Second-harmonic generation microscopy analysis reveals proteoglycan decorin is necessary for proper collagen organization in prostate.

Collagen remodeling occurs in many prostate pathologies; however, the underlying structural architecture in both normal and diseased prostatic tissues is largely unexplored. Here, we use second-harmonic generation (SHG) microscopy to specifically probe the role of the proteoglycan decorin (Dcn) on collagen assembly in a wild type (wt) and Dcn null mouse (Dcn  -    /    -  ). Dcn is required for proper organization of collagen fibrils as it regulates size by forming an arch-like structure at the end of the fibril. We have utilized SHG metrics based on emission directionality (forward-backward ratio) and relative conversion efficiency, which are both related to the SHG coherence length, and found more disordered fibril organization in the Dcn  -    /    -  . We have also used image analysis readouts based on entropy, multifractal dimension, and wavelet transforms to compare the collagen fibril/fiber architecture in the two models, where all these showed that the Dcn  -    /    -   prostate comprised smaller and more disorganized collagen structures. All these SHG metrics are consistent with decreased SHG phase matching in the Dcn  -    /    -   and are further consistent with ultrastructural analysis of collagen in this model in other tissues, which show a more random distribution of fibril sizes and their packing into fibers. As Dcn is a known tumor suppressor, this work forms the basis for future studies of collagen remodeling in both malignant and benign prostate disease

EFFECT ON MENTAL HEALTH AMONG UNDERGRADUATE COLLEGE STUDENTS OF INDIA DURING THE COVID-19 PANDEMIC: A CROSS-SECTIONAL MULTICENTRIC STUDY

Background: College students show higher prevalence of mental health issues as compared to the general population. Unfortunately, this year, students all over the world have to face, added pressure due to COVID-19. This study aimed to estimate the effect of COVID-19 pandemic and lockdown on the mental health of Medical and Engineering Students. Subjects and methods: The study was carried out at different medical and engineering colleges in Bihar, Delhi and Maharashtra, and Tamil Nadu. 699 responses were collected and analyzed during the study period. Data was collected by email/ online platform through Google form via non- probability Sampling Technique. Mental health status was determined by using Corona virus anxiety screening (CAS), GHQ (General Health Questionnaire)-12, GAD (General Anxiety Disorder)-7 scale and PHQ (Patient Health Questionnaire)-9 scales.369 (53%) MBBS and 330 (47%) Engineering students participated in the study. Results: Maximum participants in both groups did not have anxiety related to COVID-19 (MBBS (96.8%) and Engineering (95.2%). About two-third participants secured above cut off score i.e., MBBS (62.3%) and Engineering (64.8%) in GHQ-12. Approximately comparable proportion in both groups were found to have severe anxiety and depression (16% vs 20%), when applied GAD-7 and PHQ-9. Uncertainty in the timing of the exams/ Academic delay was found to be the most worrying factor (MBBS, 41.19% vs Engineering 31.82%). Conclusions: About two-thirds of medical and engineering students psychologically equally affected by current pandemic in our study. A student wellness clinic is the need of hour in current scenario, which is supported by mental health experts (Psychiatrists, Clinical Psychologists) and residents on rotation basiswhere all psychological problem including Stress, Anxiety, Interpersonal crisis, Relationship issues and Personality problems of the students are dealt effectively in institute campus near to student residential area

Isolated hydatid cyst of adrenal gland with hypertension mimicking Conn’s syndrome: a very rare case

Hydatid cyst of the adrenal gland is one of the rare conditions caused by the larval stage of Echinococcus granulosus. The incidence of adrenal gland involvement is less than 1% of all hydatid disease in humans and isolated adrenal involvement is extremely rare. Hydatid disease is frequent in endemic regions and sheep farming areas with equal sex distribution. Here, a case of 23 year old female with isolated adrenal gland hydatid cyst is presented, that was evaluated clinically, investigated radiographicaly and by blood investigations and finally histopathology confirmed the diagnosis. No complications occurred at peri and postoperative period. The patient was given 6 cycles of albendazole (10 mg/kg in two divided doses), each for a period of four weeks followed by a week’s rest. The patient is on regular follow-up without recurrence in last 1 year

Percutaneous nephrolithotripsy for renal pelvis stone in a crossed fused ectopic kidney: a case report

Crossed renal ectopia is the second most common fusion anomaly of the kidney after horseshoe kidney. The incidence of both fused and unfused cases is 1 in 7000 in autopsies. Percutaneous nephrolithotripsy (PCNL) is a well-established technique in the surgical management of nephrolithiasis. The conventional fluoroscopic guidance of PCNL will be of limited value in ectopic anomalous kidneys due to the abnormal anatomical landmarks with consequent compromise of the procedure’s safety.  A 30-year old male patient, previously healthy, presented to our urology outpatient clinic complaining of dull flank pain of six month duration with tenderness in the right renal area and an enlarged right kidney and 1 episode of gross haematuria. Radiological investigations showed left side crossed ectopia with nephrolithiasis. Patient was managed successfully by fluoroscopic guided percutaneous nephrolithotripsy. The position of the stone-containing ectopic kidney can make it easy to reach the pelvis of the target kidney without injuring any adjoining structure. The superimposition of the different soft tissue densities in the radiologic view may limit the ability of the operator to distinguish between different tissue identities. Laparoscopic guidance can represent as a practical solution to this technical problem

EFFECT ON MENTAL HEALTH AMONG UNDERGRADUATE COLLEGE STUDENTS OF INDIA DURING THE COVID-19 PANDEMIC: A CROSS-SECTIONAL MULTICENTRIC STUDY

