Sex Disparities in Chlamydia and Gonorrhea Treatment in US Adult Emergency Departments: A Systematic Review and Meta-analysis.

Importance: In US emergency departments (EDs), empiric antibiotic treatment for gonorrhea (GC) and chlamydia (CT) is common due to the unavailability of immediate test results. Evidence suggests sex-based disparities in treatment practices, with females potentially receiving less empiric treatment than males. Objective: To investigate sex differences in empiric antibiotic treatment for GC and CT in EDs, comparing practices to subsequent laboratory-confirmed results. Design Setting and Participants: This systematic review and meta-analysis included studies from US EDs reporting GC/CT testing and empiric antibiotic treatment from January 2010 to February 2021. A total of 1,644 articles were screened, with 17 studies (n = 31,062 patients) meeting inclusion criteria. Main Outcomes and Measures: The primary outcomes were GC/CT test positivity, empiric antibiotic treatment rates, and discordance between treatment and test results, stratified by sex. Data were analyzed using a random-effects model. Results: Overall GC/CT positivity was 14% (95% CI, 11%-16%): 11% (95% CI, 8%-14%) in females and 25% (95% CI, 23%-26%) in males. Empiric antibiotic treatment was administered in 46% (95% CI, 38%-55%) of cases: 31% (95% CI, 24%-37%) in females and 73% (95% CI, 65%-80%) in males. Among patients without a laboratory-confirmed infection, 38% (95% CI, 30%-47%) received treatment: 27% (95% CI, 20%-34%) of females and 64% (95% CI, 55%-73%) of males. Conversely, 39% (95% CI, 31%-48%) of patients with laboratory-confirmed infections were not treated: 52% (95% CI, 46%-57%) of females and 15% (95% CI, 12%-17%) of males. Conclusions and Relevance: There is significant discordance between ED empiric antibiotic treatment and laboratory-confirmed results, with notable sex-based disparities. Females were 3.5 times more likely than males to miss treatment despite confirmed infection. These findings highlight the need for improved strategies to reduce sex-based disparities and enhance empiric treatment accuracy for GC/CT in ED settings. Key Points: Question: Are there sex-based differences in empiric antibiotic treatment for gonorrhea and chlamydia in US emergency departments (EDs), and how do these practices compare to laboratory-confirmed results?Findings: In this systematic review and meta-analysis of 17 studies with 31,062 patients, females were significantly less likely than males to receive empiric antibiotic treatment for gonorrhea and chlamydia. Additionally, 39% of patients with a laboratory-confirmed infection were not empirically treated, with females 3.5 times more likely to miss treatment than males.Meaning: The findings indicate significant sex disparities in ED empiric antibiotic treatment for sexually transmitted infections, underscoring the need for improved strategies to ensure equitable and accurate treatment across sexes.

Demographic and geographic distribution of diabetes and pre-diabetes risk in rural settings: results from a cross-sectional, countywide rural health survey in Sullivan County, New York.

OBJECTIVE: To perform a detailed characterisation of diabetes burden and pre-diabetes risk in a rural county with previously documented poor health outcomes in order to understand the local within-county distribution of diabetes in rural areas of America. DESIGN, SETTING, AND PARTICIPANTS: In 2021, we prospectively mailed health surveys to all households in Sullivan County, a rural county with the second-worst health outcomes of all counties in New York State. Our survey included questions on demographics, medical history and the American Diabetes Association's Pre-diabetes Risk Test. PRIMARY OUTCOME AND METHODS: Our primary outcome was an assessment of diabetes burden within this rural county. To help mitigate non-response bias in our survey, raking adjustments were performed across strata of age, sex, race/ethnicity and health insurance. We analysed diabetes prevalence by demographic characteristics and used geospatial analysis to assess for clustering of diagnosed diabetes cases. RESULTS: After applying raking procedures for the 4725 survey responses, our adjusted diagnosed diabetes prevalence for Sullivan County was 12.9% compared with the 2019 Behavioural Risk Factor Surveillance System (BRFSS) estimate of 8.6%. In this rural area, diagnosed diabetes prevalence was notably higher among non-Hispanic Black (21%) and Hispanic (15%) residents compared with non-Hispanic White (12%) residents. 53% of respondents without a known history of pre-diabetes or diabetes scored as high risk for pre-diabetes. Nearest neighbour analyses revealed that hotspots of diagnosed diabetes were primarily located in the more densely populated areas of this rural county. CONCLUSIONS: Our mailed health survey to all residents in Sullivan County demonstrated higher diabetes prevalence compared with modelled BRFSS estimates that were based on small telephone samples. Our results suggest the need for better diabetes surveillance in rural communities, which may benefit from interventions specifically tailored for improving glycaemic control among rural residents.

