Cause Of Death Research Articles

Astragaloside IV attenuates ferroptosis and protects against iron overload-induced retinal injury

Retinal injury may be exacerbated by iron overload. Astragaloside IV (AS-IV) has potential applications in the food and healthcare industry to promote eye health. We sought to determine the mechanisms responsible for the protective effects of AS-IV on photoreceptor and retinal pigment epithelium cell death induced by iron overload. We conducted in vitro and in vivo experiments involving AS-IV pretreatment. We tested AS-IV for its ability to protect iron-overload mice from retinal injury. In particular, we analyzed the effects of AS-IV on iron overload-induced ferroptosis in 661W and ARPE-19 cells. AS-IV not only attenuated iron deposition and retinal injury in iron-overload mice but also effectively reduced iron overload-induced ferroptotic cell death in 661W and ARPE-19 cells. AS-IV effectively prevented ferroptosis by inhibiting iron accumulation and lipid peroxidation. In addition, inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) eliminated the protective effect of AS-IV against ferroptosis. The results suggest that ferroptosis might be a significant cause of retinal cell death associated with iron overload. AS-IV provides protection from iron overload-induced ferroptosis, partly by activating the Nrf2 signaling pathway.

Inequalities in lifespan and mortality risk in the US, 2015–2019: a cross-sectional analysis of subpopulations by social determinants of health

ObjectiveTo quantify inequalities in lifespan across multiple social determinants of health, how they act in tandem with one another, and to create a scoring system that can accurately identify subgroups...

Evaluation of therapeutic response to algorithm assisted improvement of oral mucosa damage in male AIDS patients

HIV/AIDS is now the biggest cause of mortality in Africa and the fourth highest cause of death globally. Half or more of HIV-infected individuals and as many as 80% of AIDS patients develop oral lesions. People living with HIV/AIDS may benefit from early testing, diagnosis, and treatment if oral lesions are detected, as they are the initial clinical characteristics of the infection and strong indicators of immunodeficiency. Oral candidiasis (OPC), oral hairy leukoplakia (OHL), oral Kaposi’s sarcoma (OKS), and HIV-associated periodontal diseases were the subjects of this comprehensive review designed to assess the available data for the management of these and other common oral mucosa damage that are linked to HIV. Further exacerbating the condition are host variables such as xerostomia, smoking, dental caries, oral prosthesis, diabetes, and cancer treatments. A separate portion of this Worldwide Workshop discusses the treatment of salivary gland illness linked with HIV. Oral mucosa injury in AIDS patients does not have a reliable diagnostic approach. Improving the early diagnosis of Oral Mucosa damage in male AIDS patients was the primary goal of this work, which sought to construct an Artificial Intelligence (AI) diagnostic model with high sensitivity. To demonstrate a Gradient Boosting Regression (GBR) based method for assessing the efficacy of treatments for oral mucosa damage in AIDS patients. Both investigation and diagnostic applications may benefit from this predictor. Results show that, compared to existing models, the suggested AI and GBR methods can accurately predict oral mucosa deterioration in AIDS patients. This study significantly contributes to the profession by improving the accuracy of diagnoses and providing useful information for treatment options.

Myeloid Cells in Myocardial Ischemic Injury: The Role of the Macrophage Migration Inhibitory Factor

Ischemic heart disease, manifesting as myocardial infarction (MI), remains the leading cause of death in the western world. Both ischemia and reperfusion (I/R) cause myocardial injury and result in cardiac inflammatory responses. This sterile inflammation in the myocardium consists of multiple phases, involving cell death, tissue remodeling, healing, and scar formation, modulated by various cytokines, including the macrophage migration inhibitory factor (MIF). Meanwhile, different immune cells participate in these phases, with myeloid cells acting as first responders. They migrate to the injured myocardium and regulate the initial phase of inflammation. The MIF modulates the acute inflammatory response by affecting the metabolic profile and activity of myeloid cells. This reviewsummarizes the role of the MIF in regulating myeloid cell subsets in MI and I/R injury and discusses emerging evidence of metabolism-directed cellular inflammatory responses. Based on the multifaceted role of the MIF affecting myeloid cells in MI or I/R, the MIF can be a therapeutic target to achieve metabolic balance under pathology and alleviate inflammation in the heart.

