PHARMACEUTICAL AND ANALYTICAL STUDY OF TRINETRA RAS – HERBO-MINERAL FORMULATION

Trinetraras is a Kharliya Rasayan mentioned in Yogratnakar for the treatment of Hridroga (Yogratnakar Uttarardha Hridroga Chikitsa 1,2). It consists of Shuddha Parad, Shuddhagandhak and Abhrakbhasma where Bhavanadravya is Arjuna bark decoction. Aim: Pharmaceutical and analytical study of Trinetraras. Materials and methods: Paradshodhan, Gandhakshodhan, Vajrabhrakshodhan, Dhanyabhraknirmana, preparation of Abhrakbhasma, preparation of Kajjali are the procedures required to be performed before the preparation of Trinetraras. Total 40 times Abhrak was subjected to Maransanskar in Gajaputa (40 puti Abhrakbhasma). Trinetraras can be prepared from Shuddha Parad, Shuddhagandhak and Abhrakbhasma, Arjuna bark decoction is needed for 21 Bhavana. Total three batches of Trinetra Ras were prepared as per the classical method mentioned in the reference. Observations and results: Prepared samples of Trinetraras and Abhrakbhasma were tested on the basis of organoleptic and physicochemical parameters. Along with Ayurvedic parameters modern parameters such as L.O.D., L.O.I., pH, conductivity, successive solubility, elemental assay of Hg, S and Fe, TLC, phenolic assay etc. were applied to the samples of Trinetraras. Conclusion: Analytical study of Trinetraras revealed the uniformity of the procedures in the three samples of Trinetraras, as evidenced by the observations of the analytical values of the three samples were not much variation found. Analytical profile showed the presence of the ingredients used. Data generated from pharmaceutical, analytical studies can be used to develop a preliminary standard profile for the formulation of Trinetra Ras

Role of fine needle aspiration cytology in diagnosis of breast lumps

Background: Breast cancer is the most common cancer in women worldwide. Fine needle aspiration cytology is a cost effective, easy procedure in the diagnosis of breast lump.Methods: This was a one year retrospective study between January 2016 and December 2016. Needle aspiration was done in 100 patients presenting with breast lump. Histopathology correlation was done in 33 cases.Results: Fibroadenoma were most common lesions. Malignancy was reported in 13 cases. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were found to be 85%, 100%, 100%, 96.3% and 97% respectively.Conclusions: Fine needle aspiration cytology is a simple, easy, OPD based, cost effective procedure with high sensitivity, specificity and accuracy in diagnosis of breast lumps

Assessing the impact of environmental factors influencing the spatio-temporal distribution of Johnius belangerii (Cuvier, 1830) Belanger's croaker along Mumbai, Northwest Coast of India

903-907The aim of this study was to assess the impact of environmental factors influencing the spatio-temporal distribution of Johnius belangerii. Fishery independent fortnightly resource surveys were conducted in Mumbai waters from September, 2017 to May, 2018 to determine the effect of environmental variables on spatio-temporal distribution. A Generalized Additive Modelling (GAM) approach showed that distribution and abundance of J. belangerii varied spatio-temporally, and environmental factors were found to be influential. GAM models demonstrated that higher catch was located in waters of Sea Surface Temperature (SST) from 25.1 - 31.1  °C with Sea Bottom Temperature (SBT) values ranging from 26-31 °C and salinity of more than 34 0/00. Correlation of environment variables with Catch per Unit Effort (CPUE) suggests significant relationship with SST (0.81), SBT (0.85) and Sea Bottom Chlorophyll-a (0.73). The result of this study will be helpful for clearly understanding the intricacies of spatial distributions of fish in relation to changing habitat condition which will be useful in the sustainable management of aquatic resources

Loss of Function Mutation in Ank Causes Aberrant Mineralization and Acquisition of Osteoblast-Like-Phenotype by the Cells of the Intervertebral Disc

Pathological mineralization of intervertebral disc is debilitating and painful and linked to disc degeneration in a subset of human patients. An adenosine triphosphate efflux transporter, progressive ankylosis (ANK) is a regulator of extracellular inorganic pyrophosphate levels and plays an important role in tissue mineralization. However, the function of ANK in intervertebral disc has not been fully explored. Herein we analyzed the spinal phenotype of Ank mutant mice (ank/ank) with attenuated ANK function. Micro-computed tomography and histological analysis showed that loss of ANK function results in the aberrant annulus fibrosus mineralization and peripheral disc fusions with cranial to caudal progression in the spine. Vertebrae in ank mice exhibit elevated cortical bone mass and increased tissue non-specific alkaline phosphatase-positive endplate chondrocytes with decreased subchondral endplate porosity. The acellular dystrophic mineral inclusions in the annulus fibrosus were localized adjacent to apoptotic cells and cells that acquired osteoblast-like phenotype. Fourier transform infrared spectral imaging showed that the apatite mineral in the outer annulus fibrosus had similar chemical composition to that of vertebral bone. Transcriptomic analysis of annulus fibrosus and nucleus pulposus tissues showed changes in several biological themes with a prominent dysregulation of BMAL1/CLOCK circadian regulation. The present study provides new insights into the role of ANK in the disc tissue compartments and highlights the importance of local inorganic pyrophosphate metabolism in inhibiting the mineralization of this important connective tissue

