Prophylaxis Research Articles

D-limonene suppresses RANKL-induced osteoclast differentiation and promotes osteoblast activity in-vitro.

Treatments for osteoporosis are typically given post-fracture. Therefore, identifying safe prophylactic interventions to reduce fracture risk would be beneficial. One approach is to utilise the bioactive properties of natural compounds to modify osteoclast and osteoblast activity. D-limonene a well-tolerated, anti-inflammatory monoterpene found in citrus fruits holds promise due to its suppressive effect on NFκB, a key regulator of bone cell activity. We found that limonene promoted osteoblast differentiation and bone nodule formation and inhibited RANKL-indued osteoclast formation and bone resorption in-vitro. Limonene also reduced the pro-resorptive signal provided by osteoblast, augmenting markers of osteoblast differentiation (alkaline phosphatase, osterix and osteocalcin) and significantly decreased osteoclastogenic cytokine production (PTHrP, IL-1β and TNF-α). Therefore, limonene supplementation represents a potential route in combination with current interventions to optimise bone cell activity to maintain or enhance bone mass.

Abstract 4138220: Traditional and HIV-specific Risk Factors Are Associated with Incident Non-valvular Atrial Fibrillation and Atrial Flutter among Underrepresented Racial and Ethnic Minority Groups Living with HIV

Introduction: With effective antiretroviral therapy (ART), HIV can now be managed as a chronic disease. Chronic disease and cardiovascular risk factor management is especially important for underrepresented racial and ethnic minority groups (UREG). Non-valvular atrial fibrillation and atrial flutter (NVAF) have not been adequately studied in UREG with HIV. Research Questions: Among UREG with HIV, what is the incidence of NVAF? What factors are associated with incident NVAF? Aims: To narrow an evidence gap among UREG with HIV by 1) describing the incidence of NVAF and 2) identifying factors associated with incident NVAF. Methods: This is an ancillary study of the Pathways to Cardiovascular Disease Prevention and Impact of Specialty Referral in Underrepresented Racial and Ethnic Minorities with HIV (PATHWAYS) study, a retrospective population-based study of HIV care patterns among UREG with HIV. Patients without a known history of NVAF entered our study cohort at the date of their first documented HIV diagnosis. We computed the cumulative incidence of NVAF over five years of follow-up (mean 3.4, SD 1.6), handling death as a competing risk. Cox regression analysis was used to examine the univariate associations between characteristics at HIV diagnosis and incident NVAF, adjusting for site and date of HIV diagnosis. Results: From 2015-2019, 10,945 UREG meeting entry criteria were identified. On average, patients were 67.1% male, 94.4% Black, and 8.5% Hispanic. Average CHA2DS2VASc score was 0.92 (SD 1.1) and 63.4% were on ART. Cumulative incidence of NVAF at one and five years after HIV diagnosis were 0.48% (95% CI 0.36-0.63) and 2.16% (95% CI 1.85-2.51), respectively. HIV-related factors associated with incident NVAF included baseline CD4 count <200 (HR 1.84, 95% CI 1.20-2.80) and initial ART including protease inhibitors (HR 1.56, 95% CI 1.14-2.13) and/or integrase strand transfer inhibitors (HR 1.47, 95% CI 1.08-1.99). Additional associated factors included older age, Medicare, cardiology visit(s) in prior year, and co-morbid diseases including hypertension, hyperlipidemia, coronary and peripheral artery disease, prior stroke/transient ischemic attack, heart failure, and chronic kidney disease. Conclusions: In a large cohort of UREG living with HIV, both traditional and HIV-specific risk factors are associated with increased risk of incident NVAF. Interventions to mitigate NVAF risk in this population will require interdisciplinary, team-based approaches.

