A Highly Selective Fluorescent Probe for Monitoring the Thyroid Hormone Transporter Activity in Mammalian Cells.

Monocarboxylate transporter 8 (MCT8) is a trans-membrane transporter, which mediates the cellular delivery of thyroid hormones, L-thyroxine (T4) and 3,5,3 '-triiodo-L-thyronine (T3). In humans, the MCT8 protein is encoded by the SLC16A2 gene and mutations in the transporter cause a genetic neurological disorder known as Allan-Herndon-Dudley syndrome (AHDS). MCT8 deficiency leads to impaired transport of thyroid hormones in the brain. Radiolabelled T4 and T3 or LC/MS-MS methods have been used to monitor the thyroid hormone uptake through MCT8. Herein, we developed a fluorescent based assay to monitor the thyroid hormone uptake through MCT8. A dansyl-based fluorescent probe having L-thyroxine moiety is found to be highly selective towards MCT8 in living cells. The high selectivity of the probe towards MCT8 can be attributed to the halogen bond-mediated recognition by the transporter protein. The presence of a free carboxylic acid group is essential for the specificity of the probe towards MCT8. Additionally, the selectivity of the probe for MCT8 is abolished upon esterification of the carboxylic group. Similarly, MCT8 does not recognize the probe when it contains a free amine group.

Illicitly Manufactured Fentanyl-Involved Overdose Deaths with Detected Xylazine - United States, January 2019-June 2022.

In 2022, provisional data indicated that more than two thirds (68%) of the reported 107,081 drug overdose deaths in the United States involved synthetic opioids other than methadone, principally illicitly manufactured fentanyls (IMFs) (1). Xylazine, a nonopioid sedative not approved for human use and with no known antidote, has been increasingly detected in IMF products in the U.S. drug supply* and in IMF-involved overdose deaths (2). Limited studies suggest xylazine can cause central nervous system depression, respiratory depression, bradycardia, and hypotension in humans (3,4); chronic use might lead to severe withdrawal symptoms† as well as skin ulcerations (4). This report uses data from CDC's State Unintentional Drug Overdose Reporting System (SUDORS) to describe IMF-involved§ overdose deaths with and without xylazine detected that occurred during January 2019-June 2022. Among 21 jurisdictions, which included 20 states and the District of Columbia, the monthly percentage of IMF-involved deaths with xylazine detected increased 276%, from 2.9% to 10.9%. Among IMF-involved deaths during January 2021-June 2022 in 32 jurisdictions, xylazine was detected in a higher percentage of jurisdictions in the Northeast U.S. Census Bureau region; listing detected xylazine as a cause of death varied across jurisdictions. Expanded postmortem and illicit drug product testing for xylazine is needed to clarify prevalence in drug supplies; further investigation of xylazine's effects on humans is necessary to characterize morbidity and overdose risk. It is important for overdose prevention and response messages to highlight the potential presence of xylazine in IMF products and emphasize the need for respiratory and cardiovascular support to address the sedative effects of xylazine.

Diverging trends in US male-female condom use by STI risk factors: a nationally representative study.

OBJECTIVE: Condom use behaviours are proximal to recent STI increases in the USA, yet it remains unclear whether the use of condoms has changed over time among unmarried, non-cohabiting young men who have sex with women (MSW) and how this variability is influenced by STI risk factors. METHODS: To examine condom use over time among MSW aged 15-29, we used three cross-sectional surveys from the 2002, 2006-2010 and 2011-2017 National Survey of Family Growth. We estimated weighted percentages, adjusted prevalence ratios (APRs) and 95% confidence intervals (CI) to assess changes in condom use, stratified by whether MSW reported any STI risk factors in the past 12 months (ie, perceived partner non-monogamy, male-to-male sex, sex in exchange for money or drugs, sex partner who injects illicit drugs, or an HIV-positive sex partner). RESULTS: We observed a divergence in trends in condom use at last sex between men aged 15 -29 with STI risk factors in the past 12 months and those without such history. We saw significant declines in condom use from 2002 to 2011-2017 among men with STI risk factors (APR=0.80, 95% CI 0.68 to 0.95), specifically among those aged 15-19 (APR=0.73, 95% CI 0.57 to 0.94) or non-Hispanic white (APR=0.71, 95% CI 0.54 to 0.93). In contrast, trends in condom use among men with no STI factors remained stable or increased. Across all time periods, the most prevalent STI risk factor reported was perception of a non-monogamous female partner (23.0%-26.9%). Post-hoc analyses examined whether condom use trends changed once this variable was removed from analyses, but no different patterns were observed. CONCLUSIONS: While STIs have been increasing, men aged 15-29 with STI risk factors reported a decline in condom use. Rising STI rates may be sensitive to behavioural shifts in condom use among young MSW with STI risk factors.