Role and mechanisms of autophagy, ferroptosis, and pyroptosis in sepsis-induced acute lung injury

Sepsis-induced acute lung injury (ALI) is a major cause of death among patients with sepsis in intensive care units. By analyzing a model of sepsis-induced ALI using lipopolysaccharide (LPS) and cecal ligation and puncture (CLP), treatment methods and strategies to protect against ALI were discussed, which could provide an experimental basis for the clinical treatment of sepsis-induced ALI. Recent studies have found that an imbalance in autophagy, ferroptosis, and pyroptosis is a key mechanism that triggers sepsis-induced ALI, and regulating these death mechanisms can improve lung injuries caused by LPS or CLP. This article summarized and reviewed the mechanisms and regulatory networks of autophagy, ferroptosis, and pyroptosis and their important roles in the process of LPS/CLP-induced ALI in sepsis, discusses the possible targeted drugs of the above mechanisms and their effects, describes their dilemma and prospects, and provides new perspectives for the future treatment of sepsis-induced ALI.

Genetic Polymorphisms and Genetic Risk Scores Contribute to the Risk of Coronary Artery Disease (CAD) in a North Indian Population

Coronary artery disease (CAD) is the leading cause of death in India. Many genetic polymorphisms play a role in regulating oxidative stress, blood pressure and lipid metabolism, contributing to the pathophysiology of CAD. This study examined the association between ten polymorphisms and CAD in the Jat Sikh population from Northern India, also considering polygenic risk scores. This study included 177 CAD cases and 175 healthy controls. The genetic information of GSTM1 (rs366631), GSTT1 (rs17856199), ACE (rs4646994), AGT M235T (rs699), AGT T174M (rs4762), AGTR1 A1166C (rs5186), APOA5 (rs3135506), APOC3 (rs5128), APOE (rs7412) and APOE (rs429358) and clinical information was collated. Statistical analyses were performed using SPSS version 27.0 and SNPstats. Significant independent associations were found for GST*M1, GST*T1, ACE, AGT M235T, AGT T174M, AGTR1 A1166C and APOA5 polymorphisms and CAD risk (all p < 0.05). The AGT CT haplotype was significantly associated with a higher CAD risk, even after controlling for covariates (adjusted OR = 3.93, 95% CI [2.39–6.48], p < 0.0001). The APOA5/C3 CC haplotype was also significantly associated with CAD (adjusted OR = 1.86, 95% CI [1.14–3.03], p < 0.05). A higher polygenic risk score was associated with increased CAD risk (adjusted OR = 1.98, 95% CI [1.68–2.34], p < 0.001). Seven polymorphisms were independently associated with an increase in the risk of CAD in this North Indian population. A considerable risk association of AGT, APOA5/C3 haplotypes and higher genetic risk scores is documented, which may have implications for clinical and public health applications.

Discovery of Novel Imidazo[1,2-a]pyridine-Based HDAC6 Inhibitors as an Anticarcinogen with a Cardioprotective Effect.

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.

Years of potential life lost due to hepatitis B with or without Delta agent in the Kyrgyz Republic

