Public Health Burden Research Articles

Full Genome Characterization of the First Oropouche Virus Isolate Imported in Europe from Cuba.

On 27 May 2024, the Cuban Ministry of Health reported the first outbreak of Oropouche fever on the island. The etiologic agent, Oropouche virus (OROV), is a poorly understood arbovirus that has been known since the 1960s and represents a public health burden in Latin America. We report the whole-genome characterization of the first European OROV isolate from a returning traveler from Cuba with Oropouche fever-like symptoms. The isolate was obtained from the patient's serum; whole-genome sequencing was performed by next-generation sequencing, followed by phylogenetic analysis and genetic variability studies. The analysis showed that the most closely related sequence was from the French Guiana 2020 outbreak. Interestingly, our isolate is a reassortant virus, included in a highly supported monophyletic clade containing recent OROV cases (Brazil 2015-Colombia 2021), separated from the other four previously known genotypes. More deeply, it was found to be included in a distinct branch containing the sequences of the Brazil 2022-2024 outbreak. The reassortment event involved the S and L segments, which have high similarity with sequences belonging to a new cluster (here defined as OROV_SCDC_2024), while the M segment shows high similarity with older sequences. These results likely describe the viral strain responsible for the current outbreak in Cuba, which may also reflect the ongoing outbreak in Latin America. Further studies are needed to understand how OROV evolves towards traits that facilitate its spread and adaptation outside its original basin, and to track its spread and evolution in the European continent.

Small Molecule Assembly Agonist Alters the Dynamics of Hepatitis B Virus Core Protein Dimer and Capsid.

Chronic hepatitis B virus (HBV) poses a significant public health burden worldwide, encouraging the search for curative antivirals. One approach is capsid assembly modulators (CAMs), which are assembly agonists. CAMs lead to empty and defective capsids, inhibiting the formation of new viruses, and can also lead to defects in the release of the viral genome, inhibiting new infections. In this study, we employed hydrogen-deuterium exchange mass spectrometry (HDX-MS) to assess the impact of one such CAM, HAP18, on HBV dimers, capsids composed of 120 (or 90) capsid protein dimers, and cross-linked capsids (xl-capsids). HDX analysis revealed hydrogen bonding networks within and between the dimers. HAP18 disrupted the hydrogen bonding network of dimers, demonstrating a previously unappreciated impact on the dimer structure. Conversely, HAP18 stabilized both unmodified and cross-linked capsids. Intriguingly, cross-linking the capsid, which was accomplished by forming disulfides between an engineered C-terminal cysteine, increased the overall rate of HDX. Moreover, HAP18 binding induced conformational changes beyond the binding sites. Our findings provide evidence for allosteric communication within and between capsid protein dimers. These results show that CAMs are capable of harnessing this allosteric network to modulate the dimer and capsid dynamics.

A Programme of Hepatitis C Surveillance With Active Linkage to Care (HEAL) for Inpatients in Two Tertiary Hospitals in Jiangsu, China.

Hepatitis C virus (HCV) infection is a major public health burden in China, affecting more than 10 million individuals. We aimed to evaluate the effectiveness of a hospital-based intervention programme for HCV Surveillance with linkage to care (HEAL) in a prospective cohort. The HEAL programme was carried out targeting inpatients from non-infectious departments of two tertiary hospitals in Jiangsu, China. It consisted of an educational campaign to raise awareness of physicians from non-IDs to promote HCV surveillance, a patient-navigator-centred clinical algorithm responsible for the efficient follow-up of patients with positive HCV antibody, including comprehensive testing, diagnosis and treatment. We characterised the rate of linkage to HCV diagnosis, care and treatment during the pre-intervention period (from 1 July 2016 and June 30, 2018) and after the intervention (from March 2019 to May 2021). During the pre-intervention period, 89,303 (45.3%) out of 196,780 non-ID inpatients were screened for anti-HCV, and 631 patients were tested positive. One hundred and fifty-six (24.7%) patients was followed up for HCV RNA confirmatory testing, and 58 (37.1%) of patients further were diagnosed with chronic HCV infection (CHC). Only 18 (31.3%) of the diagnosed patients with CHC were linked to hepatitis C clinics for treatment, 10 (55.6%) patients received antiviral regimen. Among them, two (11.1%) received DAA treatment, while eight (44.4%) adopted peginterferon/ribavirin regimen. During the intervention period, 232,275 patients were hospitalised in non-infectious department and 151,203 (65.1%) were screened for anti-HCV. Of these, 960 patients tested positive for HCV antibodies, resulting in a prevalence of anti-HCV positivity of 0.63%. Six hundred and seventy (69.8%) patients were enrolled, and 100% were followed up for HCV RNA confirmatory testing. Two hundred and ninety-one (43.4%) individuals with active HCV were identified. Two hundred and thirty-eight (81.8%) of HCV-infected individuals were linked to HCV care, and 157 (65.9%) were linked to treatment. Compared to the pre-intervention period, there was a 2.61-fold increase in the percentage of patients linked to care and a 5.94-fold increase in the proportion of patients who started DAAs therapy. This HEAL programme achieved enhanced HCV Surveillance with linkage to care, which has been demonstrated as an effective strategy in the hospital setting to improve the hepatitis C care continuum by identifying inpatients unaware of their HCV status and facilitating their access to HCV treatment.

Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines

Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs. RNA vaccines offer the potential to accelerate production and improve efficacy of influenza vaccines. We leveraged the nucleoside-modified RNA (modRNA) platform technology and lipid nanoparticle formulation process of the COVID-19 mRNA vaccine (BNT162b2; Comirnaty®) to create modRNA vaccines encoding hemagglutinin (HA) (modRNA-HA) for seasonal human influenza strains and evaluated their preclinical immunogenicity and toxicity. In mice, a monovalent modRNA vaccine encoding an H1 HA demonstrated robust antibody responses, HA-specific Th1-type CD4+ T cell responses, and HA-specific CD8+ T cell responses. In rhesus and cynomolgus macaques, the vaccine exhibited durable functional antibody responses and HA-specific IFN-γ+ CD4+ T cell responses. Immunization of mice with monovalent, trivalent, and quadrivalent modRNA-HA vaccines generated functional antibody responses targeting the seasonal influenza virus(es) encoded in the vaccines that were greater than, or similar to, those of a licensed quadrivalent influenza vaccine. Monovalent and quadrivalent modRNA-HA vaccines were well-tolerated by Wistar Han rats, with no evidence of systemic toxicity. These nonclinical immunogenicity and safety data support further evaluation of the modRNA-HA vaccines in clinical studies.

Activation of Heme Metabolism Promotes Tissue Health After Intraarticular Injury or Surgical Exposure.

Posttraumatic osteoarthritis (PTOA) is a well-recognized public health burden without any disease modifying treatment. This occurs despite noted advances in surgical care in the past 50 years. Mitochondrial oxidative damage pathways initiate PTOA after severe injuries like intraarticular fracture that often require surgery and contribute to PTOA after less severe injuries that may or may not require surgery like meniscal injuries. When considering the mitochondrial and redox environment of the injured joint, we hypothesized that activation of heme metabolism, previously associated with healing in many settings, would cause prototypic mitochondrial reprogramming effects in cartilage ideally suited for use at the time of injury repair. Activation of heme metabolism can be accomplished through the gasotransmitter carbon monoxide (CO), which activates hemeoxygenase-1 (HO1) and subsequent heme metabolism. In this study, we employed unique carbon monoxide (CO)-containing foam (COF) to stimulate heme metabolism and restore chondrocyte oxygen metabolism in vitro and in vivo . Doxycycline-inducible, chondrocyte-specific HO1 overexpressing transgenic mice show similar mitochondrial reprogramming after induction compared to COF. CO is retained at least 24 h after COF injection into stifle joints and induces sustained increases in heme metabolism. Lastly, intraarticular injection of COF causes key redox outcomes without any adverse safety outcomes in rabbit stifle joints ex vivo and in vivo . We propose that activation of heme metabolism is an ideal adjuvant to trauma care that replenishes chondrocyte mitochondrial metabolism and restores redox homeostasis.

AIE-based ruthenium complexes as photosensitizers for specifically photo-inactivate gram-positive bacteria

The emergence of multidrug-resistant bacterial have caused severe burden for public health. Particularly, Staphylococcus aureus as one of ESKAPE pathogens have induced various infectious diseases and resulted in increasing deaths. Developing new antibacterial agents is still urgent and challenging. Fortunately, in this study, based on aggregation-induced emission (AIE) ruthenium complexes were designed and synthesized, which realized the high efficiency of reactive oxygen species generation and remarkably killed S. aureus unlike conventional antibiotics action. Significantly, owing to good singlet oxygen production ability, Ru1 at only 4 μg/mL of concentration displayed good antibacterial photodynamic therapy effect upon white light irradiation and could deplete essential coenzyme NADH to disrupt intracellular redox balance. Also, the electrostatic interaction between Ru1 and bacteria enhanced the possibility of antibacterial. Under light irradiation, Ru1 could efficiently inhibit the biofilm growth and avoid the development of drug-resistant. Furthermore, Ru1 possessed excellent biocompatibility and displayed remarkable therapy effect in treating mice-wound infections in vivo. These findings indicated that AIE-based ruthenium complexes as new antibacterial agent had great potential in photodynamic therapy of bacteria and addressing the drug-resistance crisis.

