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Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is a molecular and functional imaging modality with better restaging accuracy over conventional imaging for detecting prostate cancer in men suspected of lymph node (LN) progression after definitive therapy. However, the availability of PSMA PET/CT is limited in both low-resource settings and for repeating imaging surveillance. In contrast, CT is widely available, cost-effective, and routinely performed as part of patient follow-up or radiotherapy workflow. Compared with the molecular activities, the morphological and texture changes of subclinical LNs in CT are subtle, making manual detection of positive LNs infeasible. Instead, we harness the power of artificial intelligence for automated LN detection on CT. We examined 68Ga-PSMA-11 PET/CT images from 88 patients (including 739 PSMA PET/CT-positive pelvic LNs) who experienced a biochemical recurrence after radical prostatectomy and presented for salvage radiotherapy with prostate-specific antigen

Introduction: Currently, there is no consensus regarding the management of intermittent exotropia (IXT), which includes both surgical and non-surgical treatment options. Nonsurgical management of IXT has been suggested and includes watchful observation, patching, overminus lenses, prism, and vision therapy/orthoptics. While a significant portion of IXT patients are treated by surgery, it is reported that there is a substantial tendency for reoperation or recurrence of IXT. This paper provides a comprehensive review of non-surgical and surgical treatment options for the IXT. Methods: Search strategies involving combination of keywords including intermittent exotropia, divergence excess, basic exotropia, refractive error, glasses, spectacles, natural history, untreated, observe, occlusion, patch, overminus, overcorrecting minus, prism, vision therapy, orthoptic, anti-suppression, fusion exercise, and surgery were used in Medline. All English articles from 01/01/1900 to 01/09/2020 were reviewed. The reference list of the identified articles was also checked for additional relevant articles. Studies focused on animal models or strabismus associated with neurologic disorders or injury were excluded. The following filters were used for surgical management due to the abundance of reports: full text, randomized controlled trial, review, in the last 5 years. Results: Appropriate optical correction of refractive error is generally the starting point for all management approaches, but there is a lack of randomized clinical trial data regarding this treatment modality. Randomized clinical trial data indicate that both observation and occlusion are reasonable management options for children 3–10 years old, and there were insufficient data to recommend occlusion for children 12–35 months old. While overminus lenses were found to improve the control of IXT when assessed wearing overminus spectacles, this improvement did not persist after the treatment ended. The result of the only randomized clinical trial on the effectiveness of base-in prism indicated that this treatment is no more effective than nonprism spectacles for improving control. A recent randomized clinical trial showed that vision therapy/orthoptics is effective in improving the control of IXT when compared to observation alone. Surgery was found to alter a number of clinical characteristics of IXT, including reducing the distance and near angle of deviation, reducing photophobia, improving health-related quality of life, stereopsis, and the Newcastle Control Score. However, there are no randomized clinical trial data comparing surgery with a control group such as placebo or a no treatment observation group. Discussion: Rigorously designed clinical trials to investigate the effectiveness of non-surgical and surgical treatments for intermittent exotropia are needed. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the short‐term (1 week after completion of treatment) effect of office‐based vergence and anti‐suppression therapy (OBVAT) on the Office Control Score when compared to observation alone in children with small‐to‐moderate angle intermittent exotropia (IXT). Methods: In this single‐masked (examiner masked), two‐arm, single‐centre randomised clinical trial, 40 participants, 6 to <18 years of age with untreated IXT, were randomly assigned to OBVAT or observation alone. Participants assigned to therapy received 60 min of OBVAT with home reinforcement once per week for 16 weeks. Therapy included vergence, accommodation and anti‐suppression techniques. The primary outcome measure was the comparison of the distance Office Control Score between the two groups at the primary outcome visit (i.e., 17‐week follow‐up visit). Results: At the primary outcome visit, the OBVAT group (n = 20) had a significantly better distance Office Control Score (adjusted mean difference: −0.9; 95% CI: −0.2 to −1.5; p = 0.008; partial eta squared: 0.19) than the observation group (n = 16). Participants from the OBVAT group were more likely than those from the observation group to have ≥1 point of improvement at the 17‐week visit (OBVAT group: 75%; Observation group: 25%; p = 0.006). Conclusions: In this randomised clinical trial of participants aged 6 to <18 years with IXT, we found that the OBVAT group had a significantly better distance Office Control Score than the observation group at the 17‐week visit. This study provides the first data from a randomised clinical trial demonstrating the effectiveness of OBVAT for improving the control of IXT. Eye care practitioners should consider OBVAT as a viable, non‐surgical treatment option for IXT. A full‐scale randomised clinical trial investigating the long‐term effectiveness of OBVAT in treating IXT is warranted. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is a molecular and functional imaging modality with better restaging accuracy over conventional imaging for detecting prostate cancer in men suspected of lymph node (LN) progression after definitive therapy. However, the availability of PSMA PET/CT is limited in both low-resource settings and for repeating imaging surveillance. In contrast, CT is widely available, cost-effective, and routinely performed as part of patient follow-up or radiotherapy workflow. Compared with the molecular activities, the morphological and texture changes of subclinical LNs in CT are subtle, making manual detection of positive LNs infeasible. Instead, we harness the power of artificial intelligence for automated LN detection on CT. We examined 68Ga-PSMA-11 PET/CT images from 88 patients (including 739 PSMA PET/CT-positive pelvic LNs) who experienced a biochemical recurrence after radical prostatectomy and presented for salvage radiotherapy with prostate-specific antigen < 1 ng/mL. Scans were divided into a training set (nPatient = 52, nNode = 400), a validation set (nPatient = 18, nNode = 143), and a test set (nPatient = 18, nNodes = 196). Using PSMA PET/CT as the ground truth and consensus pelvic LN clinical target volumes as search regions, a 2.5-dimensional (2.5D) Mask R-CNN based object detection framework was trained. The entire framework contained whole slice imaging pretraining, masked-out region fine-tuning, prediction post-processing, and "window bagging". Following an additional preprocessing step—pelvic LN clinical target volume extraction, our pipeline located positive pelvic LNs solely based on CT scans. Our pipeline could achieve a sensitivity of 83.351%, specificity of 58.621% out of 196 positive pelvic LNs from 18 patients in the test set, of which most of the false positives can be post-removable by radiologists. Our tool may aid CT-based detection of pelvic LN metastasis and triage patients most unlikely to benefit from the PSMA PET/CT scan. [ABSTRACT FROM AUTHOR]