Abstract 4147617: Depression and the Development of Cardiovascular Disease: Insights from All of Us Research Program

Introduction/Background: Depression is recognized as a risk factor for worse outcomes in patients with cardiovascular disease, but there is limited research on whether individuals with depression have an increased incidence of future cardiovascular disease. Research questions/Hypothesis: Do individuals with depression have an increased incidence of cardiovascular disease? Goals/Aims: This study was conducted to evaluate the association between a diagnosis of depression and the risk of developing future cardiovascular events, to determine whether the treatment of depression should be considered as a primary form of cardiovascular disease prevention. Methods/Approach: We conducted a prospective analysis using the “All Of Us” Research Program dataset. Participants who responded to the historical depression status in the “Personal/Family History Survey” and with linked electronic health records data were considered eligible for this study. We used Cox regression models to calculate the incidence of myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF) and the hazard ratio (HR) of a diagnosis of depression. Models were adjusted for sex, race, age, and prevalent hypertension, diabetes mellitus, hyperlipidemia, and smoking. The survival analysis of the four outcomes was conducted in parallel. We conducted sensitivity analysis by excluding participants with documentation of prior MI, stroke, HF, and/or AF. Results/Data: 100,030 participants were included in this study, with a mean age of 53.2 (standard deviation of 16.5). 68.4% of participants were female, 10% were Hispanic, 9.6% were Black, and 37.1% had a diagnosis of depression. The median follow up time was 3 years. Compared to participants without depression, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.05–1.41), stroke (aHR 1.68, 95% CI 1.06–2.68), HF (aHR 1.28, 95% CI 1.15–1.43), and AF (aHR 1.14, 95% CI 1.02–1.27). In the sensitivity analysis, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.03–1.44), stroke (aHR 1.68, 95% CI 1.06–2.68), and HF (aHR 1.31, 95% CI 1.15–1.48) but not AF (aHR 1.12, 95% CI 0.99–1.27). Conclusions: This study indicates that patients with a diagnosis of depression were more likely to develop cardiovascular disease, even if they had no known history of cardiovascular disease. Providers should include the treatment of depression as a part of a holistic approach to cardiovascular disease prevention.

Unlocking insights: Mahout's perceptions and practices in managing Elephant Endotheliotropic Herpesvirus (EEHV) infection among captive Asian elephants in Surin province, Thailand.

Surin, situated in the northeastern region of Thailand, has earned the reputation of being an "elephant village" due to its high captive elephant population and unique tradition of elephant rearing. However, the continuous occurrence of elephant endotheliotropic herpesvirus (EEHV) infection poses a significant threat to elephants, particularly the young ones. This study investigated various aspects of EEHV-related elephant care among ninety-two mahouts at the Surin Elephant Kingdom Project. This study used semi-structured interviews and observations to assess the mahouts' knowledge, attitude, and practice (KAP scores) toward EEHV transmission, prevention, and management. The result revealed knowledge and practice scores below expectations, indicating an insufficient understanding the nature of disease and preventive measures. However, the mahouts exhibited awareness of the severity of the disease and factors contributing to transmission risk. Regarding the relationship among KAP scores, a positive correlation was observed at a low level (p < 0.05) between the knowledge and practice scores. Interestingly, approximately 55% of the survey respondents were confident that their elephants would not receive EEHV, leading to inadequate prevention measures. From the result, it is crucial to provide comprehensive knowledge about the nature of the disease and preventive measures to all mahouts. This education should emphasize the importance of early monitoring signs, appropriate weaning age, and preventing viral transmission practices. The KAP survey offers valuable insights that can identify areas requiring improvement and guide the development of effective and targeted disease prevention programs within the specific population. Therefore, it is recommended that the KAP survey should be employed in other parts of the country where the elephant management system differs.

Abstract 4134707: Metabolomics Discovery and Epicardial Adipose Tissue : a PROMISE Clinical Trial Substudy

