Functional and perceptive differences between conventional and advanced ankle foot orthoses in community ambulators post-limb trauma: the injuries managed with advanced bracing of the lower extremity (IM ABLE) study.

Introduction: Many military service members and civilians suffer from lower extremity trauma. Despite recent advancements in lower limb bracing technology, it remains unclear whether these newer advanced braces offer improved comfort and functionality compared to conventional options. The IDEO (Intrepid Dynamic Exoskeletal Orthosis), a type of "advanced" orthosis was developed to assist in maintaining high functional performance in patients who have experienced high-energy lower extremity trauma and underwent limb salvage surgeries. Methods: A cross-sector multi-site initiative was completed to study the efficacy of advanced ankle foot orthoses (AFO) for lower limb trauma and injury compared to a conventional AFO. Following fitting, training, and accommodation, the subjects were assessed in each AFO system for mobility, self-reported function, safety and pain, and preference. Results: They preferred the advanced over the conventional AFO and the mobility and exertion perception improved with the advanced AFO with no difference in pain or overall health status scores. Discussion: Thus, an advanced AFO is an option for trauma affecting the lower limb. Long-term studies are required to better understand the accommodation and learning process of using an advanced AFO.

An Outbreak of Renal Failure in Asian Dogs Due to s-Triazine Adulteration of Pet Food Raw Material: Analysis of Unique, Green Kidney Stones Formed as a Result.

Renoliths were removed at necropsy from dogs that had died from acute kidney injury in Asia in 2004 and submitted to our laboratories for analysis including elemental composition, mass spectrometry, and nuclear magnetic resonance spectroscopy. The presence of a mixed s-triazine matrix comprising melamine, cyanuric acid, and ammelide, but no detectable ammeline, was found in the stone samples we analyzed. The unusual and unique green coloration of these stones was determined to be due to the presence of biliverdin. The occurrence of these green stones distinguished the 2004 incident from another incident in 2007 in the USA and other reported cases. The presence of crystals was reported in renal tubules and collecting ducts in both outbreaks, but no stones were reported in the 2007 incident. This difference suggested a variation in the disease process caused by mixed s- triazine ingestion. Careful monitoring of food additives is warranted to prevent future problems in animals and humans.

Hydroxymethanesulfonate and Sulfur(IV) in Fairbanks Winter During the ALPACA Study.

Hydroxymethanesulfonate (HMS) in fine aerosol particles has been reported at significant concentrations along with sulfate under extreme cold conditions (-35 °C) in Fairbanks, Alaska, a high latitude city. HMS, a component of S(IV) and an adduct of formaldehyde and sulfur dioxide, forms in liquid water. Previous studies may have overestimated HMS concentrations by grouping it with other S(IV) species. In this work, we further investigate HMS and the speciation of S(IV) through the Alaskan Layered Pollution and Chemical Analysis (ALPACA) intensive study in Fairbanks. We developed a method utilizing hydrogen peroxide to isolate HMS and found that approximately 50% of S(IV) is HMS for total suspended particulates and 70% for PM2.5. The remaining unidentified S(IV) species are closely linked to HMS during cold polluted periods, showing strong increases in concentration relative to sulfate with decreasing temperature, a weak dependence on particle water, and similar particle size distributions, suggesting a common aqueous formation process. A portion of the unidentified S(IV) may originate from additional aldehyde-S(IV) adducts that are unstable in the water-based chemical analysis process, but further chemical characterization is needed. These results show the importance of organic S(IV) species in extreme cold environments that promote unique aqueous chemistry in supercooled liquid particles.

Napa Valley Cabernet Sauvignon Proanthocyanidin Changes During Fruit Ripening: A Multi-Appellation Survey.

