Prevalence Of Disease Research Articles

Prevalence of Chronic Kidney Disease and its Association with Pesticide Exposure in Bargarh District, Odisha, India

Background: Bargarh, a district in Odisha, is known for intense agricultural activities because of uninterrupted irrigation from the Hirakud reservoir. The number of chronic kidney disease (CKD) cases in the district is increasing rapidly. The present study assesses the prevalence of CKD and CKDu (of unknown etiology) in the district and its association with pesticide application. Materials and Methods: A door-to-door survey was conducted to find out the CKD hotspots in the different blocks of the district with the help of primary and community health centers. The prevalence of CKD in the identified hotspot villages was assessed using a random clustered sampling method along with the collection of data related to age, sex, occupation and source of drinking water. Soil and water samples collected from identified hotspot and nonhotspot villages were analyzed to assess the presence of nephrotoxic pesticide residues. Results: A total of 16 villages were identified with high CKD prevalence rates and designated as hotspot villages. Data indicate that about 21% of males under ≥ 40 years age group were found to be suffering from CKD. Cases of CKDu (85%) were more prominent in these hotspot villages. Analysis of soil and water samples demonstrated the presence of seven different nephrotoxic pesticides above the maximum residues levels (MRLs) in hotspot villages compared to nonhotspot villages. Conclusion: The presence of nephrotoxic pesticides above MRLs in the hotspot villages indicates their possible association with the onset and progression of CKD among the exposed population. Further research is needed to establish their causative association with CKDu in the study region.

Differences in clinical features according to survival and gender in patients admitted for cardiac arrest

Abstract Funding Acknowledgements None. Introduction Cardiac arrest (CA) is a condition with poor vital and neurological prognosis. Although there are widely known clinical features modifying prognosis –such as time to return of spontaneous circulation (ROSC) and neuron-specific enolase values-, there is uncertainty around whether gender, ischemic etiology or classic cardiovascular risk factors may influence in the management and prognosis. Purpose The aim of this study was to analyze the differences in baseline characteristics and management between survivors and non survivors, among patients admitted for CA in an Intensive Cardiac Care Unit. Methods A prospective unicentric registry was performed from January 2010 to December 2021, including all consecutive cardiac arrest patients admitted to an intensive cardiac care unit of a university hospital. Patients were classified into survivors –to hospital discharge- and non-survivors –deceased during hospital admission, irrespective of time of death. Univariate analysis were performed using Chi-square and Student t tests, and logistic regression was used for a multivariate analysis to compare both groups. Results A total of 324 patients were included, mean age 59.7 (DE 12.2) years, 17.9% were women. In-hospital mortality was 42% (136 patients) and 188 patients survived to hospital discharge. Survivors were significantly younger (mean of 57,37 vs 62,98 years) and had less prevalence of diabetes (17 vs 33%) and previous myocardial infarction (15 vs 25%) than non-survivors. Among survivors, there was a higher prevalence of in-hospital CA (26,6 vs 12,5%), CA due to acute coronary syndrome (68,62 vs 57,78%) and shockable first rhythm (90,43 vs 72,06%). They also had shorter ROSC (mean 22,13 vs 34,25 minutes) and no flow times (mean 2,54 vs 5,67 minutes). Gender, arterial hypertension, dyslipidemia and smoking habit did not modify prognosis. When comparing genders, women had significantly less prevalence of smoking habit and previous ischemic heart disease, their time to ROSC was lower and they received less coronary angiographies than men. The multivariate analysis showed significant in-hospital mortality risk increase with age (OR 1,04 per year), ROSC (OR 1,04 per minute) and no-flow (OR 1,09 per minute) times, out of hospital CA (OR 2,26) and non shockable rhythm. Conclusions In a consecutive cohort of 324 patients admitted after cardiac arrest, survivors were significantly younger, and had less prevalence of diabetes mellitus and previous myocardial infarction. In-hospital arrest, shockable rhythm, and shorter ROSC and no-flow times were associated with better survival. No differences in survival were found between genders, although women had significantly shorter resuscitation times.Univariate analysisMultivariate analysis

A simple yet effective H2S‐activated fluorogenic probe for precise imaging of hepatitis and arthritis in situ