Introduction: Epicardial adipose tissue (EAT) is a metabolically active tissue associated with cardiometabolic disease. EAT likely has local paracrine inflammatory and atherogenic effects on coronary vessels, but the metabolic underpinnings related to systemic metabolic pathways has not been evaluated. Hypothesis: We hypothesized that metabolic markers of lipid and fatty acid oxidation will be positively associated with volume of EAT. Methods: In a biomarker substudy of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) clinical trial which randomized participants to computed tomography angiography (CTA) vs. stress testing, we analyzed 1542 participants randomized to the CTA arm with available plasma at baseline. CTA phenotyping of EAT volume indexed to body surface area (cm 3 /m 2 ) was determined using a validated deep-learning algorithm. Comprehensive metabolomic profiling was performed on plasma samples using mass spectrometry. Principal components analysis (PCA) was used for dimensionality reduction of 571 named metabolites. Linear regression tested the association of metabolomic factors with EAT. Univariate models were adjusted for multiple comparisons and multivariate models were adjusted for age, race and ethnicity, sex, diabetes, BMI, LDL-C, HDL-C and metabolic syndrome. Results: Of 82 PCA-derived metabolomic factors, 16 were associated with EAT in univariate models and nine were associated with EAT in multivariate models (p=0.001-0.046); 116 individual metabolites heavily loaded within these factors were significantly associated with EAT volume in multivariate models ( Figure 1 ). This included three linoleic acid derivatives, six cholesterol esters, and glycine that were inversely associated with EAT volume (p&lt;0.04) and 106 metabolites positively associated with EAT volume including di- and triacylcerols, glycerophospholipids, fatty acyls and dimethylguanidino valeric acid (p&lt;0.05). Conclusions: Leveraging a large clinical trial of CTA to study metabolomics of EAT, we have identified circulating lipid species associated with EAT independent of BMI and conventional lipids. These findings highlight biomarkers of systemic metabolic dysregulation as risk modifiers and therapeutic targets in cardiometabolic disease prevention and treatment.

Active enhancers: recent research advances and insights into disease.

Precise regulation of gene expression is crucial to development. Enhancers, the core of gene regulation, determine the spatiotemporal pattern of gene transcription. Since many disease-associated mutations are characterized in enhancers, the research on enhancer will provide clues to precise medicine. Rapid advances in high-throughput sequencing technology facilitate the characterization of enhancers at genome wide, but understanding the functional mechanisms of enhancers remains challenging. Herein, we provide a panorama of enhancer characteristics, including epigenetic modifications, enhancer transcripts, and enhancer-promoter interaction patterns. Furthermore, we outline the applications of high-throughput sequencing technology and functional genomics methods in enhancer research. Finally, we discuss the role of enhancers in human disease and their potential as targets for disease prevention and treatment strategies.

Pseudoalteromonas flavipulchra as a dual-functional probiotic for aquaculture: enhancing microalgae growth and antagonizing Vibrio pathogens

Vibrio disease is a prevalent bacterial infection in aquaculture, and using bacteria with antagonistic properties against Vibrio species as probiotics has emerged as a promising method for disease prevention. Additionally, low biomass productivity of microalgae feed remains a significant bottleneck in bivalve aquaculture. Therefore, it is essential to screen for bacteria that both enhance microalgae growth and inhibit Vibrio pathogens. In this study, seven bacterial strains capable of promoting microalgae growth were screened for their ability to inhibit three Vibrio pathogens, i.e., Vibrio vulnificus, Vibrio parahaemolyticus and Vibrio cholerae, and thus serve as a dual-functional probiotic for aquaculture. The antagonistic mechanism of these bacteria was further investigated by analyzing the inhibitory effects of their extracellular products (ECP) on Vibrio species. Results indicated that Pseudoalteromonas flavipulchra exhibited antagonistic effects against all three Vibrio species tested. The ECP of P. flavipulchra displayed stable antibacterial activity, though this ability was lost after the ECP was treated with heat, alkali, or proteinase K. The proteinaceous fraction isolated from the ECP by precipitation with 90% saturated ammonium sulfate demonstrated concentration-dependent antibacterial activity. These findings suggest that P. flavipulchra could serve as a promising dual-functional probiotic for aquaculture, warranting further research to optimize its application in this field.

Abstract 4125957: Feasibility and Acceptability of Behavioral Weight Loss Programs for Men in Trade and Labor Occupations