The past decades have seen growing interest and application of interventions targeting the change of multiple behaviors at once. We advance this work by using the diffusion of innovations theory (DOI) to consider constellations of behaviors as innovation packages : multiple innovations that are logically related, interdependent in their use or effects, and often promoted as a set (Rogers, 2003). In addition, we embraced DOI's focus on behavioral decisions as a continual process that can include adoption and discontinuance over time, especially as new innovations (e.g., COVID-19 vaccine) appear. To that end, we conducted a latent transition analysis of COVID-19 mitigation behaviors ( N  = 697; 97% received a COVID-19 vaccine) across three time points in the pandemic: initial outbreak; a secondary, record-breaking rise in cases; and after the CDC recommended that fully vaccinated adults could discontinue wearing masks. This analysis allowed us to identify latent classes based on shared behavioral patterns and transitions between classes over time. The results showed evidence of three possible packages: (a) a package of traditional, symptom-management behaviors (covering coughs and sneezes, staying home if ill, and seeking medical care), (b) a package of just-novel COVID-19 behaviors (wearing masks, keeping six feet apart, and avoiding mass gatherings), and (c) a package of all COVID-19 mitigation behaviors. Movement between classes exemplified adoption and discontinuance of different packages, as well as widespread discontinuance with the replacement innovation: COVID-19 vaccines. Additional analyses showed that increases in hope were associated with sustained and delayed adoption; decreases in social approval were associated with discontinuance. Future directions in theorizing around innovation packages are discussed.

