Cassia occidentalis Linn (CO) is an annual/perennial plant having traditional uses in the treatments of ringworm, gastrointestinal ailments and piles, bone fracture, and wound healing. Previously, we ...confirmed the medicinal use of the stem extract (ethanolic) of CO (henceforth CSE) in fracture healing at 250 mg/kg dose in rats and described an osteogenic mode of action of four phytochemicals present in CSE. Here we studied CSE's preclinical safety and toxicity. CSE prepared as per regulations of Current Good Manufacturing Practice for human pharmaceuticals/phytopharmaceuticals and all studies were performed in rodents in a GLP-accredited facility. In acute dose toxicity as per New Drug and Clinical Trial Rules, 2019 (prior name schedule Y), in rats and mice and ten-day dose range-finding study in rats, CSE showed no mortality and no gross abnormality at 2500 mg/kg dose. Safety Pharmacology showed no adverse effect on central nervous system, cardiovascular system, and respiratory system at 2500 mg/kg dose. CSE was not mutagenic in the Ames test and did not cause clastogenicity assessed by in vivo bone marrow genotoxicity assay. By a sub chronic (90 days) repeated dose (as per OECD, 408 guideline) study in rats, the no-observed-adverse-effect-level was found to be 2500 mg/kg assessed by clinico-biochemistry and all organs histopathology. We conclude that CSE is safe up to 10X the dose required for its osteogenic effect.
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•In safety pharmacology studies, CSE at 2500 mg/kg dose had no adverse effect.•CSE is devoid of mutagenicity in vitro.•In acute toxicity study the LD50 of CSE was >2500 mg/kg.•In sub chronic toxicity study, the no-observed-adverse-effect-level >2500 mg/kg (10X more than therapeutic dose).
Ionosphere is found to be affected by phenomenon taking place above and below it. Troposphere incidents of thunderstorm and lightning, influence ionospheric temperatures and ion density, from D ...region to a region of high altitude. Low latitude upper ionosphere in the altitude range of 425–625km over Indian subcontinent is studied for ion density variation during the event of active thunderstorm. Study is done with the help of ionospheric data obtained from in situ measurements made by Indian satellite SROSS C2, and thunderstorm and other related data obtained from Indian Meteorological Department. Ion density in this region found to show a regular fall from 5 to 65% during the event of thunderstorm over normal day values but consistent heating of ions takes place. O+ being the main part of the composition of ionosphere at this altitude so total ion density variation show a similar trend as that of O+ ion, while other ions like O2+, He+ and H+ do not follow any regular trend with the activity of thunderstorm.
Docetaxel (DTX), an FDA approved chemotherapeutic agent, is used as a first-line treatment for triple-negative breast cancer (TNBC). Its poor aqueous solubility, rapid metabolism, short half-life, ...and effective targeting to the cancer cells limits its optimal therapeutic use. Herein, we report folate targeted amphiphilic lipopolymer grafted with cholesterol conjugated carbonate and DL-lactide prepared by microwave assisted ring opening polymerization, for the efficient actively targeted delivery of DTX. The DTX-loaded folate-targeted lipopolymeric nanoparticles (F-DTX-LPNs) prepared by the emulsion solvent evaporation method exhibited a smaller size of ∼115.17 nm with a PDI of 0.205 and encapsulation efficiency of >80%. Further, these lipopolymeric nanoparticles (F-DTX-LPNs) showed a good on-bench stability and sustained DTX release for 7 days. Cell-based assays in MDA-MB-231 cells revealed a significant enhancement in the intracellular uptake of folate-targeted lipopolymeric nanoparticles compared to non-targeted nanoparticles. Further, methyl beta-cyclodextrin (Mβ-CD) completely inhibited the uptake of these nanoparticles in the cells, indicating a lipid raft-mediated uptake mechanism. The developed F-DTX-LPNs showed improved cytotoxicity, apoptosis, and significant fold-change in expression levels of Bcl-2, BAX and Ki-67 as compared to non-targeted DTX-LPNs and free DTX. Further, F-DTX-LPNs showed an improved
in vivo
pharmacokinetic profile in
Sprague Dawley
rats as compared to the free DTX. The bio-imaging of
ex vivo
tissues demonstrated that the DiR loaded folate targeted LPNs exhibited intense signals after 24 h because of slow release of DiR dye from the nanoparticles.
