Improved selection of canonical proteins for reference proteomes.

The 'canonical' protein sets distributed by UniProt are widely used for similarity searching, and functional and structural annotation. For many investigators, canonical sequences are the only version of a protein examined. However, higher eukaryotes often encode multiple isoforms of a protein from a single gene. For unreviewed (UniProtKB/TrEMBL) protein sequences, the longest sequence in a Gene-Centric group is chosen as canonical. This choice can create inconsistencies, selecting >95% identical orthologs with dramatically different lengths, which is biologically unlikely. We describe the ortho2tree pipeline, which examines Reference Proteome canonical and isoform sequences from sets of orthologous proteins, builds multiple alignments, constructs gap-distance trees, and identifies low-cost clades of isoforms with similar lengths. After examining 140 000 proteins from eight mammals in UniProtKB release 2022_05, ortho2tree proposed 7804 canonical changes for release 2023_01, while confirming 53 434 canonicals. Gap distributions for isoforms selected by ortho2tree are similar to those in bacterial and yeast alignments, organisms unaffected by isoform selection, suggesting ortho2tree canonicals more accurately reflect genuine biological variation. 82% of ortho2tree proposed-changes agreed with MANE; for confirmed canonicals, 92% agreed with MANE. Ortho2tree can improve canonical assignment among orthologous sequences that are >60% identical, a group that includes vertebrates and higher plants.

Underlying Reasons for Primary Care Visits Where Chlamydia Testing Was Performed in the United States, 2019 to 2022.

BACKGROUND: In the United States, most chlamydia cases are reported from non-sexually transmitted disease clinics, and there is limited information focusing on the reasons for chlamydia testing in private settings. These analyses describe clinical visits to primary care providers where chlamydia testing was performed to help discern between screening and diagnostic testing for chlamydia. METHODS: Using the largest primary care clinical registry in the United States, the PRIME registry, chlamydia tests were identified using Current Procedural Terminology procedure codes and categorized as diagnostic testing for sexually transmitted infection (STI)-related symptoms, screening for chlamydia, or "other," based on Classification of Diseases, Tenth Revision Evaluation and Management codes selected for visits. RESULTS: Of 120,013 clinical visits with chlamydia testing between January 1, 2019, and December 31, 2022, 70.4% were women; 20.6% were with STI-related symptoms, 59.9% were for screening, and 19.5% for "other" reasons. Of those 120,013 clinical visits with chlamydia testing, the logit model showed that patients were significantly more likely to have STI-related symptoms if they were female than male, non-Hispanic Black than non-Hispanic White, aged 15 to 24 years than aged ≥45 years, and resided in the South than in the Northeast. CONCLUSION: It is important to know what proportion of chlamydial infections is identified through screening programs and to have this information stratified by demographics. The inclusion of laboratory results could further facilitate a better understanding of the impact of chlamydia screening programs on the identification and treatment of chlamydia in private office settings in the United States.

Autonomic Recalibration: A Promising Approach for Alleviating Myofascial Pain Explored in a Retrospective Case Series.

This retrospective case series introduces autonomic recalibration (AR) as a novel approach for alleviating chronic myofascial pain. The manuscript explores the rationale, theory, and practice of AR, which targets the autonomic nervous system (ANS) to restore homeostasis and reduce pain. The involvement of the ANS in pain modulation and the role of autonomic imbalance in chronic pain are discussed, emphasizing the potential benefits of addressing autonomic dysregulation through AR. The technique combines manual interventions and patient education, relying on neuroplastic adaptations. Three diverse case reports are presented to illustrate the effectiveness of AR in patients with different sources of pain. Each case presents a unique clinical scenario, including a nine-year-old male diagnosed with spondylolisthesis, a 68-year-old male with a history of abdominal surgeries, and a 56-year-old male with chronic low back pain following lumbar fusion surgery. In all cases, AR resulted in pain relief, improved sleep, and restoration of functional abilities. These findings support the potential of AR as an effective alternative approach for myofascial pain. Further research is warranted to validate these outcomes and investigate the underlying mechanisms of AR.

Identifying the Need for and Availability of Evidence-Based Care for Sexually Transmitted Infections in Rural Primary Care Clinics.

BACKGROUND: Increasing rates of bacterial sexually transmitted infections (STIs) may lead to increased HIV rates, as the STI and HIV epidemics are syndemic. Centers for Disease Control and Prevention guidelines recommend including extragenital (i.e., rectal and/or pharyngeal) STI screenings for certain populations at increased risk of STIs and concurrent infections with HIV. METHODS: A descriptive study was conducted by interviewing staff members from 4 rural primary care clinics in areas of high need for STI and HIV services in South Carolina. Qualitative data about their clinical practices in 2021 were obtained. The primary outcome was to determine the awareness and availability of health care services associated with STI and HIV care in these locations. RESULTS: Clinics in target counties provided limited STI and HIV testing and treatment services, especially for populations at risk of infection, indicating the need for additional clinical training and professional development for all clinic staff. Specifically, only 1 of 4 clinics provided extragenital STI testing, and no clinics reported prescribing preexposure prophylaxis. CONCLUSIONS: Rural primary care clinics can fill important gaps in the availability of STI and HIV services with appropriate support and incentives. Findings from this study may aid in facilitating policy (state Medicaid agency) and program (state health department) decisions related to STI and HIV testing and treatment.

Quantifying Oropharyngeal Swallowing Impairment in Response to Bolus Viscosity.

PURPOSE: The purpose of this study was to test the feasibility for quantifying changes in oropharyngeal swallowing impairment in response to alteration in bolus viscosity using a reliable and valid method of observational measurement-the Modified Barium Swallow Impairment Profile (MBSImP). METHOD: This retrospective analysis included a heterogeneous cohort of 119 patients with suspected dysphagia that underwent a videofluoroscopic swallowing study as part of clinical care. Using consensus scoring, two expert clinicians assigned MBSImP scores to components related to oropharyngeal swallowing function between two bolus viscosities (thin liquid and pudding): epiglottic movement, laryngeal elevation, anterior hyoid excursion, tongue base retraction, pharyngeal stripping wave, and pharyngoesophageal segment opening (PESO). Comparisons between the two bolus viscosities were investigated for each component. RESULTS: Higher (worse) scores were observed in the thin-liquid trial compared with the pudding trial for the following MBSImP components: anterior hyoid excursion (p = .03), epiglottic movement (p < .001), pharyngeal stripping wave (p < .001), and PESO (p = .002). Lower (better) scores were observed in the liquid trial compared with the pudding trial for one component-tongue base retraction (Component 15) only (p < .001). CONCLUSION: These findings provide further evidence for positive influences of viscosity on the swallow mechanism, including influences of sensory feedback on the sensorimotor swallow program.

Use of Doxycycline to Prevent Sexually Transmitted Infections According to Provider Characteristics.

Use of doxycycline to prevent sexually transmitted infections (STIs) may lead to antimicrobial resistance. We analyzed attitudes toward this practice between US providers who commonly and less commonly treat STIs. Providers who more commonly treat STIs are more likely to prescribe prophylactic doxycycline and believe that benefits outweigh potential for increased antimicrobial resistance.

The role of primary care providers in testing for sexually transmitted infections in the MassHealth Medicaid program.