Background: Medical education has undergone significant changes over the last decades. Scientific and technological progress alongside contemporary society's changing requirements have driven demand for highly trained, competent doctors. In response to this need, university faculties of medicine have sought innovative forms of teaching and evaluating the students on their degree courses. The aim of this study was to quantify the characteristics and extent of academic training in teaching methods, of participation in innovative teaching initiatives, and training in simulation and debriefing among the teaching personnel on the degree course in medicine at the University of Granada (Spain)., Methods: This transversal descriptive study was conducted among a population of 121 educators teaching on the medical degree course at the University of Granada, Spain. All responded to a specially designed CoRe-Content Representation questionnaire. This consisted of various parts: (a) demographic data; (b) teaching experience and qualifications; (c) specific information about training in teaching skills received. The Fisher test was applied whenever the dependent variable had two values (dichotomous) and the Chi-square test when it had more than two values (polytomic). Statistical significance was established with an alpha error of 5%., Results: The results showed that 87.60% of the educators had received no training in debriefing. There was a notable gender gap, whereby women held fewer management posts, fewer were engaged in clinical activity, and fewer had undergone training in clinical simulation. Teachers with degrees in medicine had undergone less regulated training than educators with other degree qualifications., Conclusion: The main areas of medical training that require improvement (and so present challenges to be met in the years to come) are as follows: a definitive solution to the existing gender gap, general implementation of new educational models and methods (especially learning based on clinical problem-solving and simulation), closing generation gaps, and improved training processes for educators with clinical attachment., (© 2024. The Author(s).)

Background: Clinical studies have reported rising pre-treatment HIV drug resistance during antiretroviral treatment (ART) scale-up in Africa, but representative data are limited. We estimated population-level drug resistance trends during ART expansion in Uganda., Methods: We analyzed data from the population-based open Rakai Community Cohort Study conducted at agrarian, trading, and fishing communities in southern Uganda between 2012 and 2019. Consenting participants aged 15-49 were HIV tested and completed questionnaires. Persons living with HIV (PLHIV) provided samples for viral load quantification and virus deep-sequencing. Sequence data were used to predict resistance. Population prevalence of class-specific resistance and resistance-conferring substitutions were estimated using robust log-Poisson regression., Findings: Data from 93,622 participant-visits, including 4,702 deep-sequencing measurements, showed that the prevalence of NNRTI resistance among pre-treatment viremic PLHIV doubled between 2012 and 2017 (PR:1.98, 95%CI:1.34-2.91), rising to 9.61% (7.27-12.7%). The overall population prevalence of pre-treatment viremic NNRTI and NRTI resistance among all participants decreased during the same period, reaching 0.25% (0.18% - 0.33%) and 0.05% (0.02% - 0.10%), respectively ( p- values for trend = 0.00015, 0.002), coincident with increasing treatment coverage and viral suppression. By the final survey, population prevalence of resistance contributed by treatment-experienced PLHIV exceeded that from pre-treatment PLHIV, with NNRTI resistance at 0.54% (0.44%-0.66%) and NRTI resistance at 0.42% (0.33%-0.53%). Overall, NNRTI and NRTI resistance was predominantly attributable to rtK103N and rtM184V. While 10.52% (7.97%-13.87%) and 9.95% (6.41%-15.43%) of viremic pre-treatment and treatment-experienced PLHIV harbored the inT97A mutation, no major dolutegravir resistance mutations were observed., Interpretation: Despite rising NNRTI resistance among pre-treatment PLHIV, overall population prevalence of pre-treatment resistance decreased due to treatment uptake. Most NNRTI and NRTI resistance is now contributed by treatment-experienced PLHIV. The high prevalence of mutations conferring resistance to components of current first-line ART regimens among PLHIV with viremia is potentially concerning., Competing Interests: Declaration of interests We declare no competing interests.

