Death Rate Research Articles

THE INFLUENCE OF MILITARY EVENTS AS A SOCIALLY STRESS FACTOR ON THE SUICIDE MORTALITY RATE

Introduction. Russia's aggression, which began in 2014 with the occupation of Crimea and parts of Donetsk and Luhansk regions, is considered a powerful long-term socially stressful factor. The suicide rate, as an indicator of troubles in society and its health as a whole, helps to identify a vulnerable contingent of the population and evaluate the effectiveness of state preventive measures implemented in socially stressful conditions. The aim: to investigate the dynamics of suicide mortality in Ukraine for the period 2005-2021. and the impact on this indicator of a socially stressful factor – Russian aggression in order to determine the stability of Ukrainian society in the conditions of war, identify the most vulnerable contingent of the population and evaluate the state's multi-selective approach aimed at preventing suicide. Materials and methods. The research materials were official statistical data from the "Population of Ukraine" reports of the State Statistics Service of Ukraine for 2005-2021. Cases of suicide of men and women in the period 2005-2013 served as a comparison group. The analysis provided for the clarification of annual rates and dynamics of suicide mortality and its gender characteristics during the period of the social stress factor in 2014-2021, in comparison with the control period and world indicators (WHO). Bibliographic, epidemiological, analytical, statistical methods were used in the research. Results. In Ukraine, as well as in the world, in the period 2005-2021, a decrease in the death rate due to suicides is noted, however, the Ukrainian rates significantly exceed the world rates. In a relatively prosperous period, the mortality rate due to suicide was 20.8±0.3, and it decreased statistically significantly (p<0.001) to 16.1±0.36 in the socially stressful period of 2014-2021. The number of suicides among the male population significantly exceeds its number among the female population and is significantly higher than the world indicators, in contrast to the female population, where the indicators are even lower. During the socially stressful period, the number of suicides among men remains reduced to 28.76±0.92 (р<0.001) and among women to 5.64±0.3 (р<0.05), with more stable rates of decline among women. Conclusions. In Ukraine, there is a dynamic decrease in the number of deaths due to suicides, which correlates with global indicators. However, our country, despite the faster rate of decline of this indicator, still belongs to the countries with a high rate of suicide mortality. During the military events of 2014-2021, the death rate from suicides decreased significantly, compared to the previous relatively prosperous period of 2005-2013 (p<0.001), which indicates the stability of Ukrainian society in war conditions. Mortality due to suicides in Ukraine significantly prevails among men (p<0.001) and significantly exceeds global indicators, which makes them a vulnerable contingent of the population that needs socially oriented support. The positive dynamics of the decrease in the number of suicides among men (p<0.001) and women (p<0.05) in the conditions of war testifies to the effectiveness of the state's multi-selective approach aimed at preventing suicide.

Characterization of treatment resistance and viral kinetics in the setting of single- versus dual-active monoclonal antibodies against SARS-CoV-2.

Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for SARS-CoV-2 infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs. Participants were non-hospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant. Study participants receiving single- and dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared to single-active mAb, treatment with dual-active mAbs led to faster viral load decline at study day 3 (p < 0.001) and day 7 (p < 0.01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than placebo (2.6% vs 0%, P < 0.001), and more frequently detected in the setting of single-active compared to dual-active mAb treatment (7.2% vs 1.1%, p < 0.01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death. Compared to single-active mAb therapy, dual-active mAbs led to similar clinical outcomes, but significantly faster viral load decline and a lower risk of emergent resistance.

The Pattern of Motorcyclists' Death Due to Accidents and a Three-year Forecast in East Azerbaijan Province, Iran: A Time Series Study

