Evaluation of efficacy of priming dose of propofol in reducing induction dose requirements in patients undergoing elective surgeries under general anaesthesia

Background: Priming principle refers to administration of a subanaestheic dose of an agent prior to its actual anaesthetic dose. Propofol is an effective substitute to thiopentone for intravenous induction. The objectives of the study were to evaluate whether priming with propofol would reduce induction of dose, reduce the peri-intubation haemodynamic changes, influence the severity of side effects and influence recall phenomenon.Methods: Sixty patients of ASA Grade 1 and 2, between 18-55 years of age group, of both sexes, were selected on the basis of eligibility criteria and scheduled for elective surgery under general anaesthesia were divided into study and control groups of 30 patients each. The total dose of propofol including the priming (25% of total) dose of propofol, heart rate and blood pressure, baseline (before induction), immediately after intubation, 1 min, 3 min, 5 min after induction, SPO2 (% of oxygen saturation), recall phenomenon and other side effects post operatively were studied.Results: The demographic data were comparable for age, weight and sex in both the groups. Total patients were divided into two groups with 30 patients each. It was observed that total induction dose of propofol was significantly decreased in the study group 72.33±9.53mg compared to control group 115.83±9.00mg. Heart rate was better maintained in study group with minimal post-intubation response. The values of systolic, diastolic and mean blood pressure observed at 1 min after induction also showed significant decrease in control group compared to study group.Conclusions: Propofol produces smooth, rapid, pleasant and safe induction. Priming with propofol can be practiced due to its cost effectiveness and better haemodynamic profile and safety

India after the 2014 general elections:BJP dominance and the crisis of the third party system

This article critically assesses claims that India has entered a new party system after the 2014 general elections, marked by renationalisation with the BJP as the new 'dominant' party.' To assess these claims, we examine the electoral rise of the BJP in the build-up to and since the 2014 general elections until the state assembly elections in December 2018. Overall, we argue that despite the emerging dominance of the BJP, a core feature of the third party system -a system of binodal interactions- has remained largely intact albeit in a somewhat weaker form. Furthermore, by comparing the post 2014 Indian party system with key electoral features of the first three party systems, we conclude that the rise of the BJP has thrown the third-party system into crisis, but does not yet define the consolidation of a new party system

A Compendium of Key Climate Smart Agriculture Practices in Intensive Cereal Based Systems of South Asia

CSA initially proposed by FAO in 2010 at “The Hague Conference on Agriculture, Food Security and Climate Change (CC)”, to address the need for a strategy to manage agriculture and food systems, under climate change. The CSA by its original proponents describes the three objectives; i) sustainably increasing agricultural productivity to support equitable increases in incomes, food security and development; ii) adapting and building resilience to climate change from the farm to national levels; and iii) developing opportunities to reduce GHG emissions from agriculture compared with past trends. Since then, these three objectives (in short food security, adaptation and mitigation) are designated as the three “pillars” (or criteria) of CSA within the agricultural science and development communities. Climate Smart (Sustainable Management of Agricultural Resources and Techniques) Agriculture is an approach of crop production, which deals with the management of available agricultural resources with latest management practices and farm machinery, under a particular set of edaphic and environmental conditions. It works to enhance the achievement of national food security and Sustainable Development Goals (SDGs). CSA is location specific and tailored to fit the agro-ecological and socio-economic conditions of a location. CSA may be defined as “agriculture that sustainably increases productivity, resilience (adaptation), reduces/removes greenhouse gases (mitigation), and enhances achievement of national food security and development goals.” Therefore, if CSA implemented at right time with required resources, techniques and knowledge in a particular typological domain, will lead towards food security while improving adaptive capacity and mitigating potential for sustainable agriculture production

Chemoenzymatic synthesis, nanotization and anti- aspergillus activity of optically enriched fluconazole analogues

Despite recent advances in diagnostic and therapeutic advances in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of Candida antarctica lipase (CAL) for the preparation of optically enriched fluconazole analogs. Anti-Aspergillus activity was observed for an optically enriched derivative, (-)-S-2-(2’ ,4’ -difluorophenyl)-1-hexyl-amino-3-(1‴,2‴,4‴) triazol-1‴-yl-propan-2-ol, which exhibits MIC values of 15.6 μg/mL and 7.8 μg/disc in microbroth dilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1000 μg/mL. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analog exhibited improved antifungal activity against Aspergillus fumigatus (MIC = 1.63 μg/mL). These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotised counterparts, exhibiting anti-Aspergillus activity may have reduced toxicity

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial

BACKGROUND: Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease. METHODS: ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426. FINDINGS: Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years [SD 6·8], 4321 [75·5%] males, and 5676 [99·2%] white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio [HR] 1·04 [95% CI 0·89–1·21], p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 [95% CI 0·87–1·20], p=0·77). INTERPRETATION: In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care. FUNDING: UK National Institute for Health and Care Research

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Mössbauer, X-ray and magnetization studies of basic volcanic and hyperbasal rocks

119-122 The 57Fe Mössbauer, X-ray diffraction and magnetic susceptibility studies were carried on two samples, basic volcanic (basalt) and hyperbasal (dolerite) rocks, collected from Kundal area of Rajasthan, India to identify iron-bearing minerals. Room temperature Mössbauer parameters of basalt sample show the presence of hematite (Fe2O3), aluminium substituted magnesioferrite [Mg(Fe2-xAlx)O4] and illite. Iron is present as both Fe3+ and Fe2+ in illite. Temperature dependence of magnetic susceptibility measurements shows no transition around 120 K (Verway transition) for both the samples, indicating existence of (Mg, Al) substituted spinel ferrites. These results have been corroborated by X-diffraction and chemical analysis of the samples. </smarttagtype