Recent studies indicate that a marked percentage of chronic viral hepatitis B patients is coinfected with hepatitis D virus known to accelerate the progression of liver disease and contribute to unfavourable disease outcome. Data on premature mortality assessed by the Lost Years of Potential Life (LYPL) indicator, provide the most accurate social burden estimate for such coinfection able to contribute to strengthening viral hepatitis control measures. The aim of the study was to conducting comparative LYPL analyses due to acute and chronic hepatitis B infection without and with delta agent in the Kyrgyz Republic in the years 2014–2018. Materials and methods. LYPL magnitude was calculated using the number of recorded deaths in the reporting form of the 2014–2018 National Statistics Committee «C51-Distribution of deaths by sex, age groups and causes of death». Results. In 2014–2018, 145 cases of death of patients with viral hepatitis B without (HB) and with a delta agent (D) were registered in the Kyrgyz Republic. Of these, 66% (96/145) of patients died from hepatitis B, of which a third (32/96) had an acute disease course. And among those who died from hepatitis D (19/49), acute course was registered in 39%. LYPL for the 145 deceased patients totaled 3766 years, of which 63% (2365 years) were due to HB. Despite that only 35% of patients (51/145) died from acute forms of such hepatitides, their LYPL accounted for 52% (1968) of total years lost that decreased by 4.5-fold for 2014–2018 due to AHB (6.3‰ and 1.41‰, 2014 and 2018, respectively) but increased by 1.1-fold due to AHD (2.7‰ and 3.1‰, 2014 and 2018, respectively). Chronic hepatitis B vs CHD resulted in 1.6 times higher LYPL magnitude (1108 and 691, respectively). At the same time, LYPL due to CHB dynamically increased by 2.6 times, whereas due to CHD — by 6.3 times. Сonclusion. The high LYPL level due to hepatitis B and D infection related to pediatric cases evidence about a heavy burden of such diseases in the Kyrgyz Republic. The data obtained prove that it is necessary to increase adherence of adult population to hepatitis B vaccination and examine children at the site of infection, regardless of vaccination history. Abruptly increased LYPL due to chronic hepatitis cases requires strengthening secondary prevention measures and ensuring timely access to specialized care at infection sites. It is also necessary to evaluate epidemiological surveillance after fatal viral hepatitis.

Acid sphingomyelinase deficiency in France: a retrospective survival study

BackgroundAcid sphingomyelinase deficiency (ASMD) or Niemann–Pick disease types A, A/B, and B is a progressive, life-limiting, autosomal recessive disorder caused by sphingomyelin phosphodiesterase 1 (SMPD1) gene mutations. There is a need to increase the understanding of morbidity and mortality across children to adults diagnosed with ASMD.MethodsThis observational retrospective survey analysed medical records of patients with ASMD with retrievable data from 27 hospitals in France, diagnosed/followed up between 1st January 1990 and 31st December 2020. Eligible records were abstracted to collect demographic, medical/developmental history, and mortality data. Survival outcomes were estimated from birth until death using Kaplan–Meier survival analyses; standardised mortality ratio (SMR) was also explored.ResultsA total of 118 medical records of patients with ASMD (type B [n = 94], type A [n = 15], and type A/B [n = 9]) were assessed. The majority of patients were males (63.6%); the median [range] age at diagnosis was 8.0 [1.0–18.0] months (type A), 1.0 [0–3] year (type A/B), and 5.5 [0–73] years (type B). Overall, 30 patients were deceased at the study completion date; the median [range] age at death for patients with ASMD type A (n = 14) was 1 [0–3.6] year, type A/B (n = 6) was 8.5 [3.0–30.9] years, and type B (n = 10) was 57.6 [3.4–74.1] years. The median [95% confidence interval (CI)] survival age from birth in patients with ASMD type A and type A/B was 2.0 [1.8–2.7] years and 11.4 [5.5–18.5] years, respectively. Survival analysis in ASMD type B was explored using SMR [95% CI] analysis (3.5 [1.6–5.9]), which showed that age-specific deaths in the ASMD type B population were 3.5 times more frequent than those in the general French population. The causes of death were mostly severe progressive neurodegeneration (type A: 16.7%), cancer (type B: 16.7%), or unspecified (across groups: 33.3%).ConclusionsThis study illustrated a substantial burden of illness with high mortality rates in patients with ASMD, including adults with ASMD type B, in France.

Training cadres and establishment of an integrated development post for non-communicable diseases based on a mosque

Introduction: Non-communicable diseases (NCDs) are the highest cause of death due to non-communicable diseases in Indonesia. This condition is certainly very worrying, because the trend of NCDs is increasing followed by a shift in disease patterns, where previously NCDs were experienced by the elderly group, are now starting to threaten younger age groups. Public awareness of NCD risk factors needs to be increased. This requires community participation in PTM (penyakit tidak menular) integrated development activities (Posbindu). Posbindu PTM is an activity for early detection and monitoring of the main risk factors for PTM through community participation. The aim of this activity is cadre training and the establishment of a mesque-based Posbindu PTM. Methods: The method used is Asset Based Community Development (ABCD). The ABCD method is a service method that focuses on the strengths and capacities of local communities. The establishment of the PTM Posbindu was carried out at the Aisyah Abdul Latif Farah Mosque, Namorambe District, Deli Serdang Regency. There were 10 cadres recruited at Posbindu PTM Mosque. Results: The results of the establishment of the mask-based PTM Posbindu are expected to be able to detect PTM risk factors as early as possible and reduce the number of PTM congregants at mosques in particular and society in general. Conclusion: The socialization and formation of the mosque-based Posbindu PTM received positive support from the Deli Serdang Health Service and the Aisyah Abdul Latif Farah Mosque.