Ophthalmic manifestations of NAA10-related and NAA15-related neurodevelopmental syndromes: Analysis of cortical visual impairment and refractive errors.

NAA10-related (Ogden syndrome) and NAA15-related neurodevelopmental syndrome are known to present with varying degrees of intellectual disability, hypotonia, congenital cardiac abnormalities, seizures, and delayed speech and motor development. However, the ophthalmic manifestations of NAA10 and NAA15 variants are not yet fully characterized or understood. This study analyzed the prevalence of six ophthalmic conditions (cortical visual impairment, myopia, hyperopia, strabismus, nystagmus, and astigmatism) in 67 patients with pathogenic (P) or likely pathogenic (LP) variants in the NAA10 cohort (54 inherited, 10 de novo; 65 missense, 2 frameshift) and 19 patients with (L)P variants in the NAA15 cohort (18 de novo; 8 frameshift, 4 missense, 4 nonsense, and 1 splice site). Patients were interviewed virtually or in-person to collect a comprehensive medical history verified by medical records. These records were then analyzed to calculate the prevalence of these ophthalmic manifestations in each cohort. Analysis revealed a higher prevalence of ophthalmic conditions in our NAA10 cohort compared to existing literature (myopia 25.4% vs. 4.7%; astigmatism 37.3% vs. 13.2%; strabismus 28.4% vs. 3.8%; CVI 22.4% vs. 8.5%, respectively). No statistically significant differences were identified in the prevalence of these conditions between the NAA10 and NAA15 variants. Our study includes novel neuroimaging of 13 NAA10 and 5 NAA15 probands, which provides no clear correlation between globe size and severity of comorbid ophthalmic disease. Finally, anecdotal evidence was compiled to underscore the importance of early ophthalmologic evaluations and therapeutic interventions.

Neuroanatomical Features of NAA10- and NAA15-Related Neurodevelopmental Syndromes.

Background: NAA10-related (Ogden Syndrome) and NAA15-related neurodevelopmental syndromes present with varying degrees of intellectual disability, hypotonia, congenital cardiac abnormalities, seizures, and delayed speech and motor development. While there is much data on the clinical manifestations of these conditions, there are few radiologic reports describing the neuroanatomical abnormalities present on imaging. Objective: Our goal was to provide neuroimaging analyses for a subset of probands with NAA10- and NAA15-related neurodevelopmental symptoms and assess severity, common radiologic anomalies, and changes over time to better understand the pathophysiology of these disease processes. Materials and Methods: Neuroimaging studies from 26 probands (18 with pathogenic variants in NAA10, 8 with pathogenic variants in NAA15) were collected and analyzed. Size of the cerebrum, brainstem, and cerebellum, as well as myelination, brain malformations, globus pallidus hyperintensity, brain lesions, 4th ventricle size, tegmentovermian angle, cisterna magna size, pituitary size, olfactory tract, palate arch, and choroid plexus abnormalities were analyzed. In depth medical histories were also collected on all probands, including genetic testing results and social, cognitive, and developmental history. The Vineland 3 Adaptive Behavior Scale was also administered to the parents to assess functional status of the probands. Results: On average, individuals with Ogden Syndrome had 5.7 anatomical abnormalities (standard deviation (SD) = 3.0), whereas those with NAA15 related neurodevelopmental syndrome had 2.8 (SD = 2.3) (p = .02). Probands who had more anatomical abnormalities tended to score worse on Vineland assessments, suggesting a possible correlation between the two. Structural-functional anatomic differences seen were preserved such that individuals with greater defects on, for example, motor regions of their scans tested worse on motor portions of the Vineland. Probands followed longitudinally demonstrated several changes between scans, most commonly in the cerebellum, brainstem, and degree of myelination. Such changes were only observed for probands with NAA10 variants in our cohort. Conclusion: Despite clinical imaging being reported as being predominantly "normal" during routine clinical care, this analysis of a cohort of patients with NAA10-related (Ogden Syndrome) and NAA15-related neurodevelopmental syndrome by one neuroradiologist has established a range of subtle abnormalities. We hope these findings guide future research and diagnostic studies for this patient population.

Open Access Publication in Total Ankle Arthroplasty Literature Is Associated With Increased Social Media Attention, but Not Increased Citations.

