Evaluation of Fractal Dimension and Topographic Surface Roughness (Vertical Dissection) in Astore-Deosai-Skardu Region in GIS Environment Using ASTER GDEM

Fractal investigation is a valuable technique to model and quantify the composite patterns of natural similarobjects. This study investigates Neotectonics using ASTER-GDEM. Fractal technique for extraction of topographicfractal dimension (Dtopo) and vertical dissection (Rtopo-surf) were used to assess the Neotectonics deformation.Geomorphological regions can be demarcated by using above mentioned procedures as they reveal the topographicevolutionary stages as an evaluation of topographic textures. The idea is to recognize the zones that are stronglyinfluenced by Neotectonics. Astore-Deosai-Skardu (ADS) region in Gilgit-Baltistan was selected for this purpose as itlies between MKT and MMT which is experiencing surface topographic deformation (STD) caused by anti-clock-wiseprogression and subduction of Indian plate beneath Eurasia. The results obtained illustrates that Dtopo and Rtopo-surf showanomalies in the ADS region that clearly represent a robust control of nearby MMT, MKT and KkF and highlights theirsignificance to describe regions vulnerable to Neotectonics and related deadly events threatening precious human livesand infrastructure damages

Synthesis, Antiviral, and Antimicrobial Evaluation of Benzyl Protected Diversified C-nucleosides

Formyl glycals are the versatile synthetic intermediates and can serves as precursor for the synthesis of various C and N-nucleosides. Due to the presence of electron donating and electron withdrawing character on formyl sugars which makes the molecule more susceptible to nucleophilic attack. Utilizing same strategy, we propose the synthesis of diversified C-nucleosides (3-14) by reaction with N,N dinucleophiles. These nucleoside analogs were than tested against viral, bacterial and fungal strains

Gender Differences in Adverse Drug Reactions during HAART Therapy in HIV/AIDS Patients at a Tertiary Care Hospital Penang, Malaysia

Aims and objective: Current study is aimed to explore and observe adverse drug reactions occurrence of antiretroviral therapy and to examine the gender differences in treatment outcomes of HIV/AIDS patients during HAART therapy. Method: An observational retrospective study of all patients on HAART therapy diagnosed with HIV infection from January 2007 to December 2012 was conducted at infectious disease department of Hospital Pulau Pinang, Malaysia. Patients socio-demographic, clinical and laboratory data was retrieved via self developed validated data collection form. Results: Out of 743 patients 571 (76.8%) were male and 172 (23.1%) were female patients. A total number of 425 (57.2%) adverse drug reactions were reported among which 311 (73.1%) occurred in males and 114 (26.8%) in female patients, with a significant statistical relationship (p=0.02, OR=1.21). Out of total ADRs (57.2%) observed in both genders, a significant association was observed in Lipodystrophy (p=0.05), anemia (p=0.02), Peripheral Neuropathy (p=0.02) and pancreatitis (p=0.01). A total of 455 (79.6%) male and 139 (80.8%) female patients have improvement in CD4 cells count at the final follow up, a significant association (p=0.05) was observed among the mode of transmission and treatment outcome. Conclusion: Overall, the ADRs observed in both gender emphasize the importance of developing safer HAART regimens and managing these adverse effects in a timely manner in order to avoid long-term health consequences

Beta-Blocker Use Is Associated With Impaired Left Atrial Function in Hypertension

BACKGROUND: Impaired left atrial (LA) mechanical function is present in hypertension and likely contributes to various complications, including atrial arrhythmias, stroke, and heart failure. Various antihypertensive drug classes exert differential effects on central hemodynamics and left ventricular function. However, little is known about their effects on LA function. METHODS AND RESULTS: We studied 212 subjects with hypertension and without heart failure or atrial fibrillation. LA strain was measured from cine steady-state free-precession cardiac MRI images using feature-tracking algorithms. In multivariable models adjusted for age, sex, race, body mass index, blood pressure, diabetes mellitus, LA volume, left ventricular mass, and left ventricular ejection fraction, beta-blocker use was associated with a lower total longitudinal strain (standardized beta=-0.21; P=0.008), and lower LA expansion index (standardized beta=-0.30; P \u3c 0.001), indicating impaired LA reservoir function. Beta-blocker use was also associated with a lower positive strain (standardized beta=-0.19; P=0.012) and early diastolic strain rate (standardized beta=0.15; P=0.039), indicating impaired LA conduit function. Finally, beta-blocker use was associated with a lower (less negative) late-diastolic strain (standardized beta=0.15; P=0.049), strain rate (standardized beta=0.18; P=0.019), and a lower active LA emptying fraction (standardized beta=-0.27; P\u3c 0.001), indicating impaired booster pump function. Use of other antihypertensive agents was not associated with LA function. CONCLUSIONS: Beta-blocker use is significantly associated with impaired LA function in hypertension. This association could underlie the increased risk of atrial fibrillation and stroke seen with the use of beta-blockers (as opposed to other antihypertensive agents) demonstrated in recent trials