Although prognostic gene expression signatures for survival in early-stage lung cancer have been proposed, for clinical application, it is critical to establish their performance across different ...subject populations and in different laboratories. Here we report a large, training-testing, multi-site, blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) could be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early-stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas.
ObjectiveWe aim to implement the practice of birth companions (BC) (from 0% to 90%) during labor to provide respectful maternity care (RMC) during the coronavirus disease 2019 (COVID-19) ...pandemic.MethodsThis was a prospective quality improvement (QI) study conducted in the Department of Obstetrics and Gynecology at All India Institute of Medical Sciences (AIIMS), Rishikesh, India. The methodology given by the World Health Organization (WHO)’s Point of Care Continuous Quality Improvement (POCQI) manual was followed, and standard tools of quality improvement were used to attain the objective.ResultsThe QI team conducted a cause and effect analysis to understand the reasons why birth companions were not allowed during childbirth. The Pareto principle derived at three most important causes of the problem: absence of a defined policy, ignorance of guidelines promoting BC even during the pandemic, and relatives could enter wards only after a negative reverse transcriptase polymerase chain reaction (RTPCR) report, which could take up to 48 hours. Multiple change ideas were tested by means of Plan-Do-Study-Act (PDSA) cycles that were successful in bringing about desired change and improvement in the delivery of quality healthcare.ConclusionQI methodology was effective in promoting and achieving more than 90% birth companionship in labor and thus helpful in providing respectful maternity care even during the COVID-19 pandemic.
Population factors such as age, gender, ethnicity, genotype and disease state can cause inter-individual variability in pharmacokinetic (PK) profile of drugs. Primarily, this variability arises from ...differences in abundance of drug metabolizing enzymes and transporters (DMET) among individuals and/or groups. Hence, availability of compiled data on abundance of DMET proteins in different populations can be useful for developing physiologically based pharmacokinetic (PBPK) models. The latter are routinely employed for prediction of PK profiles and drug interactions during drug development and in case of special populations, where clinical studies either are not feasible or have ethical concerns. Therefore, the main aim of this work was to develop a repository of literature-reported DMET abundance data in various human tissues, which included compilation of information on sample size, technique(s) involved, and the demographic factors. The collation of literature reported data revealed high inter-laboratory variability in abundance of DMET proteins. We carried out unbiased meta-analysis to obtain weighted mean and percent coefficient of variation (%CV) values. The obtained %CV values were then integrated into a PBPK model to highlight the variability in drug PK in healthy adults, taking lamotrigine as a model drug. The validated PBPK model was extrapolated to predict PK of lamotrigine in paediatric and hepatic impaired populations. This study thus exemplifies importance of the DMET protein abundance database, and use of determined values of weighted mean and %CV after meta-analysis in PBPK modelling for the prediction of PK of drugs in healthy and special populations.
Abstract
We have developed a simple and portable device that makes precise and automated measurements of night sky extinction. Our instrument uses a commercially available telephoto lens for light ...collection, which is retrofitted to a custom-built telescope mount, a thermoelectrically cooled CCD for imaging, and a compact enclosure with electronic control to facilitate remote observations. The instrument is also capable of measuring the sky brightness and detecting the presence of thin clouds that otherwise would remain unnoticed. The measurements of sky brightness made by our simple device are more accurate than those made using a large telescope. Another capability of the device is that it can provide an instantaneous measurement of atmospheric extinction, which is extremely useful for exploring the nature of short-term extinction variation. The instrument was designed and developed primarily in order to characterize and investigate thoroughly the Indian Astronomical Observatory (IAO), Hanle for the establishment of India's future large-telescope project. The device was installed at the IAO, Hanle in 2014 May. In this paper, we present the instrument details and discuss the results of extinction data collected for about 250 nights.