6577 National Trends in Fragility Hip Fractures Among Community Dwelling Women With Low Femoral Neck Bone Mineral Density

Abstract Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: Fragility hip fractures are a major public health burden and are considered a good measure of the quality of healthcare. However, contemporary trends in fragility hip fractures in women with low femoral neck bone mineral density (BMD) in the United States are not known. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2009-10, 2013–14 and 2017–18 to include U.S. women aged ≥ 60 years with bone mineral density (BMD) T score ≤ -1 at the femur neck, which was measured by dual energy x-ray absorptiometry (DEXA) on Hologic Discovery Model A Densitometers (Hologic, Inc., Bedford, Massachusetts). Fragility fracture at the hip was defined as self-reported hip fracture resulting from a fall from standing height or less. Participants with missing BMD and fracture data were excluded. ANOVA was used for comparing means. The Cochran-Armitage test was utilized for trend analysis. Results: Overall, in women aged ≥ 60 years with femoral neck T score ≤ -1, the average age of women of low BMD decreased from 71(±7.2) years to 69.6 (±6.7) years, whereas the mean T-score modestly worsened from – 1.96 (±0.62) to -2.04 (±0.77) from 2009-10 to 2017-18. Similarly, the prevalence of women with T score ≤ -2.5 increased from 18.1% to 21.3%. We also found no significant change in proportion of women who reported treatment for osteoporosis (2009-10: 19.8%, 2013-14: 18.5%, 2017-18: 19.7%; p trend = 0.052). However, proportion of women who experienced fragility hip fractures decreased significantly (2009-10: 2.4%, 2013-14: 1.5%, 2017-18: 1.2%; p trend = 0.001). The mean age of index fragility hip fracture was 70.6 years in 2009-10, 68.3 years in 2013-14 and 71.7 years in 2017-18 (p = 0.001). Age stratified analysis showed a decreasing trend in proportion of women ≥ 80 years who experienced their index fragility hip fracture (2009-10: 25.9%, 2013-14: 14.7%, 2017-18: 15%; p trend = 0.001) and 70-79 years (2009-10: 40.9%, 2013-14: 21.1%, 2017-18: 35.8%; p trend = 0.001), while an increasing trend was seen in women 60–69 years (2009-10: 33.2%, 2013-14: 64.2%, 2017-18: 49.2%; p trend = 0.001). Discussion In this nationally representative cohort of community-dwelling US women with a low femoral neck BMD, we found a 50% decrease in burden of fragility hip fractures over a 10-year period from 2009-10 to 2017-18. This trend was observed despite worsening mean femoral neck T-scores, T score ≤ -2.5, and similar rates of osteoporosis treatment. Interestingly, the proportion of women who experienced their index fragility hip fracture showed a declining trend among the 70-79 years and ≥ 80 years age-groups. This change may be due to increasing awareness and utilization of measures to decrease falls such as exercise, nutrition, health education and environment modifications targeted towards the elderly population. Presentation: 6/2/2024

9288 National Trends in Fragility Hip Fractures Among Community Dwelling Women With Low Femoral Neck Bone Mineral Density

