Evaluation of Health Practices amongst Villagers of Raghogarh District Guna (M.P)

NFHS-3 stated that 54.9% of rural population in M.P. used contraceptive methods (any methods). Water supply and sanitation were added to the national agenda during the 1st five year plan during (1951-56).The primary responsibility for providing drinking water and sanitation facilities in the country rests with the state government and more specifically the local bodies in the urban areas

PULSATILE RELEASE OF KETOPROFEN FROM COMPRESSION COATED TABLETS USING EUDRAGIT® POLYMERS

Objective: The objective of the present research work is to develop compression coated tablet of ketoprofen as a pulsatile release system for treatment of rheumatoid arthritis.Methods: Core tablets of ketoprofen were prepared using the wet granulation method and evaluated for appearance, hardness, friability, weight variation, thickness, disintegration time and % drug release. Core tablets were coated with Eudragit S100 and Eudragit L100 by compression coating method to achieve desired lag time. The blends of core and coating materials were evaluated for bulk density, tapped density, Hausner's ratio, % Compressibility index and angle of repose. Compression coated tablets were evaluated for appearance, hardness, friability, weight variation, thickness and % drug release.Results: Core tablets, as well as compression coated tablets, showed acceptable Pharmaco technical properties. Optimized core tablets were disintegrated within 15s due to the effectiveness of super disintegrant, sodium starch glycolate. Dissolution studies of compression coated tablets in media with different pH (1.2, 6.8, and 7.4) showed that drug release could be modulated by changing the concentration of EudragitL100 and Eudragit S100. The optimized batch exhibited 80% drug release up to 6 h with a 4 h lag time. Stability study of the optimized formulation indicated no significant change in appearance, physical parameters, drug content and drug release profile at accelerated conditions for two months.Conclusion: compression coated tablet of ketoprofen was successfully developed to achieve burst drug release after specific lag time.Keywords: Chronomodulated drug delivery, Pulsatile release, Compression coated tablets, Lag tim

Survival Analysis and Prognostic Factors of the Carcinoma of Gallbladder

Background: The present study aims to evaluate the survival status of patients with gallbladder cancer (GBC) and explore the prognostic factors for the improvement and preventions. Methods: The study consists of 176 patients with clinically diagnosed gallbladder cancer; the study was conducted between 2019 and 2021 registered at Kamala Nehru Memorial Cancer Hospital, Prayagraj, India. The survival rates were analyzed by the Kaplan-Meier method; survival rate difference was analyzed by log-rank test, prognosis factors; and hazard ratio for mortality outcomes was estimated using Cox regression method.Results: The overall median survival time of patients was 5 months with the 1-year, 2-year, and 3-year survival rates of 24.4%, 8.5%, and 4.5%, respectively. The 3-year survival for patients with jaundice was 2.9%, liver infiltration (4.2%), gall- stones (0.8%), and with advanced tumor grade (1.4%). Elderly GBC patients had lower survival rates (3.8%), while the 3-year overall survival for patients residing in urban areas dropped to zero. No patients in the tumor stage (T3/T4) and with distance metastasis stage survived in 3 years, while only 1.1% of patients with advanced nodal stage survived. On receiving surgery and radiation therapy, the 3-year survival rate increased to 19.5% and 35%, respectively. The results of multivariate analysis showed that urban region (HR = 1.568, p = 0.040), gallstone or not (1.571, p = 0.049), N stage (HR = 1.468, p = 0.029), and M stage (HR = 2.289, p \u3c 0.0001) were independent risk factors for prognosis, while surgery or not (HR = 0.573, p = 0.030) was the protective factor for the prognosis of GBC. Conclusion: The overall survival of GBC in the Gangetic belt is poor. The geographical region of patients, gallstones, and N and M stage was the risk factors for prognosis, while surgery or not was the protective factor for the pro