In 2015, an experiment was designed to investigate the distribution and variance of in winegrape flavonoids across the ripening phase in the Napa Valley. This Cabernet Sauvignon experiment was intended to evaluate the polyphenol differences across Napa Valley in order to understand parameters controlling "proanthocyanidin activity." This method has shown promise in understanding proanthocyanidin (PA) astringency based on size distribution, pigmentation, conformation, and composition. Results from whole berry partial extractions showed that seed PA material was driving PA activity early in the ripening phase, while the formation of the pigmented polymer led to a decrease later in the growing season. Multivariate analysis showed that the main drivers of changes across the ripening phase were the molecular masses of PAs and the amount of pigmentation. Given the high amount of variability seen in the experiment between sites in such a small geographical area, the results suggest that manipulation of PA activity may be possible in the vineyard, perhaps explaining variations in wine mouthfeel attributes between locations. These results can be used to develop furthermore controlled experiments targeting the variables responsible for PA activity changes.

Understanding COVID-19 Impacts on the Health Workforce: AI-Assisted Open-Source Media Content Analysis.

BACKGROUND: To investigate the impacts of the COVID-19 pandemic on the health workforce, we aimed to develop a framework that synergizes natural language processing (NLP) techniques and human-generated analysis to reduce, organize, classify, and analyze a vast volume of publicly available news articles to complement scientific literature and support strategic policy dialogue, advocacy, and decision-making. OBJECTIVE: This study aimed to explore the possibility of systematically scanning intelligence from media that are usually not captured or best gathered through structured academic channels and inform on the impacts of the COVID-19 pandemic on the health workforce, contributing factors to the pervasiveness of the impacts, and policy responses, as depicted in publicly available news articles. Our focus was to investigate the impacts of the COVID-19 pandemic and, concurrently, assess the feasibility of gathering health workforce insights from open sources rapidly. METHODS: We conducted an NLP-assisted media content analysis of open-source news coverage on the COVID-19 pandemic published between January 2020 and June 2022. A data set of 3,299,158 English news articles on the COVID-19 pandemic was extracted from the World Health Organization Epidemic Intelligence through Open Sources (EIOS) system. The data preparation phase included developing rules-based classification, fine-tuning an NLP summarization model, and further data processing. Following relevancy evaluation, a deductive-inductive approach was used for the analysis of the summarizations. This included data extraction, inductive coding, and theme grouping. RESULTS: After processing and classifying the initial data set comprising 3,299,158 news articles and reports, a data set of 5131 articles with 3,007,693 words was devised. The NLP summarization model allowed for a reduction in the length of each article resulting in 496,209 words that facilitated agile analysis performed by humans. Media content analysis yielded results in 3 sections: areas of COVID-19 impacts and their pervasiveness, contributing factors to COVID-19-related impacts, and responses to the impacts. The results suggest that insufficient remuneration and compensation packages have been key disruptors for the health workforce during the COVID-19 pandemic, leading to industrial actions and mental health burdens. Shortages of personal protective equipment and occupational risks have increased infection and death risks, particularly at the pandemic's onset. Workload and staff shortages became a growing disruption as the pandemic progressed. CONCLUSIONS: This study demonstrates the capacity of artificial intelligence-assisted media content analysis applied to open-source news articles and reports concerning the health workforce. Adequate remuneration packages and personal protective equipment supplies should be prioritized as preventive measures to reduce the initial impact of future pandemics on the health workforce. Interventions aimed at lessening the emotional toll and workload need to be formulated as a part of reactive measures, enhancing the efficiency and maintainability of health delivery during a pandemic.

Vaccine Development.

This article considers ethical considerations surrounding pediatric vaccine development for pandemic preparedness, examines some historical cases of pediatric vaccines developed during past smallpox, influenza, and 2019 coronavirus disease pandemics, and discusses the current state of vaccine development for pandemic preparedness, including vaccines against smallpox/mpox, influenza, anthrax, and Ebola that are included in the US Strategic National Stockpile and vaccines being developed against priority pathogens identified by the World Health Organization.

Evidence of Plasmodium vivax circulation in western and eastern regions of Senegal: implications for malaria control.

BACKGROUND: Malaria elimination in Senegal requires accurate diagnosis of all Plasmodium species. Plasmodium falciparum is the most prevalent species in Senegal, although Plasmodium malariae, Plasmodium ovale, and recently Plasmodium vivax have also been reported. Nonetheless, most malaria control tools, such as Histidine Rich Protein 2 rapid diagnosis test (PfHRP2-RDT,) can only diagnose P. falciparum. Thus, PfHRP2-RDT misses non-falciparum species and P. falciparum infections that fall below the limit of detection. These limitations can be addressed using highly sensitive Next Generation Sequencing (NGS). This study assesses the burden of the four different Plasmodium species in western and eastern regions of Senegal using targeted PCR amplicon sequencing. METHODS: Three thousand samples from symptomatic and asymptomatic individuals in 2021 from three sites in Senegal (Sessene, Diourbel region; Parcelles Assainies, Kaolack region; Gabou, Tambacounda region) were collected. All samples were tested using PfHRP2-RDT and photoinduced electron transfer polymerase chain reaction (PET-PCR), which detects all Plasmodium species. Targeted sequencing of the nuclear 18S rRNA and the mitochondrial cytochrome B genes was performed on PET-PCR positive samples. RESULTS: Malaria prevalence by PfHRP2-RDT showed 9.4% (94/1000) and 0.2% (2/1000) in Diourbel (DBL) and Kaolack (KL), respectively. In Tambacounda (TAM) patients who had malaria symptoms and had a negative PfHRP2-RDT were enrolled. The PET-PCR had a positivity rate of 23.5% (295/1255) overall. The PET-PCR positivity rate was 37.6%, 12.3%, and 22.8% in Diourbel, Kaolack, and Tambacounda, respectively. Successful sequencing of 121/295 positive samples detected P. falciparum (93%), P. vivax (2.6%), P. malariae (4.4%), and P. ovale wallikeri (0.9%). Plasmodium vivax was co-identified with P. falciparum in thirteen samples. Sequencing also detected two PfHRP2-RDT-negative mono-infections of P. vivax in Tambacounda and Kaolack. CONCLUSION: The findings demonstrate the circulation of P. vivax in western and eastern Senegal, highlighting the need for improved malaria control strategies and accurate diagnostic tools to better understand the prevalence of non-falciparum species countrywide.

Density-mediated foraging behavioral responses of Rhyzopertha dominica (Coleoptera: Bostrichidae) and Tribolium castaneum (Coleoptera: Tenebrionidae).

Tribolium castaneum and Rhyzopertha dominica are cosmopolitan, destructive postharvest pests. Although research has investigated how high densities of T. castaneum affect attraction to the aggregation pheromone by conspecifics, research into the behavioral response of both species to food cues after high density exposure has been lacking despite its importance to foraging ecology. Our goal was to manipulate and observe the effects of crowding on the behavioral response of both species to common food and pheromonal stimuli and to determine how the headspace emission patterns from grain differed under increasing densities. Densities of colonies for both species was altered (10-500 adults) on a fixed quantity of food (10 g of flour or whole wheat), then the behavioral response to common food and pheromonal cues was evaluated in a wind tunnel and release-recapture experiment, while volatiles were examined through gas chromatography coupled with mass spectrometry. Importantly, at least for T. castaneum, crowded conditions attenuate attraction to food-based stimuli, but not pheromonal stimuli. Crowding seemed to have no effect on R. dominica attraction to food and pheromonal stimuli in the wind tunnel, but exposure to high density cues did elicit 2.1-3.8-fold higher captures in traps. The relative composition and abundance of headspace volatiles emitted varied significantly with different densities of beetles and was also species-specific. Overall, our results have implications for expanding our understanding of the foraging ecology of two economically important pests.

Barosinusitis due to routine weather changes: A cross-sectional analysis of public websites.

