Gliomatosis peritonei arising in setting of immature teratoma of ovary: a case report

A 14 years old girl presented to the gynecology OPD with pain abdomen and huge abdominal lump since 2 months. On clinical examination, a large mass of 20x15 cm size was found extended upto the xiphoid process. Serum studies showed rise of CA-125 up to 406.9U/mL and LDH up to 310U/L. USG shows right ovarian cyst of 14.8x14.1x12.8 cm with internal calcification. MRI revealed a well encapsulated mass of 21x19x17cm with solid and cystic mass and upward peritoneal extension. Exploratory laparotomy was performed with right sided salpingo- ophorectomy with infracolic omentectomy, as the omentum appeared granular. She had an uneventful post-operative recovery. Subsequently HPE showed immature teratoma NORRIS grade 3 with co-existent peritoneal gliomatosis (grade 0). She is under regular follow-up and decided to give six cycles of combination chemotherapy with BEP at regional cancer hospital

Slim U-Net: Efficient Anatomical Feature Preserving U-net Architecture for Ultrasound Image Segmentation

We investigate the applicability of U-Net based models for segmenting Urinary Bladder (UB) in male pelvic view UltraSound (US) images. The segmentation of UB in the US image aids radiologists in diagnosing the UB. However, UB in US images has arbitrary shapes, indistinct boundaries and considerably large inter- and intra-subject variability, making segmentation a quite challenging task. Our study of the state-of-the-art (SOTA) segmentation network, U-Net, for the problem reveals that it often fails to capture the salient characteristics of UB due to the varying shape and scales of anatomy in the noisy US image. Also, U-net has an excessive number of trainable parameters, reporting poor computational efficiency during training. We propose a Slim U-Net to address the challenges of UB segmentation. Slim U-Net proposes to efficiently preserve the salient features of UB by reshaping the structure of U-Net using a less number of 2D convolution layers in the contracting path, in order to preserve and impose them on expanding path. To effectively distinguish the blurred boundaries, we propose a novel annotation methodology, which includes the background area of the image at the boundary of a marked region of interest (RoI), thereby steering the model's attention towards boundaries. In addition, we suggested a combination of loss functions for network training in the complex segmentation of UB. The experimental results demonstrate that Slim U-net is statistically superior to U-net for UB segmentation. The Slim U-net further decreases the number of trainable parameters and training time by 54% and 57.7%, respectively, compared to the standard U-Net, without compromising the segmentation accuracy.Comment: Accepted in 9th ACM International Conference on Biomedical and Bioinformatics Engineering (ICBBE) 2022 http://www.icbbe.com

Human iPSC derived cardiomyocyte model reveals the transcriptomic bases of COVID-19 associated myocardial injury

Background: Multi-organ complications have been the hallmark of severe COVID-19; cardiac injuries were reported in 20% to 30% of hospitalized COVID-19 patients, although the disease etiology remains poorly understood. This study leveraged genome-wide RNA-sequence data generated using induced pluripotent stem cell (iPSC) differentiated cardiomyocytes (CMs) and in vitro modeling of SARS-CoV-2 infection in CMs, to understand the molecular mechanisms of COVID-19 myocardial injuries for novel diagnostic and therapeutic development. Methods: Raw RNA-sequence data sets, GSE165242 and GSE150392 were aligned to human genome assembly GRCh38 and gene expressions were quantified. Differentially expressed (DE) genes between experimental groups were identified using moderated t-statistics (FDR-corrected p-value ≤ 0.05) and Fold-Change analysis (FC absolute ≥ 2.0). Results: A total of 2,148 genes were significantly DE between SARS-CoV-2 infected and vehicle treated CMs and showed significant enrichment in cytokine signaling pathways (p-value=4.89E-25) and regulation of heart contraction (p-value=2.51E-19) gene-ontology biological processes. 606 of these DE genes were significantly upregulated during iPSC to CM differentiation. Disease and function annotation analysis of these 606 genes showed significant enrichment and activation of angiogenesis (p-value=4.04E-23; activation Z-score=3.7) and downregulation of heart contraction and related functions (p-value=4.24E-29; activation Z-score=-2.2) in SARS-CoV-2 infected CMs. The upstream regulator analysis identified upregulation of AGT associated proinflammatory genes and significant downregulation of TBX5 and MYOCD transcription factors and their gene networks, suggesting remodeling of CM contractility architecture. Conclusions: This study identified several AGT associated proinflammatory genes and TBX5 and MYOCD gene networks as potential targets for drug development to address COVID-19 associated cardiac injury

Disease Modeling and Disease Gene Discovery in Cardiomyopathies: A Molecular Study of Induced Pluripotent Stem Cell Generated Cardiomyocytes

The in vitro modeling of cardiac development and cardiomyopathies in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) provides opportunities to aid the discovery of genetic, molecular, and developmental changes that are causal to, or influence, cardiomyopathies and related diseases. To better understand the functional and disease modeling potential of iPSC-differentiated CMs and to provide a proof of principle for large, epidemiological-scale disease gene discovery approaches into cardiomyopathies, well-characterized CMs, generated from validated iPSCs of 12 individuals who belong to four sibships, and one of whom reported a major adverse cardiac event (MACE), were analyzed by genome-wide mRNA sequencing. The generated CMs expressed CM-specific genes and were highly concordant in their total expressed transcriptome across the 12 samples (correlation coefficient at 95% CI =0.92 ± 0.02). The functional annotation and enrichment analysis of the 2116 genes that were significantly upregulated in CMs suggest that generated CMs have a transcriptomic and functional profile of immature atrial-like CMs; however, the CMs-upregulated transcriptome also showed high overlap and significant enrichment in primary cardiomyocyte (p-value = 4.36 × 10−9), primary heart tissue (p-value = 1.37 × 10−41) and cardiomyopathy (p-value = 1.13 × 10−21) associated gene sets. Modeling the effect of MACE in the generated CMs-upregulated transcriptome identified gene expression phenotypes consistent with the predisposition of the MACE-affected sibship to arrhythmia, prothrombotic, and atherosclerosis risk