The objective of this study was to determine the prevalence and predictors of testing for sexually transmitted infections (STIs) under an accountable care model of health care delivery. Data sources were claims and encounter records from the Massachusetts Medicaid and Children's Health Insurance Program (MassHealth) for enrollees aged 13 to 64 years in 2019. This cross-sectional study examines the one-year prevalence of STI testing and evaluates social determinants of health and other patient characteristics as predictors of such testing in both primary care and other settings. We identified visits with STI testing using procedure codes and primary care settings from provider code types. Among 740,417 members, 55% were female, 11% were homeless or unstably housed, and 15% had some level of disability. While the prevalence of testing in any setting was 20% (N = 151,428), only 57,215 members had testing performed in a primary care setting, resulting in an 8% prevalence of testing by primary care clinicians (PCCs). Members enrolled in a managed care organization (MCO) were significantly less likely to be tested by a primary care provider than those enrolled in accountable care organization (ACO) plans that have specific incentives for primary care practices to coordinate care. Enrollees in a Primary Care ACO had the highest rates of STI testing, both overall and by primary care providers. Massachusetts' ACO delivery systems may be able to help practices increase STI screening with explicit incentives for STI testing in primary care settings.

STI Testing among Medicaid Enrollees Initiating PrEP for HIV Prevention in Six Southern States.

OBJECTIVES: The purpose of this study was to measure sexually transmitted infection (STI) testing among Medicaid enrollees initiating preexposure prophylaxis (PrEP) to prevent human immunodeficiency virus. Secondary data are in the form of Medicaid enrollment and claims data in six states in the US South. METHODS: Research partnerships in six states in the US South developed a distributed research network to accomplish study aims. Each state identified all first-time PrEP users in fiscal year 2017-2018 (combined N = 990) and measured the presence of STI testing for chlamydia, syphilis, and gonorrhea through 2019. Each state calculated the percentage of individuals with at least one STI test during 3-, 6-, and 12-month follow-up periods. RESULTS: The proportion of first-time PrEP users that received an STI test varied by state: 37% to 67% of all of the individuals in each state who initiated PrEP received a test within the first 6 months of PrEP treatment and 50% to 77% received a test within the first 12 months. CONCLUSIONS: Although the Centers for Disease Control and Prevention recommends STI testing at least every 6 months for PrEP users, our analysis of Medicaid data suggests that STI testing occurs less frequently than recommended in populations at elevated risk of syphilis, gonorrhea, and chlamydia.

A Description of Telehealth Use Among Sexually Transmitted Infection Providers in the United States, 2021.

BACKGROUND: Telehealth offers one approach to improving access to sexually transmitted infection (STI) prevention and care services. Therefore, we described recent telehealth use among those providing STI-related care and identified opportunities for improving STI service delivery. MATERIALS AND METHODS: Using the DocStyles Web-based, panel survey conducted by Porter Novelli from September 14 to November 10, 2021, 1500 healthcare providers were asked about their current telehealth usage, demographics, and practice characteristics, and compared STI providers (≥10% of time spent on STI care and prevention) to non-STI providers. RESULTS: Among those whose practice consisted of at least 10% STI visits (n = 597), 81.7% used telehealth compared with 75.7% for those whose practice consisted of less than 10% STI visits (n = 903). Among the providers with at least 10% STI visits in their practice, telehealth use was highest among obstetrics and gynecology specialists, those practicing in suburban areas, and those practicing in the South. Among providers whose practice consisted of at least 10% STI visits and who used telehealth (n = 488), the majority were female and obstetrics and gynecology specialists practicing in suburban areas of the South. After controlling for age, gender, provider specialty, and geographic location of their practice, providers whose practice consisted of at least 10% STI visits had increased odds (odds ratio, 1.51; 95% confidence interval, 1.16-1.97) of using telehealth compared with providers whose visits consisted of less than 10% STI visits. CONCLUSIONS: Given the widespread use of telehealth, efforts to optimize delivery of STI care and prevention via telehealth are important to improve access to services and address STIs in the United States.

Prenatal syphilis screening among pregnant Medicaid enrollees by sexually transmitted infection history as well as race and ethnicity.