Abstract Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: Fragility hip fractures are a major public health burden and are considered a good measure of the quality of healthcare. However, contemporary trends in fragility hip fractures in women with low femoral neck bone mineral density (BMD) in the United States are not known. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2009-10, 2013–14 and 2017–18 to include U.S. women aged ≥ 60 years with bone mineral density (BMD) T score ≤ -1 at the femur neck, which was measured by dual energy x-ray absorptiometry (DEXA) on Hologic Discovery Model A Densitometers (Hologic, Inc., Bedford, Massachusetts). Fragility fracture at the hip was defined as self-reported hip fracture resulting from a fall from standing height or less. Participants with missing BMD and fracture data were excluded. ANOVA was used for comparing means. The Cochran-Armitage test was utilized for trend analysis. Results: Overall, in women aged ≥ 60 years with femoral neck T score ≤ -1, the average age of women of low BMD decreased from 71(±7.2) years to 69.6 (±6.7) years, whereas the mean T-score modestly worsened from – 1.96 (±0.62) to -2.04 (±0.77) from 2009-10 to 2017-18. Similarly, the prevalence of women with T score ≤ -2.5 increased from 18.1% to 21.3%. We also found no significant change in proportion of women who reported treatment for osteoporosis (2009-10: 19.8%, 2013-14: 18.5%, 2017-18: 19.7%; p trend = 0.052). However, proportion of women who experienced fragility hip fractures decreased significantly (2009-10: 2.4%, 2013-14: 1.5%, 2017-18: 1.2%; p trend = 0.001). The mean age of index fragility hip fracture was 70.6 years in 2009-10, 68.3 years in 2013-14 and 71.7 years in 2017-18 (p = 0.001). Age stratified analysis showed a decreasing trend in proportion of women ≥ 80 years who experienced their index fragility hip fracture (2009-10: 25.9%, 2013-14: 14.7%, 2017-18: 15%; p trend = 0.001) and 70-79 years (2009-10: 40.9%, 2013-14: 21.1%, 2017-18: 35.8%; p trend = 0.001), while an increasing trend was seen in women 60–69 years (2009-10: 33.2%, 2013-14: 64.2%, 2017-18: 49.2%; p trend = 0.001). Discussion In this nationally representative cohort of community-dwelling US women with a low femoral neck BMD, we found a 50% decrease in burden of fragility hip fractures over a 10-year period from 2009-10 to 2017-18. This trend was observed despite worsening mean femoral neck T-scores, T score ≤ -2.5, and similar rates of osteoporosis treatment. Interestingly, the proportion of women who experienced their index fragility hip fracture showed a declining trend among the 70-79 years and ≥ 80 years age-groups. This change may be due to increasing awareness and utilization of measures to decrease falls such as exercise, nutrition, health education and environment modifications targeted towards the elderly population. Presentation: 6/2/2024

8421 The Effect of Dietary Glycotoxins on Insulin Resistance in Polycystic Ovary Syndrome

Abstract Disclosure: A. Weidner: None. K. Vann: None. J. Zhang: None. A. Roy: None. O. Astapova: None. Polycystic ovary syndrome (PCOS) is a chronic systemic disorder that affects both metabolism and reproduction. PCOS is characterized by hyperandrogenism and insulin resistance, which are closely intertwined in this disease pathophysiology. PCOS affects an estimated 10% of people with ovaries and increases risk of endometrial cancer, type 2 diabetes, and major cardiovascular events. Furthermore, treatment options are generally poorly tolerated. Despite its prevalence, severity, and enormous public health burden, the etiology of PCOS is not well-understood. Insulin resistance likely plays a central role in PCOS pathogenesis, and often leads to hyperinsulinemia as the pancreas attempts to compensate for insulin’s decreased efficacy in the body. Moreover, the Western diet is becoming increasingly rich in advanced glycation end products (AGEs): non-enzymatically modified biomolecules that have recently been found to have a harmful effect on insulin sensitivity and are associated with diabetes, aging, and oxidative stress. Serum AGE levels have been reported to be higher in both lean and obese PCOS patients, regardless of PCOS subtype. We have also found higher levels of AGE precursors in the serum of our chronic dihydrotestosterone-induced mouse model of PCOS. Using this mouse model, we have shown that ovarian granulosa cells (GCs) remain insulin-sensitive despite systemic insulin resistance and hyperinsulinemia, manifested by impaired glucose tolerance and increased HOMA-IR. To assess whether GCs respond to insulin through alternative receptor pathways, we knocked down insulin receptor in human granulosa-derived KGN cells and found that insulin-stimulated AKT phosphorylation was only minimally reduced, suggesting that insulin may signal in large part through the insulin-like growth factor 1 receptor (IGF1R) in these cells. Therefore, we believe that compensatory hyperinsulinemia plays a key role in chronic GC hyperstimulation, possibly by rerouting the insulin signal through IGF1R to overcome the resistance to insulin receptor activation, suggesting a mechanism for AGE toxicity in PCOS. We hypothesize that in PCOS, this results in impaired GC function and exacerbation of ovarian dysfunction. We will use our PCOS mouse model to study the effects of a reduced-AGE diet in ameliorating the reproductive and metabolic phenotype of an androgenized PCOS mouse. In preliminary experiments, we have found that a low-AGE diet results in lower fasting glucose in C57BL/6J mice after only 4 weeks. We expect that reproductive symptoms, such as estrous cyclicity, and metabolic symptoms, such as GTT and circulating insulin, will improve in our PCOS mouse model when mice are fed a low-AGE diet throughout development and adulthood. This project has significant clinical implications, as reducing dietary AGEs could provide an effective, tolerable, non-drug therapy option for patients with PCOS. Presentation: 6/3/2024

7315 Does Protein Energy Malnutrition Impact Outcomes in Hypothyroidism? A National Inpatient Sample Analysis

Abstract Disclosure: S. Karki: None. B. Neupane: None. S. Neupane: None. A. Bhandari: None. U. Farooq: None. K. Rajamani: None. Introduction: Hypothyroidism poses a significant public health burden in the United States, affecting approximately 4.6 % of the population. Various nutritional deficiencies can adversely affect thyroid function, potentially leading to thyroid disorders. Despite this, there is limited literature exploring the influence of Protein Energy Malnutrition (PEM) on outcomes in hypothyroidism. Objective of our study:This investigation aims to assess the impact of PEM on the healthcare burden and costs associated with hospitalizations in patients with and without hypothyroidism. Methods: A retrospective study was conducted using the National Inpatient Sample (NIS) data from 2017 to 2020. Among the 14,418,310 patients aged 18 and above with a primary diagnosis of hypothyroidism, two groups were formed based on the presence or absence of PEM, determined by International Classification of Diseases (ICD-10) codes. Statistical analysis was performed using STATA, employing the student’s t-test and Fischer’s exact test for continuous variables and proportions, respectively. Adjusted odds ratio was calculated through multivariate regression analysis. The primary outcome was mortality, with secondary outcomes encompassing mean length of stay (LOS), total cost, and various medical complications. Trends in mortality, LOS and total cost were compared for both groups. Results: Out of 14,418,310 hypothyroid patients, 7.06% (1,1018,310) were diagnosed with PEM. Patients with PEM exhibited higher mortality (6.80 % vs. 2.39 %, p<0.001), extended mean length of hospital stay (8.88 days vs. 4.85 days, p<0.001), and higher increased total hospitalization costs ($96,443 vs. $58,262, p<0.001). Furthermore, patients with PEM had elevated rates of various complications, including acute coronary syndrome, septic shock, pulmonary edema, mechanical ventilation, acute respiratory failure, acute respiratory distress syndrome, acute kidney injury, and cerebrovascular accident. Increasing trends in mortality, length of stay, and total cost of hospitalization were observed in hypothyroid patients with PEM. A similar upward trend was noted in hypothyroid patients without PEM. Conclusion: Our study underscores that the presence of PEM in hypothyroid patients substantially increases the healthcare burden, which is reflected in elevated mortality rates, prolonged hospital stays, higher total costs, and a range of adverse outcomes. Screening of PEM in hypothyroid patients is recommended, and early nutritional interventions, possibly involving dieticians, may mitigate these adverse effects. Further research is warranted to explore the association between PEM and hypothyroidism, as well as strategies for early identification and intervention. Presentation: 6/1/2024

Advancing Roles and Therapeutic Potentials of Pyroptosis in Host Immune Defenses against Tuberculosis.

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, remains a deadly global public health burden. The use of recommended drug combinations in clinic has seen an increasing prevalence of drug-resistant TB, adding to the impediments to global control of TB. Therefore, control of TB and drug-resistant TB has become one of the most pressing issues in global public health, which urges the exploration of potential therapeutic targets in TB and drug-resistant TB. Pyroptosis, a form of programmed cell death characterized by cell swelling and rupture, release of cellular contents and inflammatory responses, has been found to promote pathogen clearance and adopt crucial roles in the control of bacterial infections. It has been demonstrated that Mtb can cause host cell pyroptosis, and these host cells, which are infected by Mtb, can kill Mtb accompanied by pyroptosis, while, at the same time, pyroptosis can also release intracellular Mtb, which may potentially worsen the infection by exacerbating the inflammation. Here, we describe the main pathways of pyroptosis during Mtb infection and summarize the identified effectors of Mtb that regulate pyroptosis to achieve immune evasion. Moreover, we also discuss the potentials of pyroptosis to serve as an anti-TB therapeutic target, with the aim of providing new ideas for the development of TB treatments.