AbstractHepatitis and arthritis are prevalent inflammatory diseases, and the utilization of fluorogenic probes incorporating hydrogen sulfide (H2S) as a crucial mediator of inflammation presents significant opportunities for early detection. However, the poor in vivo biodistribution and limited targeted efficacy of molecule probes for inflammation imaging severely impede their ability to differentiate the extent of inflammation and provide real‐time monitoring of inflammatory levels. Therefore, we developed a highly efficient H2S‐activated near‐infrared (NIR) fluorogenic probe (hCy‐DNP) for real‐time tracking and capturing fluctuations in H2S levels within inflammatory lesions. hCy‐DNP demonstrates an exceptionally sensitive fluorescence response to H2S expression, enabling specific differentiation between various levels of lipopolysaccharide (LPS) ‐stimulated early hepatitis models in situ, while also facilitating visual monitoring for diagnosis and efficacy evaluation of arthritis. Therefore, hCy‐DNP offers an innovative tool for exploring early diagnosis and evaluating treatment effectiveness across diverse inflammatory diseases.

Animal models to study the pathogenesis and novel therapeutics of oral lichen planus.

Oral lichen planus (OLP) is a prevalent oral mucosal disease characterized by an unknown etiology and a complex pathogenesis. Patients with OLP endure a chronic course marked by alternating non-erosive and erosive lesions, with no definitive cure currently available. Particularly challenging is the treatment of recalcitrant erosive OLP, highlighting an urgent need for therapies targeting specific pathogenic pathways. In diseases like OLP, where the etiopathogenesis is intricate and elusive, animal models are indispensable for hypothesis testing and elucidating disease mechanisms. To date, only three animal models for oral lichenoid lesions have been reported in the literature. This Perspective paper evaluates these existing models, along with a novel OLP mouse model introduced at the 3rd International Conference on Oral Mucosal Immunity and Microbiome. The validity of these models is critically assessed, and their potential future applications in advancing our understanding of OLP are discussed.

VGluT2 neuron subtypes in the paraventricular thalamic nucleus regulate depression in paraquat-induced Parkinson’s disease

Parkinson's disease (PD) is a prevalent neurodegenerative disease and approximately one third of patients with PD are estimated to experience depression. Paraquat (PQ) is the most widely used herbicide worldwide and PQ exposure is reported to induce PD with depression. However, the specific brain region and neural networks underlying the etiology of depression in PD, especially in the PQ-induced model, have not yet been elucidated. Here, we report that the VGluT2-positive glutamatergic neurons in the paraventricular thalamic nucleus (PVT) promote depression in the PQ-induced PD mouse model. Our results show that PVTVGluT2 neurons are activated by PQ and their activation increases the susceptibility to depression in PD mice. Conversely, inhibition of PVTVGluT2 neurons reversed the depressive-behavioral changes induced by PQ. Similar to the effects of intervention the soma of PVTVGluT2 neurons, stimulation of their projections into the central amygdaloid nucleus (CeA) also strongly influenced depression in PD mice. PQ induced malfunctioning of the glutamate system and changes in the dendritic and synaptic morphology in the CeA through its role on PVTVGluT2 neuronal activation. In summary, our results demonstrate that PVTVGluT2 neurons are key neuronal subtypes for depression in PQ-induced PD and promote depression processes through the PVTVGluT2-CeA pathway.

Comprehensive dry eye therapy: overcoming ocular surface barrier and combating inflammation, oxidation, and mitochondrial damage

BackgroundDry Eye Disease (DED) is a prevalent multifactorial ocular disease characterized by a vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the ocular surface, all of which lead to DED deterioration and impair the patients’ quality of life and social functioning. Currently, anti-inflammatory drugs have shown promising efficacy in treating DED; however, such drugs are associated with side effects. The bioavailability of ocular drugs is less than 5% owing to factors such as rapid tear turnover and the presence of the corneal barrier. This calls for investigations to overcome these challenges associated with ocular drug administration.ResultsA novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study. In terms of delivery, PHP-DPS@INS nanoparticles (NPs) overcame the ocular surface transport barrier by adopting the strategy of “ocular surface electrostatic adhesion-lysosomal site-directed escape”. In terms of therapy, PHP-DPS@INS achieved mitochondrial targeting and antioxidant effects through SS-31 peptide, and exerted an anti-inflammatory effect by loading insulin to reduce mitochondrial inflammatory metabolites. Ultimately, the synergistic action of “anti-inflammation-antioxidation-mitochondrial function restoration” breaks the vicious cycle associated with DED. The PHP-DPS@INS demonstrated remarkable cellular uptake, lysosomal escape, and mitochondrial targeting in vitro. Targeted metabolomics analysis revealed that PHP-DPS@INS effectively normalized the elevated level of mitochondrial proinflammatory metabolite fumarate in an in vitro hypertonic model of DED, thereby reducing the levels of key inflammatory factors (IL-1β, IL-6, and TNF-α). Additionally, PHP-DPS@INS strongly inhibited reactive oxygen species (ROS) production and facilitated mitochondrial structural repair. In vivo, the PHP-DPS@INS treatment significantly enhanced the adhesion duration and corneal permeability of the ocular surface in DED mice, thereby improving insulin bioavailability. It also restored tear secretion, suppressed ocular surface damage, and reduced inflammation in DED mice. Moreover, it demonstrated favorable safety profiles both in vitro and in vivo.ConclusionIn summary, this study successfully developed a comprehensive DED management nanosystem that overcame the ocular surface transmission barrier and disrupted the vicious cycle that lead to dry eye pathogenesis. Additionally, it pioneered the regulation of mitochondrial metabolites as an anti-inflammatory treatment for ocular conditions, presenting a safe, efficient, and innovative therapeutic strategy for DED and other inflammatory diseases.