Introduction: In low- and middle-income countries, a large proportion of road users include pedestrians, cyclists, and motorcyclists, and nearly half of road traffic fatalities occur among motorcyclists. This study aimed to examine the pattern of motorcyclists' death due to accidents in East Azerbaijan, Iran between 2006 and 2021 and present a forecast. Methods: We used death data due to motorcycle accidents of Legal Medicine Department between 2006 and 2021. For time series analysis, the Box-Jenkins model was used and three stages of identification, estimation, and diagnosis were successively performed and repeated several times to achieve the best prediction model. The Box-cox transformation method was used to stabilize the variance, and the first-order seasonal differential method with a period of 12 was used to control the seasonality. Due to seasonal variations, the Seasonality Auto-Regressive Integrated Moving Average model: SARIMA (p, d, q) (P, D, Q)s was employed and the death trend was predicted for 36 months. The candidate models were compared based on Log-likelihood, AIC, and BIC indices. STATA 17 was used for data analysis. Results: About 18.6% of all accident deaths are attributed to motorcycle accidents. The death rate for all causes of accidents and motorcycle accidents were 23.13 and 4.30 per 100,000 population, respectively. Seven models were considered as candidates. The SARIMA (0, 0, 0) (1, 1, 1)12 model was selected as the best model due to better fit and used to predict the number and trend of motorcycle accident deaths. Motorcycle accident deaths are predicted to decrease gradually in the next 36 months, from June 2021 to May 2024, affected by seasonal changes. Conclusion: The trend of death due to motorcycle accidents from 2006 to 2021 in East Azerbaijan was declining, and it is predicted to decrease slightly in the next three years as well. As this reduction may be attributed to many factors, it is recommended to investigate effective factors in future studies.

TRPV4 modulation participates in paraoxon-induced brain injury via NMDA and NLRP3 regulation

ABSTRACT Background Organophosphorus pesticide poisoning can lead to severe brain damage, but the specific mechanisms involved are not fully understood. Our research aims to elucidate the function of the TRPV4 ion channel in the development of brain injury induced by paraoxon (POX). Methods In vivo, we examined the survival rate, behavioral seizures, histopathological alterations, NMDA receptor phosphorylation, as well as the expression of the NLRP3-ASC-caspase-1 complex and downstream inflammatory factors in the POX poisoning model following intervention with the TRPV4 antagonist GSK2193874. In vitro, we investigated the effects of GSK2193874 on NMDA-induced inward current, cell viability, cell death rate, and Ca2+ accumulation in primary hippocampal neurons. Results The treatment with the TRPV4 antagonist increased the survival rate, suppressed the status epilepticus, improved pathological damage, and reduced the phosphorylation level of NMDA receptors after POX exposure. Additionally, it inhibited the upregulation of NLRP3 inflammasome and inflammatory cytokines expression after POX exposure. Moreover, the TRPV4 antagonist corrected the NMDA-induced increase in inward current and cell death rate, decrease in cell viability, and Ca2+ accumulation. Conclusion TRPV4 participates in the mechanisms of brain injury induced by POX exposure through NMDA-mediated excitotoxicity and NLRP3-mediated inflammatory response.

Medical Device-Associated Biofilm Infections and Multidrug-Resistant Pathogens

Medical devices such as venous catheters (VCs) and urinary catheters (UCs) are widely used in the hospital setting. However, the implantation of these devices is often accompanied by complications. About 60 to 70% of nosocomial infections (NIs) are linked to biofilms. The main complication is the ability of microorganisms to adhere to surfaces and form biofilms which protect them and help them to persist in the host. Indeed, by crossing the skin barrier, the insertion of VC inevitably allows skin flora or accidental environmental contaminants to access the underlying tissues and cause fatal complications like bloodstream infections (BSIs). In fact, 80,000 central venous catheters—BSIs (CVC-BSIs)—mainly occur in intensive care units (ICUs) with a death rate of 12 to 25%. Similarly, catheter-associated urinary tract infections (CA-UTIs) are the most commonlyhospital-acquired infections (HAIs) worldwide.These infections represent up to 40% of NIs.In this review, we present a summary of biofilm formation steps. We provide an overview of two main and important infections in clinical settings linked to medical devices, namely the catheter-asociated bloodstream infections (CA-BSIs) and catheter-associated urinary tract infections (CA-UTIs), and highlight also the most multidrug resistant bacteria implicated in these infections. Furthermore, we draw attention toseveral useful prevention strategies, and advanced antimicrobial and antifouling approaches developed to reduce bacterial colonization on catheter surfaces and the incidence of the catheter-related infections.