Enhancement of bioavailability of herbal drugs for treating viral therapy using SNEDDS as the delivery system

SNEDDS were developed with the objective of treating low bioavailability of drugs for antiviral drugs due to its low solubility. The scientist has increased their interest in improving bioavailability and absorption of poorly-water soluble drugs using Self-Emulsifying lipid technology. SNEDDS was an isocratic mixture contains an Oil, Surfactant, Co-surfactant, and Drug in accurate amount. The SNEDDS was primarily prepared as liquid-SNEDDS, but S-SNEDDS was more stable as compared to L-SNEDDS. As viral infection was major threat for people due to its limited efficacy and Serious adverse effects. The most damaging viral diseases was treated with help of SNEDDS as delivery system. They were a leading cause of morbidity and mortality. The plant and plant source were major source from which the extracted metabolites used for synthesis of drug through metabolic pathway. The phytochemicals and extracts were better and safe alternative for synthetic drugs. The phytochemicals like Curcumin, Myricetin, Apigenin etc. used as drug for treating antivirals using SNEDDS. This technique was used for quantitative and qualitative analysis. Also, the ternary phase diagram gives dramatic representation of Oil, surfactant and Co-surfactant which shows its concentration. Some characterization techniques were Droplet size, Zeta potential, XRD, DSC, FTIR, and TGA. Also, QbD provides a platform for systemic production of drug formulations. QbD was used for its better bioavailability

Similar Events but Contrasting Impact: Appraising the Global Digital Reach of World Heart Day and Atrial Fibrillation Awareness Month

Background: With over 18.6 million deaths annually, cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. One such complication of CVDs that can result in stroke is atrial fibrillation (Afib). As part of global outreach and awareness, World Heart Day and Atrial Fibrillation Awareness Month are celebrated annually on 29 September and the month of September, respectively. Both of these events are important cardiovascular awareness initiatives to assist public education and develop awareness strategies, and they have received considerable support from leading international organizations. Objective: We studied the global digital impact of these campaigns via Google Trends and Twitter. Methods: We evaluated the overall number of tweets, impressions, popularity and top keywords/hashtags, and interest by region to determine the digital impact using various analytical tools. Hashtag network analysis was done using ForceAtlas2 model. Beyond social media, Google Trends web search analysis was carried out for both awareness campaigns to examine ‘interest by region’ over the past five years by analyzing relative search volume. Results: #WorldHeartDay and #UseHeart (dedicated social media hashtags for World Heart Day by the World Heart Federation) alone amassed over 1.005 billion and 41.89 million impressions as compared with the 1.62 million and 4.42 million impressions of #AfibMonth and #AfibAwarenessMonth, respectively. On Google Trends web search analysis, the impact of Afib awareness month was limited to the USA, but World Heart Day had a comparatively global reach with limited digital involvement in the African continent. Conclusions: World Heart Day and Afib awareness month present a compelling case study of vast digital impact and the effectiveness of targeted campaigning using specific themes and keywords. Though the efforts of the backing organizations are commended, planning and collaboration are needed to further widen the reach of Afib awareness month

Case Report: Multiple atherosclerotic plaques at its extreme in synchrony [version 3; peer review: 2 approved]

Peripheral artery (PAD) disease in association with renal artery stenosis is an important association which predicts the severity of the disease. An increase in the number of vessels affected by peripheral artery disease increases the chances of renal artery stenosis. In our case, the patient had primarily presented with anginal chest pain with complaints of claudication which on further investigation was diagnosed to be a triple vessel coronary artery disease along with bilateral subclavian and bilateral renal stenosis. On detailed history taking, risk factors like hypertension and chronic smoking was found to be present in our case which predisposed to peripheral artery disease secondary to atherosclerosis which was diagnosed on further investigations. Although the association of renal artery stenosis is not very rare in cases of severe peripheral vascular diseases, the presence of a triple vessel coronary artery disease in synchrony is what makes it unique. Take away lesson from this case report is importance of early diagnosis of dyslipidemia causing atherosclerosis and its complications. Multiple atherosclerotic lesions in synchrony i.e, bilateral renal artery stenosis with bilateral subclavian artery stenosis with coronary artery triple vessel atherosclerotic disease like in our case and its severity should create awareness among health care individuals and early treatment measures including lifestyle modifications should be considered to avoid such drastic events

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING: Bill & Melinda Gates Foundation

Global burden of peripheral artery disease and its risk factors, 1990–2019 : a systematic analysis for the Global Burden of Disease Study 2019

peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed. Findings In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99·2–128·4), with a global prevalence of 1·52% (95% UI 1·33–1·72), of which 42·6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14·91% [12·41–17·87] in those aged 80–84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69·4% (64·2–74·3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles. Interpretation The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation