Prevention Strategies Research Articles

Intermittent energy restriction inhibits tumor growth and enhances paclitaxel response in a transgenic mouse model of endometrial cancer

ObjectiveOverweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the differential benefits of intermittent energy restriction (IER) and low-fat diet (LFD), alone and in combination with paclitaxel, to reverse the procancer effects of high-fat diet (HFD)-induced obesity in a mouse model of EC. MethodsLkb1fl/flp53fl/fl mice were fed HFD or LFD to generate obese and lean phenotypes, respectively. Obese mice were maintained on a HFD or switched to a LFD (HFD-LFD) or IER (HFD-IER). Ten weeks after induction of endometrial cancer, mice in each group received paclitaxel or placebo for 4 weeks. Body and tumor weights; tumoral transcriptomic, metabolomic and oxylipin profiles; and serum metabolic hormones and chemocytokines were assessed. ResultsHFD-IER and HFD-LFD, relative to HFD, reduced body weight; reversed obesity-induced alterations in serum insulin, leptin and inflammatory factors; and decreased tumor incidence and mass, often to levels emulating those associated with continuous LFD. Concurrent paclitaxel, versus placebo, enhanced tumor suppression in each group, with greatest benefit in HFD-IER. The diets produced distinct tumoral gene expression and metabolic profiles, with HFD-IER associated with a more favorable (antitumor) metabolic and inflammatory environment. ConclusionIn Lkb1fl/flp53fl/fl mice, IER is generally more effective than LFD in promoting weight loss, inhibiting obesity-related endometrial tumor growth (particularly in combination with paclitaxel), and reversing detrimental obesity-related metabolic effects. These findings lay the foundation for further investigations of IER as an EC prevention and treatment strategies in overweight/obesity women.

Interest in I-PrEP and Willingness to Participate in Clinical Trials Among Men and Transfeminine Persons Who have Sex with Men in Sub-Saharan Africa: Quantitative and Qualitative Findings from HPTN 075.

This study explored interest in injectable PrEP (I-PrEP) and willingness to participate in clinical trials testing new biomedical HIV prevention strategies among men and transfeminine persons who have sex with men (MSM & TGP), using data collected in the HIV Prevention Trials Network (HPTN) 075 study, which took place at sites in Kenya, Malawi, and South Africa. Data result from a survey among 267 18-44years old HIV negative participants, complemented with semi-structured interviews with 80 purposively recruited persons. Correlations coefficients were calculated to identify demographic and psychosocial factors associated with interest in I-PrEP. Qualitative interviews were analyzed using concept-driven and subsequent data-driven coding. Most surveyed participants expressed an interest in I-PrEP. Quantitatively, only being interested in other HIV prevention measures was associated with interest in I-PrEP. Qualitatively, most participants preferred I-PrEP to O-PrEP and remained interested in I-PrEP despite barriers such as the somewhat invasive nature of the procedure and potential side effects of I-PrEP. Interest in I-PrEP was driven by the possibility of avoiding sexual or HIV stigma. Access to healthcare and altruism-such as assisting in the development of new HIV prevention methods-positively impacted willingness to participate in clinical trials. With I-PrEP favored by most participants, it is potentially a critical tool to prevent HIV infection among MSM & TGP in sub-Saharan Africa, with the mitigation of stigma as a major advance. Recruitment of MSM & TGP in biobehavioral clinical trials seems feasible, with altruistic reasons and receiving I-PrEP and free medical care as major motivators.

Trends and Variations in Pancreatic Cancer Mortality Among US Metro and Nonmetro Adults, 1999-2020.

Pancreatic cancer is the third leading cause of cancer deaths in the United States. Despite decreasing cancer mortality rates as a whole, pancreatic cancer death rates in the United States remain steady and demonstrate racial/ethnic disparities. Divergent cancer mortality trends have also been observed between metro and nonmetro populations. We therefore aimed to compare metro and nonmetro trends in pancreatic cancer mortality rates in the United States from 1999 to 2020 and investigate potential sex and racial/ethnic differences. We analyzed National Center for Health Statistics data for all pancreatic cancer deaths among individuals aged 25 years or older in the United States. We estimated the average annual percent change (AAPC) in age-standardized pancreatic cancer mortality rates in metro versus nonmetro areas by sex and race/ethnicity. Of the total 810,425 pancreatic cancer-related deaths identified from 1999 to 2020, 668,547 occurred in metro areas and 141,878 in nonmetro areas. Non-Hispanic Black individuals had the highest rates of pancreatic cancer mortality regardless of metropolitan status. In both metro and nonmetro areas, pancreatic cancer mortality rates among non-Hispanic White individuals increased over the study period (AAPC: metro, males, 0.32%; females, 0.27%; nonmetro, males, 0.77%; females, 0.62%). Non-Hispanic Black individuals in metro areas had a decrease in pancreatic cancer mortality (AAPC: males, -0.25%; females, -0.29%), but rates among non-Hispanic Black women in nonmetro areas increased (AAPC, 0.49%). There are variations not only in pancreatic cancer mortality by metro and nonmetro status but also by sex and race/ethnicity within these areas. Individuals who live in nonmetro areas have higher pancreatic cancer mortality rates and increasing death rates compared with their metro counterparts. These findings highlight the need for targeted cancer prevention strategies that are specific to metro or nonmetro populations.

Cost-effectiveness and budget impact analysis of screening and preventive interventions for cardiovascular disease in Myanmar: an economic modelling study

Cardiovascular diseases (CVD) remains a leading cause of mortality in Myanmar. Despite the burden, CVD preventive services receive low government and donor budgets, which has led to poor CVD outcomes. We conducted a cost-effective analysis and a budget impact analysis on CVD prevention strategies recommended by the WHO. A Markov model was used to analyse the cost and quality-adjusted life year (QALY) from healthcare provider and societal perspectives. We calculated transition probabilities from WHO CVD risk data and obtained treatment effects and costs from secondary sources. Subgroup analysis was performed on different sex and age groups. We framed the budget impact analysis from a healthcare provider perspective to assess the affordability of providing CVD preventive care. The most cost-effective strategy from the healthcare provider perspective varied. The combination of screening, primary prevention, and secondary prevention (Sc-PP-SP) (incremental cost-effectiveness ratio [ICER]: US$1574/QALY) is most cost-effective at the three times gross domestic product (GDP) per capita threshold, while at one time the GDP per capita threshold, secondary prevention is the most cost-effective strategy (ICER: US$160/QALY). Sc-PP-SP is the most cost-effective strategy from the societal perspective (ICER: US$647/QALY). Among age groups, intervention at age 45 years appeared to be the most cost-effective option for both men and women. The budget impact revealed the Sc-PP-SP would avert 55,000 acute CVD events and 28,000 CVD-related deaths with a cost of US$157 million for the first year of CVD preventive care. A combination of screening, primary prevention, and secondary prevention is cost-effective to reduce CVD-related deaths in Myanmar. This study provides evidence for the government and development partners to increase investment in and support for CVD prevention. These findings not only provide a basis for efficient resource allocation but also underscore the importance of adopting a total cardiovascular risk approach to CVD prevention, in alignment with global health goals. Pilot grant from Duke Global Health Institute, USA.

Genomic Insights for Personalized Care: Motivating At-Risk Individuals Toward Evidence-Based Health Practices.

Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies. Polygenic risk scores (PRSs) are powerful tools for patient risk stratification but have not yet been widely used in primary care for lung cancer, particularly in diverse patient populations. We propose the GREAT care paradigm, which employs PRSs to stratify disease risk and personalize interventions. We developed PRSs using large-scale multi-ancestry genome-wide association studies and standardized PRS distributions across all ancestries. We applied our PRSs to 796 individuals from the GISC Trial, 350,154 from UK Biobank (UKBB), and 210,826 from All of Us Research Program (AoU), totaling 561,776 individuals of diverse ancestry. Significant odds ratios (ORs) for lung cancer and difficulty quitting smoking were observed in both UKBB and AoU. For lung cancer, the ORs for individuals in the highest risk group (top 20% versus bottom 20%) were 1.85 (95% CI: 1.58 - 2.18) in UKBB and 2.39 (95% CI: 1.93 - 2.97) in AoU. For difficulty quitting smoking, the ORs (top 33% versus bottom 33%) were 1.36 (95% CI: 1.32 - 1.41) in UKBB and 1.32 (95% CI: 1.28 - 1.36) in AoU. Our PRS-based intervention model leverages large-scale genetic data for robust risk assessment across populations. This model will be evaluated in two cluster-randomized clinical trials aimed at motivating health behavior changes in high-risk patients of diverse ancestry. This pioneering approach integrates genomic insights into primary care, promising improved outcomes in cancer prevention and tobacco treatment.

Pathophysiology, Diagnosis, Prognosis, and Prevention of Poststroke Epilepsy: Clinical and Research Implications.

Poststroke epilepsy (PSE) is associated with higher mortality and poor functional and cognitive outcomes in patients with stroke. With the remarkable development of acute stroke treatment, there is a growing number of survivors with PSE. Although approximately 10% of patients with stroke develop PSE, given the significant burden of stroke worldwide, PSE is a significant problem in stroke survivors. Therefore, the attention of health policymakers and significant funding are required to promote PSE prevention research. The current PSE definition includes unprovoked seizures occurring more than 7 days after stroke onset, given the high recurrence risks of seizures. However, the pathologic cascade of stroke is not uniform, indicating the need for a tissue-based approach rather than a time-based one to distinguish early seizures from late seizures. EEG is a commonly used tool in the diagnostic work-up of PSE. EEG findings during the acute phase of stroke can potentially stratify the risk of subsequent seizures and predict the development of poststroke epileptogenesis. Recent reports suggest that cortical superficial siderosis, which may be involved in epileptogenesis, is a promising marker for PSE. By incorporating such markers, future risk-scoring models could guide treatment strategies, particularly for the primary prophylaxis of PSE. To date, drugs that prevent poststroke epileptogenesis are lacking. The primary challenge involves the substantial cost burden due to the difficulty of reliably enrolling patients who develop PSE. There is, therefore, a critical need to determine reliable biomarkers for PSE. The goal is to be able to use them for trial enrichment and as a surrogate outcome measure for epileptogenesis. Moreover, seizure prophylaxis is essential to prevent functional and cognitive decline in stroke survivors. Further elucidation of factors that contribute to poststroke epileptogenesis is eagerly awaited. Meanwhile, the regimen of antiseizure medications should be based on individual cardiovascular risk, psychosomatic comorbidities, and concomitant medications. This review summarizes the current understanding of poststroke epileptogenesis, its risks, prognostic models, prophylaxis, and strategies for secondary prevention of seizures and suggests strategies to advance research on PSE.

Urolithin A Inhibits Anterior Basolateral Amygdala to Ventral Hippocampal CA1 Circuit to Ameliorate Amyloid-β-Impaired Social Ability.

Anxiety and social withdrawal are highly prevalent among patients with Alzheimer's disease (AD). However, the neural circuit mechanisms underlying these symptoms remain elusive, and there is a need for effective prevention strategies. This study aims to elucidate the neural circuitry mechanisms underlying social anxiety in AD. We utilized 5xFAD mice and conducted a series of experiments including optogenetic manipulation, Tandem Mass Tag-labeled proteome analysis, behavioral assessments, and immunofluorescence staining. In 5xFAD mice, we observed significant amyloid-β (Aβ) accumulation in the anterior part of basolateral amygdala (aBLA). Behaviorally, 6-month-old 5xFAD mice displayed excessive social avoidance during social interaction. Concurrently, the pathway from aBLA to ventral hippocampal CA1 (vCA1) was significantly activated and exhibited a disorganized firing patterns during social interaction. By optogenetically inhibiting the aBLA-vCA1 pathway, we effectively improved the social ability of 5xFAD mice. In the presence of Aβ accumulation, we identified distinct changes in the protein network within the aBLA. Following one month of administration of Urolithin A (UA), we observed significant restoration of the abnormal protein network within the aBLA. UA treatment also attenuated the disorganized firings of the aBLA-vCA1 pathway, leading to an improvement in social ability. The aBLA-vCA1 circuit is a vulnerable pathway in response to Aβ accumulation during the progression of AD and plays a crucial role in Aβ-induced social anxiety. Targeting the aBLA-vCA1 circuit and UA administration are both effective strategies for improving the Aβ-impaired social ability.