MRI and Clinical Variables for Prediction of Outcomes After Pediatric Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and disability in children, and predicting functional outcome after TBI is challenging. Magnetic resonance imaging (MRI) is frequently conducted after severe TBI; however, the predictive value of MRI remains uncertain. To identify early MRI measures that predict long-term outcome after severe TBI in children and to assess the added predictive value of MRI measures over well-validated clinical predictors. This preplanned prognostic study used data from the Approaches and Decisions in Acute Pediatric TBI (ADAPT) prospective observational comparative effectiveness study. The ADAPT study enrolled 1000 consecutive children (aged <18 years) with severe TBI between February 1, 2014, and September 30, 2017. Participants had a Glasgow Coma Scale (GCS) score of 8 or less and received intracranial pressure monitoring. Magnetic resonance imaging scans performed as part of standard clinical care within 30 days of injury were collected at 24 participating sites in the US, UK, and Australia. Summary imaging measures were correlated with the Glasgow Outcome Scale-Extended for Pediatrics (GOSE-Peds), and the predictive value of MRI measures was compared with the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) core clinical predictors. Data collection, image analysis, and data analyses were completed in July 2023. Pediatric severe TBI with an MRI scan performed as part of clinical care. All measures were selected a priori. Magnetic resonance imaging measures included contusion, ischemia, diffuse axonal injury, intracerebral hemorrhage, and brainstem injury. Clinical predictors included the IMPACT core measures (GCS motor score and pupil reactivity). All models adjusted for age and sex. Outcome measures included the GOSE-Peds score obtained at 3, 6, and 12 months after injury. This study included 233 children with severe TBI who were enrolled at participating sites and had an MRI scan and preselected clinical predictors available. Their median age was 6.9 (IQR, 3.0-13.3) years, and more than half of participants (134 [57.5%]) were male. In a multivariable model including MRI measures and IMPACT core clinical variables, contusion volume (odds ratio [OR], 1.13; 95% CI, 1.02-1.26), brain ischemia (OR, 2.11; 95% CI, 1.58-2.81), brainstem lesions (OR, 5.40; 95% CI, 1.90-15.35), and pupil reactivity were each independently associated with GOSE-Peds score. Adding MRI measures to the IMPACT clinical predictors significantly improved model fit and discrimination between favorable and unfavorable outcomes compared with IMPACT predictors alone (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.72-0.85 vs 0.67; 95% CI, 0.61-0.76 for GOSE-Peds score >3 at 6 months after injury). In this prognostic study of children with severe TBI, the addition of MRI measures significantly improved outcome prediction over well-established and validated clinical predictors. Magnetic resonance imaging should be considered in children with severe TBI to inform prognosis and may also promote stratification of patients in future clinical trials.

Hypertension evaluation and management in new young patients: are we doing our female patients a disservice?