Vinpocetine Ameliorates Neuronal Injury After Cold-Induced Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI), also known as intracranial injury, is a common condition with the highest incidence rate among neurodegenerative disorders and poses a significant public health burden. Various methods are used in the treatment of TBI, but the effects of cold-induced traumatic brain injury have not been thoroughly studied. In this context, vinpocetine (VPN), derived from Vinca minor, exhibits notable anti-inflammatory and antioxidant properties. VPN is known for its neuroprotective role and is generally utilized for treating various neurodegenerative disorders. However, the function of VPN after cold-induced TBI needs to be studied in more detail. This study aims to investigate the neuroprotective effects of VPN at varying doses (5mg/kg or 10mg/kg) after cold-induced TBI. C57BL/6 mice were sacrificed 2 or 28days after cold-induced TBI. Results indicate that VPN administration significantly reduces brain infarct volume, brain swelling, blood-brain barrier disruption, and DNA fragmentation in a dose-dependent manner. Additionally, VPN enhances neuronal survival in the ipsilesional cortex. In the long term, VPN treatment (5mg/kg/day or 10mg/kg/day, initiated 48h post-TBI) improved locomotor activity, cell proliferation, neurogenesis, and decreased whole brain atrophy, specifically motor cortex atrophy. We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the underlying mechanisms to profile proteins and signaling pathways influenced by prolonged VPN treatment post-TBI. Notably, we found that 192 different proteins were significantly altered by VPN treatment, which is a matter of further investigation for the development of therapeutic targets. Our study has shown that VPN may have a neuroprotective role in cold-induced TBI.

Sociodemographic and Mental Health Factors Associated with Obesity in Resettled Refugees in Syracuse, New York.

Resettled refugees have been exposed to stressful and life-threatening events preresettlement and are among the most marginalized and vulnerable groups in society. Postresettlement, they face challenges when assimilating to an unfamiliar host country, which renders them vulnerable to adverse health outcomes including obesity, a major public health burden. This study was conducted to examine the association of mental health and sociodemographic factors, including language proficiency and educational attainment, with obesity in first-generation resettled refugees. We used data from electronic health records from the Adult Ambulatory Medicine Clinic of the State University of New York Upstate, Syracuse, NY. The probability of being overweight and obese (class I and class II) relative to normal weight was estimated using fully adjusted multinomial logistic regression models with relative risk ratios (RRRs). Relative to male refugees, female refugees were more likely to have class I obesity (RRR=1.83; 95% confidence interval [CI]=1.19, 2.80) and class II obesity (RRR=4.07; 95% CI=2.41, 6.87). Limited English proficiency increased the risk of being overweight (RRR=2.02; 95% CI=1.29, 3.17) and having class II obesity (RRR=2.14, 95% CI=1.20, 3.81). A clinical mental health diagnosis increased the risk of class I (RRR=2.00; 95% CI=1.35, 2.96) and class II (RRR=1.76; 95% CI=1.15, 2.71) obesity. Having no formal education was associated with decreased risk of class II obesity (RRR=0.42; 95% CI=0.19, 0.90). Obesity prevalence and subsequent related morbidity continue to be major public health burdens in vulnerable, often underserved populations in the United States. Further investigation into social determinants of obesity in refugees in a community setting that captures the unique experiences of heterogenous refugee groups outside the clinical setting is warranted.

Impact of baseline body mass index on antidepressant response: A study in newly diagnosed patients at a tertiary care center in Kolkata

Background: Depression, affecting 350 million globally, poses significant morbidity and mortality. The correlation between major depressive disorder (MDD) and obesity is noted, with studies indicating poorer treatment outcomes among obese individuals. Measuring weight and body mass index (BMI) could aid in predicting depression treatment outcomes, influencing drug efficacy due to their ease of measurement, amid the shared public health burden of MDD and obesity. Aims and Objectives: The aims and objectives of the study are to evaluate baseline BMI’s impact on antidepressant response in newly diagnosed outpatient department (OPD) patients at a tertiary care center. Materials and Methods: This longitudinal observational study was conducted with OPD patients at a tertiary care center, aged 18–65 years with newly diagnosed MDD. Assessment tools included the Diagnostic Criteria for Research accompanying the ICD-10, the Hamilton Rating Scale for Depression, and physical measurement devices. Sample size determination considered BMI groups: Normal to underweight (N1=120), overweight (N2=120), and obese (N3=70). The methodology involved patient history, examination, and follow-up assessments after 6 weeks, analyzing antidepressant response statistically. Results: Obese patients exhibited reduced treatment response rates compared to normal and overweight counterparts. Responders had lower mean BMI. Gender disparities in obesity prevalence were noted. Limitations: The study’s limitations include a small sample size of 310 cases, single-center design, and potential selection bias in a tertiary care setting. Conclusion: The findings underscore the complex relationship between BMI, depression severity, and treatment response. Obese individuals demonstrated higher initial depression scores and poorer treatment response, echoing previous research. The study highlights the need for personalized treatment approaches that consider individual BMI levels to optimize depression management strategies effectively.