Objective: Men who work in trade and labor occupations experience high rates of obesity and related cardiovascular disease due to high rates of sedentary leisure time and poor diet. Despite this, they are underrepresented in weight control programs. This pilot randomized trial evaluated the feasibility and acceptability of a 6-month program tailored to this occupational group versus a non-tailored standard-of-care behavioral weight loss program. Methods: Men with overweight or obesity working in trade and labor occupations were randomly assigned to either a tailored program or the DPP Group Lifestyle Balance program delivered via 16 one-hour virtual group sessions. In-person assessments were conducted at baseline, 3, and 6 months. Semi-structured interviews and self-report were used to assess the acceptability of the interventions. Feasibility was assessed using recruitment metrics and proportion group sessions and study assessments completed. Results: Participants (N = 28; median 44.0 years, interquartile range (IQR): 38.5-54.5), median 31.8 BMI, IQR 31.1-39.6) were recruited into the study over 7 months, and 71% and 79% were retained for assessments at 3 and 6 months, respectively. Overall, participants attended a median of 7 of the 16 group sessions (IQR 2.5-11.5). The tailored group completed a median of 11 of 16 weekly online progress reports (IQR 5-15). All participants reported that they would recommend the programs to other men and felt confident that they would continue using the strategies learned in the programs. Though the trial focused on feasibility rather than efficacy, median weight losses at 6 months were -3.0% in the tailored group (95% CI -9.3, -0.6) and -1.9% in the standard group (95% CI -7.4, 2.0). Conclusions: Results suggest that both the tailored and standard weight loss interventions were well received by this group, but engagement was low. Future research should focus on understanding how to increase engagement rather than exclusively tailoring the program to this occupational group to enhance this group's involvement with cardiovascular disease prevention programs.

Early prediction of Mycobacterium tuberculosis transmission clusters using supervised learning models.

Identifying individuals with tuberculosis (TB) with a high risk of onward transmission can guide disease prevention and public health strategies. Here, we train classification models to predict the first sampled isolates in Mycobacterium tuberculosis transmission clusters from demographic and disease data. We find that supervised learning, in particular balanced random forests, can be used to develop predictive models to identify people with TB that are more likely associated with TB cluster growth, with good model performance and AUCs of ≥ 0.75. We also identified the most important patient and disease characteristics in the best performing classification model, including host demographics, site of infection, TB lineage, and age at diagnosis. This framework can be used to develop predictive tools for the early assessment of potential cluster growth to prioritise individuals for enhanced follow-up with the aim of reducing transmission chains.

Annual Survey of State and Territorial Chronic Disease Prevention and Health Promotion Capacity and Organizational Development Needs—United States, 2023

Objective: The National Association of Chronic Disease Directors (NACDD) is a nonprofit organization that supports state and territorial chronic disease prevention and health promotion efforts through capacity building and technical assistance. Each year, NACDD surveys health department leaders who oversee chronic disease prevention and health promotion (hereafter, Chronic Disease Directors). We have previously used the annual survey results to inform strategic planning and resource allocation but have not historically published key findings in the peer-reviewed literature. In this paper, we report on NACDD’s 2023 survey outcomes and place those findings into the broader public health policy context. Design: State Chronic Disease Directors completed a survey about their organizational capacity and development needs. Responses were summarized in aggregate and by jurisdiction size. Results: State chronic disease units have varied staffing and responsibilities, but most address diabetes, cardiovascular diseases, and cancer screening and prevention. Chronic Disease Directors generally reported strong or improving capacity in most practice areas but ranked workforce development lower. Staffing increased slightly during 2023 compared with the 2020 baseline (median of 1.3 and 1.1 employees per 100 000 jurisdiction population, respectively). However, Chronic Disease Directors expressed ongoing concerns about turnover, hiring, and training of inexperienced staff, as well as about funding limitations and uncertainty. Looking forward to 2024, many Chronic Disease Directors expressed intentions to focus on supporting their workforce with training and development opportunities and addressing health equity. Conclusions: During this period of pandemic recovery, turnover, hiring, and training—particularly of the many new public health staff—remain key areas of concern for many chronic disease units. Continued stabilization of public health funding and increased prioritization of organizational capacity development—particularly workforce development, chronic disease data systems, and tools for addressing health equity—could help ensure chronic disease units can better address current and emerging challenges in chronic disease prevention and health promotion.