Objectives: ANCA-associated vasculitis (AAV) are chronic diseases with relapses that associate organic damage because of the disease and its treatment. Avacopan is a new treatment indicated for AAV. We present the first experiences with avacopan in Spain as part of an Early Access program., Methods: Patients with AAV who started avacopan between June 2022-September 2023 were included. For comparison, a historical cohort of patients diagnosed with AAV around the same time and treated without avacopan was also included., Results: 29 patients treated with avacopan were analyzed. Twelve patients (41.4%) were male, median age was 56 years. Most of patients were ANCA MPO positive (21/29, 72.4%). The most frequently affected organ was the kidney (23/29, 79.31%), with a mean eGFR of 23.2 ml/minMedian follow-up was 456.8 ± 181.7 days with a remission rate of 86.2%. eGFR increased from 23.2 ± 11.2-38.38 ± 18.55 ml/min after 12 months of diagnosis.2 patients had Adverse Events related to avacopan as severe neutropenia and a gastrointestinal affectation , 13 infections were reported and 1 death.Patients treated with avacopan received a significantly lower cumulative dose of prednisone at 6 and 12 months (p-values of 0.02 and <0.01, respectively) compared with historical controls. The evolution of GFR at 1 year of follow-up and the incidence of relapse were similar in both groups., Conclusion: The combination of avacopan in clinical practice presents a good safety profile and provides added value by contributing to the control of AAV activity, increase GFR, and removal of steroids., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pubertal research has primarily focused on hypothalamic-pituitary-gonadal axis (HPG) regulation of puberty, though the hypothalamic-pituitary-adrenal axis (HPA) is increasingly considered critical. Heightened HPA function proxied by increasing cortisol levels may play a role in accelerated pubertal timing. However, the extent to which cortisol varies across ages and its relation to pubertal changes in linear growth are less well substantiated. We explored relationships between age, linear growth, adiposity, C-peptide (proxy for insulin), and cortisol across puberty, and we tested whether higher cortisol levels are associated with earlier ages at menarche and peak height velocity. We utilize longitudinal data (n = 777 urine samples) from Qom females ages 7-14 (n = 46) and test our pre-registered analysis using Bayesian longitudinal mixed effects models and joint modeling techniques. We find limited evidence supporting the overarching hypothesis that HPA upregulation is associated with pubertal maturation or timing. We find some evidence that HPA upregulation, as proxied by cortisol, may be more clearly related to differences in relative linear growth at early-mid puberty, as measured by height-for-age z-scores. Transdisciplinary perspectives on puberty, including the assumption that stressors acting via cortisol accelerate pubertal development, are discussed., (© 2024 Wiley Periodicals LLC.)

Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIV AD8-EO infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs. Emergence of virus in plasma and lymph nodes (LNs) was delayed by bNAb treatment and occurred earlier in monkeys given DEL bNAbs than in those given WT bNAbs, consistent with faster clearance of DEL bNAbs from plasma. DEL bNAb-treated monkeys had higher levels of circulating virus-specific IFNγ single-producing CD8 + CD69 + T cells than the other groups. In LNs, WT bNAbs were evenly distributed between follicular and extrafollicular areas, but DEL bNAbs predominated in the latter. At week 8 post-challenge, LN monocytes and NK cells from DEL bNAb-treated monkeys upregulated proinflammatory signaling pathways and LN T cells downregulated TNF signaling via NF-κB. Overall, bNAbs with increased affinity to FcγRs shape innate and adaptive cellular immunity, which may be important to consider in future strategies of passive bNAb therapy., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

There is limited data on human immunodeficiency virus (HIV) evolutionary trends in African populations. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a 24-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from people living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994-2018) and four hyperendemic Lake Victoria fishing communities (2011-2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was evaluated using the Shannon diversity index, and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Demographic history of HIV was inferred using a coalescent-based Bayesian Skygrid model. Evolutionary dynamics were assessed among demographic and behavioral population subgroups, including by migration status. 9931 HIV sequences were available from 4999 PLHIV, including 3060 and 1939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 ( P  < .001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 ( P  < .001). The proportion of viruses classified as recombinants significantly increased by nearly four-fold from 12.2% in 1995 to 44.8% in 2017. Inter-subtype HIV diversity has generally increased. While intra-subtype p24 genetic diversity and divergence leveled off after 2014, intra-subtype gp41 diversity, effective population size, and divergence increased through 2017. Intra- and inter-subtype viral diversity increased across all demographic and behavioral population subgroups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Asthma reliever medication access is critical, especially in schools. Policies that "stock" reliever inhalers in schools provide failsafe medication access. This research aims to understand barriers and facilitators to Illinois stock inhaler policy implementation., Methods: We conducted 18 semi-structured interviews in 2021-2022 with key school-based and non-school-based partners (school administrators, nurses, governmental agencies, and advocacy leaders). Through Atlas.ti, code frequencies compared (Fisher's exact test), and a thematic analysis performed., Results: Four themes emerged: facilitators, barriers, program rationale, and process considerations. The common facilitators were "Finding a provider," having a "Champion," and "Funding". Barriers included "Not enough school nurses," "Pharmacy refusal to fill prescriptions," and "Feeling overwhelmed." All were supportive of the rationale for stock inhalers. Non-school-based informants (p < .01) were more likely to mention medication donations, while school staff reported having enough nurses as a facilitator (p < .01). School staff reported concerns about children with asthma not having their medication significantly more than other partners (p = .02)., Implications for School Health Policy, Practice, and Equity: Our analysis revealed that school partners recognize the value of stock inhalers. Barrier mitigation to support the funding, prescription access and processing, and training are essential to success of stock inhaler programming. Multilevel collaborative efforts through coalitions could be a potential solution., (© 2024 The Author(s). Journal of School Health published by Wiley Periodicals LLC on behalf of American School Health Association.)

A person's phenotypic sex (i.e., endogenous expression of primary, secondary, and endocrinological sex characteristics) can impact crucial aspects of genetic assessment and resulting clinical care recommendations. In studies with genetics components, it is critical to collect phenotypic sex, information about current organ/tissue inventory and hormonal milieu, and gender identity. If researchers do not carefully construct data models, transgender, gender diverse, and sex diverse (TGSD) individuals may be given inappropriate care recommendations and/or be subjected to misgendering, inflicting medical and psychosocial harms. The recognized need for an inclusive care experience should not be limited to clinical practice but should extend to the research setting, where researchers must build an inclusive experience for TGSD participants. Here, we review three TGSD participants in the Family History and Cancer Risk Study (FOREST) to critically evaluate sex- and gender-related survey measures and associated data models in a study seeking to identify patients at risk for hereditary cancer syndromes. Furthermore, we leverage these participants' responses to sex- and gender identity-related questions in FOREST to inform needed changes to the FOREST data model and to make recommendations for TGSD-inclusive genetics research design, data models, and processes., (© 2023 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Objectives: Understanding the pathways linking caregiver- and family-level psychosocial factors and child oral health behaviors is critical for addressing oral health disparities. The current study examined the associations between caregiver psychosocial functioning and family chaos and child toothbrushing behaviors in children at high risk for poor oral health outcomes., Methods: Data were drawn from the baseline wave of the CO-OP Chicago Cohort Study (U01DE030067), a longitudinal study on child/caregiver dyads exploring oral health behaviors and caries development in young children ( N = 296 dyads; child mean age = 5.36, SD = 1.03; caregiver mean age = 33.8 years, SD = 6.70; caregiver race = 43% Black; caregiver ethnicity = 55% Latinx). The oral health behavioral outcomes included child toothbrushing frequency, child plaque levels, and caregiver assistance with child toothbrushing. The data included demographics; caregiver depression, anxiety, post-traumatic stress disorder (PTSD) symptoms, social functioning, social support, and resilience; and family-level household chaos., Results: Multiple regression models indicated that greater household chaos was significantly related to lower caregiver assistance with child toothbrushing ( p = 0.0075). Additionally, caregiver anxiety and PTSD symptoms as well as number of children in the home significantly predicted higher levels of household chaos ( p < 0.01). Notably, 18% of caregivers reported clinically significant PTSD. The relationships between caregiver-level psychosocial factors and child oral health behaviors were not significant., Conclusions: The results suggest household chaos may play an important role in child oral health behaviors and highlight the importance of investigating family-level factors for understanding and addressing child oral health risk.

Introduction Congenital Syphilis (CS) is considered the second leading cause of preventable death in developing countries. The last report of the incidence rate of CS was made in 2017. Objective The objective of the study was to estimate the incidence of CS between 2019-2023. Materials and methods This is a retrospective study for which data were obtained from the new cases of CS reported in the Epidemiological Bulletin for 2019-2023 and from the newborn population records reported in the National Institute of Statistics and Geography and the National Population Council. Results In Mexico, the incidence rate of CS is 3.20 per 10,000 births. An increment of CS cases was observed between 2019-2023, with a higher number of cases in 2022. Conclusion A democratization of detection and prompt management is needed to reduce transmission, particularly among the most vulnerable population., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rochel-Perez et al.)