Human T-cell activation withToxoplasma gondiiantigens loaded in maltodextrin nanoparticles

Toxoplasmosis is the most prevalent parasitic zoonosis worldwide, causing ocular and neurological diseases. No vaccine has been approved for human use. We evaluated the response of peripheral blood mononuclear cells (PBMCs) to a novel construct ofToxoplasma gondiitotal antigen in maltodextrin nanoparticles (NP/TE) in individuals with varying infectious statuses (uninfected, chronic asymptomatic, or ocular toxoplasmosis). We analyzed the concentration of IFN-γ after NP/TE ex vivo stimulation using ELISA and the immunophenotypes of CD4+and CD8+cell populations using flow cytometry. In addition, serotyping of individuals with toxoplasmosis was performed by ELISA using GRA6-derived polypeptides. Low doses of NP/TE stimulation (0.9 μg NP/0.3 μg TE) achieved IFN-γ–specific production in previously exposed human PBMCs without significant differences in the infecting serotype. Increased IFN-γ expression in CD4+effector memory cell subsets was found in patients with ocular toxoplasmosis with NP/TE but not with TE alone. This is the first study to show how T-cell subsets respond to ex vivo stimulation with a vaccine candidate for human toxoplasmosis, providing crucial insights for future clinical trials.

Erythropoietin hyporesponsiveness in non-alcoholic fatty liver disease.

Treatment with erythropoietin (EPO) can correct anaemia in chronic kidney disease (CKD) patients; however, up to 10% exhibit resistance or hyporesponsiveness to EPO. Non-alcoholic fatty liver disease (NAFLD), prevalent liver disease in CKD patients, may limit EPO response because of thrombopoietin deficiency, iron homeostasis disorder and inflammation. Therefore, we hypothesized NAFLD is a risk factor for EPO responsiveness. To test our hypothesis, we evaluated the effect of EPO in healthy rats and rats with NAFLD induced by a high-fat, high-carbohydrate (HFHC) diet. After 12 weeks on the HFHC diet, NAFLD rats showed lower erythroid response to EPO treatment than healthy rats. We, then, determined that the primary cause of EPO hyporesponsiveness could be iron deficiency associated with inflammation, which reduces erythroid cell production. Specifically, the concentrations of hepcidin, ferritin, transferrin and white blood cells in NAFLD rats were 12.8-, 16.4-, 2.51- and 1.40-fold higher than those in healthy rats, respectively. However, erythroid cell types in the bone marrow of NAFLD rats were significantly reduced. In conclusion, our data suggest that NAFLD could be a risk factor for EPO responsiveness, which is attributed to functional iron deficiency associated with inflammation.

Single-cell BCR and transcriptome analysis reveals peripheral immune signatures in patients with thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is the most prevalent orbital disease in adults caused by an autoimmune disorder, which can lead to disfigurement and vision impairment. Developing effective treatments for this condition presents challenges due to our limited understanding of its underlying immune aberrations. In this study, we profiled the immune components in the peripheral blood of patients with TAO as well as healthy individuals, utilizing single-cell RNA sequencing and B-cell receptor repertoires (BCR) analysis. We observed a significant reduction in the proportions of regulatory B cells (Bregs) and type 2 conventional dendritic cells (DCs) in patients with TAO during the active phase. Conversely, there was a significant increase in the proportion of type 1 DCs. Further analysis of cell differentiation trajectory revealed potential impairment in the transition of B cells towards Breg phenotype during the active phase of TAO. Besides, the activation process of TAO appeared to involve inflammation and immune dysfunction, as indicated by the dynamic changes in the activities of key regulators. The abnormalities in the peripheral immune system, such as the reduced capacity of Bregs to suppress inflammation, were primarily driven by the enhanced interaction among Breg, DCs, and monocytes (i.e., CD22-PTPRC and BTLA-TNFRSF14). Collectively, our findings offer a comprehensive insight into the molecular regulation and cellular reconfiguration during the active phase of TAO at the single-cell level, in order to explore the pathogenesis of TAO and provide new ideas for the future treatment of TAO.

Clinical Validation of a Machine-Learned, Point-of-Care System to IDENTIFY Functionally Significant Coronary Artery Disease.

Many clinical studies have shown wide performance variation in tests to identify coronary artery disease (CAD). Coronary computed tomography angiography (CCTA) has been identified as an effective rule-out test but is not widely available in the USA, particularly so in rural areas. Patients in rural areas are underserved in the healthcare system as compared to urban areas, rendering it a priority population to target with highly accessible diagnostics. We previously developed a machine-learned algorithm to identify the presence of CAD (defined by functional significance) in patients with symptoms without the use of radiation or stress. The algorithm requires 215 s temporally synchronized photoplethysmographic and orthogonal voltage gradient signals acquired at rest. The purpose of the present work is to validate the performance of the algorithm in a frozen state (i.e., no retraining) in a large, blinded dataset from the IDENTIFY trial. IDENTIFY is a multicenter, selectively blinded, non-randomized, prospective, repository study to acquire signals with paired metadata from subjects with symptoms indicative of CAD within seven days prior to either left heart catheterization or CCTA. The algorithm's sensitivity and specificity were validated using a set of unseen patient signals (n = 1816). Pre-specified endpoints were chosen to demonstrate a rule-out performance comparable to CCTA. The ROC-AUC in the validation set was 0.80 (95% CI: 0.78-0.82). This performance was maintained in both male and female subgroups. At the pre-specified cut point, the sensitivity was 0.85 (95% CI: 0.82-0.88), and the specificity was 0.58 (95% CI: 0.54-0.62), passing the pre-specified endpoints. Assuming a 4% disease prevalence, the NPV was 0.99. Algorithm performance is comparable to tertiary center testing using CCTA. Selection of a suitable cut-point results in the same sensitivity and specificity performance in females as in males. Therefore, a medical device embedding this algorithm may address an unmet need for a non-invasive, front-line point-of-care test for CAD (without any radiation or stress), thus offering significant benefits to the patient, physician, and healthcare system.

First report of Colletotrichum karstii causing anthracnose on soybean in China.

Soybean (Glycine max) is a significant grain and oil crop. Among the various challenges faced by soybean cultivation, anthracnose stands out as one of the most prevalent diseases. In June 2023, anthracnose symptoms on leaves characterized by irregular disease spots featuring gray-white centers and brown edges, along with many small black dots on their surface, were observed in a 20-hectare soybean (variety "Liu Yuehuang") field located in Luodian County (25°40'20″ N, 106°53'50″ E, 575 m), Guizhou Province, China. Around 30% of the 300 soybean plants examined were symptomatic, and a total of ten leaves were collected. Fragments (5×5 mm) from the edge of disease spots were sheared and surface-sterilized with 3% sodium hypochlorite and 75% ethanol for 60 s and 30 s, respectively. They were then flushed twice with sterile water, dried using sterile filter papers, finally placed on potato dextrose agar (PDA) and incubated at 28°C for two days. In total, 11 isolates with identical morphological characteristics were obtained. The colonies grown with white aerial mycelia on their surface; conidia were cylindrical, both ends are rounded, aseptate, hyaline, 11.0-14.0 (12.5) × 4.5-6.0 (5.0) μm (n = 30); appressoria were nearly ovoid, brown to black, 8.5-10.5 (9.5) × 5.5-7.5 (6.0) μm (n = 30). The morphological characteristics closely resembled the description of C. karstii (Damm et al., 2012). To further identify the isolates, chitin synthase (CHS-1), actin (ACT), beta-tubulin (TUB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the internal transcribed spacer (ITS) loci were amplified by using CHS-79F/CHS-345R, ACT-512F/ACT-783R (Carbone and Kohn, 1999), Bt2F/Bt2R (Woudenberg et al., 2009), GDF/GDR (Guerber et al., 2003) and ITS1/ITS4 (White et al., 1990) PCR primers, respectively. The BLAST results showed that the sequences of two representative strains, LD 2023048-1 and LD 2023048-2, were highly similar to those of strain C. karstii CGMCC3.14194 (ITS: OR342620 (99%) and OR342621 (99%) with HM585409, ACT: OR412337 (97%) and OR423341 (100%) with HM581995, CHS-1: OR423344 (99%,) and OR423345 (100%) with HM582023, GAPDH: OR423348 (98%) and OR423349 (98%) with HM585391, and TUB: OR423352 (99%) and OR423353 (99%) with HM585428). The phylogenetic tree combined five sequences showed that the two strains clustered into a branch of C. karstii CGMCC3.14194 with high support values. Thirty-day-old soybean plants (n = 10) (variety Liu Yuehuang) were separately sprayed with 1 × 105 spore suspensions/mL of the two strains by spray method, and plants sprayed with sterile distilled water were used as the negative control (n = 5). All the plants were then covered with plastic bags and cultured in the greenhouse (28℃, 80% humidity, 12 h light dark cycle). After ten days of inoculation, plants inoculated with C. karstii began to produce typical anthracnose symptoms, while the control remained asymptomatic. The confirmation of the reisolated pathogen as C. karstii was established through a comprehensive analysis of morphology and five sequencing loci. Pathogenicity tests were repeated three times. Anthracnose on soybean is caused by Colletotrichum spp. reported in China including C. truncatum (Hu et al., 2015), C. brevisporum (Shi et al., 2021) and C. fructicola (Xu et al., 2023). As far as we know, this study is the initial report of C. karstii inducing anthracnose on soybean to date, which establishes a fundamental reference for preventing and controlling this disease.

Lifestyle intervention formetabolic dysfunction-associated fatty liver disease: a 24-h integrated behavior perspective.

The prevalence, health and socioeconomic burden of metabolic dysfunction-associated fatty liver disease (MAFLD) is growing, increasing the need for novel evidence-based lifestyle approaches. Lifestyle is the cornerstone for MAFLD management and co-existing cardiometabolic dysfunction. The aim of this review was to evaluate the evidence for lifestyle management of MAFLD, with a specific lens on 24-hour integrated behaviour and provide practical recommendations for implementation of the evidence. Weight loss ≥ 7-10% is central to lifestyle management; however, liver and cardiometabolic benefits are attainable with improved diet quality and exercise even without weight loss. Lifestyle intervention for MAFLD should consider an integrated '24-h' approach that is cognisant of diet, physical activity/exercise, sedentary behavior, smoking, alcohol intake and sleep. Dietary management emphasises energy deficit and improved diet quality, especially the Mediterranean diet, although sociocultural adaptations to meet preferences should be considered. Increasing physical activity and reducing sedentary behavior can prevent MAFLD, with strongest evidence in MAFLD supporting regular structured moderate-vigorous aerobic exercise for 150-240 min/week. Resistance training in addition to aerobic exercise should be considered and prioritised for those who are losing body mass via diet and/or pharmacological approaches and those with sarcopenia, to minimise bone and lean mass loss. Limited evidence suggests that sleep is important for MAFLD prevention. Emerging novel approaches to diet and exercise may address some of the key barriers to behaviour change (e.g. lack of time, access to resources and social support). Large-scale multidisciplinary trials in people with MAFLD with long-term follow-up, that can be scaled up into mainstream healthcare, are required. Future management guidelines should consider the heterogeneity of MAFLD and specialised models of care that coordinate the health workforce to manage the increased and growing MAFLD population.

Prevalence of Noncommunicable Disease (NCDs) risk factors in Tamil Nadu: Tamil Nadu STEPS Survey (TN STEPS), 2020.

Noncommunicable diseases (NCDs) account for nearly 75% of all deaths in Tamil Nadu. The government of Tamil Nadu has initiated several strategies to control NCDs under the Tamil Nadu Health Systems Reform Program (TNHSRP). We aimed to estimate the prevalence of NCD risk factors and determine the predictors of diabetes and hypertension, which will be helpful for planning and serve as a baseline for evaluating the impact of interventions. A state-wide representative cross-sectional study was conducted among 18-69-year-old adults in Tamil Nadu in 2020. The study used a multi-stage sampling method to select the calculated sample size of 5780. We adapted the study tools based on WHO's STEPS surveillance methodology. We collected information about sociodemographic factors, NCD risk factors and measured blood pressure and fasting capillary blood glucose. The predictors of diabetes and hypertension were calculated using generalised linear models with 95% confidence intervals (95% CI). Due to the COVID-19 pandemic lockdown, we could cover 68% (n = 3800) of the intended sample size. Among the eligible individuals surveyed (n = 4128), we had a response rate of 92%. The mean age of the study participants was 42.8 years, and 51% were women. Current tobacco use was prevalent in 40% (95% CI: 33.7-40.0) of men and 7.9% (95% CI: 6.4-9.8) of women. Current consumption of alcohol was prevalent among 39.1% (95% CI: 36.4-42.0) of men. Nearly 28.5% (95% CI: 26.7-30.4) of the study participants were overweight, and 11.4% (95% CI: 10.1-12.7) were obese. The prevalence of hypertension was 33.9% (95% CI: 32.0-35.8), and that of diabetes was 17.6% (95% CI: 16.1-19.2). Older age, men, and obesity were independently associated with diabetes and hypertension. The burden of NCD risk factors like tobacco use, and alcohol use were high among men in the state of Tamil Nadu. The prevalence of other risk factors like physical inactivity, raised blood pressure and raised blood glucose were also high in the state. The state should further emphasise measures that reduce the burden of NCD risk factors. Policy-based and health system-based interventions to control NCDs must be a high priority for the state.

Analysis of The Feasibility of Hydrogen Injection in Pipeline Gas Challenges in The Management of Acute Myocardial Infarction in Patients With Associated Comorbidities: A Review of The Literature

Objective: The objective of this study is to investigate the challenges in the management of Acute Myocardial Infarction in patients with associated comorbidities, with the aim of identifying gaps in treatment and proposing strategies to improve care. Theoretical Framework: Modifiable risk factors play a significant role in the incidence of myocardial infarction, as evidenced by a relevant international study. Understanding the epidemiology of heart attack, including its prevalence, incidence and geographic distribution, is essential to develop effective prevention and control strategies. Identifying and managing traditional risk factors, such as smoking, hypertension, hyperlipidemia and obesity, is crucial in the preventive approach to this condition. Method: Through an integrative literature review, recent studies are explored that cover everything from epidemiology and risk factors to prevention and treatment strategies. An initial selection of 153 articles was refined to 10 studies that met all criteria. Results and Discussion: The results highlight an increasing trend in the prevalence of Coronary Artery Disease (CAD), with a stabilization in the age-standardized prevalence rate, suggesting advances in prevention and treatment. The analysis emphasizes the importance of robust and inclusive public health strategies, focused on educating the population about the risks, ensuring rapid access to treatment, and reducing inequalities in access to healthcare. Research Implications: The practical and theoretical implications of this research are discussed, providing insights into how results can influence healthcare management, public policy formation, and clinical practice in cardiology. These implications may include the need for continuing education programs for healthcare professionals, the implementation of integrated care models, and the adaptation of healthcare systems to meet the specific needs of patients with comorbidities associated with AMI. Originality/Value: This study contributes to the literature by highlighting the specific challenges faced in the management of AMI in patients with comorbidities, providing valuable insights to improve the quality of AMI care and reduce disparities in treatment. The relevance and value of this research are evidenced by its contribution to a more comprehensive understanding of the factors that influence the prognosis and quality of life of these patients.

Multimorbidity-associated emergency hospital admissions: a “screen and link” strategy to improve outcomes for high-risk patients in sub-Saharan Africa: a prospective multicentre cohort study protocol

Background The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub–Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Primary objectives Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Secondary objectives Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. Methods This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng’ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways.

3D-bioprinted anti-senescence organoid scaffolds repair cartilage defect and prevent joint degeneration via miR-23b/ELOVL5-mediated metabolic rewiring

IntroductionOsteoarthritis (OA) is the most prevalent degenerative disease worldwide and commonly occurs among the elderly. At present, there is no effective treatment for OA. When OA develops to the end stage, arthroplasty is generally operated to improve the life quality of patients. Targeting senescence has been considered as a therapeutic approach for OA in recent years. Methods & resultsIn this study, we have identified P16 gene as a novel target for anti-senescence strategy and harnessed small interfering RNA (siRNA) technology to fabricate P16-siRNA encapsulated PLGA microspheres. We combined this with our previously successful three-dimensional (3D) culture of functionally bioengineered chondrogenic synovial mesenchymal stromal cell (SMSC) organoids. This served as the primary component of the bio-ink for 3D bioprinting, culminating in the creation of P16-siRNA PLGA µS and SMSC organoid hydrogel-polymer composite scaffold (PPSOH). Its superior capabilities of cartilage repair were confirmed through in vivo and in vitro experimentations. In the rabbit model of knee cartilage defects, PPSOH not only restored the superior characteristics of native healthy hyaline cartilage but also maintained post-implanted joint function. It prevented development of joint degeneration resulting from cartilage defects by mitigating intra-articular inflammatory responses and cellular senescence. Our usage of miRNA and RNA sequencing reveals that PPSOH targets the miR-23b/ELOVL5 axis and rewired cellular metabolism, therefore regulating glycolysis and fatty acid oxidation. This effectively alleviates cellular senescence, promotes relief from OA, and facilitates cartilage regeneration. ConclusionPPSOH scaffold could effectively alleviate cellular senescence, foster relief from OA, and facilitate cartilage regeneration. Further experiments disclosed that PPSOH targets the miR-23b/ELOVL5 axis and rewired cellular metabolism by regulating glycolysis and fatty acid oxidation. Therefore, PPSOH could be used as potential therapy for cartilage repair in osteoarthritic patients.

Crosstalk in extrahepatic and hepatic system in NAFLD/NASH.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease globally. Non-alcoholic steatohepatitis (NASH) represents an extremely progressive form of NAFLD, which, without timely intervention, may progress to cirrhosis or hepatocellular carcinoma. Presently, a definitive comprehension of the pathogenesis of NAFLD/NASH eludes us, and pharmacological interventions targeting NASH specifically remain constrained. The aetiology of NAFLD encompasses a myriad of external factors including environmental influences, dietary habits and gender disparities. More significantly, inter-organ and cellular interactions within the human body play a role in the development or regression of the disease. In this review, we categorize the influences affecting NAFLD both intra- and extrahepatically, elaborating meticulously on the mechanisms governing the onset and progression of NAFLD/NASH. This exploration delves into progress in aetiology and promising therapeutic targets. As a metabolic disorder, the development of NAFLD involves complexities related to nutrient metabolism, liver-gut axis interactions and insulin resistance, among other regulatory functions of extraneous organs. It further encompasses intra-hepatic interactions among hepatic cells, Kupffer cells (KCs) and hepatic stellate cells (HSCs). A comprehensive understanding of the pathogenesis of NAFLD/NASH from a macroscopic standpoint is instrumental in the formulation of future therapies for NASH.

COMPARATIVE ANALYSIS OF RENAL PROFILE AND SERUM ELECTROLYTES AMONG DIABETIC AND NON DIABETIC GROUPS IN DISTRICT PESHAWAR KP

Diabetes mellitus is a prevalent non-communicable disease worldwide, contributing significantly to morbidity and mortality. Renal complications are a significant concern in diabetes, with hyperglycemia exacerbating renal dysfunction. Objective: This study aimed to assess renal function and electrolyte balance in diabetic and non-diabetic individuals, focusing on serum urea, creatinine levels, and electrolyte imbalances. Methods: This study was conducted at Al-Khidmat Hospital and processed at the MLT Skill Lab at Abasyn University, Peshawar. A total of 100 participants were enrolled, including diabetic and non-diabetic subjects. Blood samples were collected using a questionnaire design. Renal function tests (RFTs) were analysed using a biochemistry analyser, and serum electrolytes were assessed using an Electrolytes Analyzer. Data collection duration, methodology, and statistical analysis methods were employed. Results: Among the participants, individuals aged 40 to 70 in both genders exhibited a higher prevalence of elevated urea and creatinine levels, particularly in diabetic patients. Diabetic individuals showed a significant association with azotemia. Electrolyte imbalances, notably hypokalemia, were observed, indicating potential complications in diabetic patients. Conclusion: The study highlights the importance of proactive management strategies to mitigate renal complications in diabetic individuals. Comprehensive monitoring of renal function and electrolyte balance is essential in clinical practice.

Southern blight of water lily: The first host record of Agroathelia rolfsii on Nelumbo nucifera discovered in Florida, USA.