Recent Innovations & Daily Problems. A new prosthesis in inguinal hernia repair:preliminary results of a pilot study.

Introduction: Elective surgery for inguinal hernia is affected by very low mortality « 1 per 10000 operation); in contrast, when surgery is carried out for complicated inguinal hernia, risks of postoperative complication are higher. TAPP is a world-wide accepted surgical practice in the treatment of elective bilateral or recurrent inguinal hernia, above all in young patients. Few exploratory studies were published on laparoscopic approach in the treatment of urgent complicated inguinal hernia. Aim of this study was to analyze feasibility (operative time, conversion rate), safety (postoperative morbidity, length of hospital stay) and quality of life (acute and chronic pain, return to work) of trans-abdominal pre-peritoneal laparoscopic hernia repair in acute incarcerated inguinal hernia. Rationale of laparoscopic trans-abdominal approach is the easier hernia reduction under vision and a better exploration of the abdominal cavity. Methods: from September 2012 to September 2013, 15 consecutive patients admitted in emergency at the Division of General Surgery of University "Sapienza", Polo Pontino, for acute incarcerated inguinal hernia were submitted to TAPP using 3 trocars (1 of 10 mm and 2 of 5mm) and polyester prosthesis fixed by fibrin glue. Exclusion criteria for laparoscopic approach were age III, previous abdominal surgery, signs of strangulated hernia. All of them were evaluated for operative time, conversion rate, postoperative morbidity, organ resection or other surgery required. All patients were scored for pain by Visual Analogic Scale (VAS) during postoperative in hospital stay at 7 days, 1,6 and 12 months after surgery. Results: median follow-up was 16 months and 12 as minimum. In all cases reduction of hernia was always possible and none conversion to open surgery was recorded, median operative time was 89 minutes (55-137 as range), omental resection was carried out in one patient (6,6%), no other organ resections needed, whereas contralateral hernia was diagnosed and repaired at the same time in 4 patients (26,6%). No major complications were observed, median blood loss was 100 ml, minor morbidity was contained to 18% represented by fever and wound infection of surgical umbilical scar. Median in hospital stay was 1,5 days with 1-5 days as range. Postoperative median acute pain, measured by visual analogic scale (VAS), was 2 (range:0-4), none patient referred any pain during follow-up. Median time of return to work was 6,5 days, ranged between 3 to 15 days. Patients' compliance to treatment and to follow-up was complete as well their satisfaction. Conclusions: In centres skilled for laparoscopy in emergency, TAPP could be considered a feasible and safe technique. In well-selected patients (especially if emolled in controlled clinical trial) TAPP could represent an alternative surgical approach for complicated incarcerated inguinal hernia to conventional open surgery even in urgency. The main advantages of laparoscopic approach are the ability to perform surgical hernia reduction under vision, a better exploration and evaluation of abdominal cavity and diagnosis and treatment of eventual contralateral defect of wall, otherwise often missed. Finally, the good control of acute and chronic pain, faster return to normal activity and work, better aesthetic results contributed to total satisfaction and compliance of the patients

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

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Nanotechnology intervention of the microbiome for cancer therapy

The microbiome is emerging as a key player and driver of cancer. Traditional modalities to manipulate the microbiome (for example, antibiotics, probiotics and microbiota transplants) have been shown to improve efficacy of cancer therapies in some cases, but issues such as collateral damage to the commensal microbiota and consistency of these approaches motivates efforts towards developing new technologies specifically designed for the microbiome–cancer interface. Considering the success of nanotechnology in transforming cancer diagnostics and treatment, nanotechnologies capable of manipulating interactions that occur across microscopic and molecular length scales in the microbiome and the tumour microenvironment have the potential to provide innovative strategies for cancer treatment. As such, opportunities at the intersection of nanotechnology, the microbiome and cancer are massive. In this Review, we highlight key opportunistic areas for applying nanotechnologies towards manipulating the microbiome for the treatment of cancer, give an overview of seminal work and discuss future challenges and our perspective on this emerging area