Background: TRAF7-related cardiac, facial, and digital anomalies with developmental delay (CAFDADD), a multisystemic neurodevelopmental disorder caused by germline missense variants in the TRAF7 gene, exhibits heterogeneous clinical presentations., Methods: We present a detailed description of 11 new TRAF7-related CAFDADD cases, featuring eight distinct variants, including a novel one., Results: Phenotypic analysis and a comprehensive review of the 58 previously reported cases outline consistent clinical presentations, emphasizing dysmorphic features, developmental delay, endocrine manifestations, and cardiac defects. In this enlarged collection, novelties include a wider range of cognitive dysfunction, with some individuals exhibiting normal development despite early psychomotor delay. Communication challenges, particularly in expressive language, are prevalent, necessitating alternative communication methods. Autistic traits, notably rigidity, are observed in the cohort. Also, worth highlighting are hearing loss, sleep disturbances, and endocrine anomalies, including growth deficiency. Cardiac defects, frequently severe, pose early-life complications. Facial features, including arched eyebrows, contribute to the distinct gestalt. A novel missense variant, p.(Arg653Leu), further underscores the complex relationship between germline TRAF7 variants and somatic changes linked to meningiomas., Conclusions: Our comprehensive analysis expands the phenotypic spectrum, emphasizing the need for oncological evaluations and proposing an evidence-based schedule for clinical management. This study contributes to a better understanding of TRAF7-related CAFDADD, offering insights for improved diagnosis, intervention, and patient care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Influenza infections result in considerable public health and economic impacts each year. One of the contributing factors to the high annual incidence of human influenza is the virus's ability to evade acquired immunity through continual antigenic evolution. Understanding the evolutionary forces that act within and between hosts is therefore critical to interpreting past trends in influenza virus evolution and in predicting future ones. Several studies have analyzed longitudinal patterns of influenza A virus genetic diversity in natural human infections to assess the relative contributions of selection and genetic drift on within-host evolution. However, in these natural infections, within-host viral populations harbor very few single-nucleotide variants, limiting our resolution in understanding the forces acting on these populations in vivo . Furthermore, low levels of within-host viral genetic diversity limit the ability to infer the extent of drift across transmission events. Here, we propose to use influenza virus genomic diversity as an alternative signal to better understand within- and between-host patterns of viral evolution. Specifically, we focus on the dynamics of defective viral genomes (DVGs), which harbor large internal deletions in one or more of influenza virus's eight gene segments. Our longitudinal analyses of DVGs show that influenza A virus populations are highly dynamic within hosts, corroborating previous findings based on viral genetic diversity that point toward the importance of genetic drift in driving within-host viral evolution. Furthermore, our analysis of DVG populations across transmission pairs indicates that DVGs rarely appeared to be shared, indicating the presence of tight transmission bottlenecks. Our analyses demonstrate that viral genomic diversity can be used to complement analyses based on viral genetic diversity to reveal processes that drive viral evolution within and between hosts., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Objectives: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms. We present the response to treatment in a patient with adult-onset TK2d., Methods: An adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in TK2 received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented., Results: After 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea., Discussion: Treatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MAM and CDG have received consulting fees from UCB, a pharmaceutical company that holds a license for the development of nucleosides as a treatment for TK2 deficiency., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Community health worker (CHW) models have been shown to improve health behaviors and health outcomes and reduce cost, particularly among low-income underserved populations. Consequently, health systems are increasingly employing CHWs to provide health services in clinical environments. A growing body of the literature suggests that effective integration of CHWs within the healthcare system is important to achieve the desired outcomes, but the question of how to achieve effective integration is less clear. This study seeks to explore the integration of CHWs within a large state university health system to identify factors critical to the effective integration of CHWs into the clinical care environment. We conducted a qualitative descriptive multiple embedded case study of the University of Illinois at Chicago's Hospital and Health Science System (UI Health). The embedded subunits of analysis were teams within the UI Health System that currently employ CHWs to assist with the provision of clinical care or services to patients. Data were collected via semi-structured interviews and document review. In total, six sub-units were enrolled, and 17 interviews were conducted with CHWs ( n  = 9), and administrators or healthcare providers ( n  = 8). Fourteen factors related to effective CHW integration were identified and organized in four categories: individual, team, organization, and community. Findings suggest that in addition to commonly recognized elements of effective CHW models including training, supervision, and the presence of a champion, programs must consider the organizational context in which the program is positioned as well as the ways in which both CHWs and the organization engage with communities served. This research can serve as a roadmap for health systems that seek to integrate CHWs within healthcare services and can be used to promote best practice in CHW integration.