Acute kidney injury in critically ill COVID-19 infected patients requiring dialysis : experience from India and Pakistan

Background: Acute kidney injury (AKI) was common in the first two waves of the SARS-COV-2 pandemic in critically ill patients. A high percentage of these patients required renal replacement therapy and died in the hospital. Methods: The present study examines the clinical presentation, laboratory parameters and therapeutic interventions in critically ill patients with AKI admitted to the ICU in two centres, one each in India and Pakistan. Patient and outcome details of all critically ill COVID 19 patients admitted to the ICU requiring renal replacement therapy were collected. Data was analysed to detect patient variables associated with mortality. Results: A total of 1,714 critically ill patients were admitted to the ICUs of the two centres. Of these 393 (22.9%) had severe acute kidney injury (AKIN stage 3) requiring dialysis. Of them, 60.5% were men and the mean (± SD) age was 58.78 (± 14.4) years. At the time of initiation of dialysis, 346 patients (88%) were oligo-anuric. The most frequent dialysis modality in these patients was intermittent hemodialysis (48.1%) followed by slow low efficiency dialysis (44.5%). Two hundred and six (52.4%) patients died. The mortality was higher among the Indian cohort (68.1%) than the Pakistani cohort (43.4%). Older age (age > 50 years), low serum albumin altered sensorium, need for slower forms of renal replacement therapy and ventilatory support were independently associated with mortality. Conclusion: There was a very high mortality in patients with COVID-19 associated AKI undergoing RRT in the ICUs in this cohort from the Indian sub-continent

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. Funding: Bill & Melinda Gates Foundation

The “Is mpMRI Enough” or IMRIE Study: A Multicentre Evaluation of Prebiopsy Multiparametric Magnetic Resonance Imaging Compared with Biopsy

Background: Multiparametric magnetic resonance imaging (mpMRI) is now recommended prebiopsy in numerous healthcare regions based on the findings of high-quality studies from expert centres. Concern remains about reproducibility of mpMRI to rule out clinically significant prostate cancer (csPCa) in real-world settings. / Objective: To assess the diagnostic performance of mpMRI for csPCa in a real-world setting. / Design, setting, and participants: A multicentre, retrospective cohort study, including men referred with raised prostate-specific antigen (PSA) or an abnormal digital rectal examination who had undergone mpMRI followed by transrectal or transperineal biopsy, was conducted. Patients could be biopsy naïve or have had previous negative biopsies. / Outcome measurements and statistical analysis: The primary definition for csPCa was International Society of Urological Pathology (ISUP) grade group (GG) ≥2 (any Gleason ≥7); the accuracy for other definitions was also evaluated. / Results and limitations: Across ten sites, 2642 men were included (January 2011–November 2018). Mean age and PSA were 65.3 yr (standard deviation [SD] 7.8 yr) and 7.5 ng/ml (SD 3.3 ng/ml), respectively. Of the patients, 35.9% had “negative MRI” (scores 1–2); 51.9% underwent transrectal biopsy and 48.1% had transperineal biopsy, with 43.4% diagnosed with csPCa overall. The sensitivity and negative predictive value (NPV) for ISUP GG ≥ 2 were 87.3% and 87.5%, respectively. The NPVs were 87.4% and 88.1% for men undergoing transrectal and transperineal biopsy, respectively. Specificity and positive predictive value of MRI were 49.8% and 49.2%, respectively. The sensitivity and NPV increased to 96.6% and 90.6%, respectively, when a PSA density threshold of 0.15 ng/ml/ml was used in MRI scores 1–2; these metrics increased to 97.5% and 91.2%, respectively, for PSA density 0.12 ng/ml/ml. ISUP GG ≥ 3 (Gleason ≥4 + 3) was found in 2.4% (15/617) of men with MRI scores 1–2. They key limitations of this study are the heterogeneity and retrospective nature of the data. / Conclusions: Multiparametric MRI when used in real-world settings is able to rule out csPCa accurately, suggesting that about one-third of men might avoid an immediate biopsy. Men should be counselled about the risk of missing some significant cancers. / Patient summary: Multiparametric magnetic resonance imaging (MRI) is a useful tool for ruling out prostate cancer, especially when combined with prostate-specific antigen density (PSAD). Previous results published from specialist centres can be reproduced at smaller institutions. However, patients and their clinicians must be aware that an early diagnosis of clinically significant prostate cancer could be missed in nearly 10% of patients by relying on MRI and PSAD alone

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.Peer reviewe

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Global injury morbidity and mortality from 1990 to 2017: Results from the global burden of disease study 2017

Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care