Analysis of rare mutations associated with Thalassemia and their hematological characteristics in Chenzhou region of Hunan Province

To explore the distribution and hematological characteristics of rare thalassemia-associated mutations in Chenzhou region of Hunan Province with an aim to provide a basis for genetic counseling and effective prevention. A total of 37 370 individuals enrolled from January 2015 to December 2021 were screened by routine blood test and hemoglobin electrophoresis. The genotypes were determined with high-throughput sequencing. A total of 8 455 thalassemia mutations (including 185 rare ones) were detected, which had involved 27 mutational types. Rare type α-Thalassemia --THAI and CD31 (AGG>AAG) have the typical microcytic hypochromic hematological features, whilst SEA-HPFH, CD14 (CTG>-TG), CD37 (TGG>TAG), -90(C>T), Codon 15 (G>A), IVS-I-128 (T>G), CD86 (GCC>GC-) and Chinese Gγ+(Aγδβ)0 had typical microcytic hypochromic and β-thalassemia-associated hematological features of elevated HbA2 or HbF. In addition, the -50（G>A）heterozygotes of β-thalassemia had normal or slightly decreased MCV and MCH without an increase in HbA2. Various forms of thalassemia-associated mutations have been identified in the Chenzhou region of Hunan Province. Above finding has facilitated development of preventive and control strategies for thalassemia as well as birth health programs.

Prevalent Oral Drug Delivery System for Dental Care

Abstract: Oral drug delivery systems, including fluoride supplements, constitute one of the most prevalent routes for the administration of medications, playing a crucial role in the treatment and prevention of various diseases, including dental caries. Fluorides, employed as a preventive and control measure against dental caries, are available in two primary forms: Systemic fluorides and topical fluorides. Topical fluorides are found in toothpaste, varnish, gels, mouth rinses, and washes, while systemic fluorides are administered via lozenges, tablets, and liquid formulations. : This literature work focuses on the specific challenges associated with fluoride supplement formulations and aims to shed light on potential setbacks. Among these challenges, poor patient compliance, especially in pediatric populations, and the associated risk of underdosing or overdosing, leading to fluorosis, stand out as significant concerns. If left unaddressed, these issues could compromise the efficacy of one of the most effective caries prevention methods available. : The primary objective of this study is to explore advancements in fluoride supplement formulations, with a particular emphasis on addressing the identified challenges, especially for pediatric and geriatric patients. By devising improved formulations tailored to the unique needs of these populations, we aim to mitigate compliance issues and minimize the associated risk factors, thereby strengthening the effectiveness of dental caries prevention strategies. This research endeavors to contribute valuable insights to the field of oral healthcare and pharmaceutical development, ultimately promoting better oral health outcomes for individuals of all ages.

Community-acquired pneumonia: The importance of the early detection of drug-resistant organisms

Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States. While community-acquired pneumonia (CAP) is generally considered an acute time-limited illness, it is associated with high long-term mortality, with nearly one-third of patients requiring hospitalization dying within one year. An increasing trend of detecting multidrug-resistant (MDR) organisms causing CAP has been observed, especially in the Western world. In this editorial, we discuss about a publication by Jatteppanavar et al which reported that a case of a MDR organism was the culprit in developing pneumonia, bacteremia, and infective endocarditis that led to the patient’s death. The early detection of these resistant organisms helps improve patient outcomes. Significant advances have been made in the biotechnological and research space, but preventive measures, diagnostic techniques, and treatment strategies need to be developed.

Increasing role of post-intensive care syndrome in quality of life of intensive care unit survivors

In this editorial we comment on the detrimental consequences that post-intensive care syndrome (PICS) has in the quality of life of intensive care unit (ICU) survivors, highlighting the importance of early onset of multidisciplinary rehabilitation from within the ICU. Although, the syndrome was identified and well described early in 2012, more awareness has been raised on the long-term PICS related health problems by the increased number of coronavirus disease 2019 ICU survivors. It is well outlined that the syndrome affects both the patient and the family and is described as the appearance or worsening of impairment in physical, cognitive, or mental health as consequence of critical illness. PICS was described in order: (1) To raise awareness among clinicians, researchers, even the society; (2) to highlight the need for a multilevel screening of these patients that starts from within the ICU and continues after discharge; (3) to present preventive strategies; and (4) to offer guidelines in terms of rehabilitation. An early multidisciplinary approach is the key element form minimizing the incidence of PICS and its consequences in health related quality of life of both survivors and their families.