Purpose Cardiovascular disease (CVD) is one of the leading causes of death in women, largely underpinned by hypertension. Current guidelines recommend first-line therapy with a RAAS-blocking agent especially in young people. There are well documented sex disparities in CVD outcomes and management. We evaluate the management of patients with newly diagnosed hypertension in a tertiary care clinic to assess male–female differences in investigation and treatment. Methods Clinic letters of all new patients under the age of 51 attending the Glasgow Blood Pressure Clinic between January and December 2023 were reviewed. The primary outcomes measured were first-line treatment choices, deviations from guideline-recommended treatment, investigations for secondary hypertension, and documentation of female-specific risk factors and family planning advice. Secondary outcomes included clinical characteristics such as systolic and diastolic blood pressure at referral and at the new patient appointment, age at diagnosis, age at first appointment, and the number of antihypertensive drugs prescribed at referral. Results One hundred and five (59:46, M:F) new patient encounters were reviewed after sixteen exclusions for non-attendance and inappropriate clinic coding. Choice of first line antihypertensive agent did not vary between sexes with no deviation from guideline-recommended medical therapy. Men, however, had more biochemical investigations conducted for secondary causes across all ages. This was greatest in those under 40 years old. There was suboptimal documentation of female-specific risk factors (obstetric and gynaecological history), contraceptive drug history and family planning with 35%, 20%, and 15.6%, respectively. Conclusion In 2023, women under 51 years of age seen in a tertiary care hypertension clinic received similar first-line treatment to their male peers. However, relevant female-specific histories were suboptimally documented for these patients. Whilst therapeutic approaches in men and women appear to be similar in this clinic, there are opportunities to improve CVD prevention in women, even in a specialised clinic setting.

Factors associated with the spatiotemporal distribution of dog rabies in Tunisia.

Despite continuous efforts of veterinary services to control rabies in dogs since 1982, rabies remains a cause of death in Tunisia, with more than five reported human cases in 2022. As little is known on the determinants of transmission of rabies in dogs, better understand which factors contribute to its spatial heterogeneity in Tunisia is critical for developing bespoke mitigation activities. In this context, we developed Bayesian Poisson mixed-effect spatio-temporal model upon all cases of rabid dogs reported in each delegation during the period from 2019 to 2021. The best fitting model highlighted the association between the risk of rabies and the mean average monthly temperature, the density of markets and the density of dogs in delegations. Interestingly, no relationship was found between intensity of vaccination in dogs and the risk of rabies. Our results provided insights into the spatio-temporal dynamics of dog rabies transmission and highlighted specific geographic locations where the risk of infection was high despite correction for associated explanatory variables. Such an improved understanding represent key information to design bespoke, cost-efficient, rabies prevention and control strategies to support veterinary services activities and policymaking.

Novel Approach for Cardioprotection: In Situ Targeting of Metformin via Conductive Hydrogel System

Ischemia/reperfusion (I/R) injury following myocardial infarction is a major cause of cardiomyocyte death and impaired cardiac function. Although clinical data show that metformin is effective in repairing cardiac I/R injury, its efficacy is hindered by non-specific targeting during administration, a short half-life, frequent dosing, and potential adverse effects on the liver and kidneys. In recent years, injectable hydrogels have shown substantial potential in overcoming drug delivery challenges and treating myocardial infarction. To this end, we developed a natural polymer hydrogel system comprising methacryloylated chitosan and methacryloylated gelatin modified with polyaniline conductive derivatives. In vitro studies demonstrated that the optimized hydrogel exhibited excellent injectability, biocompatibility, biodegradability, suitable mechanical properties, and electrical conductivity. Incorporating metformin into this hydrogel significantly extended the administration cycle, mitigated mitochondrial damage, decreased abnormal ROS production, and enhanced cardiomyocyte function. Animal experiments indicated that the metformin/hydrogel system reduced arrhythmia incidence, infarct size, and improved cardiac mitochondrial and overall cardiac function, promoting myocardial repair in I/R injury. Overall, the metformin-loaded conductive hydrogel system effectively mitigates mitochondrial oxidative damage and improves cardiomyocyte function, thereby offering a theoretical foundation for the potential application of metformin in cardioprotection.

Enriched marine oil supplements in pregnancy for the modulation of maternal inflammatory- associated causes of preterm delivery