Abstract 4143228: Uncovering Hidden Disparities in Surgical Mortality among Texas Medicaid-Insured Infants with Critical Congenital Heart Disease

Background: Data shows that publicly insured patients with critical congenital heart disease (CCHD) have higher surgical mortality than privately insured patients. However, little is known about disparities within Medicaid-insured cohorts. We hypothesized that disparities in surgical mortality exist within the Medicaid population, with the highest mortality being among the most socially vulnerable patients. Methods: We conducted a retrospective cohort study using Texas Birth Defects Registry records of infants with CCHD born 2010-2014 who underwent cardiac surgery &lt;1 year old (CCHDs). Patients with CCHD as defined by the Centers for Disease Control or ductal dependent anatomy were included, and records for study inclusion were reviewed by a pediatric cardiologist. Cases were linked with death certificates and the Medicaid database, and Medicaid patients were stratified into Primary (PM) and Secondary (SM) cohorts. The PM cohort was comprised of patients with the highest scores (most socioeconomically vulnerable) based on the census tract derived Social Vulnerability Index (SVI). The primary predictor was race/ethnicity and primary outcome was infant mortality. Descriptive sociodemographics were analyzed using chi-square. Infant mortality was analyzed using stratified univariable Cox Proportional-Hazards models. Results: We identified 2525 infants with CCHD S , of whom 14.5% had PM and 56.9% had SM. The Medicaid-cohort had more single ventricle, chromosomal, and extracardiac defects than the Non-Medicaid (NM) cohort (p&lt;0.0001). Compared to the SM cohort, CCHD S infants with PM were more likely to be born preterm, and be born to mothers who are non-White, have &lt; a high school education (p&lt;0.0001, respectively), and who drove further to surgical facility (p&lt;0.005). Cox regression showed no racial/ethnic mortality disparities in the PM cohort. In the SM cohort, infant mortality was 2.2x higher among Black patients (HR 2.21, CI 1.41-3.45). In the NM cohort, Hispanic patients had nearly 2x (HR 1.93, CI 1.12-3.33) and Black patients had 3x (HR 3.01, CI 1.42-5.96) higher risk of infant mortality than White CCHDs infants. Conclusions: We completed one of the largest analyses of Medicaid-insured CCHD S infants using a novel SVI stratification. Despite worse SVI, racial/ethnic disparities in CCHD S mortality were not observed among PM-insured patients. Future database work should include stratified Medicaid populations to accurately interpret outcomes in patients with CCHD.

Comprehensive pan-genome analysis of Mycobacterium marinum: insights into genomic diversity, evolution, and pathogenicity.

Mycobacteria is a diverse genus that includes both innocuous environmental species and serious pathogens like Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium ulcerans, the causative agents of tuberculosis, leprosy, and Buruli ulcer, respectively. This study focuses on Mycobacterium marinum, a closely related species known for its larger genome and ability to infect ectothermic species and cooler human extremities. Utilizing whole-genome sequencing, we conducted a comprehensive pan-genome analysis of 100M. marinum strains, exploring genetic diversity and its impact on pathogenesis and host specificity. Our findings highlight significant genomic diversity, with clear distinctions in core, dispensable, and unique genes among the isolates. Phylogenetic analysis revealed a broad distribution of genetic lineages, challenging previous classifications into distinct clusters. Additionally, we examined the synteny and diversity of the virulence factor CpnT, noting a wide range of C-terminal domain variations across strains, which points to potential adaptations in pathogenic mechanisms. This study enhances our understanding of M. marinum's genomic architecture and its evolutionary relationship with other mycobacterial pathogens, providing insights that could inform disease control strategies for M. tuberculosis and other mycobacteria.

Crop rotation and fungicides impact microbial biomass, diversity and enzyme activities in the wheat rhizosphere

