AIMS: To examine the national trend in per-capita medical expenditures among U.S. adults with diabetes from 2000 to 2022. METHODS: We analyzed data from the Medical Expenditure Panel Survey in U.S. adults aged ≥18 years with self-reported diabetes. We calculated the expenditure in total and by component, including outpatient services, inpatient services, emergency room (ER) visits, prescription drugs, and other medical services. We used joinpoint regression to identify changes in trends. RESULTS: Estimated total per-capita expenditure increased 66 %, from $9,700 (95 % CI $8,736-$10,663) in 2000 to $16,067 (95 % CI $15,049-$17,086) in 2022. Specifically, spending on prescription drugs, outpatient, ER, and other medical services increased by 144 %, 96 %, 122 %, and 135 %, respectively, while inpatient spending decreased by 28 %. Two significant upward trend periods (2000-2004 and 2011-2018) were identified for total expenditure. Spending trends by component varied, with an accelerated increase in prescription drug spending after 2012; by 2022, prescription drugs accounted for the largest share (39 %) of total expenditures. CONCLUSIONS: The economic burden of diabetes on the national health care system has been increasing, with spending changes varying by medical service category. Interventions to prevent diabetes and its complications may help mitigate this growing economic burden.

INTRODUCTION: This study examined the association between American Heart Association's (AHA) cardiovascular health (CVH) metrics, Life's Essential 8 (LE8), and predicted heart age among U.S. adults. METHODS: The sample comprised 7,075 participants aged 30-74 years without CVD and/or stroke from the National Health and Nutrition Examination Survey (NHANES) 2015-March 2020. LE8 was measured according to AHA's metrics (overall score ranging from 0 to 100 points), and nonlaboratory-based Framingham Risk Score was used to estimate predicted heart age. Analyses were completed in June 2024. RESULTS: Median LE8 scores were 62.8 for men and 66.0 for women. Over 80% of participants had less than optimal CVH scores, affecting 141.5 million people and 1-in-6 participants had a low CVH score, impacting 30.0 million people. Mean predicted heart age and excess heart age (EHA, difference between actual and predicted heart age) were 56.6 (95% CI 56.1-57.1) and 8.6 (8.1-9.1) years for men and 54.0 (53.4-54.7) and 5.9 (5.2-6.5) years for women. Participants in the low CVH group (scores<50), had an EHA that was 20.7 years higher than those in the high CVH group (score 80-100). Compared to the high CVH group, participants in low CVH group had 15 times (for men) and 44 times (for women) higher risk of having EHA ≥10 years. The pattern of differences in predicted heart age, EHA, and prevalence of EHA ≥10 years by LE8 groups remained largely consistent across subpopulations. CONCLUSIONS: These findings highlight the importance of maintaining a healthy lifestyle to improve cardiovascular health and reduce excess heart age.

BACKGROUND: Phthalate exposure during pregnancy has been associated with preterm birth, but mechanisms of action may depend on the timing of exposure. OBJECTIVE: Investigate critical periods of susceptibility during pregnancy for associations between urinary phthalate metabolite concentrations and preterm birth. METHODS: Individual-level data were pooled from 16 US cohorts (N = 6045, n = 539 preterm births). We examined trimester-averaged urinary phthalate metabolite concentrations. Most phthalate metabolites had 2248, 3703, and 3172 observations in the first, second, and third trimesters, respectively. Our primary analysis used logistic regression models with generalized estimating equations (GEE) under a multiple informant approach to estimate trimester-specific odds ratios (ORs) of preterm birth and significant (p < 0.20) heterogeneity in effect estimates by trimester. Adjusted models included interactions between each covariate and trimester. RESULTS: Differences in trimester-specific associations between phthalate metabolites and preterm birth were most evident for di-2-ethylhexyl phthalate (DEHP) metabolites. For example, an interquartile range increase in mono (2-ethylhexyl) phthalate (MEHP) during the first and second trimesters was associated with ORs of 1.15 (95 % confidence interval [CI]: 0.99, 1.33) and 1.11 (95 % CI: 0.97, 1.28) for preterm birth, respectively, but this association was null in the third trimester (OR = 0.91 [95 % CI: 0.76, 1.09]) (p-heterogeneity = 0.03). CONCLUSION: The association of preterm birth with gestational biomarkers of DEHP exposure, but not other phthalate metabolites, differed by the timing of exposure. First and second trimester exposures demonstrated the greatest associations. Our study also highlights methodological considerations for critical periods of susceptibility analyses in pooled studies.

INTRODUCTION: The association between various disparity factors and cardiovascular disease (CVD) prevalence among older US adults with diabetes has not been comprehensively explored. We examined disparities in CVD prevalence among Medicare beneficiaries with diabetes. METHODS: Data were from the 2015-2019 Medicare Current Beneficiary Survey. Diabetes and CVD conditions - myocardial infarction (MI), stroke, and heart failure - were self-reported. We estimated the adjusted prevalence ratios (APRs) of CVD by race and ethnicity, education, income-to-poverty ratio (IPR), urbanicity, food insecurity, and social vulnerability using logistic regressions that controlled for these factors as well as age and sex. RESULTS: Annually, an estimated 9.2 million Medicare beneficiaries aged 65 years or older had diabetes. Among them, 16.7% had MI, 13.7% had stroke, and 12.5% had heart failure. Beneficiaries who were food insecure, socially vulnerable, with an IPR less than or equal to 135%, and residing in rural areas had a higher crude CVD prevalence. After controlling for other factors, low IPR and food insecurity were linked to a higher prevalence of CVD. Hispanic beneficiaries had lower stroke and heart failure prevalence than non-Hispanic (NH) White and NH Black beneficiaries. NH Black beneficiaries had lower MI prevalence but higher heart failure prevalence compared with NH White beneficiaries. Female respondents with an IPR less than or equal to 135% had higher MI and stroke prevalence; this was not seen in male respondents. CONCLUSION: Low IPR and food insecurity were associated with higher MI, stroke, and heart failure prevalence among Medicare beneficiaries with diabetes. Our findings can inform targeted interventions to reduce CVD disparities in these populations.