Preterm birth is a major cause of perinatal complications and neonatal deaths. Furthermore, in the field of obstetrics many clinical entities like uterine contractions or the occurrence of pre- eclampsia remain to be serious complications during pregnancy and represent a major psychological, financial, and economic burden for society. Several published guidelines, studies and recommendations have highlighted the importance of supplementation of omega-3 long chain polyunsaturated fatty acids (PUFAs) during pregnancy. This narrative review aims at giving an overview on the modern perception of inflammatory processes and the role of specialized pro-resolving mediators (SPMs) in their resolution, especially in obstetrics. Additionally, we highlight the possible role of SPMs in the prevention of obstetric complications through oral supplementation using enriched marine oil nutritional’s. The intake of PUFAs may result in an overall improvement of pregnancy outcomes by contributing to fetal brain growth and neurological development but more importantly though modulation of inflammation-associated pathologies. Especially the use of SPMs represents a promising approach for the management of obstetric and perinatal complications. SPMs are monohydroxylates derived from enriched marine oil nutritional’s that involve certain pro-resolutive metabolites of omega-3 long chains PUFAs and may contribute to an attenuation of inflammatory diseases. This may be obtained through various mechanisms necessary for a proper resolution of inflammation such as the termination of neutrophil tissue infiltration, initiation of phagocytosis, downregulation of pro-inflammatory cytokines or tissue regeneration. In this way, acute and chronic inflammatory diseases associated with serious obstetrical complications can be modulated, which might contribute to an improved pregnancy outcome.

The influence of air masses on human mortality in the contiguous United States.

Temperature-related mortality is the leading cause of weather-related deaths in the United States. Herein, we explore the effect of air masses (AMs) - a relatively novel and holistic measure of environmental conditions - on human mortality across 61 cities in the United States. Geographic and seasonal differences in the effects of each AM on deseasonalized and detrended anomalous lagged mortality are examined using simple descriptive statistics, one-way analyses of variance, relative risks of excess mortality, and regression-based artificial neural network (ANN) models. Results show that AMs are significantly related to anomalous mortality in most US cities, and in most seasons. Of note, two of the three cool AMs (Cool and Dry-Cool) each show a strong, but delayed mortality response in all seasons, with peak mortality 2 to 4days after they occur, with the Dry-Cool AM having nearly a 15% increased risk of excess mortality. Humid-Warm (HW) air masses are associated with increases in deaths in all seasons 0 to 1days after they occur. In most seasons, these near-term mortality increases are offset by reduced mortality for 1-2weeks afterwards; however, in summer, no such reduction is noted. The Warm and Dry-Warm AMs show slightly longer periods of increased mortality, albeit slightly less intensely as compared with HW, but with a similar lag structure by season. Meanwhile, the most seasonally consistent results are with transitional weather, whereby passing cold fronts are associated with a significant decrease in mortality 1day after they occur, while warm fronts are associated with significant increases in mortality at that same lag time. Finally, ANN modeling reveals that AM-mortality relationships gleaned from a combined meta-analysis can actually lead to more skillful modeling of these relationships than models trained on some individual cities, especially in the cities where such relationships might be masked due to low average daily mortality.

Ovarian Cancer Staging—How CT Scan Descriptions Differ from Surgical Findings

Ovarian cancer is one of the most common causes of cancer death in women worldwide. Most often, it is detected in an advanced stage due to its insidious onset and lack of symptoms in stages I and II. That is why imaging diagnostics is so important. Therefore, we assessed the consistency of the image seen on CT with the actual image assessed during surgery. Objectives: The aim of this study is to compare preoperative evaluation based on CT reports with those obtained during ovarian cancer surgery to determine whether CT is helpful in assessing the possibility of optimal or complete cytoreduction. Methods: This retrospective study included patients diagnosed with ovarian cancer who underwent diagnostic laparoscopy or laparotomy with cytoreduction. We compared ovarian cancer lesions described by radiologists on CT scans to those described during laparoscopy or laparotomy; the Wilcoxon signed-rank test for paired observations was used to compare the variables. Results: We observed that the morphology of the tumor, mesenteric infiltration, and the assessment of the involvement of the abdominal, para-aortic, and iliac lymph nodes may differ in CT examination and during surgery. Conclusions: The site of the tumor exit on a CT scan does not always reflect the original site seen during surgery.