Sustainable crop production systems should promote large and diverse soil microbial communities to enhance biological soil processes rather than depend solely on chemical interventions that include pesticide applications. Crop rotation increases above-ground temporal diversity which, relative to monoculture, usually increases soil microbial diversity. But comparisons between short and long crop rotations that also include pesticide effects are rare. A 5-yr (2013-2017) field study was conducted to investigate crop rotation and fungicide effects on the soil microbiome and activity. There were nine rotations, with or without fungicide applications, that included four 2-yr rotations (wheat preceded by canola, barley, pea, or flax), four 3-yr rotations where barley or canola were added to the 2-yr rotations, and one rotation where canola and wheat were stacked (canola-canola-wheat-wheat). In 2017, soil microbial biomass, composition, diversity and enzyme activities were measured in the rhizosphere of the final wheat crop in each rotation. Fungicides reduced fungal richness (the number of different fungal taxa) in the wheat rhizosphere (e.g., Chao1 indices of 64.0 vs. 79.9) especially in 2-yr rotations, but rotation length/type and the crops that preceded wheat had different effects on different taxa. Two of the three most predominant prokaryotic phyla, Proteobacteriota and Actinobacteriota, responded differently to rotation length: 3-yr rotations enriched the former (27.4% vs. 20.1% relative abundances), but 2-yr rotations enriched the latter (19.9% vs. 28.3% relative abundances). Relative to oilseed crops preceding the sampled wheat, a field pea preceding crop enriched Actinobacteriota (31.7% vs. 24.8% relative abundances) and the most abundant fungal class, Sordariomycetes (39.1% vs. 22.1% relative abundances), in addition to increasing microbial biomass carbon (MBC) and arylsulphatase activity by 33% and 57%, respectively. Correlations of the relative abundances of fungal or prokaryotic genera with β-glucosidase and arylsulphatase activities were similar (both positive or negative), but they were the opposite of correlations with acid phosphomonoesterase, suggesting a close link between C and S cycling. Besides the nutrient cycling implications of these soil microbial characteristics, there is need to study their biological disease control significance.

Real-world outcomes of everolimus-based treatment in a Taiwanese cohort with metastatic HR+/HER2- breast cancer.

Everolimus was the first orally targeted therapy for certain cancers. It was introduced before CDK4/6 inhibitors and is widely used to treat advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This study presents comprehensive findings including updated data and long-term survival analyses focusing on patients with HR+/HER2- metastatic breast cancer who received everolimus-based treatment. The objectives were to assess the impact of everolimus on overall survival (OS) and progression-free survival (PFS) by treatment line, and to evaluate its role in therapeutic strategies in a real-world setting. We included 299 women aged over 20 years with histologically confirmed HR+/HER2- breast cancer who received everolimus-based treatment from multiple medical centers in Taiwan. Survival curves were generated using the Kaplan-Meier method, with the log-rank test for comparisons. Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events version 5.0. The median PFS was 5.6 months, and the median OS was 60.1 months. Patients receiving everolimus treatment in three or more lines and those who underwent chemotherapy prior to everolimus-based treatment had a significantly shorter PFS but longer OS. Patients with liver and central nervous system metastases had significantly shorter PFS and OS. The disease control rate was 51.5%, and the overall response rate was 8.0%. These findings support current guidelines and advocate for the inclusion of everolimus in treatment plans for patients with metastatic HR+/HER2- breast cancer, particularly in late-line treatment, with careful consideration of the benefit-risk profile for each patient.

PREVENTION AND CONTROL OF CHRONIC DISEASES IN VULNERABLE POPULATIONS

Chronic diseases such as diabetes, hypertension and cardiovascular diseases are prevalent in vulnerable populations, who often face difficulties in accessing adequate medical care. Primary care, especially family medicine, plays a central role in the prevention and control of these diseases, as it offers continuous, comprehensive and personalized care, focused on health promotion and the prevention of complications. This model of care is especially effective in communities that face economic, social and cultural barriers, allowing for early intervention and appropriate management of chronic conditions. The aim of this study is to analyze strategies for the prevention and control of chronic diseases in vulnerable populations, with a focus on family medicine. The aim is to identify effective approaches that can be used to improve the quality of life of these populations and reduce the incidence and progression of chronic diseases. The research was carried out through a qualitative literature review, focusing on articles published between 2017 and 2022. The aim was to explore the advances and challenges in the management of chronic diseases, with an emphasis on primary health practices, the impact of social determinants of health, and the role of technologies such as telemedicine in the management of these conditions. By providing continuous and comprehensive care, family medicine uses various strategies to prevent and control chronic diseases. These include regular patient follow-up, early screening for conditions such as hypertension and diabetes, and health education, which guides individuals on healthy behaviors and self-care. In addition, disease monitoring programs and interventions such as modifying eating habits and promoting physical activity have shown positive results in the management of chronic diseases. However, there are still significant challenges, such as the scarcity of resources and the lack of qualified professionals, which limit the effectiveness of these approaches in certain regions and social groups. Overcoming these barriers requires a joint effort between health professionals, managers and public policies. It is concluded that family medicine is a fundamental approach to the control and prevention of chronic diseases, especially in vulnerable populations. The strategies adopted in this model of care, such as continuous monitoring, health education and early intervention, have shown significant results in improving quality of life and reducing complications associated with chronic diseases. However, in order to optimize the results, it is necessary to overcome challenges related to access and the training of professionals, as well as ensuring adequate support for the implementation of public health programs that favour the population in situations of vulnerability. Implementing efficient public policies and expanding access to primary health care are essential to achieving effective control of chronic diseases.