Background: Open access (OA) publications are increasingly common in orthopaedic literature. However, whether OA publications are associated with increased readership or citations among total ankle arthroplasty (TAA) literature is unclear. We hypothesize that compared with non-OA status, OA status is associated with increased social media dissemination, and readership, but not with citation count. This study aimed to analyze social media attention, citations, readership, and cost of TAA OA and non-OA publications. Methods: Using a PubMed query search, there were 368 publications from 81 journals, with 25% (91/368) being OA articles and 75% (277/368) non-OA articles from 2016 to 2023. We analyzed the Altmetric Attention Score (AAS), Mendeley readership score, and citations between OA vs non-OA articles. Citations and cost of OA articles were determined using an altered timeline and publisher's website, respectively. Subgroup analysis was performed among articles published in the top 5 TAA journals (Tables 2 and 3). Negative binomial regression was used while adjusting for days since publication. Significance was considered at P <.05. Results: OA publication was associated with a larger mean AAS score (8.7 ± 37.0 vs 4.8 ± 26.3), Mendeley readership (42.4 ± 41.6 vs 34.9 ± 25.7), and Twitter mentions (4.6 ± 7.4 vs 3.3 ± 8.1), but not citations (19.7 ± 24.8 vs 20.3 ± 23.5) (Table 1). Conclusion: TAA OA publications and top 5 journals were associated with significantly increased social media attention but not Mendeley readership or citation counts.

A Natural History of NAA15 -related Neurodevelopmental Disorder Through Adolescence.

NAA15 is a member of the NatA N-terminal acetyltransferase complex, which also includes the NAA10 enzymatic sub-unit. Individuals with variants in the NAA15 coding region develop NAA15 -related neurodevelopmental syndrome, which presents with a wide array of manifestations that affect the heart, brain, musculoskeletal system, and behavioral and cognitive development. We tracked a cohort of 27 participants (9 females and 18 males) over time, each with a pathogenic NAA15 variant, and administered the Vineland-3 assessment to assess their adaptive functioning. We found that the cohort performed significantly worse compared to the normalized Vineland values. On average, females performed better than males, and they performed significantly better on the Motor Domain and Fine Motor Sub-Domain portions of the assessment. Over time, females showed a decrease in adaptive functioning, with the decline being especially correlated at the Coping, Domestic, and Fine motor sub-domains. Males (after excluding one outlier) showed a moderate positive correlation between age and ABC standard score. Ultimately, additional longitudinal data should be collected to determine the validity of the between sex-differences and to better understand the change in adaptive behavioral outcomes of individuals with NAA15 -neurodevelopmental disorder as they age.

Food insecurity in high-risk rural communities before and during the COVID-19 pandemic.

Objective: To perform a geospatial analysis of food insecurity in a rural county known to have poor health outcomes and assess the effect of the COVID-19 pandemic. Methods: In 2020, we mailed a comprehensive cross-sectional survey to all households in Sullivan County, a rural county with the second-worst health outcomes among all counties in New York State. Surveys of households included validated food insecurity screening questions. Questions were asked in reference to 2019, prior to the pandemic, and for 2020, in the first year of the pandemic. Respondents also responded to demographic questions. Raking adjustments were performed using age, sex, race/ethnicity, and health insurance strata to mitigate non-response bias. To identify significant hotspots of food insecurity within the county, we also performed geospatial analysis. Findings: From the 28,284 households surveyed, 20% of households responded. Of 4725 survey respondents, 26% of households reported experiencing food insecurity in 2019, and in 2020, this proportion increased to 35%. In 2020, 58% of Black and Hispanic households reported experiencing food insecurity. Food insecurity in 2020 was also present in 58% of unmarried households with children and in 64% of households insured by Medicaid. The geospatial analyses revealed that hotspots of food insecurity were primarily located in or near more urban areas of the rural county. Conclusions: Our countywide health survey in a high-risk rural county identified significant increases of food insecurity in the first year of the COVID-19 pandemic, despite national statistics reporting a stable rate. Responses to future crises should include targeted interventions to bolster food security among vulnerable rural populations.

The Mouse Inferior Colliculus Responds Preferentially to Non-Ultrasonic Vocalizations.