Encapsulation of Lactiplantibacillus plantarum CRD7 in sub-micron pullulan fibres by spray drying: Maximizing viability with prebiotic and thermal protectants

Pullulan was used as the wall material for microencapsulation of L. plantarum CRD7 by spray drying, while isomalto-oligosaccharides (IMO) was used as prebiotic. Also, the effect of different thermal protectants on survival rate during microencapsulation was evaluated. Taguchi orthogonal array design showed that pullulan at 14 % concentration, IMO at 30 % concentration and whey protein isolate at 20 % rate were the optimized wall material, prebiotic and thermal protectant, respectively for microencapsulation of L. plantarum. FESEM images revealed that the spray-dried encapsulates were fibrous similar to those produce by electrospinning, while fluorescence microscopy ascertained that most of the probiotic cells were alive and intact after microencapsulation. The adsorption-desorption isotherm was of Type II and the encapsulate had specific surface area of 1.92 m2/g and mean pore diameter of 15.12 nm. The typical amide II and III bands of the bacterial proteins were absent in the FTIR spectra, suggestive of adequate encapsulation. DSC thermogram showed shifting of melting peaks to wider temperature range due to interactions between the probiotic and wall materials. IMO at 30 % (w/w) along with WPI at 20 % concentration provided the highest storage stability and the lowest rate of cell death of L. plantarum after microencapsulation. Acid and bile salt tolerance results confirmed that microencapsulated L. plantarum could sustain the harsh GI conditions with >7.5 log CFU/g viability. After microencapsulation, L. plantarum also possessed the ability to ferment milk into curd with pH of 4.62.

Chinese expert consensus on treatment of osteoporotic fractures with teriparatide (2024 edition)

Osteoporotic fracture is the most serious complication of osteoporosis, which is a special type of pathologic fracture of the skeleton that occurs because of osteoporosis. It is characterized by delayed fracture healing, high risk of re-fracture, high rate of disability and death, difficulty in treatment and long treatment time, and re-fracture has a"cascade effect". Guidelines in different countries recommend that patients with osteoporotic fractures and those at very high risk of fracture should consider anabolic agents as first treatment choice. Teriparatide is the only anabolic agent approved by National Medical Products Administration (NMPA), and it has the clinical efficacy of improving fracture healing, reducing the risk of re-fracture, and improving bone microstructure in the treatment of osteoporotic fracture. Due to deficiencies in the current standardization of clinical use of teriparatide, Committee of Accelerated Rehabilitation After Osteoporotic Fractures of China Association of Rehabilitation Technology Transformation and Promotion, Bone and Joint Group of Chinese Society of Osteoporosis and Bone Mineral Research and Osteoporosis Working Committee of Chinese Association of Orthopedic Surgeons developed this consensus. The development of this consensus follows the modified Delphi method and forms 8 evidence-based medical recommendations, aiming to propose methods and precautions for standardizing the application of teriparatide, and to emphasize the importance of teriparatide application for the treatment of patients with osteoporotic fracture.

Curcuma aromatica rhizomes ethanol extract: A potential therapeutic agent against HepG2 Hepatoma cells

Curcuma aromatica, a Vietnamese medicinal plant, exhibits diverse therapeutic applications including blood loss, blood stasis, bloody urination, bloody vomiting, irregular menstruation, epilepsy, and cancer treatment. C. aromatica rhizomes ethanol extract and curcumol content have been shown strong inhibition of cancer growth. HepG2 cells were exposed to different doses of ethanol extract and curcumol extract. The degree of cell growth inhibition was determined using the WST-1 assay, and Hoechst 33258 spectrofluorometric assay, while the rate of cell death by apoptosis was assessed using the annexin-propidium iodide double-staining assay. Flow cytometry was employed to study the cell cycle, while the transwell assay was used to assess cell migration and invasion. The expression of bax and bcl-2 genes was analyzed using real-time reverse transcription-PCR. C. aromatica rhizomes ethanol extract (CE) consisted of a total phenolic content value of 15.02±0.18 (mg/g extract) and a curcumol level of 849.8 ± 23.73 (?g/g extract). The growth of HepG2 cells was suppressed in a dose-dependent manner by C. aromatica rhizomes ethanol extract. Following a 72-hour exposure to an (CE) concentration of 100 ?g/mL, the inhibition rate was measured to be 34.559 ± 0.456 %, the IC50 value was determined to be 44.79 ?g/mL and the inhibition of curcumol was 50.961± 0.641 %, and the IC50=93.48. The application of CE induced late apoptosis in HepG2 cells. The CE also induced programmed cell death (apoptosis) in HepG2 cancer cells, effectively suppressing their growth, movement, and invasion by controlling the synthesis of Bcl-2 mRNA. This work gives novel insights into the antihepatoma action of (CE) and establishes a foundation for the development of preliminary anticancer medications.

Design, Rationale and Initial Findings From HERA-FIB on 10 222 Patients With Atrial Fibrillation Presenting to an Emergency Department Over An 11-Year Period.

For the majority of patients with atrial fibrillation (AF), disease management has improved in recent years. However, there are still populations underrepresented or excluded in current registries and randomized controlled trials. HERA-FIB (Heidelberg Registry of Atrial Fibrillation) was planned to assess real-world evidence for the prevalence, demographic characteristics and management of patients with the diagnosis of AF presenting consecutively to a chest pain unit. HERA-FIB is a retrospective, observational, single-center study on patients with a diagnosis of AF presenting to a chest pain unit from June 2009 until March 2020. This article describes the structure, governance, outcome assessment, quality and data collection processes of the registry. Additionally, characteristics of populations of special interest are described. The study consecutively enrolled 10 222 patients presenting with AF to the chest pain unit of the University Hospital of Heidelberg. Clinical parameters and patient characteristics were assessed retrospectively. Outcome parameters included rates for all-cause death, stroke, myocardial infarction and major bleedings. We were able to investigate patient cohorts of special interest such as advanced chronic kidney disease, octogenarians, and those with acute coronary syndrome who are often underrepresented in current studies and randomized controlled trials. HERA-FIB is one of the largest real-world single-center retrospective registries on patients with AF, which captures the era of transition from vitamin K antagonists to non-vitamin K oral anticoagulation regimens in clinical practice and offers the possibility to investigate patient populations usually underrepresented or excluded in current available randomized controlled trials and registries. URL: https://www.clinicaltrials.gov; unique identifier: NCT05995561.

How do new crises impact HIV risk behaviour – exploring HIV risk behaviour according to COVID-19-related orphanhood status in South Africa?

ABSTRACT The COVID-19 pandemic resulted in high death rates globally, and over 10.5 million children lost a parent or primary caregiver. Because HIV-related orphanhood has been associated with elevated HIV risk, we sought to examine HIV risk in children affected by COVID-19 orphanhood. Four hundred and twenty-one children and adolescents were interviewed, measuring seven HIV risk behaviours: condom use, age-disparate sex, transactional sex, multiple partners, sex associated with drugs/alcohol, mental health and social risks. Approximately 50% (211/421) experienced orphanhood due to COVID-19, 4.8% (20/421) reported living in an HIV-affected household, and 48.2% (203/421) did not know the HIV status of their household. The mean age of the sample was 12.7 years (SD:2.30), of whom 1.2% (5/421) were living with HIV. Eighty percent (337/421) reported at least one HIV risk behaviour. HIV sexual risk behaviours were more common among children living in HIV-affected households compared to those not living in HIV-affected households and those with unknown household status (35.0% vs. 13.6% vs.10.8%, X2 = 9.25, p = 0.01). Children living in HIV-affected households had poorer mental health and elevated substance use (70.0% vs. 48.5%, X2 = 6.21, p = 0.05; 35.0% vs. 19.9%, X2 = 4.02, p = 0.1306, respectively). HIV-affected households may require specific interventions to support the health and well-being of children and adolescents.

Mathematical modelling of stem and progenitor cell dynamics during ruxolitinib treatment of patients with myeloproliferative neoplasms

IntroductionThe Philadelphia chromosome-negative myeloproliferative neoplasms are a group of slowly progressing haematological malignancies primarily characterised by an overproduction of myeloid blood cells. Patients are treated with various drugs, including the JAK1/2 inhibitor ruxolitinib. Mathematical modelling can help propose and test hypotheses of how the treatment works.Materials and methodsWe present an extension of the Cancitis model, which describes the development of myeloproliferative neoplasms and their interactions with inflammation, that explicitly models progenitor cells and can account for treatment with ruxolitinib through effects on the malignant stem cell response to cytokine signalling and the death rate of malignant progenitor cells. The model has been fitted to individual patients’ data for the JAK2 V617F variant allele frequency from the COMFORT-II and RESPONSE studies for patients who had substantial reductions (20 percentage points or 90% of the baseline value) in their JAK2 V617F variant allele frequency (n = 24 in total).ResultsThe model fits very well to the patient data with an average root mean square error of 0.0249 (2.49%) when allowing ruxolitinib treatment to affect both malignant stem and progenitor cells. This average root mean square error is much lower than if allowing ruxolitinib treatment to affect only malignant stem or only malignant progenitor cells (average root mean square errors of 0.138 (13.8%) and 0.0874 (8.74%), respectively).DiscussionSystematic simulation studies and fitting of the model to the patient data suggest that an initial reduction of the malignant cell burden followed by a monotonic increase can be recapitulated by the model assuming that ruxolitinib affects only the death rate of malignant progenitor cells. For patients exhibiting a long-term reduction of the malignant cells, the model predicts that ruxolitinib also affects stem cell parameters, such as the malignant stem cells’ response to cytokine signalling.

Contribution of Endoscopy in the Diagnosis of Digestive Pathologies in Children in the Pediatrics Department of Gabriel TOURE Hospital

Introduction: Upper GI endoscopy is a method of visual exploration of the upper part of the digestive tract using an optical tube fitted with a lighting system called an endoscope or fiberscope. In Mali, very few data are available on digestive endoscopy in children. The aim of our study was to demonstrate the role of endoscopy in the diagnosis of digestive pathologies in the pediatric department of Gabriel Toure hospital. Material and Methods: we conducted a retrospective study from January 2017 to December 2019 of children aged 0 to 15 years who had undergone upper GI endoscopy. Results: during our study period, 52 cases of digestive endoscopy were recorded out of 24326 children hospitalized in the Department of Pediatrics at Gabriel Touré hospital, representing a frequency of occurrence of 0.21%. The sex ratio was 0.92. 40.4% of our patients underwent endoscopy before 24 hours. Lesions were located in the esophagus in 28.8% of cases. Only 11.5% of children underwent biopsy, and the death rate was 3.8%. Conclusion: Digestive endoscopy is now a routine technique in paediatric gastrology, and represents a reliable diagnostic tool, provided that it is performed by an endoscopist trained in children and that the equipment is suitable

Prediction of mortality in young adults with cardiovascular disease using artificial intelligence

&lt;b&gt;Background:&lt;/b&gt; Young mortality is prevalent among patients with cardiovascular disease (CVD). To develop prediction models for CVD mortality in young adults, it is crucial to assess CVD risks. Early detection of cardiac disorders using machine learning algorithms, a branch of artificial intelligence (AI) is crucial for preventing more damage to coronary arteries and saving lives.&lt;br /&gt; &lt;b&gt;Aims:&lt;/b&gt; To predict mortality versus a life outcome among young adults (18-45 years) with CVD using AI technique known as Chi-squared automatic interaction detector (CHAID) algorithms.&lt;br /&gt; &lt;b&gt;Methods:&lt;/b&gt; A large-scale dataset was extracted from the electronic health records of 809 young adult patients diagnosed with CVD using a retrospective design. Information was retrieved regarding young adults from Jordan who were admitted to public health institutions between 2015 and the end of 2021.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; CHAID algorithms were chosen among seven prediction models based on accuracy and area under curve to predict mortality vs life in young individuals (18-45 years old) with CVD. The mortality prediction algorithms started with pulse pressure, then diastolic blood pressure, then ischemic heart disease, and last geographical location.&lt;br /&gt; &lt;b&gt;Conclusions:&lt;/b&gt; CHAID model used in our study indicated how the death rate was classified and distributed among a variety of parameters. As a result, we may argue that AI model could provide additional information on how many aspects are articulated in connection to CVD patient fatality situations.

Global, regional, and national burden of atrial fibrillation/flutter related to metabolic risks over three decades: estimates from the global burden of disease study 2019.

Atrial fibrillation/atrial flutter (AF/AFL) remains a significant public health concern on a global scale, with metabolic risks playing an increasingly prominent role. This study aimed to investigate comprehensive epidemiological data and trends concerning the metabolic risks related-AF/AFL burden based on the data from the Global Burden of Disease (GBD) study 2019. The analysis of disease burden focused on numbers, age-standardized rates (ASR) of deaths, disability-adjusted life years (DALYs), and estimated annual percentage change (EAPC), while considering factors of age, sex, sociodemographic index (SDI), and locations. In 2019, there was a culmination of 137179 deaths and 4099146 DALYs caused by metabolic risks related-AF/AFL worldwide, with an increase of 162.95% and 120.30% respectively from 1990. High and high-middle SDI regions predominantly carried the burden of AF/AFL associated with metabolic risks, while a shift towards lower SDI regions had been occurring. Montenegro had the highest recorded death rate (7.6 per 100000) and DALYs rate (146.3 per 100000). An asymmetrically inverted V-shaped correlation was found between SDI and deaths/DALYs rates. Moreover, females and the elderly exhibited higher AF/AFL burdens, and young adults (over 40 years old) also experienced an annual increase. The global AF/AFL burden related to metabolic risks has significantly increased over past three decades, with considerable spatiotemporal, gender-based, and age-related heterogeneity. These findings shed valuable light on the trends in the burden of metabolic risks related-AF/AFL, and offered insights into corresponding strategies.

The Impact of COVID-19 on Mortality and Clinical Characteristics in Hospitalized Patients With Peripheral Artery Disease in the Year 2020 in Germany.

The COVID-19 pandemic developed its full destructive capacity in 2020. This retrospective study aimed to examine the effects of COVID-19 on the mortality and the clinical characteristics in PAD patients with COVID-19 compared to PAD patients without COVID-19. Data derived from a German nationwide register of the year 2020 which encompassed all hospitalized patients with PAD (n = 173.075); N = 2553 also suffered from a COVID-19 infection and had significantly higher mortality rates of 11.2%. PAD + COVID-19 patients presented more clinical complications like major amputations (11.59%), myocardial infarction (2.08%), cardiogenic shock (2.98%), chronic kidney failure with GFR<= 15mL/min (5.33%) and prolonged ventilation time >48 h (3.37%). Rates of pulmonary thromboembolism (0.24%), myocardial infarction (2.08%), and stroke (1.02%) were low in patients with PAD + COVID-19. Adjusted regression analyses for risk differences revealed possible causes of higher mortality rates, such as prolonged ventilation time, pneumonia, major amputations, multiple organ system failure, and length of hospital stay in patients with severe PAD (Rutherford 5-6) + COVID-19. Pneumonia and major amputations were associated with high mortality rates in PAD + COVID-19 in 2020. However, we could not detect a relevant influence of pulmonary thromboembolism, myocardial infarction or stroke on higher death rates of PAD + COVID-19.

Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome

BackgroundShort bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. Methods and resultsThrough testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors. ConclusionsOCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation.

Protease-activated receptor 2: a promising therapeutic target for women's cancers.

Cancers affecting women, such as breast, uterine, ovarian, endometrial and cervical cancers, have become increasingly prevalent. The growing incidence and death rates associated with these cancers warrant the development of innovative and alternative approaches to current treatments. This article investigates the association of women's cancers with a molecular target known as protease-activated receptor 2 (PAR2), a G-protein coupled receptor that is expressed on the surface of cancer cells. Expression levels of the PAR2 gene were curated from publicly available databases and were found to be significantly overexpressed in tissues from patients with breast, uterine, ovarian, endometrial or cervical cancer compared to normal tissues. PAR2 overexpression has been previously linked to tumor progression and, in some cases, tumor growth. Activation of PAR2 by either endogenous proteases or synthetic agonists triggers certain downstream intracellular signaling pathways that have been associated with tumor progression, cell migration and invasion, angiogenesis and apoptosis of cancer cells. While recent advances have led to the identification of several PAR2 antagonists, none has yet been developed for human use. Additionally, PAR2 inhibition has been shown also to increase the efficacy of chemotherapeutic drugs, allowing them to be potentially used at less toxic doses in combination therapies for cancer. The present work briefly summarizes the current status of PAR2 as a potential therapeutic target for treating women's cancers. Significance Statement This article highlights potential roles for PAR2 in cancers affecting women. Overexpression of the PAR2 gene in women's cancers is associated with various oncogenic processes such as tumor progression, cell migration and invasion, ultimately contributing to poorer patient prognoses. Given the increasing incidence of women's cancers, there is an urgent need to develop novel therapeutic drugs and PAR2 represents a promising target for developing new treatments.

Long-Term Comparative Efficacy and Safety of Risdiplam and Nusinersen in Children with Type1 Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disease characterized by a loss of motor neurons and progressive muscle weakness. Children with untreated type1 SMA never sit independently and require increasing levels of ventilatory support as the disease progresses. Without intervention, and lacking ventilatory support, death typically occurs before the age of 2years. There are currently no head-to-head trials comparing available treatments in SMA. Indirect treatment comparisons are therefore needed to provide information on the relative efficacy and safety of SMA treatments for healthcare decision-making. The long-term efficacy and safety of risdiplam versus nusinersen in children with type1 SMA was evaluated using indirect treatment comparison methodology to adjust for differences between population baseline characteristics, to reduce any potential bias in the comparative analysis. An unanchored matching-adjusted indirect comparison was conducted using risdiplam data from 58 children in FIREFISH (NCT02913482) and published aggregate nusinersen data from 81 children obtained from the ENDEAR (NCT02193074) and SHINE (NCT02594124) clinical trials with at least 36months of follow-up. Children with type1 SMA treated with risdiplam had a 78% reduction in the rate of death, an 81% reduction in the rate of death or permanent ventilation, and a 57% reduction in the rate of serious adverse events compared with children treated with nusinersen. Children treated with risdiplam also had a 45% higher rate of achieving a Hammersmith Infant Neurological Examination, Module2 motor milestone response and a 186% higher rate of achieving a ≥ 4-point improvement in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders compared with children treated with nusinersen. Long-term data supported risdiplam as a superior alternative to nusinersen in children with type1 SMA. Video abstract available for this article. Video abstract (MP4 184542 KB).

EFFECT OF DAPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES IN HFREF PATIENTS: IMPACT OF DIABETES MELLITUS TYPE 2 STATUS

Dapagliflozin has shown promise in the treatment of heart failure with reduced ejection fraction (HFrEF), but its effects in patients with and without diabetes remain unclear. Objective: This study aimed to assess the effects of dapagliflozin in HFrEF patients, both with and without diabetes. Methods: From January to July 2023, a six-month case-control study was conducted in the cardiology department of a Tertiary Care Hospital in Peshawar, Pakistan. All patients received an additional dose of dapagliflozin (10 mg) alongside their usual treatment plans. The primary outcome was a composite of heart failure exacerbation or cardiovascular death. Data analysis was performed using SPSS version 22. Results: Patients with diabetes mellitus type 2 (DMT2) exhibited a higher rate of cardiovascular death (22%) and hospitalization for heart failure (14.4%) compared to those without diabetes. The hospitalisation rate for heart failure was also higher in the DMT2 group (12.21%) than in the non-diabetic group (8.6%). Over the trial period, cardiovascular death occurred in 12.44% of patients with DMT2 compared to 7.30% in those without DMT2. Patients with diabetes experienced a significantly higher number of first and recurrent hospitalizations for heart failure and cardiovascular death compared to those without diabetes (32.45% vs. 19.20%, p=0.021). Conclusion: Dapagliflozin therapy in HFrEF patients demonstrated varying effects between those with and without diabetes. The study underscores the importance of personalised management strategies considering comorbid medical conditions. Despite dapagliflozin treatment, patients with both heart failure and diabetes continued to experience cardiovascular complications, highlighting the need for individualised treatment plans that account for a patient's complete medical profile.

Outcomes of Pregnancies in Women with Congenital Heart Disease: A Study in a Tertiary Care Hospital in Bangladesh

Background: Pregnancies in individuals with congenital heart disease (CHD) frequently pose complex challenges. The presence of CHD elevates the risks not only for the expectant mother but also for the well-being of the developing fetus. Additionally, careful monitoring and specialized medical care are crucial throughout the pregnancy to ensure the best possible outcomes for both. Objective: This study was aimed to assess the outcomes of pregnancies in women with congenital heart disease. Methods: This was a cross-sectional observational study that was conducted in the Combined Military Hospital (CMH), Dhaka, Bangladesh from January 2020 to December 2021. A total 30 pregnant women with congenital heart disease were enrolled through purposive sampling. All the demographic and clinical information was recorded. Data were processed, analyzed, and disseminated by using MS Office tools. Results: Among participants, Lower Segment Cesarean Section (LSCS) was the most common delivery (43.3%), followed by vaginal delivery (36.7%). Instrumental delivery, specifically through outlet forceps, was found in 6.7% of cases. Pregnancy termination occurred in 6.7% due to inevitable abortion and 3.3% for medical reasons, resulting in one maternal death (3.3%). Perinatal outcomes included 90% live births and 81.5% with Apgar scores ≥9. Neonatal Intensive Care Unit (NICU) admission was required for 33.3%, with a 3.3% perinatal death rate. Conclusions: In pregnant women with congenital heart diseases, common delivery modes are Lower Segment Cesarean Section (LSCS) and vaginal delivery. Termination and maternal fatality rates are low. Perinatal outcomes are generally positive, with most births resulting in live infants with Apgar scores ≥9 and high newborn survival rates, although some require Neonatal Intensive Care Unit (NICU) admission. J Rang Med Col. March 2024; Vol. 9, No. 1: 50-54