Efficacy Of Indicated Homoeopathic Medicine in The Management Of Primary Dysmenorrhoea Using VAS & WaLIDD SCORE: A Sequential Controlled Trial

Background: Dysmenorrhoea is a common gynaecological condition encountered by the females of reproductive age group characterised by cramping pain in the lower abdomen radiating to back and knees. Sometimes also associated with headache, nausea and vomiting, tiredness, fatigue and dizziness. Objectives: The objective of the study is to establish to efficacy of indicated homoeopathic medicine over placebo in cases of primary dysmenorrhoea using VAS & WaLIDD scales. Methodology: An open label study conducted on 60 patients. The data was collected in 2 parts of 3 months each. In first part Placebo was administered to all the patients & in second indicated homoeopathic medicine was prescribed. Changes in VAS & WaLIDD score was noted on monthly basis. ANOVA test was applied to compare the observations. Results: The mean of VAS at baseline 8.16 remained 8.16 after 3 months of treatment with placebo p=1 (p>0.05), not significant. After 3 months with indicated homoeopathic medicine VAS 8.16 shifted to 2.98 p value = 0 (p<0.05), statistically significant. Similarly, WaLIDD at baseline 9.48 with placebo remained 9.41, p value 0.159 (p>0.05) not statistically significant. With indicated homoeopathic medicine mean WaLIDD from 9.41 shifted to 3.8 p=0, (p<0.05) statistically significant. Frequently administered medicines were Pulsatilla nigricans, Sepia officinalis, Nux vomica, Sulphur and Belladonna. Conclusion: The study demonstrates the efficacy of indicated homoeopathic medicine over placebo in the management of primary dysmenorrhoea using VAS & WaLIDD score in a sequential trail

Developing and Applying a Single Strategy for Improved Intestinal Permeability of Diverse and Complex Phytomolecules: Nanoformulations of Rutin, Quercetin, Thymoquinone Provide Proof-of-Concept

Purpose: The clinical use and efficacy of phytomolecules are often hampered as their complex structure, poor aqueous solubility and low biological stability restricts their intestinal permeability which results in low oral bioavailability. Rutin (RT), quercetin (QU), thymoquinone (TQ) are few of such potent and therapeutically versatile phytomolecules that await maximal utilization. To address this lacuna, an attempt was made to develop a single strategy for enhanced intestinal permeation that can be applied to diverse phytomolecules. Method: A simple idea with easy-to-apply method was developed that involved preparing nanoparticles of the phytomolecules RT, QU, TQ using Eudragit matrix (RT-PNP, QU-PNP, TQ-PNP) and examined for particle characteristics, EE, in vitro release and kinetics. Phytomolecule loaded nanoparticle (PNPs) were encapsulated in HPMC grade capsule shell and evaluated for intestinal permeability by everted gut sac method. Result: The average particle sizes of RT-PNP, QU-PNP, TQ-PNP were 446±0.152, 39.6±0.006 and 186±0.513 nm, polydispersity indices were<0.5 with negative zeta potential. The % release of respective phytomolecule from RT-PNP, QU-PNP, TQ-PNP was significantly higher (P<0.05) at pH 6.8 than pH 1.2. PNPs followed Higuchi kinetics with non-Fickian diffusion mechanisms. The apparent intestinal permeability (Papp) of RT-PNP, QU-PNP, TQ-PNP were 14.45±4.85, 12.96±1.73 and 30.87±8.75 µg/cm2 , respectively, significantly (<0.5) greater vs RT, QU, TQ, respectively. CLSM confirmed significantly higher (P<0.05) intestinal permeation of RT-PNP, QU-PNP, TQ-PNP vs RT, QU, TQ, respectively. Conclusion: Developed PNPs appear to be a good approach to increase the permeability of hydrophobic phytomolecules

Improved Enzymatic Hydrolysis of Pilot Scale Pretreated Rice Straw at High Total Solids Loading