Introduction: Antibody-mediated rejection (ABMR) is one of the major determinants of graft survival. Although diagnostic precision and treatment options have improved, response to therapy and graft ...survival has not improved very significantly. The phenotypes of early and late acute ABMR differ in many ways. In this study, we assessed the clinical characteristics, response to therapy, DSA positivity, and outcomes of early and late ABMR. Methods: During the study period, 69 patients with acute ABMR diagnosed on renal graft histopathology were included with a median follow-up of 10 months after rejection. Recipients were stratified into early acute ABMR (<3 months of transplant; n = 29) and late acute ABMR (>3 months of transplant; n = 40). Graft survival, patient survival, response to therapy, and doubling of serum creatinine were assessed and compared between the two groups. Results: Baseline characteristics and immunosuppression protocols were comparable between the early and late ABMR groups. Late acute ABMR had an increased risk of doubling of serum creatinine than the early ABMR group (P = 0.002). Graft and patient survival were not statistically different between the two groups. Response to therapy was inferior in the late acute ABMR group (P = 0.00). Pretransplant DSA was present in 27.6% in the early ABMR group. Late acute ABMR was frequently associated with nonadherence or suboptimal immunosuppression and low DSA positivity (15%). Infections such as CMV, bacterial, and fungal infections were similar in the earlier and late ABMR groups. Conclusion: Late acute ABMR group had a poor response to anti-rejection therapy and also an increased risk of doubling of serum creatinine compared to the early acute ABMR group. There was also a tendency toward increased graft loss in late acute ABMR patients. Late acute ABMR patients are more frequently associated with nonadherence/suboptimal immunosuppression. There was also a low incidence of anti-HLA DSA positivity in late ABMR.
We studied the impact of residual renal function (RRF) on clinical outcome and quality of life in 61 patients on peritoneal dialysis (PD). They were assigned to two groups, at the time of initiation ...of PD, based on their estimated glomerular filtration rate (eGFR). The high RRF group had eGFR ≥5 mL/min/1.73 m2 and the low RRF group hade GFR <5 mL/min/1.73 m2. All patients were followed up at regular intervals for clinical and biochemical variables. Baselines characteristics including age, sex, body mass index and cause of the kidney disease were similar in both groups. The high RRF group had a higher rate of continuous ambulatory peritoneal dialysis discontinuation. The incidence of peritonitis was higher in the low RRF group. Other infections (cellulitis, gastroenteritis, sepsis) were more common in patients with low RRF, compared to the high RRF group. The quality of life as assessed by depression score, restless leg syndrome, and sleep quality were poor in patients with reduced RRF. We found that a high RRF at the time of initiation of PD, significantly decreased the incidence of infections, depression, better nutrition, and lower levels of alkaline phosphatase; providing indirect evidence of better renal clearance of phosphorous, in those with preserved RRF.
Improvement of grain protein content (GPC), loaf volume, and resistance to rusts was achieved in 11 Indian wheat cultivars that are widely grown in four different agro-climatic zones of India. This ...involved use of marker-assisted backcross breeding (MABB) for introgression and pyramiding of the following genes: (i) the high GPC gene
Gpc-B1
; (ii) HMW glutenin subunits 5 + 10 at
Glu-D1
loci, and (iii) rust resistance genes,
Yr36
,
Yr15
,
Lr24
, and
Sr24
. GPC increased by 0.8 to 3.3%, although high GPC was generally associated with yield penalty. Further selection among high GPC lines allowed identification of progenies with higher GPC associated with improvement in 1000-grain weight and grain yield in the backgrounds of the following four cultivars: NI5439, UP2338, UP2382, and HUW468. The high GPC progenies (derived from NI5439) were also improved for grain quality using HMW glutenin subunits 5 + 10 at
Glu-D1
loci. Similarly, progenies combining high GPC and rust resistance were obtained in the backgrounds of following five cultivars: Lok1, HD2967, PBW550, PBW621, and DBW1. The improved pre-bred lines developed following multi-institutional effort should prove a valuable source for the development of cultivars with improved nutritional quality and rust resistance in the ongoing wheat breeding programmes.
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