Vital Signs: Drug Overdose Deaths, by Selected Sociodemographic and Social Determinants of Health Characteristics - 25 States and the District of Columbia, 2019-2020.

INTRODUCTION: Drug overdose deaths increased approximately 30% from 2019 to 2020 in the United States. Examining rates by demographic and social determinants of health characteristics can identify disproportionately affected populations and inform strategies to reduce drug overdose deaths. METHODS: Data from the State Unintentional Drug Overdose Reporting System (SUDORS) were used to analyze overdose death rates from 2019 to 2020 in 25 states and the District of Columbia. Rates were examined by race and ethnicity and county-level social determinants of health (e.g., income inequality and treatment provider availability). RESULTS: From 2019 to 2020, drug overdose death rates increased by 44% and 39% among non-Hispanic Black (Black) and non-Hispanic American Indian or Alaska Native (AI/AN) persons, respectively. Significant disparities were found across sex, age, and racial and ethnic subgroups. In particular, the rate in 2020 among Black males aged ≥65 years (52.6 per 100,000) was nearly seven times that of non-Hispanic White males aged ≥65 years (7.7). A history of substance use was frequently reported. Evidence of previous substance use treatment was lowest for Black persons (8.3%). Disparities in overdose deaths, particularly among Black persons, were larger in counties with greater income inequality. Opioid overdose rates in 2020 were higher in areas with more opioid treatment program availability compared with areas with lower opioid treatment availability, particularly among Black (34.3 versus 16.6) and AI/AN (33.4 versus 16.2) persons. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Health disparities in overdose rates continue to worsen, particularly among Black and AI/AN persons; social determinants of health, such as income inequality, exacerbate these inequities. Implementation of available, evidence-based, culturally responsive overdose prevention and response efforts that address health disparities impacting disproportionately affected populations are urgently needed.

Chlamydia Screening Among Women Aged 15 to 44 Years Who Reported Anal Sex During the Past 12 Months in the United States, 2013 to 2017.

ABSTRACT: Using the 2013-2017 National Survey of Family Growth, 37.6% of women with ≥1 anal sex partner in the last 12 months reported chlamydia testing at unspecified anatomic sites in the past 12 months. Women whose medical provider asked about type of sex (i.e., vaginal, oral, anal), compared with those whose provider did not, reported higher chlamydia testing.

Estimating the Direct Medical Outpatient Costs of Diagnosis and Treatment of Trichomoniasis Among Commercially Insured Patients in the United States, 2016 to 2018.

ABSTRACT: We used 2016-2018 outpatient claims data to calculate direct outpatient medical costs per case of trichomoniasis in 2019 US dollars. The outpatient, drug, and total costs per treated case of trichomoniasis were $174, $39, and $213, respectively. Total costs were higher for female patients ($220) than for male patients ($158).

Estimating the Direct Medical Costs and Productivity Loss of Outpatient Chlamydia and Gonorrhea Treatment.

ABSTRACT: We used 2016-2017 administrative claims data to calculate the direct medical cost and productivity loss per diagnosed case of chlamydia and gonorrhea treatment. In 2018 US dollars, the direct cost per diagnosed case was $151 for chlamydia (n = 9180) and $85 for gonorrhea (n = 3048); productivity loss was $206 (n = 31) and $246 (n = 7), respectively, among those missing work seeking care.

Lifetime Medical Costs of Genital Herpes in the United States: Estimates From Insurance Claims.

BACKGROUND: The purpose of this study was to estimate the lifetime direct medical costs per incident case of genital herpes in the United States. METHODS: We used medical claims data to construct a cohort of people continuously enrolled in insurance for at least 48 consecutive months between 2010 and 2018. From this cohort, we identified initial genital herpes diagnoses as well as the cost of related clinical visits and medication during the 36 months after an initial diagnosis. Lifetime costs beyond 36 months were estimated based on treatment use patterns observed in the 36 months of follow-up. RESULTS: The present value of lifetime direct medical costs of genital herpes was estimated to be $972 per treated case or $165 per infection (2019 dollars), not including costs associated with prevention or treatment of neonatal herpes. The clinical visit at which genital herpes was first diagnosed accounted for 27% of lifetime costs. Subsequent clinical visits and medications related to genital herpes accounted for an additional 13% and 60% of lifetime costs, respectively. CONCLUSIONS: The results from this study can inform cost-effectiveness analysis of genital herpes control interventions as well as help quantify the cost burden of sexually transmitted infections in the United States.

The Estimated Lifetime Medical Cost of Chlamydia, Gonorrhea, and Trichomoniasis in the United States, 2018.

BACKGROUND: The purpose of this study was to provide updated estimates of the average lifetime medical cost per infection for chlamydia, gonorrhea, and trichomoniasis. METHODS: We adapted a published decision tree model that allowed for 7 possible outcomes of infection: (1) symptomatic infection, treated, no sequelae; (2) symptomatic infection, not treated, sequelae; (3) symptomatic infection, not treated, no sequelae; (4) asymptomatic infection, treated, sequelae; (5) asymptomatic infection, treated, no sequelae; (6) asymptomatic infection, not treated, sequelae; and (7) asymptomatic infection, not treated, no sequelae. The base case values and ranges we applied for the model inputs (i.e., the probability and cost assumptions) were based on published studies. RESULTS: The estimated lifetime medical costs per infection for men and women, respectively, were $46 (95% credibility interval, $32-$62) and $262 ($127-$483) for chlamydia, $78 ($36-$145) and $254 ($96-$518) for gonorrhea, and $5 ($1-$14) and $36 ($17-$58) for trichomoniasis. Cost estimates for men were most sensitive to assumptions regarding the probability that the infection is symptomatic, the probability of treatment if asymptomatic, and the cost of treatment of infection. Cost estimates for chlamydia and gonorrhea in women were most sensitive to assumptions regarding the probability and cost of subsequent pelvic inflammatory disease. CONCLUSIONS: These estimates of the lifetime medical cost per infection can inform updated estimates of the total annual cost of sexually transmitted infections in the United States, as well as analyses of the value and cost-effectiveness of sexually transmitted infection prevention interventions.

The Estimated Direct Lifetime Medical Costs of Sexually Transmitted Infections Acquired in the United States in 2018.

BACKGROUND: We estimated the lifetime medical costs attributable to sexually transmitted infections (STIs) acquired in 2018, including sexually acquired human immunodeficiency virus (HIV). METHODS: We estimated the lifetime medical costs of infections acquired in 2018 in the United States for 8 STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), hepatitis B, and HIV. We limited our analysis to lifetime medical costs incurred for treatment of STIs and for treatment of related sequelae; we did not include other costs, such as STI prevention. For each STI, except HPV, we calculated the lifetime medical cost by multiplying the estimated number of incident infections in 2018 by the estimated lifetime cost per infection. For HPV, we calculated the lifetime cost based on the projected lifetime incidence of health outcomes attributed to HPV infections acquired in 2018. Future costs were discounted at 3% annually. RESULTS: Incident STIs in 2018 imposed an estimated $15.9 billion (25th-75th percentile: $14.9-16.9 billion) in discounted, lifetime direct medical costs (2019 US dollars). Most of this cost was due to sexually acquired HIV ($13.7 billion) and HPV ($0.8 billion). STIs in women accounted for about one fourth of the cost of incident STIs when including HIV, but about three fourths when excluding HIV. STIs among 15- to 24-year-olds accounted for $4.2 billion (26%) of the cost of incident STIs. CONCLUSIONS: Incident STIs continue to impose a considerable lifetime medical cost burden in the United States. These results can inform health economic analyses to promote the use of cost-effective STI prevention interventions to reduce this burden.

Sexually transmitted disease clinics in the United States: Understanding the needs of patients and the capabilities of providers.

Reports of bacterial sexually transmitted infections are at the highest levels ever reported in the United States, and state and local budgetary issues are placing specialized sexually transmitted disease (STD) care at risk. This study collected information from 4138 patients seeking care at 26 STD clinics in large metropolitan areas across the United States with high levels of reported STDs to determine patient needs and clinic capabilities. Surveys were provided to patients attending these STD clinics to assess their demographic information as well as reasons for coming to the clinic and surveys were also provided to clinic administrators to determine their operational capacities and services provided by the clinic. For this initial study, we conducted univariate analyses to report all data collected from these surveys. Patients attending STD clinics across the country indicated that they do so because of the relative ease of getting an appointment; including walk-in and same-day appointments as well as the welcoming environment and expertise of the staff at the clinic. Additionally, STD clinics provide specialized care to patients; including HIV testing and counseling as well as on-site, injectable medications for the treatment of gonorrhea and syphilis in an environment that helps to reduce the role of stigma in seeking this kind of care. Sexually transmitted disease clinics continue to play an important role in helping to curb the rising epidemic of sexually transmitted infections.

Reviewing PrEP's Effect on STI Incidence Among Men Who Have sex with Men-Balancing Increased STI Screening and Potential Behavioral Sexual Risk Compensation.

Though pre-exposure prophylaxis (PrEP) can prevent HIV acquisition, it provides no protection against bacterial sexually transmitted infections (STIs). PrEP use may increase STI acquisition due to sexual risk compensation, but that could be counterbalanced by increased STI screening at regular PrEP visits. We conducted a literature search of studies with quantitative data published prior to March 2020, assessing sexual risk compensation or STI screening among men who have sex with men (MSM) before and after PrEP initiation. We identified 16 relevant publications. Changes in condom use were inconsistent across studies. Partner acquisition following PrEP initiation decreased in most studies, likely due to behavioral counseling. In publications comparing a PrEP arm to a non-PrEP arm, serodiscordance increased in the PrEP arm and decreased in the non-PrEP arm. STI screening among MSM was low within a month of PrEP initiation. Monitoring trends in sexual risk compensation and STI screening will be critical to understand PrEP's effects on STI burden.

Frequency of Sexually Transmitted Infection/HIV Testing Among Commercially Insured Patients With International Classification of Disease Tenth Revision Specified Sex Partners.

BACKGROUND: High-risk sexual behaviors (HRSB) are associated with sexually transmitted infections (STIs). The Centers for Disease Control and Prevention and US Preventive Services Task Force recommend routine testing for patients with HRSB. Providers can classify patients with HRSB based on the sex of their sex partners using the International Classification of Disease Tenth Revision. We analyzed STI/human immunodeficiency virus (HIV) testing frequencies among patients with HRSB. METHODS: This study used a large US administrative outpatient medical claims data set from 2015 to 2017. Patients aged 15 to 64 years were identified with HRSB using International Classification of Disease Tenth Revision codes. An initial HRSB diagnosis in 2016 served as the index date. We assessed chlamydia, gonorrhea, syphilis, and HIV testing by HRSB at the index date, and 4 time intervals of 1 to 6 months, and 7 to 12 months before and after the index date. RESULTS: We identified 52,160 patients with HRSB: 90.3% were patients with opposite-sex partners, 7.7% patients with same-sex partners, and 2.1% patients with same- and opposite-sex partners. There were 77.5% and 82.1% of the patients insured 6 months before and after the index, respectively. On the index date, patients with opposite-sex partners tested most for chlamydia (65.3%) and gonorrhea (65.2%), patients with same-sex partners tested most for syphilis (51.5%) and HIV (57.8%). Among insured patients, follow-up STI/HIV testing was 89.5% during 1 to 6 months and 33.1% during 7 to 12 months after the index date. Patients tested on the index date were more likely to have an STI/HIV test within 1 to 6 months after the index date. CONCLUSIONS: The STI/HIV testing among patients with HRSB could improve. It is important for patients identified as HRSB to get tested and continue testing patients based on recommendations.

Examining correlates of alcohol related condom-less sex among youth living in the slums of Kampala, Uganda.

This study examined factors associated with alcohol related condom-less sex (ARCS) among youth living in Kampala, Uganda. Analyses are based on 2014 cross-sectional survey data of urban service-seeking youth participating in a Uganda Youth Development Link (UYDEL) drop-in center. The analytic sample consisted of only youth reporting alcohol use (n = 347). Logistic regression analyses were computed to determine the factors associated with ARCS. In the bivariable analysis, ARCS was associated with being female (OR: 1.86; 95% CI: 1.21, 2.85), age of first drinking being between ages 13-16 (OR: 2.63; 95% CI: 1.42,4.86), age of first time drunk being between ages 13-16 (OR: 2.88; 95% CI: 1.47, 5.67), binge drinking (OR: 3.64; 95% CI: 2.21, 5.98), rape (OR: 2.69; 95% CI: 1.64, 4.41), sex work (OR: 5.91; 95% CI: 3.09, 11.29), and being able to refuse sex when intoxicated (OR: 1.69; 95% CI: 1.10, 2.61). In the multivariable analysis, ARCS was associated with binge drinking (AOR: 2.97; 95% CI: 1.71, 5.17) and sex work (AOR: 3.48; 95% CI: 1.62, 7.49). These findings emphasize unmet needs of this population. Strategies seeking to prevent teenage alcohol use, particularly delaying initial alcohol use, may be beneficial for reducing ARCS in this population.

Lung Entrapment Secondary to Loculated Rheumatoid Effusions Treated With Alteplase and Dornase.

Rheumatoid arthritis is a multisystemic inflammatory disease that can involve the respiratory system, including the pleural space. Most rheumatoid pleural effusions (PE) are incidentally found and do not require any treatment. Very rarely, however, they can become symptomatic and loculated, leading to lung entrapment or trapped lung. Surgical decortication remains the mainstay of management in such circumstances, although recent studies showed comparable efficacy of intrapleural fibrinolytics (alteplase and dornase alfa) in non-rheumatoid complicated effusions. We present a case of rheumatoid PE leading to lung entrapment successfully treated with intrapleural fibrinolytics without complications and good clinical status at six-month follow-up.

A Diagnostic Dilemma: Clindamycin-Resistant Group A Streptococcal Toxic Shock Syndrome Leading to Acute Respiratory Distress Syndrome (ARDS) With Multiple Possible Sources.

Group A Streptococcal (GAS) infections can potentially progress into streptococcal toxic shock syndrome (STSS) with multiorgan failure. Even with a benign presentation, GAS can rapidly lead to fatal necrotizing infections. While myositis and cutaneous infections are the typical initial presentation of STSS, genitourinary infections are a less common source. This report presents a case of a previously healthy woman with the chief complaint of ankle pain who subsequently developed streptococcal toxic shock syndrome and multiorgan failure from a Group A streptococcus infection of the genitourinary tract. She was treated with antibiotics and medical management for her septic shock and required prone ventilation for her acute respiratory distress syndrome (ARDS) but eventually recovered without surgery. This case highlights the importance of recognizing unusual presentations of Group A Strep infections, which have the potential to lead to rapid deterioration in patients. Also described are antibiotic and ventilator strategies that can be used to treat these severe systemic infections.

Isopropyl Alcohol Intoxication Treated With Hemodialysis: A Case Report and Short Review.

Isopropyl alcohol (IPA) is a common constituent of rubbing alcohol, household cleaning agents, and antiseptic agents. Ingestion of IPA usually leads to self-resolving mild symptoms in most cases but can result in severe symptoms, including central nervous system depression or hemodynamic instability. Treatment is mainly supportive, and hemodialysis is generally reserved for severe intoxication. Limited data are available on the use of hemodialysis to treat IPA intoxication. We are presenting a case of accidental ingestion of IPA in an elderly female with dementia leading to severe intoxication requiring hemodialysis at relatively non-toxic serum levels of IPA. The patient had a prompt recovery without any post-procedural or hospital-acquired complications.

Epidemiologic Analysis of a Postelimination Measles Outbreak in Central Ohio, 2022-2023.

Importance: Postelimination outbreaks threaten nearly a quarter century of measles elimination in the US. Understanding these dynamics is essential for maintaining the nation's measles elimination status. Objective: To examine the demographic characteristics and transmission dynamics of the 2022 to 2023 central Ohio measles outbreak. Design, Setting, and Participants: This cross-sectional study used electronic medical records and publicly available measles reports within an extensive central Ohio primary care network involving inpatient and outpatient settings. Participants included 90 children in Ohio with confirmed measles cases in 2022. Exposure: The exposure of interest was confirmed measles cases in Ohio in 2022. This included 5 internationally imported cases and 85 locally acquired cases. Main Outcomes and Measures: The primary outcome involved documenting and analyzing confirmed measles cases in Ohio in 2022, focusing on demographic characteristics, immunization status, and transmission links in outbreak-related cases. Results: This study analyzed 90 measles cases (47 [52.2%] male participants) in Ohio during 2022. Most participants self-identified as African or American Black (72 [80.0%]), with additional race categories including Asian, Hispanic, multirace (6 [6.7%]), White, and unknown (6 [6.7%]). Most participants were of Somali descent (64 [71.1%]), with additional ethnicity categories including American (16 [17.8%]), Guatemalan, Nepali, and unknown (6 [6.7%]). Participants were predominantly younger than 6 years (86 [95.5%]), unimmunized (89 [98.9%]), and resided in Franklin County, Ohio (83 [92.2%]). Prior to November 20, 2022, all cases occurred among unimmunized children of Somali descent in the Columbus area. Nosocomial superspreading events expanded the outbreak beyond the initially affected community. Conclusions and Relevance: This cross-sectional study of measles cases in Ohio during 2022 found that the outbreak primarily affected unimmunized children of Somali descent, highlighting the necessity for culturally tailored public health strategies to maintain measles elimination in the US. These findings underscore the importance of implementing targeted interventions and enhancing community engagement to increase vaccination rates.

A Redox Modulatory SOD Mimetic Nanozyme Prevents the Formation of Cytotoxic Peroxynitrite and Improves Nitric Oxide Bioavailability in Human Endothelial Cells.

The endothelium-derived signalling molecule nitric oxide (NO) in addition to controlling multifarious servo-regulatory functions, suppresses key processes in vascular lesion formation and prevents atherogenesis and other vascular abnormalities. The conversion of NO into cytotoxic and powerful oxidant peroxynitrite (ONOO- ) in a superoxide (O2 .- )-rich environment has emerged as a major reason for reduced NO levels in vascular walls, leading to endothelial dysfunction and cardiovascular complications. So, designing superoxide dismutase (SOD) mimetics that can selectively catalyze the dismutation of O2 .- in the presence of NO, considering their rapid reaction is challenging and is of therapeutic relevance. Herein, the authors report that SOD mimetic cerium vanadate (CeVO4 ) nanozymes effectively regulate the bioavailability of both NO and O2 .- , the two vital constitutive molecules of vascular endothelium, even in the absence of cellular SOD enzyme. The nanozymes optimally modulate the O2 .- level in endothelial cells under oxidative stress conditions and improve endogenously generated NO levels by preventing the formation of ONOO- . Furthermore, nanoparticles exhibit size- and morphology-dependent uptake into the cells and internalize via the clathrin-mediated endocytosis pathway. Intravenous administration of CeVO4 nanoparticles in mice caused no definite organ toxicity and unaltered haematological and biochemical parameters, indicating their biosafety and potential use in biological applications.

An Epidemic Model for Multi-Intervention Outbreaks.

Modeling is an important tool to utilize at the beginning of an infectious disease outbreak, as it allows estimation of parameters - such as the basic reproduction number, R0-that can be used to postulate how the outbreak may continue to spread. However, there exist many challenges that need to be accounted for, such as an unknown first case date, retrospective reporting of 'probable' cases, changing dynamics between case count and death count trends, and the implementation of multiple control efforts and their delayed or diminished effects. Using the near-daily data provided from the recent outbreak of Sudan ebolavirus in Uganda as a case study, we create a model and present a framework aimed at overcoming these aforementioned challenges. The impact of each challenge is examined by comparing model estimates and fits throughout our framework. Indeed, we found that allowing for multiple fatality rates over the course of an outbreak generally resulted in better fitting models. On the other hand, not knowing the start date of an outbreak appeared to have large and non-uniform effects on parameter estimates, particularly at the beginning stages of an outbreak. While models that did not account for the decaying effect of interventions on transmission underestimated R0, all decay models run on the full dataset yielded precise R0 estimates, demonstrating the robustness of R0 as a measure of disease spread when examining data from the entire outbreak.