Assessing the predictive potential of ADAM8 for disease control in chronic rhinosinusitis with nasal polyps

BackgroundA disintegrin and metalloproteinase 8 (ADAM8) has been implicated in eosinophilic inflammation; however, its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains to be elucidated. This study aimed to investigate the predictive significance of ADAM8 levels in nasal secretions for the endotypes and disease control status of CRSwNP.MethodsA cohort comprising 120 CRSwNP patients and 45 healthy controls (HCs) was assembled, delineating 53 non-eosinophilic CRSwNP (neCRSwNP) and 67 eosinophilic CRSwNP (eCRSwNP) patients. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were utilized to measure ADAM8 levels in nasal mucosal tissues and secretions from all participants. The receiver operating characteristic (ROC) curves and Pearson correlation analysis were employed to assess the predictive capability of ADAM8 levels in predictiving CRSwNP endotypes and disease control status.ResultsADAM8 levels in nasal secretions were elevated in CRSwNP patients compared to HCs, with a more pronounced increase observed in eCRSwNP patients. Elevated ADAM8 concentrations in nasal secretions were positively correlated with peripheral blood eosinophil counts and percentages, tissue eosinophil counts, serum total IgE, Lund–Mackay scores, and Lund-Kennedy scores. Ultimately, 103 CRSwNP patients completed the follow-up protocol, with 72 classified as the controlled group and 31 as the uncontrolled group. Uncontrolled CRSwNP patients exhibited significantly higher ADAM8 levels in nasal secretions compared to the controlled group. The ROC curves indicated that ADAM8 in nasal secretions exhibits robust discriminatory capacity for eCRSwNP and postoperative disease control status.ConclusionADAM8 in nasal secretions emerges as a potential novel biomarker for the prognostication of CRSwNP endotypes and the postoperative disease control status.

Comparative Analyses of Biologically Active Substances and Antioxidant Activity in Fresh and Stored Fruits of Apple Varieties from the Republic of Tajikistan

Our purpose was to carry out a comparative phytochemical analysis of fruits (both fresh and stored for 1 month) of two local apple varieties of the Republic of Tajikistan. Assays were carried out to quantify total phenolic compounds, flavonols, catechins, tannins, phenolcarboxylic acids, pectins, and protopectins by UV spectrometry and ascorbic acid by titration. The profile and levels of phenolic compounds were investigated by high-performance liquid chromatography. Antiradical activity was quantitated by means of free radical DPPH (2,2-diphenyl-1-picrylhydrazyl). In fresh fruits, total levels of tannins (19 mg/g) and phenolcarboxylic acids (15 mg/g) (including chlorogenic acid: 451 μg/g) and of a flavonol (quercetin: 26 μg/g) and two catechins [epigallocatechin (173 μg/g) and L-epicatechin (50 µg/g)] were shown to be higher in the Surkhseb apple variety than in the Kosimsarkori variety. The antioxidant activity of water–ethanol extracts from Surkhseb apples (20 mg/mL) was also higher in comparison with Kosimsarkori apples. In the latter, concentrations of other detected biologically active substances, such as flavonols (0.78 mg/g), ascorbic acid (65 mg/100 g), and pectins (37 mg/g), were found to be higher, suggesting that the fruits of this apple variety have biological effects other than antioxidant, potentially anti-inflammatory, or antidiabetic. Further phytochemical and pharmacological studies on Kosimsarkori fruits may identify these other potential biological effects that may be useful in the prevention of disease. Fruits of the analyzed apple varieties should preferably be consumed fresh because after the apples were stored in the refrigerator for 1 month, indicators of antioxidant activity (22 mg/g in Surkhseb apples) and levels of almost all biologically active substances (tota) levels of tannins (14 mg/g), phenolcarboxylic acids (9 mg/g) (including chlorogenic acid: 250 μg/g) and catechin L-epicatechin (30 µg/g) in Surkhseb apples decreased. This study highlights the importance of conserving local, unique varieties of major worldwide crop plants because they may unearth novel combinations of compounds beneficial to humanity.