Anthracycline-Induced Cardiomyopathy in Cancer Survivors: Management and Long-Term Implications.

Recent advancements in personalized treatments, such as anthracycline chemotherapy, coupled with timely diagnoses, have contributed to a decrease in cancer-specific mortality rates and an improvement in cancer prognosis. Anthracyclines, a potent class of antibiotics, are extensively used as anticancer medications to treat a broad spectrum of tumors. Despite these advancements, a considerable number of cancer survivors face increased risks of treatment complications, particularly the cardiotoxic effects of chemotherapeutic drugs like anthracyclines. These effects can range from subclinical manifestations to severe consequences such as irreversible heart failure and death, highlighting the need for effective management of chemotherapy side effects for improved cancer care outcomes. Given the lack of specific treatments, early detection of subclinical cardiac events post-anthracycline therapy and the implementation of preventive strategies are vital. An interdisciplinary approach involving cardiovascular teams is crucial for the prevention and efficient management of anthracycline-induced cardiotoxicity. Various factors, such as age, gender, duration of treatment, and comorbidities, should be considered significant risk factors for developing chemotherapy-related cardiotoxicity. Tools such as electrocardiography, echocardiography, nuclear imaging, magnetic resonance imaging, histopathologic evaluations, and serum biomarkers should be appropriately used for the early detection of anthracycline-related cardiotoxicity. Furthermore, understanding the underlying biological mechanisms is key to developing preventive measures and personalized treatment strategies to mitigate anthracycline-induced cardiotoxicity. Exploring specific cardiotoxic mechanisms and identifying genetic variations can offer fresh perspectives on innovative, personalized treatments. This chapter aims to discuss cardiomyopathy following anthracycline therapy, with a focus on molecular mechanisms, preventive strategies, and emerging treatments.

Gender differences in homicides. A comparative analysis of 106 fatalities in forensic autopsy data.

While most homicides worldwide are committed against men, women and girls are disproportionately affected by domestic violence and its fatal consequences. The Istanbul Convention mandates the prevention of gender-based violence, particularly against women. This study analyzes the characteristics of male and female victims of homicides to provide a comprehensive understanding of the different situations and ways in which men and women are killed. Files of 106 forensic autopsies of homicide victims aged 14 years and older (51.9% males, 48.1% females) from 2012 to 2019 were reviewed. Demographic data, previous history with a focus on the perpetrator-victim relationship, substance influence, type of violence and law enforcement data were recorded. A gender-separated statistical analysis was carried out. Male victims were killed most often outside their own home (63.6%) by acquaintances or friends (54.5%). They were frequently under the influence of substances (56.4%). The perpetrators suffered from addictive diseases in 49.1%, and 52.7% had prior convictions. In both groups, stab/cut injuries were the most common causes of death, but stab/cut and gunshot injuries occurred more frequently in male victims. Female victims were killed most often in their own homes (76.5%) by intimate partners (62.7%). Compared to male victims, violent asphyxiation and blunt force trauma were more common causes of death. Furthermore, there was a higher frequency of multiple injuries (33.3%). The prevalence of a guilty verdict of the perpetrators was nearly equal in both groups. Gender-specific aspects should be considered when investigating homicides and establishing prevention and intervention strategies for interpersonal violence. Protective concepts are easier to establish in the public sphere than in private homes, which is why homicides against women require special attention in society, law enforcement, and legislation. Significant gender differences were found in the circumstances and the perpetrator-victim relationships of homicides. Gender-specific aspects should be taken into account when investigating homicides and developing prevention and intervention strategies. Homicides against women require special attention in society, law enforcement and legislation.

Prevalence and Characteristics of Alcohol Use in Substance-Involved Deaths in St. Louis, Missouri from 2011-2022.