Nelumbo nucifera Gaertn. (Nelumbonaceae, Eudicots), also known as water lily or sacred lotus, is a nonnative and invasive plant commonly found in artificial ponds and natural lakes throughout Florida (UF-IFAS 2023; Wunderlin et al. 2023). In August 2020, a single sample of water lily plants showing large leaf spots were collected at a residence in Dunnellon, Marion County, Florida (80% disease prevalence with 40% leaf coverage). Symptoms and signs of the disease were necrotized adaxial leaf spots only, bordered by whitish mycelia and hyphae with clamp connections, and whitish to light brown sclerotia formed in the center (<0.7 mm diameter). Symptomatic tissue was plated on acid potato dextrose agar (APDA) amended with chloramphenicol (100 mg/L) and ampicillin (30mg/L), and incubated at 20 °C for one week. Data supporting the molecular identification of this putative pathogen were gathered by PCR amplification and Sanger sequencing of the complete internal transcribed spacer (ITS) and a fragment of the large subunit (LSU) of the rRNA gene (~1.5 kb) using primers ITS1F and LR5 (FDACS-DPI PPST 2020-105211, GenBank OR492009) (White et al. 1990). The identification of the host was confirmed by Sanger sequencing of three plant barcode fragments: ITS2 (ITS2-S2F/ITS4, OR492008), ribulose 1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) (rbcLa-F/rbcLa-R, GenBank OR502388), and Maturase K (matK) (matK-KIM1R/matK-KIM3F, GenBank OR502389) (Fazekas et al. 2012). MegaBLAST queries of the ITS/LSU sequence obtained here recovered a 99.61% match to the fungal pathogen Agroathelia (=Athelia) rolfsii (Sacc.) Redhead & Mullineux. (Redhead and Mullineux 2023) (Amylocorticiaceae, Agaricomycotina) strain GP3 (GenBank JABRWF010000005) (Yan et al. 2021). MegaBLAST queries of three host plant DNA barcodes recovered matches of greater than 99.62% similarity to N. nucifera sequences. After diagnosis, symptomatic dried leaf samples were deposited at Plant Industry Herbarium Gainesville (PIHG 17807) and an axenic culture was deposited at the Agricultural Research Services Culture Collection (NRRL 66964). Koch's postulates were fulfilled by the inoculation of sclerotia (as in Terrones-Salgado et al. 2022) on adaxial leaf surface of four-week- old water lily transplants obtained from an artificial pond on campus (two plants with five leaves each). One additional transplant was not inoculated and served as a control; this plant remained asymptomatic during the experimentation period. Each transplant was kept in a 27-gallon plastic container (21W × 30L × 14H in) filled with tap water containing one tablespoon of 20-20-20 all-purpose-water-soluble plant fertilizer (VPG, TX, USA) in a plant biosafety level 2 greenhouse (23 °C, >50% relative humidity, and a 12-h/12-h photoperiod). All inoculated leaves showed necrotized areas after one week and new sclerotia were observed floating on the water surface after three weeks. Fungal pathogen was reisolated and reidentified subsequently. Agroathelia rolfsii is the causal agent of southern blight, also known as grey rot, and is reported from at least in 260 plant genera, including specialty crops such as citrus, cucumber, pepper, peanuts, pumpkin, and strawberry (Farr and Rossman 2018). Agroathelia rolfsii usually causes lower stem, crown, and root rots; consequently, leaf spots are a noteworthy presentation of symptoms for this fungus.

Trends and Disparities in Treatment and Control of Atherosclerotic Cardiovascular Disease in US Adults, 1999 to 2018.

Although cardiovascular mortality continued declining from 2000 to 2019, the rate of this decrease decelerated. We aimed to assess the trends and disparities in risk factor control and treatment among US adults with atherosclerotic cardiovascular disease to find potential causes of the deceleration. A total of 55 ,021 participants, aged ≥20 years, from the 1999 to 2018 National Health and Nutrition Examination Survey were included, of which 5717 were with atherosclerotic cardiovascular disease. Risk factor control was defined as hemoglobin A1c <7%, blood pressure <140/90 mm Hg, and non-high-density lipoprotein cholesterol <100 mg/dL. The prevalence of atherosclerotic cardiovascular disease oscillated between 7.3% and 8.9% from 1999 to 2018. A significant increasing trend was observed in the prevalence of diabetes, obesity, heavy alcohol consumption, and self-reported hypertension within the population with atherosclerotic cardiovascular disease (Ptrend≤0.001). Non-high-density lipoprotein cholesterol <100 mg/dL increased from 7.1% in 1999 to 2002 to 15.7% in 2003 to 2006, before plateauing. Blood pressure control (<140/90 mm Hg) increased until 2011 to 2014, but declined to 70.1% in 2015 to 2018 (Ptrend<0.001, Pjoinpoint=0.14). Similarly, the proportion of participants achieving hemoglobin A1c control began to decrease after 2006 (Pjoinpoint=0.05, Ptrend=0.001). The percentage of participants achieving all 3 targets increased significantly from 4.5% to 18.6% across 1999 to 2018 (Ptrend=0.02), but the increasing trend decelerated after 2005 to 2006 (Pjoinpoint<0.001). Striking disparities in risk factor control and medication use persisted between sexes, and between different racial and ethnic populations. Worsened control of glycemia, blood pressure, obesity, and alcohol consumption, leveled lipid control, and persistent socioeconomic disparities may be contributing factors to the observed deceleration in decreasing cardiovascular mortality trends.