Zambia's battle against cholera outbreaks and the path to public health resilience: a narrative review

ABSTRACT In Zambia, cholera has been a persistent public health concern for decades, mainly attributed to inadequate sanitation and restricted access to clean water in some parts of the country. The literature was collected from PubMed, Google Scholar, and public health organization websites, focusing on cholera outbreaks in Zambia since 2000. Key search terms included ‘cholera prevention’ and ‘Zambia outbreaks.’ A total of 30 articles were analyzed to assess public health strategies and identify gaps for future planning. Periodic outbreaks of cholera have characterized Zambia's history by significant fluctuations in case numbers and fatalities since 1977. Notably, the years 1993, 1999, 2003/2004, 2005/2006, 2010, 2017/2018, and the most recent outbreak from October 2023 to February 2024 have marked significant episodes in the country's struggle against this waterborne disease. This narrative review examines the recurrent outbreaks of cholera in Zambia to understand the recent outbreak's extraordinary spread and severity in the context of public health resilience. The most recent outbreak with staggering 19,719 cases and 682 deaths, underscores the unprecedented scale and severity of the current public health emergency. The findings highlight the need for a holistic public health approach that prioritizes resilience in disease prevention.

A Systematic Review: Quercetin—Secondary Metabolite of the Flavonol Class, with Multiple Health Benefits and Low Bioavailability

The main goal of this systematic review on the flavonol class secondary metabolite quercetin is to evaluate and summarize the existing research on quercetin’s potential health benefits, therapeutic properties, and effectiveness in disease prevention and treatment. In addition to evaluating quercetin’s potential for drug development with fewer side effects and lower toxicity, this type of review attempts to collect scientific evidence addressing quercetin’s roles as an antioxidant, anti-inflammatory, antibacterial, and anticancer agent. In the first part, we analyze various flavonoid compounds, focusing on their chemical structure, classification, and natural sources. We highlight their most recent biological activities as reported in the literature. Among these compounds, we pay special attention to quercetin, detailing its chemical structure, physicochemical properties, and process of biosynthesis in plants. We also present natural sources of quercetin and emphasize its health benefits, such as its antioxidant and anti-inflammatory effects. Additionally, we discuss methods to enhance its bioavailability, analyzing the latest and most effective delivery systems based on quercetin.

Enlarged Frontal Sinusotomy and Chronic Rhinosinusitis with Nasal Polyps: An Effective Strategy to Control the Disease.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease with a strong impact on the quality of life (QoL) which treatment is based on local intranasal corticosteroids (ICS) and iterative courses of systemic corticosteroids (SCS) in case of relapse. When medical treatment is insufficient, surgery is indicated. We investigated the impact of enlarged frontal sinusotomies (EFS: Draf IIb or Draf III) on QoL and annual SCS consumption of patients with severe uncontrolled CRSwNP. This is a retrospective cohort study of 38 patients, who underwent EFS at Lariboisière University Hospital (CHU) in Paris, France, between 2006 and 2020. All patients were asked to complete SNOT-22 questionnaires concerning pre- and post-op status. Patients' medical and sinus surgery history as well as the number of SCS treatments per year before and after surgery were also collected. Of the 38 patients, 33 underwent a Draf III procedure and 5 a Draf IIb, with no major complications reported. Surgery resulted in a significant improvement in SNOT-22 scores (-32.7 ± 19.3, P < 0.001), with 19/22 items improving significantly. The number of annual SCS treatments decreased significantly from a mean of 4.8 ± 4.3 to 0.6 ± 1.2 (P < 0.001). During the follow-up (mean 88 months), 95% of our patients showed a satisfying disease control and only 2 patients required revision surgery for poor disease control 5 years after EFS. EFS appears to be an effective and durable therapeutic option to improve the QoL of patients with severe CRSwNP and to reduce their SCS consumption without major complications.