Correlation of Cause of Death Issued in Medico Legal Deaths in Hospitals and Cause of Death Found at Autopsy

Background:The death certificate is essential for legal investigations and public health planning. This study examines theaccuracy of causes of death reported by hospitals versus post-mortem findings and evaluates the completeness of deathcertificates.Method: A prospective, descriptive study was conducted in 99 cases, with hospital-issued death certificates, broughtfor medico-legal autopsy to the Department of Forensic Medicine, Institute of Medicine, Maharajgunj Medical Campus.Cases which were brought dead to the hospital but still were issued with death certificates and cases where the cause ofdeath remained undetermined even after autopsy were excluded. Data was recorded in a pro-forma and analyzed using theSPSS software Version 20.Result: The study involved individuals aged 13 to 30 years, mostly male. Private hospitals issued 66.7% of death certificates,with 55.6% by house officers. Only 62.6% met WHO standards. Autopsies were performed within 24 hours in 67.7% ofcases, revealing blunt force head injury as the leading cause of death (26.3%). There was a 67.7% discrepancy betweenhospital and autopsy causes of death, with house officers and government hospitals showing notable inconsistencies.Conclusion: Factors like the use of standard or non-standard death certificates, the designation of doctors, and the typeof hospital issuing the certificates influence the discrepancies between the causes of death listed by hospitals and thosedetermined after autopsies. This study aims to enhance the existing knowledge on the accuracy of death certificates and islikely the first systematic study of its kind in Nepal, laying the groundwork for future research.

Trends in life expectancy and life disparity in Turkiye before and during the Covid-19 period

Objective: This descriptive study examines Turkiye's life expectancy trends from 2013 to 2022, encompassing the COVID-19 period. Methods: This study used the Turkish Statistical Institute (TURKSTAT) cause of death data and explored trends in life expectancy and life disparity by using the line-integral decomposition model. Results: According to results, before the pandemic, increased male life expectancy and reduced disparity resulted from improved outcomes in unintentional injuries and malignant neoplasms during adulthood. Female life expectancy gains were driven by declining cardiovascular diseases in old age. However, during COVID-19, males experienced a greater loss of life expectancy than females in youth and adulthood, while females faced higher mortality rates in old age than males. The pandemic has exacerbated the female-male gap in life expectancy and disparity, with all causes of death increasing except for an improvement in malignant neoplasms among males. Conclusion: The study suggests prioritizing policies that address the health challenges faced by elderly females and young/adult males to mitigate the pandemic's impact on public health.

Transcriptomic analyses of lung tissues reveal key genes associated with progression of systemic sclerosis-interstitial lung disease (SSc-ILD)

Systemic sclerosis-interstitial lung disease (SSc-ILD) is the leading cause of death in SSc, affecting around 50% of the patients. Lung tissue of patients with early-stage SSc-ILD is characterized by a predominant inflammatory response with inconspicuous fibrosis, which may progress to honeycombing fibrosis. Hence, a better understanding of the molecular mechanisms underpinning SSc-ILD pathogenesis is needed to improve treatment options and progression prediction. This transcriptomic study aims to reveal the differential gene expression between control (ctrl) lung tissue and inflammatory, prefibrotic and fibrotic lung tissue to capture progression of early to late phase SSc-ILD. Twelve explanted lungs from patients with SSc-ILD were used to analyze gene expression from formalin-fixed paraffin-embedded lung tissues with varying stages of ILD (n=18) and control lung tissue (n=6). The SSc-ILD tissues were stratified into three ROIs: inflammatory, prefibrotic, and fibrotic using histological assessments to define a longitudinal simulation of early to late phases of SSc-ILD. The nanoString (nS) nCounter Human Fibrosis Panel was used to profile the transcriptome in the regions of interest. Validation of potential targetswas performed with immunohistochemistry in the same tissues that were used for transcriptome analysis. To validate our simulation model, we performed subgroup analysis that showed an incremental increase in pathway scores related to the severity of fibrosis. Ctrl vs SSc-ILD comparison demonstrated 24 differentially expressed genes, two of which had the most pronounced p-values. Cyclin-dependent kinase inhibitor (cdkn2c) was overexpressed (P=0.00052) in SSc-ILD compared to ctrl, while expression of Pellino E3 ubiquitin-protein ligase 1 (peli1) showed lower expression (P=0.0012). Additionally, in all four groups, cdkn2c and peli1 gene expression showed an incremental increase and decrease, respectively. Immunohistochemistry of cdkn2c showed consistent results with the nS analysis. More cdkn2c and less peli1 expression were associated with more advanced stages of SSc-ILD on histologic assessment. We report the potential of the cell cycle inhibitor and senescence marker, cdkn2c (p18) to be associated with fibrosis progression.