Study of potential drug-drug interactions between benzodiazepines and four commonly used antiepileptic drugs in mice

Background: Benzodiazepines (BZD) is one of the commonly used drug groups for certain neurological diseases. As sometimes, the anti-epileptic drugs (AEDs) may be used concomitantly with BZD there is a potential for drug-drug interactions. Study aimed to study potential drug-drug interactions between four commonly used AEDs (phenytoin, carbamazepine (CBZ), phenobarbitone, sodium valproate) and BZD (diazepam, clonazepam) in mice using maximal electroshock seizure (MES) method and pentylenetetrazole (PTZ) method.Methods: Adult male albino mice were divided into four different groups of six animals each and anti-epileptic activity was assessed using MES method and PTZ method. Group I acted as a control, Group II received any one of the four AEDs (phenytoin, CBZ, phenobarbitone or sodium valproate) in sub-effective doses, Group III received diazepam or clonazepam alone, Group IV received a combination of diazepam or clonazepam with any one of the AEDs.Results: In MES method, the groups receiving combination of diazepam with phenytoin and CBZ showed significant protection compared to the control group (p<0.01 and p<0.02), respectively. However, diazepam in combination with sodium valproate and phenobarbitone did not show any significant protection compared to the control group and individual antiepileptic group. All the four antiepileptic showed significant protection against MES seizure in combination with clonazepam when compared to control group. In PTZ method, combination of sodium valproate with clonazepam showed significant protection compared to control group (p<0.02). However, this was not observed with diazepam-valproate combination.Conclusion: Clonazepam potentiates the action of all the four anti-epileptics while diazepam potentiates only phenytoin and CBZ against MES seizures. Clonazepam but not diazepam potentiates the action of sodium valproate against PTZ seizures

Efficacy of combined phenotypic methods for methicillin-resistant Staphylococcus aureus detection and antibiotic susceptibility

Background: The main aim of our study is to demonstrate comparative evaluation of oxacillin disc diffusion (ODD), oxacillin screen agar (OSA), CHROM agar (CA) with cefoxitin disc diffusion (CDD) method for the detection of methicillin-resistant Staphylococcus aureus obtained from various clinical samples.Methods: This prospective study was conducted to detect Methicillin resistance among staphylococcus aureus by four phenotypic methods isolated from various clinical samples received in the Department of microbiology MMIMSR, Mullana.Results: The data was statistically analyzed, compiled in form of tables, graphs, percentage and test of significance will also be done wherever necessary (using Microsoft Excel, 2008 version) CDD+ODD+OSA+CA proved to be 100% followed by ODD+OSA+CA and CDD+OSA+CA 82.07% and CDD+ODD+OSA 80.1%.Conclusions: Combined phenotypic methods are better in evaluating and studying MRSA infections in hospitals as compared to tests done in isolation for proper diagnosis and timely treatment of infections

Hybrid Energy Management System Consisting of Battery and Supercapacitor for Electric Vehicle

This paper is mainly focused on Hybrid Energy Management System (HEMS) consisting of Battery (BT) and Super capacitor (SC). Two energy sources connected in with same DC link in parallel manner with the help of Bidirectional DC-DC converter, which is used to separate control of power flow of each source. Here Permanent magnet dc motor (PMDC) motor used as a load and speed control of PMDC motor can be done by PWM method for this purpose chopper circuit is used. Input of chopper circuit is DC link and output of the chopper is given to PMDC motor. This method of energy management gives power splitting between two sources based on State of Charge (SOC) of each individual source during different state of vehicle such as acceleration, constant running and deceleration. Improved filter-based power splitting techniques is implemented. Three acceleration reference points were taken for power splinting at different SOC levels of both energy sources. Objective of this proposed method is best use of both the sources i.e. battery and supercapacitor and maximum use of supercapacitor energy at the time of transient conditions. Battery supply energy during normal running condition or very less load condition. Hence during transient condition SC directly react with system and gives peak power requirement, so stress on battery is reduces hence lifetime of battery is increase, also power available during braking is store in SC and battery, so independence of Electric Vehicle (EV) is increases. Because of less peak power requirement, batteries with less peak output power is used so it is reduced size and cost of batteries. Matlab- Simulink software is used for simulation and also small scale hardware is also implemented of proposed method

Hybrid Energy Management System Consisting of Battery and Supercapacitor for Electric Vehicle

This paper is mainly focused on Hybrid Energy Management System (HEMS) consisting of Battery (BT) and Super capacitor (SC). Two energy sources connected in with same DC link in parallel manner with the help of Bidirectional DC-DC converter, which is used to separate control of power flow of each source. Here Permanent magnet dc motor (PMDC) motor used as a load and speed control of PMDC motor can be done by PWM method for this purpose chopper circuit is used. Input of chopper circuit is DC link and output of the chopper is given to PMDC motor. This method of energy management gives power splitting between two sources based on State of Charge (SOC) of each individual source during different state of vehicle such as acceleration, constant running and deceleration. Improved filter-based power splitting techniques is implemented. Three acceleration reference points were taken for power splinting at different SOC levels of both energy sources. Objective of this proposed method is best use of both the sources i.e. battery and supercapacitor and maximum use of supercapacitor energy at the time of transient conditions. Battery supply energy during normal running condition or very less load condition. Hence during transient condition SC directly react with system and gives peak power requirement, so stress on battery is reduces hence lifetime of battery is increase, also power available during braking is store in SC and battery, so independence of Electric Vehicle (EV) is increases. Because of less peak power requirement, batteries with less peak output power is used so it is reduced size and cost of batteries. Matlab- Simulink software is used for simulation and also small scale hardware is also implemented of proposed method

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

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

A comparative study of phosphate binders in patients with end stage kidney disease undergoing hemodialysis

In the present study, a comparative evaluation of the effects of calcium acetate, calcium carbonate, sevelamer hydrochloride and lanthanum carbonate was carried out in 120 patients with end stage kidney disease (ESKD) undergoing hemodialysis. Biochemical parameters, like serum phosphorous, serum calcium and serum alkaline phosphatase level and intact parathyroid hormone level, were measured. A statistically significant reduction in serum phosphorous, serum calcium, calcium × phosphorous and serum alkaline phosphatase level were observed with all phosphate binders during 3 months of treatment. Reduction in serum phosphorous were observed with calcium acetate (1.5 mg/dL), calcium carbonate (1.3 mg/dL), sevelamer hydrochloride (2.1 mg/dL) and lanthanum carbonate (1.79 mg/dL). The reduction of serum alkaline phosphatase was observed more commonly with sevelamer (107.37 IU/L) and lanthanum (104.33 IU/L) treatments than with calcium acetate (93.9 IU/L) and calcium carbonate (86.57 IU/L). There was no statistically significant change in serum calcium observed with sevelamer and lanthanum treatments, while calcium-based phosphate binders caused a significant rise in the serum calcium level. Serum intact parathyroid hormone level was significantly reduced with all phosphate binder treatments. This decline was highest with sevelamer and lowest with calcium carbonate. All treatments were well tolerated and safety profiles were consistent with previous reports in hemodialysis patients. It is concluded that all phosphate binders are safe and effective for the treatment of hyperphosphatemia in patients with ESKD undergoing hemodialysis. However, sevelamer hydrochloride seems to be superior among all with lowering incidence of hypercalcemia