Enzymatic hydrolysis at high solids loading has the potential to reduce both capital and operational expenditures. Here, pretreatment of rice straw (PRS) with dilute acid was carried out at a pilot scale (250 kg per day) at 162°C for 10 min and 0.35% acid concentration, followed by enzymatic hydrolysis at different total solids loadings. It showed that although the total sugar concentration increased from 48 to 132 g/l, glucan conversion reduced by 27% (84–66.2%) with increasing solids from 5 to 20% in batch mode. Therefore, two different fed-batch approaches were evaluated to improve the glucan conversion by the sequential addition of a substrate and/or enzyme. At 20% solid loadings and a 3 filter paper units/g enzyme dosage, the highest glucan conversion obtained was 66% after 30 h of hydrolysis in batch mode. However, in an optimized fed-batch approach, the glucan yield was improved to 70% by simply dividing the substrate feeding into three batches, that is, 50% at 0 h, 25% each after 4 h, and 8 h of hydrolysis reaction. The addition of surfactant (Ecosurf E6) further improved the conversion to 72% after 30 h. The role of critical factors, that is, inhibitors, enzyme–lignin binding, and viscosity, was investigated during the course of hydrolysis in the batch and fed-batch approaches. This study suggests a sustainable approach for improved hydrolysis at high solids loadings by fine-tuning a simple process

Synergistic Enzyme Cocktail to Enhance Hydrolysis of Steam Exploded Wheat Straw at Pilot Scale

Multiple enzymes are required for efficient hydrolysis of lignocellulosic biomass and no wild type organism is capable of producing all enzymes in desired levels. In this study, steam explosion of wheat straw was carried out at pilot scale and a synthetic enzyme mixture (EnzMix) was developed by partially replacing the cellulase with critical dosages of commercially available accessory enzymes (β-glucosidase, xylanase and laccase) through central composite design. Highest degree of synergism (DS) was observed with β-glucosidase (1.68) followed by xylanase (1.36). Finally, benchmarking of EnzMix (Celluclast, β-glucosidase and xylanase in a protein ratio of 20.40: 38.43: 41.16, respectively) and other leading commercial enzymes was carried out. Interestingly, hydrolysis improved by 75% at 6 h and 30% at 24 h, respectively in comparison of control. By this approach, 25% reduction in enzyme dosage was observed for obtaining the same hydrolysis yield with opitimized enzyme cocktail. Thus, development of enzyme cocktail is an effective and sustainable approach for high hydrolysis efficiency

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Evaluation of antimicrobial efficacy of flavonoids of Mimusops elengi L.

Objective: The antimicrobial activity was evaluated using flavonoid extract of leaf; stem; bark and fruit of Mimusops elengi L. Methodology: The flavonoids were extracted using cold extraction method. Antimicrobial activity of free and bound flavonoid extract was evaluated by disc diffusion assay against bacterial strains viz. Escherichia coli; Bacillus subtilis; Pseudomonas putida. Minimum inhibitory concentration (MIC) of the extract was evaluated through micro broth dilution method. Results: Free flavonoid plant part extract of M. elengi L. exhibited significant activity against Escherichia coli; Bacillus subtilis and show no activity against Pseudomonas putida. Free flavonoid extract of bark of plant showed maximum inhibitory activity (DIZ = 14.0 + 1.00 mm) at 50mg/ml against Escherichia coli with MIC of 12.5 mg/ml. Bound flavonoid plant part extract of M. elengi L. exhibited significant activity against Escherichia coli; Pseudomonas putida with no activity against Bacillus subtilis. Bound flavonoid extracts of leaf significantly showed maximum antibacterial activity (DIZ =21.0 + 1.00 mm) at 50mg/ml against Escherichia coli with MIC of 6.25 mg/ml. Bound flavonoid extracts of bark also showed maximum antibacterial activity (DIZ =19.33 + 1.15 mm) at 50mg/ml against Pseudomonas putida with MIC of 6.25 mg/ml. Conclusion: Results obtained advocates that use of plant parts especially leaf and bark of the selected plant could be used as natural antimicrobial agent against tested microorganism and upcoming resistant pathogens.</jats:p