Alcohol contributes to a large number of deaths annually, both in terms of deaths fully attributed to alcohol (e.g., alcohol poisoning) and deaths where alcohol is a contributing cause (e.g., motor-vehicle accidents). Nationally, alcohol-involved deaths are increasing. This study examines alcohol's role in substance-involved deaths and factors that are associated with alcohol-involvement in the St. Louis, Missouri region. The present study examines 7,641 substance-involved deaths that occurred in the St. Louis, Missouri region. Data were provided by city and county medical examiner offices and comprise all substance-involved deaths between 2011 and 2022. We examined the prevalence of alcohol stratified by manner of death, sex, and race. We conducted logistic regression predicting odds of alcohol involvement based demographic factors, presence of medical conditions, involvement of other substances, and year of death. Overall, 26.29% (2,009/7,671) of substance-involved deaths involved alcohol, and annual alcohol-involved deaths increased 54.33% from 2011 to 2022. Most substance-involved deaths were overdose deaths (82.54%, 6,307/7,641). Alcohol-involved overdose deaths increased 60.76% from 2011 to 2022. Prevalence of alcohol was higher for overdose deaths involving opioids and benzodiazepines (18-24%) than for other drug classes (7-16%). Odds of alcohol involvement in overdose deaths increased with age (OR=1.02, 95% CI:[ 1.01, 1.02]) and were higher for males (OR=1.67, 95% CI: [1.43-1.96]). The St. Louis metropolitan area saw increases in alcohol-involved fatalities for all manner of deaths, particularly overdose deaths and deaths among Black men. To improve prevention strategies for alcohol fatalities, further research is needed to investigate the role of alcohol in polysubstance overdose deaths.

Incidence and outcomes of cytomegalovirus reactivation after chimeric antigen receptor T-cell therapy

AbstractCytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation recipients; however, data on CMV reactivation after chimeric antigen receptor (CAR) T-cell therapy are limited. We report the incidence and outcomes of 95 adult CMV-seropositive patients who received CAR T-cell therapy between February 2018 and February 2023. CMV outcomes were CMV reactivation (any viremia) and clinically significant CMV infection (cs-CMV). Thirty-one patients (33%) had evidence of CMV reactivation (any viremia) and 10 patients (11%) had cs-CMV. The median time from CAR T-cell infusion to CMV reactivation was 19 days (interquartile range [IQR], 9-31). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3 to 4 cytokine release syndrome (67 vs 28%; P = .01), and those who received corticosteroids (39 vs 21%; P = .03), anakinra (56 vs 28%; P = .02), or ≥2 immunosuppressants (41 vs 21%; P = .02). Receipt of corticosteroids (18 vs 0%; P = .004), tocilizumab (14 vs 0%; P = .04), anakinra (33 vs 7%; P = .008), and ≥2 immunosuppressants (20 vs 0%; P = .001) were all associated with cs-CMV. Receiving ≥2 immunosuppressants was associated with a twofold increase in CMV reactivation in multivariate analyses (adjusted odds ratio [aOR], 2.27; 95% confidence interval, 1.1-4.8; P = .03). Overall, the 1-year mortality was significantly higher in those with CMV reactivation (57% vs 23%; P = .001). Immunosuppression, particularly with corticosteroids, for the management of CAR T-cell toxicities, is a major risk factor for CMV reactivation.

Quantifying relational change in community organisations participating in a Veteran suicide prevention learning collaborative: a social network analysis

BackgroundVeteran suicide remains a significant issue, as 17.5 Veterans die by suicide each day. The US Department of Veteran Affairs (VA) has implemented a robust suicide prevention program within its...

CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024.

No vaccines and few chemoprophylaxis options exist for the prevention of bacterial sexually transmitted infections (STIs) (specifically syphilis, chlamydia, and gonorrhea). These infections have increased in the United States and disproportionately affect gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW). In three large randomized controlled trials, 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%. This report outlines CDC's recommendation for the use of doxycycline postexposure prophylaxis (doxy PEP), a novel, ongoing, patient-managed biomedical STI prevention strategy for a selected population. CDC recommends that MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should receive counseling that doxy PEP can be used as postexposure prophylaxis to prevent these infections. Following shared decision-making with their provider, CDC recommends that providers offer persons in this group a prescription for doxy PEP to be self-administered within 72 hours after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 mg every 24 hours.Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach, including risk reduction counseling, STI screening and treatment, recommended vaccination and linkage to HIV PrEP, HIV care, or other services as appropriate. Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3-6 months thereafter. Ongoing need for doxy PEP should be assessed every 3-6 months as well. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.

Common clinical findings identified in working equids in low- and middle-income countries from 2005 to 2021.