The inferior colliculus (IC), the midbrain auditory integration center, analyzes information about social vocalizations and provides substrates for higher level processing of vocal signals. We used multichannel recordings to characterize and localize responses to social vocalizations and synthetic stimuli within the IC of female and male mice, both urethane anesthetized and unanesthetized. We compared responses to ultrasonic vocalizations (USVs) with other vocalizations in the mouse repertoire and related vocal responses to frequency tuning, IC subdivisions, and sex. Responses to lower frequency, broadband social vocalizations were widespread in IC, well represented throughout the tonotopic axis, across subdivisions, and in both sexes. Responses to USVs were much more limited. Although we observed some differences in tonal and vocal responses by sex and subdivision, representations of vocal responses by sex and subdivision were largely the same. For most units, responses to vocal signals occurred only when frequency response areas overlapped with spectra of the vocal signals. Since tuning to frequencies contained within the highest frequency USVs is limited (<15% of IC units), responses to these vocalizations are correspondingly limited (<5% of sound-responsive units). These results highlight a paradox of USV processing in some rodents: although USVs are the most abundant social vocalization, their representation and the representation of corresponding frequencies are less than lower frequency social vocalizations. We interpret this paradox in light of observations suggesting that USVs with lower frequency elements (<50 kHz) are associated with increased emotional intensity and engage a larger population of neurons in the mouse auditory system.

The Mouse Inferior Colliculus Responds Preferentially to Non-Ultrasonic Vocalizations.

The inferior colliculus (IC), the midbrain auditory integration center, analyzes information about social vocalizations and provides substrates for higher level processing of vocal signals. We used multi-channel recordings to characterize and localize responses to social vocalizations and synthetic stimuli within the IC of female and male mice, both urethane-anesthetized and unanesthetized. We compared responses to ultrasonic vocalizations (USVs) with other vocalizations in the mouse repertoire and related vocal responses to frequency tuning, IC subdivisions, and sex. Responses to lower frequency, broadband social vocalizations were widespread in IC, well represented throughout the tonotopic axis, across subdivisions, and in both sexes. Responses to USVs were much more limited. Although we observed some differences in tonal and vocal responses by sex and subdivision, representations of vocal responses by sex and subdivision were largely the same. For most units, responses to vocal signals occurred only when frequency response areas overlapped with spectra of the vocal signals. Since tuning to frequencies contained within the highest frequency USVs is limited (< 15% of IC units), responses to these vocalizations are correspondingly limited (< 5% of sound-responsive units). These results highlight a paradox of USV processing in some rodents: although USVs are the most abundant social vocalization, their representation and the representation of corresponding frequencies is less than lower frequency social vocalizations. We interpret this paradox in light of observations suggesting that USVs with lower frequency elements (<50 kHz) are associated with increased emotional intensity and engage a larger population of neurons in the mouse auditory system. SIGNIFICANCE STATEMENT: The inferior colliculus (IC) integrates multiple inputs to analyze information about social vocalizations. In mice, we show that the most common type of social vocalization, the ultrasonic vocalization or USV, was poorly represented in IC compared to lower frequency vocalizations. For most neurons, responses to vocal signals occurred only when frequency response areas overlapped with vocalization spectra. These results highlight a paradox of USV processing in some rodent auditory systems: although USVs are the most abundant social vocalization, their representation and representation of corresponding frequencies is less than lower frequency social vocalizations. These results suggest that USVs with lower frequency elements (<50 kHz)-associated with increased emotional intensity-will engage a larger population of neurons in the mouse auditory system.

Ophthalmic Manifestations of NAA10-Related and NAA15-Related Neurodevelopmental Syndrome: Analysis of Cortical Visual Impairment and Refractive Errors.

NAA10-related and NAA15-related neurodevelopmental syndrome, otherwise known as Ogden Syndrome, is known to present with varying degrees of intellectual disability, hypotonia, congenital cardiac abnormalities, seizures, and delayed speech and motor development. However, the ophthalmic manifestations of NAA10 and NAA15 mutations are not yet fully characterized or understood. This study analyzed the prevalence of six ophthalmic conditions (cortical visual impairment, myopia, hyperopia, strabismus, nystagmus, and astigmatism) in 67 patients with pathogenic mutations in the NAA10 cohort (54 inherited, 10 de novo; 65 missense, 2 frameshift) and 19 patients with pathogenic mutations in the NAA15 cohort (18 de novo; 8 frameshift, 4 missense, 4 nonsense, and 1 splice site). Patients were interviewed virtually or in-person to collect a comprehensive medical history verified by medical records. These records were then analyzed to calculate the prevalence of these ophthalmic manifestations in each cohort. Analysis revealed a higher prevalence of ophthalmic conditions in our NAA10 cohort compared to existing literature (myopia 25.4% vs. 4.7%; astigmatism 37.3% vs. 13.2%; strabismus 28.4% vs. 3.8%; CVI 22.4% vs. 8.5%, respectively). No statistically significant differences were identified between the NAA10 and NAA15 mutations. Our study includes novel neuroimaging of 13 NAA10 and 5 NAA15 probands, which provides no clear correlation between globe size and severity of comorbid ophthalmic disease. Finally, anecdotal evidence was compiled to underscore the importance of early ophthalmologic evaluations and therapeutic interventions.