Treatment response and clinical features of snakebite envenomation in Alborz province, Iran: A cross-sectional study.

Snakebite envenomation is a significant yet neglected public health burden. Our aim was to investigate the clinical and demographic factors of snakebite envenomation, as well as the factors associated with its severity and response to treatment, in Alborz province, northern Iran. In this cross-sectional study, we included 50 patients diagnosed with snakebite envenomation, referring to the Poison Control Centre of Alborz University of Medical Sciences. The presenting signs and symptoms, demographic data, treatment dose, response to treatment, complications, laboratory findings, and snakebite severity scale (SSS) were collected. Forty-six patients (92%) were men, the total mean age was 31.7 ± 12.06 years, and mean SSS was 6.54 ± 3.39. The patients were admitted for a median of 2 days, and 11 patients needed ICU admissions. The majority of snakebites were in upper extremities (60%) and they mainly occurred in summer (56%). SSS was significantly associated with response to treatment, ICU admission, gastrointestinal adverse events, thrombocytopenia, and length of stay. Similarly, response to treatment was significantly related to the history of snakebite, ICU admission, gastrointestinal adverse events, thrombocytopenia, length of stay, and SSS. Gastrointestinal symptoms, higher severity scores, and longer hospital stays were associated with poor treatment response. Importantly, no mortality was observed in this cohort. Further research is needed to confirm these findings and optimize treatment strategies for snakebite management.

The PrescIT platform: An interoperable Clinical Decision Support System for ePrescription to Prevent Adverse Drug Reactions and Drug-Drug Interactions.

Preventable medication errors have been proven to cause significant public health burden, and ePrescription is a key part of the process where medication errors and adverse effects could be prevented. Information systems and "intelligent" computational approaches could provide a valuable tool to prevent such errors with profound impact in clinical practice. The PrescIT platform is a Clinical Decision Support System (CDSS) that aims to facilitate the prevention of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in the phase of ePrescription in Greece. The proposed platform could be relatively easily localized for use in other contexts too. The PrescIT platform is based on the use of Knowledge Engineering (ΚΕ) approaches, i.e., the use of Ontologies and Knowledge Graphs (KGs) developed upon openly available data sources. Open standards (i.e., RDF, OWL, SPARQL) are used for the development of the platform enabling the integration with already existing IT systems or for standalone use. The main KG is based on the use of DrugBank, MedDRA, SemMedDB and OpenPVSignal. In addition, the Business Process Management Notation (BPMN) has been used to model long-term therapeutic protocols used during the ePrescription process. Finally, the produced software has been pilot tested in three hospitals by 18 clinical professionals via in-person think-aloud sessions. The PrescIT platform has been successfully integrated in a transparent fashion in a proprietary Hospital Information System (HIS), and it has also been used as a standalone application. Furthermore, it has been successfully integrated with the Greek National ePrescription system. During the pilot phase, one psychiatric therapeutic protocol was used as a testbed to collect end-users' feedback. Summarizing the feedback from the end-users, they have generally acknowledged the usefulness of such a system while also identifying some challenges in terms of usability and the overall user experience. The PrescIT platform has been successfully deployed and piloted in real-world environments to evaluate its ability to support safer medication prescriptions.

Hesperitin prevents non-alcoholic steatohepatitis by modulating mitochondrial dynamics and mitophagy via the AMPKα-Drp1/PINK1-Parkin signaling pathway