The effect of preexisting neutralizing antibodies (NAb) on SARS-CoV-2 shedding in postvaccination infection (PVI) is not well understood. We characterized viral shedding longitudinally in nasal specimens in relation to baseline (pre/periinfection) serum NAb titers in 125 participants infected with SARS-CoV-2 variants. Among 68 vaccinated participants, we quantified the effect of baseline NAb titers on maximum viral RNA titers and infectivity duration. Baseline NAbs were higher and targeted a broader range of variants in participants with monovalent ancestral booster vaccinations compared with those with a primary vaccine series. In Delta infections, baseline NAb titers targeting Delta or Wuhan-Hu-1 correlated negatively with maximum viral RNA. Per log10 increase in Delta-targeting baseline NAb IC50, maximum viral load was reduced -2.43 (95% CI: -3.76, -1.11) log10 nucleocapsid copies, and infectious viral shedding was reduced -2.79 (95% CI: -4.99, -0.60) days. Conversely, in Omicron infections (BA.1, BA.2, BA.4, or BA.5), baseline NAb titers against Omicron lineages or Wuhan-Hu-1 did not predict viral outcomes. Our results provide robust estimates of the effect of baseline NAbs on the magnitude and duration of nasal viral replication after PVI (albeit with an unclear effect on transmission) and show how immune escape variants efficiently evade these modulating effects.

OBJECTIVES: After respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high-burden settings, which have limited data, by comparing with RSV-positive and other cases. METHODS: Children aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (adjusted OR [aOR]) were calculated using logistic regression. Aetiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics. RESULTS: hMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p ≤ 0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR, 0.18), especially RSV (aOR, 0.11; all p < 0.0001), and positively associated with the detection of bacteria (aORs, 1.77; p 0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value for hMPV aetiology was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than that among other cases (9.6%). DISCUSSION: HMPV-associated severe paediatric pneumonia in high-burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.

With the increasing demand of power and energy, more and more cells are packed into battery modules. Consequently, the electromagnetic (EM) emissions from batteries also intensify. These emissions have been observed to interfere with nearby electronic safety and health devices, causing malfunctions. While conventional methods, such as shielding, filtering, and distance separation, are commonly used to mitigate the interference issue, each has its own limitations and may not be applicable in all situations. On the other hand, magnetic field cancellation methods found in certain applications offer distinct advantages in addressing challenging magnetic field shielding or compensation issues. In this article, we introduce a novel approach to mitigate EM emissions from batteries consisting of common cylindrical form cells. The new approach leverages the coherent nature of battery cell currents when powering external load and the paired structure present in the battery pack, and then rearranges the cells so that the magnetic fields of the loops of paired cells are canceling one another. We demonstrate the validity of our approach in addressing the EM interference issue that exists in an electronic device currently used in underground coal mines. The results show a significant reduction in EM emission from the battery, highlighting the effectiveness of our approach in real applications. U.S. Government work not protected by U.S. copyright.

OBJECTIVES/BACKGROUND: We evaluated patterns of serum concentrations of endocrine disrupting chemicals (EDCs), namely polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs), in a U.S. military sample by race/ethnicity (R/E) and sex. METHODS: Twenty-three EDCs were measured in stored serum samples obtained between 1995 and 2010 for 708 service members from the Department of Defense Serum Repository. For each EDC, geometric means (GM) were estimated using log-transformed concentrations in a linear regression model, for eight combined R/E/sex groups: non-Hispanic White (NHW), non-Hispanic Black (NHB), non-Hispanic Asian (NHA), and Hispanic men and women, adjusted for age and service branch and stratified by age tertile ("younger age": 17-23, "middle age": 24-30, and "older age": 31-52 years). Comparisons were made between our military sample and the National Health and Nutrition Examination Survey (NHANES) 2003-2004 data for NHW and NHB groups. RESULTS: Within our military sample, the highest PCB concentrations were among older age NHB men and women and highest OCP concentrations among older age NHB women and NHA men. PBDE concentrations were generally highest in middle age Hispanic women and NHA men, though based on small sample size. Generally, NHB men and women had higher concentrations of EDCs in both the military and NHANES. CONCLUSIONS: We found patterns of elevated EDC concentrations among NHB, NHA, and Hispanic groups in the military sample and for NHB men and women in NHANES. There were no consistent patterns of higher or lower EDCs comparing the military to NHANES. Future studies of EDCs and health outcomes should stratify by R/E/sex to account for potential disparities in EDC concentrations.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