Study Objectives: To examine the risk of increased health care utilization (HU) linked to individual sleep disorders in children with chronic medical conditions., Methods: Medicaid claims data from a cohort of 16,325 children enrolled in the Coordinated Healthcare for Complex Kids (CHECK) project were used. Sleep disorders and chronic medical conditions were identified using International Classification of Diseases, Ninth , and 10th Revision , codes. Three HU groups were identified based on participants' prior hospitalizations and emergency department (ED) visits in the 12 months prior to enrollment: low (no hospitalization or ED visit), medium (1-2 hospitalizations or 1-3 ED visits), and high (≥ 3 hospitalizations or ≥ 4 ED visits). The odds of being in an increased HU group associated with specific sleep disorders after controlling for confounding factors were examined., Results: Children with chronic medical conditions and any sleep disorder had nearly twice the odds (odds ratio = 1.83; 95% confidence interval: 1.67-2.01) of being in an increased HU group compared with those without a sleep disorder. The odds of being in the increased HU group varied among sleep disorders. Only sleep-disordered breathing (odds ratio = 1.51; 95% confidence interval : 1.17-1.95), insomnia (odds ratio = 1.46; 95% confidence interval : 1.06-2.02), and circadian rhythm sleep disorder (odds ratio = 2.45; 95% confidence interval : 1.07-5.64) increased those odds. Younger age and being White were also linked to increased HU., Conclusions: Sleep disorders are associated with increased risk of heightened HU (ED visits and/or hospitalizations) in children with chronic medical conditions. This risk varies by specific sleep disorders. These findings indicate the need for careful evaluation and management of sleep disorders in this high-risk cohort., Citation: Adavadkar PA, Brooks L, Pappalardo AA, Schwartz A, Rasinski K, Martin MA. Association between sleep disorders and health care utilization in children with chronic medical conditions: a Medicaid claims data analysis. J Clin Sleep Med . 2024;20(4):595-601., (© 2024 American Academy of Sleep Medicine.)

Novel, public behaviors, such as masking, should be susceptible to normative influence. This paper advances the theory of normative social behavior by considering a new set of moderators of normative influence - superdiffuser traits - and by clarifying the antecedents and consequences of exposure to collective norms. We use data from a two-wave survey of a cohort living in one U.S. county during the pandemic ( N  = 913) to assess normative effects on masking. We also used a bipartite network (based on people shopping for food in the same stores) to examine exposure to collective norms. The results show different superdiffuser traits have distinct effects on the relationship between perceived injunctive norms and masking intentions. Exposure to collective norms influences masking, but this influence depends on how people interact with their social environments. Network analysis shows that behavioral homophily is a significant predictor of selective exposure to collective norms earlier (but not later) in the pandemic. Implications for understanding normative influence in a context where opinion leadership matters are discussed.

Background: There is a paucity of data on the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces of lactating women with coronavirus disease 2019 (COVID-19) and their breastfed infants as well as associations between fecal shedding and symptomatology., Objective: We examined whether and to what extent SARS-CoV-2 is detectable in the feces of lactating women and their breastfed infants following maternal COVID-19 diagnosis., Methods: This was a longitudinal study carried out from April 2020 to December 2021 involving 57 breastfeeding maternal-infant dyads: 33 dyads were enrolled within 7 d of maternal COVID-19 diagnosis, and 24 healthy dyads served as controls. Maternal/infant fecal samples were collected by participants, and surveys were administered via telephone over an 8-wk period. Feces were analyzed for SARS-CoV-2 RNA., Results: Signs/symptoms related to ears, eyes, nose, and throat (EENT); general fatigue/malaise; and cardiopulmonary signs/symptoms were commonly reported among mothers with COVID-19. In infants of mothers with COVID-19, EENT, immunologic, and cardiopulmonary signs/symptoms were most common, but prevalence did not differ from that of infants of control mothers. SARS-CoV-2 RNA was detected in feces of 7 (25%) women with COVID-19 and 10 (30%) of their infants. Duration of fecal shedding ranged from 1-4 wk for both mothers and infants. SARS-CoV-2 RNA was sparsely detected in feces of healthy dyads, with only one mother's and two infants' fecal samples testing positive. There was no relationship between frequencies of maternal and infant SARS-CoV-2 fecal shedding ( P =0.36), although presence of maternal or infant fever was related to increased likelihood (7-9 times greater, P ≤0.04) of fecal shedding in infants of mothers with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pace, King-Nakaoka, Morse, Pascoe, Winquist, Caffé, Navarrete, Lackey, Pace, Fehrenkamp, Smith, Martin, Barbosa-Leiker, Ley, McGuire, Meehan, Williams and McGuire.)