Despite several millions of working equids worldwide, there are few published studies regarding the epidemiology of their health and welfare. Data collected by non-governmental organisations (NGOs) operating in the working equid sphere therefore have important epidemiological value and could be used towards animal health surveillance. The aim of this study was to identify common clinical findings and mortality patterns of working equids in low- and middle-income countries and investigate their epidemiology using data collected from an international NGO. A retrospective analysis was conducted to determine the proportion of clinical findings and mortality risk by equid species, year and region. Negative binomial regression models were generated to investigate differences in mortality risk and proportion of key clinical findings between equid species, hemispheres and calendar month. A total of 4,313,606 presentations were reported from 14 countries between January 2005 and March 2021 (mean 22,121; SD ± 7,858 per month). Wounds and abscesses were the most reported clinical finding for all equid species (mean proportion 35%; SD ±0.19 of all findings). A higher proportion of wounds (mean proportion 41.7%; SD±0.2) was recorded in donkeys than mules or horses (P<0.001). Mules had higher reported mortality risk (1.2%; 95% CI 0.94-1.46%) than horses (0.4%; 95% CI 0.36-0.55%; p<0.001) or donkeys (0.2%; 95% CI 0.14-0.22%). Work-related wounds were the predominant finding in working equids, particularly so in donkeys. Prevention strategies should focus on improvements to work equipment and practices for all equids. Future investigations required include refinement of diagnostic approaches for donkeys and investigation of risk factors to understand the higher mortality in mules. Routine monitoring of clinical findings reported by national or international NGOs could be included in animal health surveillance strategies, although standardisation of data for this purpose is needed so that changes in prevalence following implementation of prevention strategies can be monitored.

Pediatric high-altitude pulmonary edema and acute mountain sickness: Clinical features and risk determinants.

This investigation aimed to delineate the clinical manifestations associated with high-altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) in pediatric populations and find the risk factors of HAPE. We conducted a retrospective analysis of clinical data from children under 18 years diagnosed with HAPE and AMS at an average altitude of 3000 m. The clinical data between these two groups were compared. The study encompassed 74 pediatric patients, 27 with AMS and 47 with HAPE. HAPE presentations included classic HAPE (55.3%), reentry HAPE (27.7%), and high-altitude resident pulmonary edema (HARPE, 17.0%). Notably, 87.2% of HAPE cases were male, and 68.1% had a high body mass index (BMI). HARPE instances followed viral infections, prominently SARS-CoV-2. HAPE cases exhibited higher BMI, respiratory tract infections within 1 week preceding symptom onset, an increase in white blood cell counts (WBCs), lower peripheral arterial oxygen saturation (SpO2), and higher heart rate compared to the AMS group. Multivariate logistic regression pinpointed high BMI as an independent HAPE risk factor (odds ratio = 19.389, 95% confidence interval: 1.069-351.759, p = .045). HAPE occurs predominantly in males, with high BMI identified as a critical independent risk factor. The study underscores the need for heightened awareness and preventive strategies against HAPE in children at high altitudes.

Introduction and temporospatial tracing of piscine orthoreovirus-1 (PRV-1) in Norwegian farmed Atlantic salmon (Salmo salar) after local fallowing.

Piscine orthoreovirus-1 (PRV-1) is a prevalent agent in Atlantic salmon (Salmo salar) and the causative agent of heart and skeletal muscle inflammation (HSMI), an important disease in farmed Atlantic salmon. Investigations into the introduction and dissemination routes of PRV-1 in a field setting have been limited. This study aimed to better understand PRV-1 infections and HSMI-associated mortality under field conditions. We tracked introduction and spread of PRV-1 over one production cycle in a geographically isolated region in Norwegian aquaculture. From five sites, a total of 32 virus isolates were sequenced and genogrouped. The results indicated multiple introductions of PRV-1 to the area, but also revealed a high level of genetic homogeneity among the virus variants. The variants differed from that of the previous production cycle at two out of three sites investigated, suggesting that synchronized fallowing can be a useful tool for preventing dissemination of PRV-1 between generations of fish. Exposure to PRV-1 at the freshwater stage was identified as a potential source of introduction. A low level of HSMI-associated mortality was observed at all sites, with the onset of mortality showing some variation across PRV-1 genogroups. However, the study highlighted the complexity of associating viral genogroups with mortality in a field setting. Overall, this study contributes valuable insights into PRV-1 dynamics in a real-world aquaculture setting, offering potential strategies for disease management and prevention.