PURPOSE: To examine associations between pregnancy timing relative to the COVID-19 pandemic, maternal SARS-CoV-2 infection, and perinatal outcomes. METHODS: We conducted a retrospective cohort study of 189,097 singleton births in South Carolina (2018-2021). Pregnancy timing relative to the pandemic was classified as pre-pandemic (delivered before March 1, 2020), partial pandemic overlap (conceived before and delivered during the pandemic), or pandemic (conceived and delivered during the pandemic). We examined COVID-19 testing, severity, and timing. Modified Poisson regression models with robust variance were used. RESULTS: Compared to the pre-pandemic group, the partial overlap group had lower risks of low birthweight (LBW) (aRR=0.93, 95 % CI 0.89-0.97) and preterm birth (PTB) (aRR=0.91, 95 % CI 0.88-0.95). The pandemic group had increased risks of LBW (aRR=1.10, 95 % CI 1.06-1.14), PTB (aRR=1.10, 95 % CI 1.07-1.14), and NICU admissions (aRR=1.13, 95 % CI 1.09-1.17) but a decreased risk of breastfeeding initiation (aRR=0.98, 95 % CI 0.97-0.98). Moderate-to-severe COVID-19 symptoms increased PTB (aRR=1.34, 95 % CI 1.13-1.58). Third-trimester COVID-19 infection increased LBW (aRR=1.23, 95 % CI 1.10-1.37), PTB (aRR=1.18, 95 % CI 1.07-1.30), and NICU admissions (aRR=1.17, 95 % CI 1.05-1.30). CONCLUSIONS: Our findings highlight the importance of considering both maternal COVID-19 infection and pandemic-related factors in optimizing perinatal outcomes.

INTRODUCTION: Population risk for neural tube defects (NTDs) can be determined using red blood cell (RBC) folate. However, a paucity of biomarker and surveillance data among non-lactating, non-pregnant women of reproductive age (NPWRA) from Africa limits accurate assessment. Our study assessed folate and vitamin B12 status among non-lactating NPWRA and predicted population risk of NTDs in Tanzania. METHODS: A cross-sectional biomarker survey of non-lactating NPWRA (15-49 years) in the Morogoro region, Tanzania was conducted during June-October 2019. Questionnaire interview responses and non-fasting blood samples were collected. Folate was assessed using the CDC microbiologic assay kit and vitamin B12 was measured using an electrochemiluminescence immunoassay. Complex survey design analyses were conducted using SAS-callable SUDAAN (v11.0.1). RESULTS: Of the 761 participating non-lactating NPWRA, 294 (39.8%) had RBC folate insufficiency (<748 mol/L). The prevalence of RBC folate insufficiency was lower among non-lactating NPWRA living in urban than rural areas (PR: 0.72, 95% CI: 0.52-0.99) but did not differ by age or household wealth index. Vitamin B12 insufficiency was uncommon (< 221 pmol/L, 2.7%). The estimated NTD risk was 10.5 (95% uncertainty interval: 8.1-13.3) per 10,000 births. DISCUSSION: Elevated NTD risk was predicted in the Morogoro region of Tanzania, where ∼ 40% of non-lactating NPWRA had RBC folate insufficiency and < 3% had vitamin B12 insufficiency. The NTD risk is consistent with surveillance data for the area, limited folic acid fortification of staple foods, and low vitamin B12 insufficiency. Further studies are needed to better understand the context of these findings, especially the impact of micronutrient fortification in Tanzania.

INTRODUCTION: We assessed state-level disparities in diabetes prevalence among adults in rural and urban areas in the United States. METHODS: We estimated state-specific diabetes prevalence in rural and urban areas in 41 states with applicable data from the 2021 Behavioral Risk Factor Surveillance System. Rural areas were defined based on the 2013 National Center for Health Statistics Urban-Rural Classification Scheme. We estimated diabetes odds ratios (ORs) in rural versus urban areas in each state by using logistic regressions adjusted for sociodemographic characteristics and obesity status. Analyses were conducted in 2023. RESULTS: In rural areas, diabetes prevalence was 14.3%, ranging from 8.4% in Colorado to 21.3% in North Carolina. In urban areas, the prevalence was 11.2%, ranging from 6.9% in Colorado to 15.5% in West Virginia. Unadjusted diabetes ORs in rural versus urban areas were significant (P < .05) and greater than 1 for 19 states. After adjusting for age, sex, race, and ethnicity, the ORs were significant and greater than 1 for 7 states (Florida, Illinois, Kentucky, Maryland, North Carolina, Oregon, and Virginia). With additional adjustment for education, income, and obesity status, diabetes ORs in rural versus urban areas remained significant and greater than 1 for 2 states (North Carolina and Oregon). CONCLUSION: Our findings reveal significant geographic disparities in diabetes prevalence between rural and urban areas in 19 states. The differences in most states may have been explained by rural-urban differences in sociodemographic characteristics and obesity rates. Our findings could inform decision makers to identify effective ways to reduce rural-urban disparities within states.