Non-alcoholic fatty liver disease (NAFLD) is becoming a global public health burden, yet effective therapeutic strategies are notably lacking. NAFLD development may be mediated by mitochondrial dysfunction, according to new research. Producing mitochondrial regulators from plant-based substances to treat mitochondrial dysfunction is an appealing approach to treating NAFLD. Hesperetin (HES) is a flavonoid that is found naturally and is a member of the flavanone family. This study aims to clarify the mechanism of HES in preventing NAFLD which is caused by a high-fat diet (HFD). Serum and liver biochemical parameters, liver histology, lipid profiles, and mitochondrial function were evaluated in HFD-induced NAFLD Sprague-Dawley (SD) rats. HES treatment significantly reduced body weight gain, liver weight, and the liver index, while also improving hepatic steatosis, lipid metabolism disorders, and mitochondrial dysfunction in rats with NAFLD. The mechanism was investigated and confirmed using western blot and real-time quantitative polymerase chain reaction (RT-qPCR). We showed that in the liver of NAFLD rats, HES decreased the expression of dynamic-related protein 1 (Drp1), phosphorylated Drp1 at serine-616 (Drp1-pS616) and induced phosphorylated Drp1 at serine-637 (Drp1-pS637), PTEN-induced kinase 1 (PINK1), and E3 Ubiquitin-Protein Ligase Parkin (Parkin) via an AMP-activated protein kinase alpha (AMPKα)-dependent mechanism. Moreover, HES increased the expression of the mitochondrial fusion proteins mitofusin-2 (Mfn2) and optic atrophy 1 (Opa1) while suppressing the expression of fission protein 1 (Fis1). In this work, we identify a unique mechanism by which HES prevents NAFLD from developing. HES may be an attractive potential therapeutic agent to cure NAFLD.

Investigation of the causal relationship between cholelithiasis and Parkinson's disease: A bidirectional Mendelian randomization study.

Parkinson's disease (PD) and cholelithiasis are a huge public health burden. Although observational studies have suggested a potential link between PD and cholelithiasis, the causal relationship between the two remains uncertain. To address this gap, we performed a two-sample bidirectional Mendelian randomization analysis using genetic tools. Genome-wide association study summary statistics for all traits were obtained from publicly available databases. We used strict control steps in instrumental variable selection to screen for single nucleotide polymorphisms (SNPs) from summary-level genome-wide association studies. In addition, all F-statistics were >10, indicating no weak instrumental bias. The inverse variance weighting (IVW) method was the primary method used to assess causal associations. Four other MR methods (MR-Egger, Weighted Median, Simple mode, and Weighted mode) were also used to complement IVW. Various sensitivity tests were also performed to assess reliability: (1) Cochrane's Q test for assessing heterogeneity, (2) MR-Egger intercept test and MR-PRESSO global test for assessing horizontal multiplicity, and (3) leave-one-out sensitivity test for determining stability. We selected a total of 30 SNPs as instrumental variables. It was demonstrated that cholelithiasis had a causal effect on the risk of PD (OR = 1.146, 95% CI: 1.062-1.236, p < 0.001) in IVW method. The results of our analysis revealed an increased risk effect of cholelithiasis against PD, which may give light on new approaches to PD prevention and therapy.

Activity of the hypothalamic neuropeptide Y increases in adult and decreases in old rats.

Middle-aged obesity and aging anorexia with muscle loss (sarcopenia) of old people present public health burden. These alterations may appear both in humans and rodents suggesting the role for regulatory alterations. Previously, we demonstrated that biphasic changes in the weight-reducing (catabolic) effects of neuropeptides of the hypothalamus-adipose tissue axis (e.g. leptin) may contribute to both trends. With regard to the anabolic effects of the hypothalamic neuropeptide Y (NPY) inhibited by leptin, we hypothesized non-linear age-related changes with shifts in the opposite directions. We investigated the orexigenic and hypometabolic effects of intracerebroventricularly administered NPY (hyperphagia induced by NPY injection or changes in food intake, body weight, heart rate, body temperature, locomotor activity during a 7-day NPY infusion), the immunoreactivity and gene expression of NPY in the hypothalamic arcuate nucleus of male Wistar rats of five age groups from young to old. The orexigenic/hypometabolic efficacy and the immunoreactivity of NPY increased in middle-aged animals preceding the peak of adiposity observed in aging rats, then decreased preceding anorexia and weight loss in old rats. These shifts may contribute to the development of both age-related obesity and aging anorexia, sarcopenia, and should be considered in future drug development targeting the NPY system.

Seeking a Treatable Cause of Out-of-Hospital Cardiac Arrest during and after Resuscitation

Out-of-hospital cardiac arrest (OHCA) represents a significant global public health burden, characterized by low survival and few established diagnostic tools to guide intervention. OHCA presents with a wide variety of etiologies in a heterogeneous population, posing a clinical challenge to care teams. In this review, we describe evolving research focused on diagnostic approaches to OHCA following resuscitation, including electrocardiography, coronary angiography, computed tomography, ultrasonography, and serologic biomarker assessment. These diagnostic tools have been employed in post-resuscitative efforts for diagnosing ischemic and non-ischemic cardiac, respiratory, neurologic, vascular, traumatic, and metabolic causes of arrest.