Background: College students show higher prevalence of mental health issues as compared to the general population. Unfortunately, this year, students all over the world have to face, added pressure due to COVID-19. This study aimed to estimate the effect of COVID-19 pandemic and lockdown on the mental health of Medical and Engineering Students. Subjects and methods: The study was carried out at different medical and engineering colleges in Bihar, Delhi and Maharashtra, and Tamil Nadu. 699 responses were collected and analyzed during the study period. Data was collected by email/ online platform through Google form via non- probability Sampling Technique. Mental health status was determined by using Corona virus anxiety screening (CAS), GHQ (General Health Questionnaire)-12, GAD (General Anxiety Disorder)-7 scale and PHQ (Patient Health Questionnaire)-9 scales.369 (53%) MBBS and 330 (47%) Engineering students participated in the study. Results: Maximum participants in both groups did not have anxiety related to COVID-19 (MBBS (96.8%) and Engineering (95.2%). About two-third participants secured above cut off score i.e., MBBS (62.3%) and Engineering (64.8%) in GHQ-12. Approximately comparable proportion in both groups were found to have severe anxiety and depression (16% vs 20%), when applied GAD-7 and PHQ-9. Uncertainty in the timing of the exams/ Academic delay was found to be the most worrying factor (MBBS, 41.19% vs Engineering 31.82%). Conclusions: About two-thirds of medical and engineering students psychologically equally affected by current pandemic in our study. A student wellness clinic is the need of hour in current scenario, which is supported by mental health experts (Psychiatrists, Clinical Psychologists) and residents on rotation basiswhere all psychological problem including Stress, Anxiety, Interpersonal crisis, Relationship issues and Personality problems of the students are dealt effectively in institute campus near to student residential area

A Swollen Seed Found in a Child’s Ear Amidst COVID-19 Lockdown: A Case Report

Foreign body lodgement in external auditory canal in pediatric age group is a common problem encountered by Otolaryngologists in emergency as well as in outpatient department.  A case report of swollen seed found in external auditory canal in right ear, of a 6-year-old boy out of poverty, neglect and unavailable ENT consultant OPD due to lockdown for the serious pandemic condition

Testosterone levels in men with type 2 diabetes mellitus

Background: To study testosterone levels in men with type 2 diabetes mellitus in age group of 30-50 years.Methods: In this cross sectional study of 193 type 2 diabetes men aged between 30-50 years, total and free testosterone levels were calculated along with other relevant clinical variables like hypertension, BMI, dyslipidemia, peripheral neuropathy, retinopathy.Results: The study group had study out of 193 patients 34.7% have low total testosterone levels, 29.53% have low free testosterone levels and 23.3% have both low and free testosterone levels. Maximum number of patients with low total testosterone levels were in the age group between 46-50 years (41.0%) and with low free total testosterone levels were in the age group between 36-40 years (41.8%).Conclusions: Type 2 diabetes mellitus is associated with low levels of total and free testosterone. Obesity and dyslipidemia are also associated with low testosterone levels

Structural and functional characterization of peste des petits ruminants virus coded hemagglutinin protein using various in-silico approaches

Peste des petits ruminants (PPR), a disease of socioeconomic importance has been a serious threat to small ruminants. The causative agent of this disease is PPR virus (PPRV) which belongs to the genus Morbillivirus. Hemagglutinin (H) is a PPRV coded transmembrane protein embedded in the viral envelope and plays a vital role in mediating the entry of virion particle into the cell. The infected host mounts an effective humoral response against H protein which is important for host to overcome the infection. In the present study, we have investigated structural, physiological and functional properties of hemagglutinin protein using various computational tools. The sequence analysis and structure prediction analysis show that hemagglutinin protein comprises of beta sheets as the predominant secondary structure, and may lack neuraminidase activity. PPRV-H consists of several important domains and motifs that form an essential scaffold which impart various critical roles to the protein. Comparative modeling predicted the protein to exist as a homo-tetramer that binds to its cognate cellular receptors. Certain amino acid substitutions identified by multiple sequence alignment were found to alter the predicted structure of the protein. PPRV-H through its predicted interaction with TLR-2 molecule may drive the expression of CD150 which could further propagate the virus into the host. Together, our study provides new insights into PPRV-H protein structure and its predicted functions

DNA DSB Repair Dynamics following Irradiation with Laser-Driven Protons at Ultra-High Dose Rates

Protontherapy has emerged as more effective in the treatment of certain tumors than photon based therapies. However, significant capital and operational costs make protontherapy less accessible. This has stimulated interest in alternative proton delivery approaches, and in this context the use of laser-based technologies for the generation of ultra-high dose rate ion beams has been proposed as a prospective route. A better understanding of the radiobiological effects at ultra-high dose-rates is important for any future clinical adoption of this technology. In this study, we irradiated human skin fibroblasts-AG01522B cells with laser-accelerated protons at a dose rate of 10 9 Gy/s, generated using the Gemini laser system at the Rutherford Appleton Laboratory, UK. We studied DNA double strand break (DSB) repair kinetics using the p53 binding protein-1(53BP1) foci formation assay and observed a close similarity in the 53BP1 foci repair kinetics in the cells irradiated with 225 kVp X-rays and ultra- high dose rate protons for the initial time points. At the microdosimetric scale, foci per cell per track values showed a good correlation between the laser and cyclotron-accelerated protons indicating similarity in the DNA DSB induction and repair, independent of the time duration over which the dose was delivered

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