted in Tertiary Care Hospital of Ahmedabad, Gujarat

Introduction: Viral hepatitis is a major health problem in both developing countries. Caused mainly by 5 hepatotropic viruses designated as hepatitis A, B, C, D, E. The present study was aimed to study the impact of various epidemiological factors, to compare the etiological profile of common viral agents and to study the outcome of children admitted with acute viral hepatitis. Methodology: This was a hospital based cross sectional study. All the children admitted in paediatric ward with symptoms of acute viral hepatitis during the study period were enrolled in the study. In this study data collected. Patients were treated according to protocol and final outcome was recorded. Results: Out of total 150 patients, maximum numbers of patients (45.33%) were less than 5 years of age and 108 (72%) were male. Most common complication was Fulminant Hepatic Failure (20%). Other complications were encephalopathy (5.33%), acute kidney injury (4%), DIC (2.67%) and spontaneous bacterial peritonitis (1.33%). Out of total 150, 142 (94.67%) were discharged suggesting acute viral hepatitis infection has good outcome. Conclusion: From the present study we concluded that fulminant hepatic failure due to hepatitis A virus is more common at younger age with high mortality. Safe drinking water and food and early active immunization may reduce mortality and improve outcome