BACKGROUND: Congenital syphilis can cause severe morbidity, including miscarriage and stillbirth, and rates are increasing rapidly within the United States. However, congenital syphilis can be prevented with early detection and treatment of syphilis during pregnancy. Current screening recommendations propose that all women should be screened early in pregnancy, whereas women with elevated risks for congenital syphilis should be screened again later in pregnancy. The rapid increase in congenital syphilis rates suggests that there are still gaps in prenatal syphilis screening. OBJECTIVE: This study aimed to examine associations between the odds of prenatal syphilis screening and sexually transmitted infection history or other patient characteristics across 3 states with elevated rates of congenital syphilis. STUDY DESIGN: We used the Medicaid claims data from Kentucky, Louisiana, and South Carolina for women with deliveries between 2017 and 2021. Within each state, we examined the log-odds of prenatal syphilis screening as a function of the mother's health history, demographic factors, and Medicaid enrollment history. Patient history was established using a 4-year lookback period of the Medicaid claims data; in state A, sexually transmitted infection surveillance data were used to improve the sexually transmitted infection history. RESULTS: The prenatal syphilis screening rates varied by state, ranging from 62.8% to 85.1% of deliveries to women without a recent history of sexually transmitted infections and from 78.1% to 91.1% of deliveries to women with a previous sexually transmitted infection. For the main outcome of syphilis screening at any time during pregnancy, deliveries associated with previous sexually transmitted infections had 1.09 to 1.37 times higher adjusted odds ratios of undergoing screening. Deliveries to women with continuous Medicaid coverage throughout the first trimester also had higher odds of syphilis screening at any time (adjusted odds ratio, 2.45-3.15). Among deliveries to women with a previous sexually transmitted infection, only 53.6% to 63.6% underwent first-trimester screening and this rate was still just 55.0% to 69.5% when considering only deliveries to women with a previous sexually transmitted infection and full first-trimester Medicaid coverage. Fewer delivering women underwent third-trimester screening (20.3%-55.8% of women with previous sexually transmitted infection). Compared with deliveries to White women, deliveries to Black women had lower odds of first-trimester screening (adjusted odds ratio, 0.85 in all states) but higher odds of third-trimester screening (adjusted odds ratio, 1.23-2.03), potentially impacting maternal and birth outcomes. For state A, linkage to surveillance data doubled the rate of detection of a previous sexually transmitted infection because 53.0% of deliveries by women with a previous sexually transmitted infection would not have had sexually transmitted infection history detected using Medicaid claims alone. CONCLUSION: A previous sexually transmitted infection and continuous preconception Medicaid enrollment were associated with higher rates of syphilis screening, but Medicaid claims alone do not fully capture the sexually transmitted infection history of patients. The overall screening rates were lower than would be expected given that all women should undergo prenatal screening, but the rates in the third trimester were particularly low. Of note, there are gaps in early screening for non-Hispanic Black women who had lower odds of first-trimester screening when compared with non-Hispanic White women despite being at elevated risk for syphilis.

Congenital Syphilis in the Medicaid Program: Assessing Challenges and Opportunities Through the Experiences of Seven Southern States.

INTRODUCTION: Rates of congenital syphilis cases are increasing, particularly among lower socioeconomic populations within the southern United States. Medicaid covers a significant portion of these births, which provides an opportunity to improve birth outcomes. This project sought to collect information from key stakeholders to assess facilitators of and barriers to Medicaid funding of prenatal syphilis screening and to provide insight into improving screening and lowering incidence through the Medicaid program. METHODS: Seven southern states (Alabama, Georgia, Kentucky, Louisiana, North Carolina, South Carolina, and Tennessee) were identified for this assessment. Researchers conducted a legal and policy analysis for each state to gather information on factors affecting congenital syphilis prevention, identify knowledge gaps, and inform the development of interview guides. Seventeen structured interviews with 29 participants were conducted to gather information on facilitators and barriers to receiving timely prenatal syphilis screening through the Medicaid program. Interview transcripts were analyzed and compared to identify key themes. RESULTS: Barriers to timely prenatal syphilis screening include varied laws among the states on the timing of screening, Medicaid reimbursement policies that may not adequately incentivize testing, Medicaid enrollment issues that affect both enrollment and continuity of care, and lack of clear understanding among providers on recommended testing. CONCLUSION: This work provides insight into systemic issues that may be affecting rates of prenatal syphilis screening and incidence among Medicaid enrollees and others in the U.S. South. To address rising congenital syphilis cases, policymakers should consider requiring third trimester syphilis screening, adopting policies to enhance access to prenatal care, adapting Medicaid payment and incentive models, and promoting collaboration between Medicaid and public health agencies.