BACKGROUND: Seasonal influenza illness and acute respiratory infections can impose a substantial economic burden in low- and middle-income countries (LMICs). We assessed the cost of influenza illness and acute respiratory infections across household income strata. METHODS: We conducted a secondary analysis of data from a prior systematic review of costs of influenza and other respiratory illnesses in LMICs and contacted authors to obtain data on cost of illness (COI) for laboratory-confirmed influenza-like illness and acute respiratory infection. We calculated the COI by household income strata and calculated the out-of-pocket (OOP) cost as a proportion of household income. RESULTS: We included 11 studies representing 11 LMICs. OOP expenses, as a proportion of annual household income, were highest among the lowest income quintile in 10 of 11 studies: in 4/4 studies among the general population, in 6/7 studies among children, 2/2 studies among older adults, and in the sole study for adults with chronic medical conditions. COI was generally higher for hospitalizations compared with outpatient illnesses; median OOP costs for hospitalizations exceeded 10% of annual household income among the general population and children in Kenya, as well as for older adults and adults with chronic medical conditions in China. CONCLUSIONS: The findings indicate that influenza and acute respiratory infections pose a considerable economic burden, particularly from hospitalizations, on the lowest income households in LMICs. Future evaluations could investigate specific drivers of COI in low-income household and identify interventions that may address these, including exploring household coping mechanisms. Cost-effectiveness analyses could incorporate health inequity analyses, in pursuit of health equity.

OBJECTIVE: To investigate the biodynamics of human-exoskeleton interactions during patient handling tasks using a subject-specific modeling approach. BACKGROUND: Exoskeleton technology holds promise for mitigating musculoskeletal disorders caused by manual handling and most alarmingly by patient handling jobs. A deeper, more unified understanding of the biomechanical effects of exoskeleton use calls for advanced subject-specific models of complex, dynamic human-exoskeleton interactions. METHODS: Twelve sex-balanced healthy participants performed three simulated patient handling tasks along with a reference load-lifting task, with and without wearing the exoskeleton, while their full-body motion and ground reaction forces were measured. Subject-specific models were constructed using motion and force data. Biodynamic response variables derived from the models were analyzed to examine the effects of the exoskeleton. Model validation used load-lifting trials with known hand forces. RESULTS: The use of exoskeleton significantly reduced (19.7%-27.2%) the peak lumbar flexion moment but increased (26.4%-47.8%) the peak lumbar flexion motion, with greater moment percent reduction in more symmetric handling tasks; similarly affected the shoulder joint moments and motions but only during two more symmetric handling tasks; and significantly reduced the peak motions for the rest of the body joints. CONCLUSION: Subject-specific biodynamic models simulating exoskeleton-assisted patient handling were constructed and validated, demonstrating that the exoskeleton effectively lessened the peak loading to the lumbar and shoulder joints as prime movers while redistributing more motions to these joints and less to the remaining joints. APPLICATION: The findings offer new insights into biodynamic responses during exoskeleton-assisted patient handling, benefiting the development of more effective, possibly task- and individual-customized, exoskeletons.

BACKGROUND: Tuberculosis (TB) Building and Strengthening Infection Control Strategies (TB BASICS) aimed to achieve improvements in TB infection prevention and control (IPC) through structured training and mentorship. METHODS: TB BASICS was implemented in six Chinese provinces from 2017-2019. Standardized, facility-based risk assessments tailored to inpatient, laboratory, and outpatient departments were conducted quarterly for 18 months. Knowledge, attitudes, and practices surveys were administered to healthcare workers (HCW) at nine participating facilities during the first and last assessments. Kruskal-Wallis rank sum test assessed score differences between departments (alpha = 0.05). RESULTS: Fifty-seven departments received risk assessments. IPC policies and practices improved substantially during follow up. Facility-based assessment scores were significantly lower in outpatient departments than other departments (p <0.05). All indicators achieved at least partial implementation by the final assessment. Low scores persisted for implementing isolation protocols, while personal protective equipment use among staff was consistent among all departments. Overall, we observed minimal change in IPC knowledge among HCW. In general, HCW had favorable views of their own IPC capabilities, but reported limited agency to improve institutional IPC. CONCLUSIONS: TB BASICS demonstrated improvements in TB IPC implementation. Structured training and mentorship engaged HCW to maintain confidence and competency for TB prevention.

BACKGROUND: PFAS may impair bone health, but effects of PFAS exposure assessed during pregnancy and the perimenopause-life stages marked by rapidly changing bone metabolism-on later life bone health are unknown. METHODS: We studied 531 women in the Boston-area Project Viva cohort. We used multivariable linear, generalized additive, and mixture models to examine associations of plasma PFAS concentrations during early pregnancy [median (IQR) maternal age 32.9 (6.2) years] and midlife [age 51.2 (6.3)] with lumbar spine, total hip, and femoral neck areal bone mineral density (aBMD) and bone turnover biomarkersassessed in midlife. We examined effect modification by diet and physical activity measured at the time of PFAS exposure assessment and by menopausal status in midlife. RESULTS: Participants had higher PFAS concentrations during pregnancy [1999-2000; e.g., PFOA median (IQR) 5.4 (3.8) ng/mL] than in midlife [2017-2021; e.g. , PFOA: 1.5 (1.2) ng/mL]. Women with higher PFOA, PFOS and PFNA during pregnancy had higher midlife aBMD, especially of the spine [e.g., 0.28 (95% CI: 0.07, 0.48) higher spine aBMD T-score, per doubling of PFOA], with stronger associations observed among those with higher diet quality. In contrast, higher concentrations of all PFAS measured in midlife were associated with lower concurrent aBMD at all sites [e.g., -0.21 (-0.35, -0.07) lower spine aBMD T-score, per doubling of PFOA]; associations were stronger among those who were postmenopausal. The associations of several PFAS with bone resorption (loss) were also stronger among postmenopausal versus premenopausal women. DISCUSSION: Plasma PFAS measured during pregnancy versus in midlife had different associations with midlife aBMD. We found an adverse association of PFAS measured in midlife with midlife aBMD, particularly among postmenopausal women. Future studies with longer follow-up are needed to elucidate the effect of PFAS on bone health during the peri- and postmenopausal years.

INTRODUCTION: Intimate partner violence accounts for up to one half of all homicides of women in the United States. Rates of intimate partner homicide are associated with both race/ethnicity and social determinants of health, but their relative contribution is incompletely understood. METHODS: We used negative binomial regression to model the relationship between counties' racial/ethnic composition and their rates of intimate partner homicide of women, controlling for urbanicity, median income, gender pay gap, unemployment, school funding, and violent crime rate. We used data from 49 states and the District of Columbia between 2016 and 2021. Analyses were conducted in 2024. RESULTS: In unadjusted analysis, counties with a lower proportion of White residents experienced higher rates of intimate partner homicide (IRR = 1.11; 95% CI: 1.08 - 1.13). When controlling for social determinants of health, this association was not observed (IRR = 1.01; 95% CI: 0.97 - 1.04). Median income, school funding, and violent crime rate were independent predictors of intimate partner homicide in the multivariate model. CONCLUSIONS: Racial/ethnic composition of a population does not independently predict its rate of intimate partner homicide when controlling for social determinants of health. Racial/ethnic inequities in intimate partner homicide are largely attributable to structural factors, which may be modifiable through policy changes.

BACKGROUND: Tracking the emergence, introduction and spread of SARS-CoV-2 variants of concern are essential for informing public health strategies. In 2021, Cambodia faced two major epidemic waves of SARS-CoV-2 triggered by the successive rise of the Alpha and Delta variants. METHODS: Phylodynamic analysis of 1,163 complete SARS-CoV-2 genomes from Cambodia, along with global sequences, were conducted between February and September 2021 to infer viral introductions, molecular epidemiology and population dynamics. The relationship between epidemic trends and control strategies were evaluated. Bayesian phylogeographic reconstruction was employed to estimate and contrast the spatiotemporal dynamics of the Alpha and Delta variants over time. RESULTS: Here we reveal that the Alpha variant displays rapid lineage diversification, accompanied by the acquisition of a spike E484K mutation that coincides with the national implementation of mass COVID-19 vaccination. Despite nationwide control strategies and increased vaccination coverage, the Alpha variant was quickly displaced by Delta variants that exhibits a higher effective reproductive number. Phylogeographic inference indicates that the Alpha variant was introduced through south-central region of Cambodia, with strong diffusion rates from the capital of Phnom Penh to other provinces, while the Delta variant likely entered the country via the northern border provinces. CONCLUSIONS: Continual genomic surveillance and sequencing efforts, in combination with public health strategies, play a vital role in effectively tracking and responding to the emergence, evolution and dissemination of future emerging variants. | Tracking how SARS-CoV-2, the virus that causes COVID-19, changes over time is important for public health. In Cambodia, there were two major COVID-19 waves in 2021, driven by the Alpha and Delta variants. We analyzed 1,163 virus samples from Cambodia, plus samples from other places, to understand how these variants spread. We found that the Alpha variant quickly spread and changed as Cambodia started a mass vaccination campaign. Despite efforts to control it, the Delta variant, which spreads more easily, soon took over. The Alpha variant likely came into Cambodia from the south, while the Delta variant probably entered from the north. Monitoring these changes helps us respond better to future outbreaks. | eng

Endurance exercise training (ExT) induces metabolic, structural, and functional adaptations via lipidomic modifications, yet the systematic elucidation of lipidome alterations in response to ExT remains incomplete. As a part of the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we leveraged non-targeted and targeted lipidomics for the systematic discovery of lipid alterations in the brown adipose tissue, heart, hippocampus, kidney, liver, lung, skeletal muscle gastrocnemius, subcutaneous white adipose tissue, and plasma in response to 1, 2, 4 or 8 weeks of ExT in 6-month-old male and female Fischer-344 rats. This study demonstrates that these tissues, each with distinct lipidomic features, underwent dynamic, sexually dimorphic lipid remodeling. Exercise trained animals showed reduced whole-body adiposity and improved cardiorespiratory fitness, along with enhanced utilization of lipid stores and dynamic triacylglycerol remodeling compared to sedentary controls in all tissues except hippocampus. They also showed modifications in phospholipids, lysophospholipids, oxylipins, and ceramides in several tissues. Coordinated changes across tissues reflect systemic tissue communication, with liver-plasma-heart connection potentially playing a key role in systemic lipid metabolism during ExT. These data will improve our understanding of lipid-associated biological processes underlying the health-promoting benefits of ExT.

OBJECTIVES: Trivalent inactivated influenza vaccine effectiveness was low in a prospective cohort of healthcare personnel (HCP) in Israel from 2016 to 2019. We conducted a randomised immunogenicity trial of quadrivalent recombinant influenza vaccine (RIV4) and standard-dose inactivated influenza vaccine (IIV4) among frequently and infrequently vaccinated previous cohort participants. METHODS: From October 2019 to January 2020, we enrolled and randomly allocated HCP from two Israeli hospitals to receive IIV4 or RIV4. Hemagglutination inhibition (HAI) antibody titres against 2019-2020 vaccine reference influenza viruses were compared between vaccine groups using geometric mean titre (GMT) ratios from sera collected one-month post-vaccination and by frequency of vaccination in the past 5 years (>2 vs ≤2). RESULTS: Among 415 HCP, the GMT ratio comparing RIV4 to IIV4 was 2.0 (95% confidence interval [CI] 1.7-2.7) for A(H1N1)pdm09, 1.6 (95% CI: 1.3-1.9) for A(H3N2), 1.8 (95% CI: 1.4-2.2) for B(Yamagata), and 1.1 (95% CI: 0.9-1.4) for B(Victoria). Similarly, RIV4 elicited higher HAI titres than IIV4 against all 2019-2020 vaccine reference viruses except B(Victoria) among infrequently and frequently vaccinated HCP (lower bound of GMT ratio 95% CIs ≥1.0). CONCLUSION: RIV4 had improved immunogenicity for influenza vaccine strains among both infrequent and frequent vaccinees compared to standard-dose IIV4. CLINICAL TRIALS REGISTRATION: NCT04523324.

BACKGROUND: Unfavorable health-related social needs (HRSNs) have the potential to worsen health and well-being and drive health disparities. Its associations with cardiovascular health (CVH), assessed by Life's Essential 8, have not been comprehensively examined among US adults. METHODS AND RESULTS: We used the National Health and Nutrition Examination Survey 2011 to March 2020 data for adults aged ≥20 years. We grouped Life's Essential 8 scores as low (0-49), moderate (50-79), and high (80-100) CVH. We identified 8 unfavorable HRSNs and assigned a value of 1 for the unfavorable status of each. The number of unfavorable HRSNs was summed and ranged from 0 to 8, with higher numbers indicating more unfavorable HRSNs. We used multivariable linear and multinomial logistic regression to examine the association between HRSNs and CVH. A total of 14 947 participants were included (n=7340 male [49.3%]; mean [SE] age, 46.4 [0.35] years). A higher number of unfavorable HRSNs were associated with worse CVH: comparing adults with unfavorable HRSNs of 1-2, 3-4, and ≥5 to those with none, the fully adjusted prevalence ratios (95% CI) for low CVH were 1.42 (1.17-1.73), 2.11 (1.69-2.63), and 2.42 (1.90-3.08), respectively. The corresponding prevalence ratios (95% CI) for high CVH were 0.77 (0.68-0.87), 0.58 (0.49-0.67), and 0.46 (0.38-0.55). The associations were consistent across subgroups and in sensitivity analyses. CONCLUSIONS: There was a graded association between unfavorable HRSNs and a higher prevalence of low CVH or lower prevalence of high CVH. Public health interventions targeting HRSNs might reduce health disparities and promote CVH.

Introduction: Heart disease poses a significant health and economic burden in the U.S., with considerable variations in outcomes across different racial and ethnic groups. The COVID-19 pandemic has further highlighted the disparities in healthcare utilization and costs associated with heart disease. Methods: The authors used the 2021 Merative MarketScan Medicaid claims database to estimate the medical costs and healthcare utilization associated with heart disease by racial and ethnic groups and COVID-19 diagnosis status. This study focused on individuals aged ≥18 years continuously enrolled in a noncapitated insurance plan in 2021. The outcome measures included total medical expenditures and healthcare utilization, including the numbers of emergency department visits and inpatient admissions and length of inpatient stay. The authors employed a generalized linear model with a family of gamma and log links for medical costs, and a negative binomial regression was used for healthcare utilization. Three-way interactions of heart disease, COVID-19 diagnosis, and race and ethnicity categories were implemented after adjusting for age, sex, and comorbidities. The authors reported average marginal effects with 95% CIs. Results: Among 1,008,166 Medicaid beneficiaries, 8% had heart disease in 2021. The cost associated with heart disease was $10,819 per beneficiary in 2021 (95% CI=10,292; 11,347; p<0.001). The cost was $15,840 (95% CI=14,389; 17,291; p<0.001) for non-Hispanic Black individuals; $9,945 (95% CI=9,172; 10,718; p<0.001) for non-Hispanic White; and $8,511 (95% CI=7,490; 9,531; p<0.001) for Hispanic individuals. Individuals with a COVID-19 diagnosis ($19,638) had $9,541 (95% CI=7,049; 12,032; p<0.001) higher costs associated with heart disease than those without COVID-19 ($10,098) (p<0.001). Individuals with heart disease had higher numbers of emergency department visits (0.937 per beneficiary, 95% CI=0.913; 0.960), inpatient admissions (0.463 per beneficiary, 95% CI=0.455; 0.471), and average length of stay (2.541 days per admission, 95% CI=2.405; 2.677) than those without heart disease. Conclusions: The study's findings showed that costs and healthcare utilization associated with heart disease are substantial in all racial and ethnic groups and the highest among non-Hispanic Black individuals. Furthermore, individuals with a COVID-19 diagnosis had approximately 2 times higher costs associated with heart disease than individuals without a COVID-19 diagnosis. © 2024

Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately 80% of fungal diseases [D. W. Denning, Lancet Infect Dis, 24:e428-e438, 2024, https://doi.org/10.1016/S1473-3099(23)00692-8], tend to follow a predictive pattern, while those by occasional opportunists are more variable. For this reason, it is recommended that diseases caused by primary pathogens and the common opportunists are named after the etiologic agent, for example, histoplasmosis and aspergillosis, while this should not be done for occasional opportunists that should be named as [causative fungus] [clinical syndrome], for example, Alternaria alternata cutaneous infection. The addition of a descriptor that identifies the location or clinical type of infection is required, as the general name alone may cover widely different clinical syndromes, for example, "rhinocerebral mucormycosis." A list of major recommended human and animal disease entities (nomenclature) is provided in alignment with their causative agents. Fungal disease names may encompass several genera of etiologic agents, consequently being less susceptible to taxonomic changes of the causative species, for example, mucormycosis covers numerous mucormycetous molds.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a multisystem genetic disorder that classically presents with symptoms associated with myotonia, early onset cataracts, and muscular weakness, although the presentation and pattern of disease progression is quite varied. Presenting symptoms are well documented among adults with DM1. However, less is known about the co-occurrence of symptoms over time. We aimed to use factor analysis to explore the correlation pattern of signs and symptoms (S/S) that emerged during the clinical course. RESULTS: Clinical records of 228 individuals with adult onset DM1 were abstracted using the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) from a six-site cohort in the United States during an eight-year study period. Factor analysis was used to group the correlated S/S into latent factors. Three factors were identified. Group 1: 'Facial Weakness/Myotonia' includes the two most common S/S, as indicated by its name. Group 2: 'Skeletal Muscle Weakness' includes eight muscular S/S and is more frequently reported by males and those with older age at onset. Group 3: 'Gastrointestinal distress/Sleepiness' includes four non-muscular S/S and hand stiffness. The abstracted medical records reported that over 63% of individuals had S/S from all three groups. Associations of covariates with factor scores were also examined using linear regression. CTG repeat length was significantly positively associated with higher factor scores for all three factors. CONCLUSIONS: This study identified three latent factors of S/S which accumulated during the clinical course of adult onset DM1.

Pregnancy is associated with increased risk for severe illness and complications associated with influenza infection. Insufficient knowledge about the risk for influenza among pregnant women and their health care providers in China is an important barrier to increasing influenza vaccination coverage and treating influenza and its complications among pregnant women. Improved influenza incidence estimates might promote wider vaccine acceptance and higher vaccination coverage. In Suzhou, active population-based surveillance during October 2018-September 2023 estimated that the annual rate of hospitalization for acute respiratory or febrile illness (ARFI) among women who were pregnant or <2 weeks postpartum was 11.1 per 1,000 live births; the annual rate of laboratory-confirmed influenza-associated ARFI (influenza ARFI) hospitalization in this group was 2.1 per 1,000 live births. A majority of hospitalized pregnant or early postpartum patients with ARFI (82.6%; 2,588 of 3,133) or influenza ARFI (85.5%; 423 of 495) were admitted to obstetrics wards rather than respiratory medicine wards. Only one (0.03%) pregnant or postpartum ARFI patient had received influenza vaccination, and 31.3% of pregnant or postpartum women hospitalized for influenza ARFI received antiviral treatment; the lowest percentage of hospitalized women with influenza ARFI who received antiviral treatment was among women admitted to obstetrics and gynecology wards (29.6% and 23.1%, respectively), compared with 54.1% of those admitted to a respiratory medicine ward. These findings highlight the risk for influenza and its associated complications among pregnant and postpartum women, the low rates of influenza vaccination among pregnant women, and of antiviral treatment of women with ARFI admitted to obstetrics and gynecology wards. Increasing awareness of the prevalence of influenza ARFI among pregnant women, the use of empiric antiviral treatment for ARFI, and the infection control in obstetrics wards during influenza seasons might help reduce influenza-associated morbidity among pregnant and postpartum women.

Globally, nearly half of all pregnancies are unintended, ~1.3 million new human immunodeficiency virus (HIV) infections are reported every year, and more than 500 million people are estimated to have a genital herpes simplex virus (HSV-2) infection. Here we report the first 3D printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for prevention of HIV, HSV-2, and unintended pregnancy. The IVRs were fabricated using state-of-the-art Continuous Liquid Interface Production (CLIP™) 3D printing technology using a biocompatible silicone-urethane based resin. Anti-HIV drug (Dapivirine, DPV), anti-herpes drug (Pritelivir, PTV) and a contraceptive drug (Levonorgestrel, LNG) were loaded in a macaque size IVR (25 mm outer diameter, OD; 6.0 mm cross-section, CS) allometrically scaled from the human size (54 mm OD; 7.6 mm CS) IVR analogue. All three active pharmaceutical ingredients (APIs) were loaded in the IVR using a single-step drug loading process driven by absorption. DPV, PTV, and LNG elicited zero-order release kinetics in vitro in simulated vaginal fluid (SVF) at pH 4 and pH 8 relevant to human and macaque vaginal pH respectively. CLIP 3D printed MPT IVRs remained stable after 6 months of storage at 4 °C with no change in physical, dimensional, or mechanical properties and no change in drug concentration and absence of drug degradation byproducts. The MPT IVRs elicited sustained release of all three APIs in macaques for 28 days with median plasma concentrations of 138 pg/mL (DPV), 18,700 pg/mL (PTV), and 335 pg/mL (LNG). Safety studies demonstrated that the MPT IVRs were safe and well tolerated in the macaques with no observed change or abnormalities in vaginal pH and no significant changes in any of the 22 mucosal cytokines and chemokines tested including pro-inflammatory (IL-1β, IL-6, IL-8, IFN-γ, TNF-α, IL-17, IL-18) and anti-inflammatory (IL-10, IL-12) cytokines while the MPT IVR was in place or after its removal. Additionally, MPT IVRs elicited no observed alterations in systemic CD4+ and CD8+ T cells during the entire study. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls against unintended pregnancy against two highly prevalent sexually transmitted infections (STIs).

INTRODUCTION: To examine the long-term health and economic impact of a lifestyle diabetes prevention program in people with high risk of developing type 2 diabetes in Germany. RESEARCH DESIGN AND METHODS: We assessed the lifetime cost-effectiveness of a 2-year pragmatic lifestyle program for preventing type 2 diabetes targeting German adults aged 35-54 and 55-74 years old with hemoglobin A1c (HbA1c) from 6.0% to 6.4%. We used the Centers for Disease Control and Prevention RTI Diabetes Cost-Effectiveness Model to run a simulation on the program effectiveness. We estimated incremental health benefits in quality-adjusted life years (QALYs) and costs using an established simulation model adapted to the German context, from a healthcare system and societal perspective. The cost-effectiveness of the program was measured by incremental cost-effectiveness ratios (ICERs) in cost per QALY. We projected the number of type 2 diabetes cases prevented by participation rate if the program was implemented nationwide. RESULTS: The lifestyle program would result to more QALYs and higher costs. The lifetime ICERs were 14 690€ (35-54 years old) and 14 372€ (55-74 years old) from a healthcare system perspective and cost saving (ICER=-3805€) and cost-effective (ICER=4579€), respectively, from a societal perspective. A total of 10 527 diabetes cases would be prevented over lifetime if the program was offered to all eligible people nationwide and 25% of those would participate in the program. CONCLUSIONS: Implementing the lifestyle intervention for people with HbA1c from 6.0% to 6.4% could be a cost-effective at standard willingness to pay level strategy for type 2 diabetes prevention. The intervention in the younger cohort could be cost saving from a societal perspective. The successful implementation of a lifestyle-based diabetes prevention program could be an important component of a successful National Diabetes Strategy in Germany.

In recent decades, the use of assisted reproductive technology (ART) has increased rapidly. To assess the relationship between ART and autism diagnosis, we linked California birth records from 2000 through 2016 with contemporaneous records from the National ART Surveillance System (NASS) and autism caseload records from California's Department of Developmental Services from 2000 through November 2019. All 95 149 birth records that were successfully linked to a NASS record, indicating an ART birth, were matched 1:1 using propensity scores to non-ART births. We calculated the hazard risk ratio for autism diagnosis and the proportions of the relationship between ART conception and autism diagnosis mediated by multiple birth pregnancy and related birth complications. The hazard risk ratio for autism diagnosis following ART compared with non-ART conception is 1.26 (95% CI, 1.17-1.35). Multiple birth, preterm birth, and cesarean delivery jointly mediate 77.9% of the relationship between ART conception and autism diagnosis. Thus, increased use of single embryo transfer in the United States to reduce multiple births and related birth complications may be a strategy to address the risk of autism diagnosis among ART-conceived children.

In 2018, the Navi Mumbai Municipal Corporation implemented phase 1 of a public sector typhoid conjugate vaccine campaign in Navi Mumbai, India, targeting all children aged 9 months to 14 years within its administrative boundaries. To assess associations with receipt of vaccine in phase 1, we used generalized estimating equations to calculate estimates of vaccination by child-, household-, and community-level demographics (child education and age; household head education, income, and occupation; community informal settlement percent). Campaign vaccine receipt was most associated with children enrolled in school (odds ratio [OR] = 3.84, 95% CI: 2.18-6.77), the lowest household income tertile when divided into three equal parts (OR = 1.64, 95% CI: 1.43-1.84), and lower community-level socioeconomic status (OR = 1.06, 95% CI: 1.04-1.08 per 10% informal settlement proportion). The campaign was successful in reaching the most underserved populations of its target communities.

Prior to 2017, the family Bunyaviridae included five genera of arthropod and rodent viruses with tri-segmented negative-sense RNA genomes related to the Bunyamwera virus. In 2017, the International Committee on Taxonomy of Viruses (ICTV) promoted the family to order Bunyavirales and subsequently greatly expanded its composition by adding multiple families for non-segmented to polysegmented viruses of animals, fungi, plants, and protists. The continued and accelerated discovery of bunyavirals highlighted that an order would not suffice to depict the evolutionary relationships of these viruses. Thus, in April 2024, the order was promoted to class Bunyaviricetes. This class currently includes two major orders, Elliovirales (Cruliviridae, Fimoviridae, Hantaviridae, Peribunyaviridae, Phasmaviridae, Tospoviridae, and Tulasviridae) and Hareavirales (Arenaviridae, Discoviridae, Konkoviridae, Leishbuviridae, Mypoviridae, Nairoviridae, Phenuiviridae, and Wupedeviridae), for hundreds of viruses, many of which are pathogenic for humans and other animals, plants, and fungi.