While the importance of human milk in shaping infant immune function is well established, the impact of at-the-nipple (ATN) breastfeeding on maternal immune status has been understudied. Since lactation evolved to support infant survival and boost maternal fitness, we predict that ATN breastfeeding will confer benefits on maternal immune function. We measure the absolute and relative frequency of different infant feeding methods (ATN breastfeeding, pumping, donated milk, other supplementation) used by postpartum women in Seattle, WA (USA). We implement Bayesian modeling to estimate the effects of ATN breastfeeding on diurnal change in secretion rate of "pro-inflammatory" salivary cytokines and C-reactive protein (CRP). Our results show that most mothers in our sample used a variety of infant feeding methods, with pumping as the most common alternative to ATN breastfeeding. We find that ATN breastfeeding is associated with non-linear effects on diurnal IL-8 and CRP. Furthermore, we find that women who report zero versus ubiquitous ATN breastfeeding exhibit opposing diurnal patterns in CRP secretion rate. This study provides evidence that variation in maternal lactation practices corresponds to differences in maternal immune responses, highlighting how measuring lactation as a continuous variable can further enhance understanding of postpartum maternal physiology., (© 2024. The Author(s).)

Background: To foster community engaged research in the communities most impacted by COVID-19, the National Institutes of Health (NIH) formed 21 teams of Community Engagement Alliance Against COVID-19 Disparities (CEAL). The national CEAL initiative developed a Common Survey to investigate attitudes and behaviors to the COVID-19 vaccine and clinical trials. This article describes survey implementation at the Chicagoland CEAL Program (CCP)., Methods: This community-based participatory research project was the result of a strong collaboration between academic institutions, and a community-based non-profit health equity-focused partner organization. The survey implementation was developed and refined with strong input from CHWs, participants, and staff in the partner organizations and institutions. Survey data were collected with Qualtrics, a web-based survey tool., Results: Survey implementation resulted in data collection for 852 participants during the period 12/18/2021-02/18/2023. Excluding participants on the basis of missing data resulted in a sample of 690, 601 of which (87.10%) indicated that they had received at least one dose or intended to get vaccinated. Overall, 54 (7.83%) respondents reported that they had not received the vaccine and were not planning to., Conclusion: Hard to reach populations present two unique challenges in emerging infectious disease events. Reaching populations vulnerable to poor outcomes with vaccines was essential to addressing the COVID-19 pandemic. Additionally, learning about barriers and hesitancy toward vaccine uptake is difficult in these communities. CCP's partnership of five academic institutions, a community research center, and a community-based non-profit health equity-focused organization shows what is possible when traditional models of research and inquiry are reconsidered for community-based participatory research. Results shown here are drawn from a collaboratively designed and implemented survey, collected in person, with over 90% completion., (© 2024. W. Montague Cobb-NMA Health Institute.)

To describe the reach, implementation, and sustainability of COVID-19 vaccination programs delivered by social service community organizations. Five academic institutions in the Chicagoland CEAL (Community Engagement Alliance) program partnered with 17 community organizations from September 2021-April 2022. Interviews, community organizations program implementation tracking documents, and health department vaccination data were used to conduct the evaluation. A total of 269 events were held and 5,432 COVID-19 vaccines delivered from May 2021-April 2022. Strategies that worked best included offering vaccinations in community settings with flexible and reliable hours; pairing vaccinations with ongoing social services; giving community organizations flexibility to adjust programs; offering incentives; and vaccinating staff first. These strategies and partnership structures supported vaccine uptake, community organization alignment with their missions and communities' needs, and trust. Community organizations delivering social services are local community experts and trusted messengers. Pairing social service delivery with COVID-19 vaccination built individual and community agency. Giving COs creative control over program implementation enhanced trust and vaccine delivery. When given appropriate resources and control, community organizations can quickly deliver urgently needed health services in a public health crisis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we sequenced saliva and nasal samples collected daily from vaccinated and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both unvaccinated and vaccinated individuals appeared largely stochastic; however, in rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of viral variants between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.IMPORTANCEWe detail the within-host evolutionary dynamics of SARS-CoV-2 during acute infection in 31 individuals using daily longitudinal sampling. We characterized patterns of mutational accumulation for unvaccinated and vaccinated individuals, and observed that temporal variant dynamics in both groups were largely stochastic. Comparison of paired nasal and saliva samples also revealed significant genetic compartmentalization between tissue environments in multiple individuals. Our results demonstrate how selection, genetic drift, and spatial compartmentalization all play important roles in shaping the within-host evolution of SARS-CoV-2 populations during acute infection., Competing Interests: The authors declare no conflict of interest.