Racial, Ethnic, and Rural/Urban Disparities in HIV and Sexually Transmitted Infections in South Carolina.

Examining the current incidence rates of HIV and STIs among racial and ethnic minority and rural residents is crucial to inform and expand initiatives and outreach efforts to address disparities and minimize the health impact of these diseases. A retrospective, cross-sectional study was conducted using Medicaid administrative claims data over a 2-year period (July 2019-June 2021) in South Carolina. Our main outcomes of interest were claims for chlamydia, gonorrhea, syphilis, and HIV. Any beneficiary with at least one claim for a relevant diagnosis throughout the study period was considered to have one of these diseases. Descriptive analyses and multivariable regression models were used to estimate the association between STIs, HIV, race and ethnicity, and rurality. Overall, 158,731 Medicaid beneficiaries had at least one medical claim during the study period. Most were female (86.6%), resided in urban areas (66.6%), and were of non-Hispanic Black race/ethnicity (42.6%). In total, 6.3% of beneficiaries had at least one encounter for chlamydia, 3.2% for gonorrhea, 0.5% for syphilis, and 0.8% for HIV. In multivariable models, chlamydia, gonorrhea, and HIV claims were significantly associated with non-Hispanic Black or other minority race/ethnicity compared to non-Hispanic white race/ethnicity. Rural residents were more likely to have a claim associated with chlamydia and gonorrhea compared to urban residents. The opposite was observed for syphilis and HIV. Providing updated evidence on disparities in STIs and HIV among racial/ethnic minority and rural populations in a southern state is essential for shaping state Medicaid policies to address health disparities.

Comparison of detection methods and genome quality when quantifying nuclear mitochondrial insertions in vertebrate genomes.

The integration of mitochondrial genome fragments into the nuclear genome is well documented, and the transfer of these mitochondrial nuclear pseudogenes (numts) is thought to be an ongoing evolutionary process. With the increasing number of eukaryotic genomes available, genome-wide distributions of numts are often surveyed. However, inconsistencies in genome quality can reduce the accuracy of numt estimates, and methods used for identification can be complicated by the diverse sizes and ages of numts. Numts have been previously characterized in rodent genomes and it was postulated that they might be more prevalent in a group of voles with rapidly evolving karyotypes. Here, we examine 37 rodent genomes, and an additional 26 vertebrate genomes, while also considering numt detection methods. We identify numts using DNA:DNA and protein:translated-DNA similarity searches and compare numt distributions among rodent and vertebrate taxa to assess whether some groups are more susceptible to transfer. A combination of protein sequence comparisons (protein:translated-DNA) and BLASTN genomic DNA searches detect 50% more numts than genomic DNA:DNA searches alone. In addition, higher-quality RefSeq genomes produce lower estimates of numts than GenBank genomes, suggesting that lower quality genome assemblies can overestimate numts abundance. Phylogenetic analysis shows that mitochondrial transfers are not associated with karyotypic diversity among rodents. Surprisingly, we did not find a strong correlation between numt counts and genome size. Estimates using DNA: DNA analyses can underestimate the amount of mitochondrial DNA that is transferred to the nucleus.

Choosing the Emergency Department as an Alternative for STD Care: Potential Disparities in Access.