Genetically engineered mouse model of pleomorphic liposarcoma: Immunophenotyping and histologic characterization.

INTRODUCTION: Pleomorphic liposarcoma is a rare and aggressive subset of soft-tissue sarcomas with a high mortality burden. Local treatment largely consists of radiation therapy and wide surgical resection, but options for systemic therapy in the setting of metastatic disease are limited and largely ineffective, prompting exploration of novel therapeutic strategies and experimental models. As with other cancers, sarcoma cell lines and patient-derived xenograft models have been developed and used to characterize these tumors and identify therapeutic targets, but these models have inherent limitations. The establishment of genetically engineered mouse models represents a more realistic framework for reproducing clinically relevant conditions for studying pleomorphic liposarcoma. METHODS: Trp53fl/fl/Rb1fl/fl/Ptenfl/fl (RPP) mice were used to reliably generate an immunocompetent model of mouse pleomorphic liposarcoma through Cre-mediated conditional silencing of the Trp53, Rb1, and Pten tumor suppressor genes. Evaluation of tumor-infiltrating lymphocytes was assessed with immunostaining for CD4, CD8, and PD-L1, and flow cytometry with analysis of CD45, CD3, CD4, CD8, CD19, F4/80, CD11b, and NKp46 sub-populations. RESULTS: Mice reliably produced noticeable soft-tissue tumors in approximately 6 weeks with rapid tumor growth between 100 and 150 days of life, after which mice reached euthanasia criteria. Histologic features were consistent with pleomorphic liposarcoma, including widespread pleomorphic lipoblasts. Immunoprofiling and assessment of tumor-infiltrating lymphocytes was consistent with other soft-tissue sarcomas. CONCLUSION: Genetically engineered RPP mice reliably produced soft-tissue tumors consistent with pleomorphic liposarcoma, which immunological findings similar to other soft-tissue sarcomas. This model may demonstrate utility in testing treatments for this rare disease, including immunomodulatory therapies.

Integrated multi-omics analysis of RB-loss identifies widespread cellular programming and synthetic weaknesses.

Inactivation of RB is one of the hallmarks of cancer, however gaps remain in our understanding of how RB-loss changes human cells. Here we show that pRB-depletion results in cellular reprogramming, we quantitatively measured how RB-depletion altered the transcriptional, proteomic and metabolic output of non-tumorigenic RPE1 human cells. These profiles identified widespread changes in metabolic and cell stress response factors previously linked to E2F function. In addition, we find a number of additional pathways that are sensitive to RB-depletion that are not E2F-regulated that may represent compensatory mechanisms to support the growth of RB-depleted cells. To determine whether these molecular changes are also present in RB1-/- tumors, we compared these results to Retinoblastoma and Small Cell Lung Cancer data, and identified widespread conservation of alterations found in RPE1 cells. To define which of these changes contribute to the growth of cells with de-regulated E2F activity, we assayed how inhibiting or depleting these proteins affected the growth of RB1-/- cells and of Drosophila E2f1-RNAi models in vivo. From this analysis, we identify key metabolic pathways that are essential for the growth of pRB-deleted human cells.

A Robotic Platform to Study the Foreflipper of the California Sea Lion.

The California sea lion (Zalophus californianus), is an agile and powerful swimmer. Unlike many successful swimmers (dolphins, tuna), they generate most of their thrust with their large foreflippers. This protocol describes a robotic platform designed to study the hydrodynamic performance of the swimming California sea lion (Zalophus californianus). The robot is a model of the animal's foreflipper that is actuated by motors to replicate the motion of its propulsive stroke (the 'clap'). The kinematics of the sea lion's propulsive stroke are extracted from video data of unmarked, non-research sea lions at the Smithsonian Zoological Park (SNZ). Those data form the basis of the actuation motion of the robotic flipper presented here. The geometry of the robotic flipper is based a on high-resolution laser scan of a foreflipper of an adult female sea lion, scaled to about 60% of the full-scale flipper. The articulated model has three joints, mimicking the elbow, wrist and knuckle joint of the sea lion foreflipper. The robotic platform matches dynamics properties-Reynolds number and tip speed-of the animal when accelerating from rest. The robotic flipper can be used to determine the performance (forces and torques) and resulting flowfields.