Background: Sinusitis is a common diagnosis that can be erroneously associated with routine weather-related barometric pressure changes. In actuality, these pressure changes likely exacerbate migraine headaches, which can cause facial pain and pressure rather than true sinus inflammation. Objective: The present study sought to characterize the representation of both sinusitis and migraine in association with barometric pressure changes across websites on the Internet. Methods: An Internet search for relevant terms was conducted, and content of the resulting pages was assessed for associations between weather-related pressure changes and either sinusitis or migraine. Variations in reported results across different subtypes of Internet sources were analyzed. The primary outcomes measured were (1) whether a given media source associated barometric weather changes with sinusitis, (2) whether that source associated barometric weather changes with migraine, and (3) treatment options offered by that source. Results: Of the 116 included webpages, 36 (31.03%) associated sinusitis and routine barometric pressure changes. Of these, 10 (27.77%) were otolaryngology practice sites. Sixty-seven webpages (57.76%) associated migraine and routine barometric pressure changes. Of these, nonotolaryngology webpages were more likely to report this link. Conclusions: Otolaryngology practice sites were observed to be the most frequent professional medical resource reporting the unsubstantiated claim that routine barometric pressure changes are associated with sinusitis. Nonotolaryngology sources were more likely to link weather-related pressure changes to migraine. These results suggest that opportunities exist for otolaryngology practice sites to educate patients about nonrhinogenic headache etiologies.

Otolaryngology residency program factors associated with female resident representation.

Objective: Female representation in the field of otolaryngology is lacking. Residency is the first point at which medical school graduates specialize in a chosen field and thus represents an opportunity to recruit and train more female otolaryngologists. This study sought to identify program factors associated with greater female representation among resident physicians. Methods: Departmental websites of all 124 otolaryngology residency programs in the United States and Puerto Rico were examined for a list of residents. For programs with a resident roster available, the genders of residents, faculty, program directors, and chairpersons were recorded. Location and city population for each program was also recorded, as was female resident representation. Programs were compared using Pearson Chi-squared univariate tests. Results: 1,632 residents and 2,605 faculty were included in the analysis of 109 programs. The median female resident representation was 40%. Programs with larger faculty sizes, more female faculty, and urban location were associated with an above-median female resident representation. Programs with a larger residency cohort approached significance regarding above-median female resident representation. Higher female faculty representation, program director gender, chairperson gender, and US region were not associated with variation in female resident representation. Conclusions: Greater female otolaryngology residency representation was associated with programs having an urban location and greater numbers of female and total faculty. It was also likely that a larger resident cohort size may affect female resident representation. The proportions of female faculty, program director, and chairperson gender, as well as the US region, were not associated with variation in female resident gender representation.

PACAP sequence modifications modulate the peptide antimicrobial activity against bacterial pathogens affecting aquaculture.

The global aquaculture industry has significant losses each year due to disease outbreaks. Antibiotics are one of the common methods to treat fish infections, but prolonged use can lead to the emergence of resistant strains. Aeromonas spp. Infections are a common and problematic disease in fish, and members of this genera can produce antibiotic resistant strains. Antimicrobial peptides (AMPs) have emerged as an alternative method to treat and prevent infections and pituitary adenylate cyclase activating polypeptide (PACAP) is a prominent member of this family. The objective of this research was to study PACAP's direct antimicrobial activity and its toxicity in fish cells. Four synthetic variants of the natural PACAP from Clarias gariepinus were tested in addition to the natural variant. The experimental results show a different antimicrobial activity against A. salmonicida and A. hydrophila of each PACAP variant, and for the first time show dependence on the culture broth used. Furthermore, the results suggest that the underlying mechanism of PACAP antimicrobial activity includes a bacterial membrane permeabilizing effect, classifying PACAP as a membrane disruptive AMP. This study also demonstrated that the five PACAP variants evaluated showed low toxicity in vitro, at concentrations relevant for in vivo applications. Therefore, PACAP could be a promising alternative to antibiotics in the aquaculture sector.

February 2024 ACIP Meeting Update: Meningococcal, RSV, COVID-19, and Other Vaccines.

The Advisory Committee on Immunization Practices, a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The Advisory Committee on Immunization Practices met February 28 to 29, 2024, to discuss coronavirus disease 2019 vaccines, chikungunya vaccines, diphtheria-tetanus vaccine, influenza vaccines, polio vaccines, respiratory syncytial virus vaccines, meningococcal vaccines, pneumococcal vaccines, and Vaxelis (Diphtheria, Tetanus, Pertussis, Inactivated Poliovirus, Haemophilus influenzae b Conjugate, and Hepatitis B Vaccine). This update summarizes the proceedings of these meetings, with an emphasis on topics that are most relevant to the pediatric population. Major updates for pediatric clinicians include information about changes on influenza vaccine composition, meningococcal vaccination considerations, updated guidance for children with a contraindication to pertussis-containing vaccines, and recommendations of the world's first chikungunya vaccine for certain populations.

Quantitative analysis of pertussis, tetanus, and diphtheria antibodies in sera and breast milk from Tdap vaccinated women using a qualified multiplex assay.

Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies. IMPORTANCE: Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.

Assessing the Oxidative Potential of Outdoor PM2.5 in Wintertime Fairbanks, Alaska.

The oxidative potential (OP) of outdoor PM2.5 in wintertime Fairbanks, Alaska, is investigated and compared to those in wintertime Atlanta and Los Angeles. Approximately 40 filter samples collected in January-February 2022 at a Fairbanks residential site were analyzed for OP utilizing dithiothreitol-depletion (OPDTT) and hydroxyl-generation (OPOH) assays. The study-average PM2.5 mass concentration was 12.8 µg/m3, with a 1 h average maximum of 89.0 µg/m3. Regression analysis, correlations with source tracers, and contrast between cold and warmer events indicated that OPDTT was mainly sensitive to copper, elemental carbon, and organic aerosol from residential wood burning, and OPOH to iron and organic aerosol from vehicles. Despite low photochemically-driven oxidation rates, the water-soluble fraction of OPDTT was unusually high at 77%, mainly from wood burning emissions. In contrast to other locations, the Fairbanks average PM2.5 mass concentration was higher than Atlanta and Los Angeles, whereas OPDTT in Fairbanks and Atlanta were similar, and Los Angeles had the highest OPDTT and OPOH. Site differences were observed in OP when normalized by both the volume of air sampled and the particle mass concentration, corresponding to exposure and the intrinsic health-related properties of PM2.5, respectively. The sensitivity of OP assays to specific aerosol components and sources can provide insights beyond the PM2.5 mass concentration when assessing air quality.

Indoor-Outdoor Oxidative Potential of PM2.5 in Wintertime Fairbanks, Alaska: Impact of Air Infiltration and Indoor Activities.

The indoor air quality of a residential home during winter in Fairbanks, Alaska, was investigated and contrasted with outdoor levels. Twenty-four-hour average indoor and outdoor filter samples were collected from January 17 to February 25, 2022, in a residential area with high outdoor PM2.5 concentrations. The oxidative potential of PM2.5 was determined using the dithiothreitol-depletion assay (OPDTT). For the unoccupied house, the background indoor-to-outdoor (I/O) ratio of mass-normalized OP (OPmDTT), a measure of the intrinsic health-relevant properties of the aerosol, was less than 1 (0.53 ± 0.37), implying a loss of aerosol toxicity as air was transported indoors. This may result from transport and volatility losses driven by the large gradients in temperature (average outdoor temperature of -19°C/average indoor temperature of 21 °C) or relative humidity (average outdoor RH of 78%/average indoor RH of 11%), or both. Various indoor activities, including pellet stove use, simple cooking experiments, incense burning, and mixtures of these activities, were conducted. The experiments produced PM2.5 with a highly variable OPmDTT. PM2.5 from cooking emissions had the lowest OP values, while pellet stove PM2.5 had the highest. Correlations between volume-normalized OPDTT (OPvDTT), relevant to exposure, and indoor PM2.5 mass concentration during experiments were much lower compared to those in outdoor environments. This suggests that mass concentration alone can be a poor indicator of possible adverse effects of various indoor emissions. These findings highlight the importance of considering both the quantity of particles and sources (chemical composition), as health metrics for indoor air quality.

Overview of the Alaskan Layered Pollution and Chemical Analysis (ALPACA) Field Experiment.

The Alaskan Layered Pollution And Chemical Analysis (ALPACA) field experiment was a collaborative study designed to improve understanding of pollution sources and chemical processes during winter (cold climate and low-photochemical activity), to investigate indoor pollution, and to study dispersion of pollution as affected by frequent temperature inversions. A number of the research goals were motivated by questions raised by residents of Fairbanks, Alaska, where the study was held. This paper describes the measurement strategies and the conditions encountered during the January and February 2022 field experiment, and reports early examples of how the measurements addressed research goals, particularly those of interest to the residents. Outdoor air measurements showed high concentrations of particulate matter and pollutant gases including volatile organic carbon species. During pollution events, low winds and extremely stable atmospheric conditions trapped pollution below 73 m, an extremely shallow vertical scale. Tethered-balloon-based measurements intercepted plumes aloft, which were associated with power plant point sources through transport modeling. Because cold climate residents spend much of their time indoors, the study included an indoor air quality component, where measurements were made inside and outside a house to study infiltration and indoor sources. In the absence of indoor activities such as cooking and/or heating with a pellet stove, indoor particulate matter concentrations were lower than outdoors; however, cooking and pellet stove burns often caused higher indoor particulate matter concentrations than outdoors. The mass-normalized particulate matter oxidative potential, a health-relevant property measured here by the reactivity with dithiothreiol, of indoor particles varied by source, with cooking particles having less oxidative potential per mass than pellet stove particles.

Prescription Drug Dispensing and Patient Costs After Implementation of a No Behavioral Health Cost-Sharing Law.

Importance: On January 1, 2022, New Mexico implemented a No Behavioral Cost-Sharing (NCS) law that eliminated cost-sharing for mental health and substance use disorder (MH/SUD) treatments in plans regulated by the state, potentially reducing a barrier to treatment for MH/SUDs among the commercially insured; however, the outcomes of the law are unknown. Objective: To assess the association of implementation of the NCS with out-of-pocket spending for prescription for drugs primarily used to treat MH/SUDs and monthly volume of dispensed drugs. Design, Settings, and Participants: This retrospective cohort study used a difference-in-differences research design to examine trends in outcomes for New Mexico state employees, a population affected by the NCS, compared with federal employees in New Mexico who were unaffected by NCS. Data were collected on prescription drugs for MH/SUDs dispensed per month between January 2021 and June 2022 for New Mexico patients with a New Mexico state employee health plan and New Mexico patients with a federal employee health plan. Data analysis occurred from December 2022 to January 2024. Exposure: Enrollment in a state employee health plan or federal health plan. Main Outcomes and Measures: The primary outcomes were mean patient out-of-pocket spending per dispensed MH/SUD prescription and the monthly volume of dispensed MH/SUD prescriptions per 1000 employees. A difference-in-differences estimation approach was used. Results: The implementation of the NCS law was associated with a mean (SE) $6.37 ($0.30) reduction (corresponding to an 85.6% decrease) in mean out-of-pocket spending per dispensed MH/SUD medication (95% CI, -$7.00 to -$5.75). The association of implementation of NCS with the volume of prescriptions dispensed was not statistically significant. Conclusions and Relevance: These findings suggest that the implementation of the New Mexico NCS law was successful in lowering out-of-pocket spending on prescription medications for MH/SUDs, but that there was no association of NCS with the volume of medications dispensed in the first 6 months after implementation. A key challenge is to identify policies that protect from high out-of-pocket spending while also promoting access to needed care.

Self-administered versus clinician-performed BinaxNOW COVID rapid test: a comparison of accuracy.

We conducted a single-center study at a free community testing site in Baltimore City to assess the accuracy of self-performed rapid antigen tests (RATs) for COVID-19. Self-administered BinaxNOW RATs were compared with clinician-performed RATs and against a reference lab molecular testing as the gold standard. Of the 953 participants, 14.9% were positive for SARS- CoV-2 as determined by RT-PCR. The sensitivity and specificity were similar for both self- and clinician-performed RATs (sensitivity: 83.9% vs 88.2%, P = 0.40; specificity: 99.8% vs 99.6%, P = 0.6). Subgroup comparisons based on age and race yielded similar results. Notably, 5.2% (95% CI: 1.5% to 9.5%) of positive results were potentially missed due to participant misinterpretation of the self-test card. However, the false-positive rate for RATs was reassuringly comparable in accuracy to clinician-administered tests. These findings hold significant implications for physicians prescribing treatment based on patient-reported, self-administered positive test results. Our study provides robust evidence supporting the reliability and utility of patient-performed RATs, underscoring their comparable accuracy to clinician-performed RATs, and endorsing their continued use in managing COVID-19. Further studies using other rapid antigen test brands are warranted.IMPORTANCEAccurate and accessible COVID-19 testing is crucial for effective disease control and management. A recent single-center study conducted in Baltimore City examined the reliability of self-performed rapid antigen tests (RATs) for COVID-19. The study found that self-administered RATs yielded similar sensitivity and specificity to clinician-performed tests, demonstrating their comparable accuracy. These findings hold significant implications for physicians relying on patient-reported positive test results for treatment decisions. The study provides robust evidence supporting the reliability and utility of patient-performed RATs, endorsing their continued use in managing COVID-19. Furthermore, the study highlights the need for further research using different rapid antigen test brands to enhance generalizability. Ensuring affordable and widespread access to self-tests is crucial, particularly in preparation for future respiratory virus seasons and potential waves of reinfection of SARS-CoV-2 variants such as the Omicron variant.

Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity.

There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer's disease. The role of amyloid beta 42 (Aß42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aß42, which is increased from adipose tissue of male mice with obesity and is associated with higher plasma Aß42. Increasing circulating Aß42 levels in male mice without obesity has no effect on systemic glucose homeostasis but has obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. The closely related Aß40 isoform does not have these same effects on the heart. Administration of an Aß-neutralising antibody prevents obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aß-neutralising antibody administration in established obesity prevents further deterioration of cardiac function. Multi-contrast transcriptomic analyses reveal that Aß42 impacts pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aß42 inhibits mitochondrial complex I. These data reveal a role for systemic Aß42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer's disease could be effective in combating obesity-induced heart failure.

Chemical Catalysis Guides Structural Identification for the Major In Vivo Metabolite of the BET Inhibitor JQ1.

The bromodomain inhibitor (+)-JQ1 is a highly validated chemical probe; however, it exhibits poor in vivo pharmacokinetics. To guide efforts toward improving its pharmacological properties, we identified the (+)-JQ1 primary metabolite using chemical catalysis methods. Treatment of (+)-JQ1 with tetrabutylammonium decatungstate under photochemical conditions resulted in selective formation of an aldehyde at the 2-position of the thiophene ring [(+)-JQ1-CHO], which was further reduced to the 2-hydroxymethyl analog [(+)-JQ1-OH]. Comparative LC/MS analysis of (+)-JQ1-OH to the product obtained from liver microsomes suggested (+)-JQ1-OH as the major metabolite of (+)-JQ1. The 2-thienyl position was then substituted to generate a trideuterated (-CD3, (+)-JQ1-D) analog having half-lives that were 1.8- and 2.8-fold longer in mouse and human liver microsomes, respectively. This result unambiguously confirmed (+)-JQ1-OH as the major metabolite of (+)-JQ1. These studies demonstrate an efficient process for studying drug metabolism and identifying the metabolic soft spots of bioactive compounds.