This analysis was designed to determine if there existed differences by race in seeking sexually transmitted disease (STD) care in an emergency department (ED). METHODS: Data were collected from 4,138 patients attending 26 STD clinics across the United States (U.S.). The questionnaire asked where the patient would have sought care if the STD clinic had not been available that day. Responses were stratified by race and differences were tested for statistical significance. RESULTS: Black/African American patients chose hospital emergency room as an alternative for STD clinic care at a rate approximately 2.5 times that of White patients (15.5% v. 5.8%, p < .05). This difference persisted among Black/African American patients after controlling for demographic variables (adjusted OR 2.91; 2.21-3.82 95% CI). DISCUSSION: Receiving appropriate care is key to stemming the increases in sexually transmitted infections in the U.S. These findings suggest that disparities in access to STD care exist for Black/African American people.

Clinical shadowing experience PIF rubric.

BACKGROUND: The purpose of this study was to develop and evaluate a tool for documenting professional identity formation (PIF) among preclinical medical students, via reflective writings (RWs) about their clinical shadowing experiences. APPROACH: To address our key questions, stakeholders conducted comprehensive literature analysis, and the authors developed an analytic rubric through an iterative immersion/crystallisation process. EVALUATION: Rubric iterations were empirically tested, assessed for interrater reliability, refined and then applied in successive development phases to medical student RW narratives. Twenty-nine first-year RWs on their shadowing experiences were included for this developmental evaluation. IMPLICATIONS: The clinical shadowing experience PIF rubric is a theory-informed analytic tool that demonstrates feasibility of measuring PIF in preclinical medical students' RWs. Reliable use of this tool currently requires a team approach that could be improved by machine learning.

Determining Swallowing Biomechanics Underlying Modified Barium Swallow Impairment Profile Scoring Using Computational Analysis of Swallowing Mechanics.

PURPOSE: The elements of impaired swallowing biomechanics are visually assessed and scored by clinicians using a standardized and validated tool for assessing type and severity of physiological impairments using the Modified Barium Swallow Impairment Profile (MBSImP). However, the functional anatomical correlates that underly noted impairments using MBSImP scoring have not been measured. The purpose of this study was to determine whether differences in MBSImP component scores represent differences in underlying swallowing mechanics as measured by computational analysis of swallowing mechanics (CASM) to better define underlying mechanisms of impairment. METHOD: A retrospective analysis of modified barium swallow studies from physician-referred adult patients with dysphagia was scored using the MBSImP for laryngeal elevation, anterior hyoid excursion, epiglottic movement, pharyngoesophageal segment opening, and tongue base retraction. A canonical variate analysis (CVA) was performed to determine the movement of anatomical landmarks associated with MBSImP component scores using the CASM method. Mahalanobis distances (D) were then used to detect differences among MBSImP scores for each component assessed. RESULTS: CVA showed significant differences (p < .0001) in Mahalanobis distance (D > 1) between MBSImP component scores of 0-1, 0-2, 0-3, or 0-4, as applicable, depending on the component. Discriminant function analyses revealed concomitant increase/worsening in MBSImP score with changes in anatomical positioning of structures. CONCLUSIONS: Ratings of swallowing impairment and physiology using the MBSImP have distinct biomechanical correlates with anatomical movements of swallowing. These data further demonstrate how swallowing mechanics are highly interrelated. Understanding these linkages between anatomical and physiological movement within impaired swallowing biomechanics is essential in more specific characterization and treatment of dysphagia. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20816788.

Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster.

Host behavioural changes are among the most apparent effects of infection. 'Sickness behaviour' can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here, using a real-time tracking and behavioural profiling platform, we show that in Drosophila melanogaster, several systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in some lethal infections. Using multiple bacteria and D. melanogaster immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with Micrococcus luteus, a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the Toll ligand spätzle. In contrast, increased activity after infection with Francisella novicida, a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of both Toll and the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response.