Towards continuous bioprocessing of lentiviral vectors

Lentiviral vectors (LV) represent a key tool for cell and gene therapy applications. The production of these vectors in sufficient quantities for clinical applications remains a hurdle, prompting the field toward developing suspension processes that are conducive to large-scale production. Advanced upstream bioprocessing approaches will need to be complemented by appropriate downstream processes in order to reduce overall manufacturing costs and address the current viral vector supply gap. In this study, stable HEK293 producer cell lines were employed that grow in suspension, thus offering direct scalability, and producing a green fluorescent protein (GFP)-expressing lentiviral vector in the 106-7 transduction units (TU)/mL range in batch culture without optimization. HEK293 stable producer cells were retained in 3 L bioreactors operated in perfusion mode using either a BioSep acoustic cell filter (Applisens), an XCell™ ATF system (Repligen) or a VHU™ Perfusion Filter (Artemis Biosystems). Cultures were grown up to 1 – 1.5 ×106 cells/mL in batch mode. Perfusion was started at 0.5 volume of medium per reactor volume per day (VVD) and induction was carried out after reaching the targeted cell density of 5 ×106 cells/mL. Perfusion was then continued at 1 VVD with fresh medium containing inducers for 3 – 4 days. In all perfusion runs, harvests were collected and the LV-containing supernatant was kept on ice or at 4ºC until clarification (once daily) and subsequently stored at -80ºC until quantification using the GTA assay. We are currently working on bioprocess development integrating this upstream process with suitable downstream approaches supported through the use of process development-enabling analytical methods. Our study demonstrates that LV production in perfusion mode using the VHU filter outperformed our routine perfusion approach using an acoustic cell filter. Cells were retained in the bioreactor while LV particles passed through the filtration device with the harvest. Using this novel device, the cumulative functional LV titers were increased by up to 30-fold compared to batch mode, reaching a cumulative total yield of \u3e2 ×1011 TU/L of bioreactor culture. This approach is easily amenable to large scale production and commercial manufacturing. Purification processes used to manufacture LVs need to be tailored to the unstable nature of LVs to counter vector instability and yields need to be improved through process optimization, such as the application of novel purification methodologies in continuous or semi-continuous mode. We will describe what DSP strategy we will use to most effectively integrate up- and downstream processing for lentiviral vectors. We also expect that our bioprocessing strategy will be transferable to other modalities having similar properties than LV

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

Reaching the poor with health interventions: Programme-incidence analysis of seven randomised trials of women's groups to reduce newborn mortality in Asia and Africa

Background Efforts to end preventable newborn deaths will fail if the poor are not reached with effective interventions. To understand what works to reach vulnerable groups, we describe and explain the uptake of a highly effective community-based newborn health intervention across social strata in Asia and Africa. Methods We conducted a secondary analysis of seven randomised trials of participatory women's groups to reduce newborn mortality in India, Bangladesh, Nepal and Malawi. We analysed data on 70 574 pregnancies. Socioeconomic and sociodemographic differences in group attendance were tested using logistic regression. Qualitative data were collected at each trial site (225 focus groups, 20 interviews) to understand our results. Results Socioeconomic differences in women's group attendance were small, except for occasional lower attendance by elites. Sociodemographic differences were large, with lower attendance by young primigravid women in African as well as in South Asian sites. The intervention was considered relevant and interesting to all socioeconomic groups. Local facilitators ensured inclusion of poorer women. Embarrassment and family constraints on movement outside the home restricted attendance among primigravid women. Reproductive health discussions were perceived as inappropriate for them. Conclusions Community-based women's groups can help to reach every newborn with effective interventions. Equitable intervention uptake is enhanced when facilitators actively encourage all women to attend, organise meetings at the participants' convenience and use approaches that are easily understandable for the less educated. Focused efforts to include primigravid women are necessary, working with families and communities to decrease social taboos

Uncovering Genomic Regions Associated With 36 Agro-Morphological Traits in Indian Spring Wheat Using GWAS

Wheat genetic improvement by integration of advanced genomic technologies is one way of improving productivity. To facilitate the breeding of economically important traits in wheat, SNP loci and underlying candidate genes associated with the 36 agro-morphological traits were studied in a diverse panel of 404 genotypes. By using Breeders’ 35K Axiom array in a comprehensive genome-wide association study covering 4364.79 cM of the wheat genome and applying a compressed mixed linear model, a total of 146 SNPs (-log10P ≥ 4) were found associated with 23 traits out of 36 traits studied explaining 3.7–47.0% of phenotypic variance. To reveal this a subset of 260 genotypes was characterized phenotypically for six quantitative traits [days to heading (DTH), days to maturity (DTM), plant height (PH), spike length (SL), awn length (Awn_L), and leaf length (Leaf_L)] under five environments. Gene annotations mined ∼38 putative candidate genes which were confirmed using tissue and stage specific gene expression data from RNA Seq. We observed strong co-localized loci for four traits (glume pubescence, SL, PH, and awn color) on chromosome 1B (24.64 cM) annotated five putative candidate genes. This study led to the discovery of hitherto unreported loci for some less explored traits (such as leaf sheath wax, awn attitude, and glume pubescence) besides the refined chromosomal regions of known loci associated with the traits. This study provides valuable information of the genetic loci and their potential genes underlying the traits such as awn characters which are being considered as important contributors toward yield enhancement

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention