Search

Caitlin M Brumfiel,1 Meera H Patel,2 Katheryn A Bell,1 Michael A Cardis3 1Georgetown University School of Medicine, Washington, DC, USA; 2Creighton University School of Medicine, Phoenix Regional Campus, Phoenix, AZ, USA; 3MedStar Washington Hospital Center/Georgetown University Hospital Department of Dermatology, Washington, DC, USACorrespondence: Caitlin M BrumfielGeorgetown University School of Medicine, 3900 Reservoir Road, Washington, DC, 20007, USATel +1 513-260-3948Email cmb373@georgetown.eduAbstract: Acne vulgaris is a common skin condition of the face and trunk that negatively impacts quality of life. Trifarotene is a new first-in-class fourth-generation topical retinoid that has been uniquely studied in the treatment of both facial and truncal acne. Through selective agonism of retinoic acid receptor (RAR)-gamma, the most predominant RAR isotype in the epidermis, trifarotene exerts more targeted, skin-specific effects than earlier generation retinoids. This narrative review summarizes all currently available literature regarding the use of trifarotene in acne vulgaris. We focus on efficacy, safety, and tolerability data and highlight quality of life outcomes and patient-reported satisfaction. Future clinical trials and the clinical applicability of this novel medication in the treatment of acne are also discussed.Keywords: acne vulgaris, trifarotene, retinoid, randomized controlled trials

A laboratory system has been developed in which the atmosphere and fluid dynamics of the upper tracheobronchial (TB) tree of the human are simulated. It is used to measure the hygroscopic growth rates of monodisperse NaCl and bronchodilator (Isuprel® hydrochloride with and without glycerine) aerosols. Dry particles are mixed with water vapour-laden air at the entrance to a growth chamber temperature controlled at 37°C with a relative humidity (RH) between 88 and 95%. Hygroscopic growth rates increased with degree of RH and magnitude of Reynolds number in the chamber. The growth data are incorporated into an aerosol deposition model to calculate the effect of hygroscopic growth upon the dose distribution of medicinal aerosols in the human TB network. The model uses some original deposition formulae to compute particle deposition efficiencies. Calculations show that the rate of water vapour absorption within TB airways is an important factor affecting the fate of particles used in aerosol therapy. © 1982 British Occupational Hygiene Society.

A new technique to fix tobacco smoke aerosols by methyl-2-cyanoacrylate vapor is applied to the study of the size distribution of sodium chloride droplets generated from a commercial inhalation nebulizer. The count mode diameter of the fixed droplets agrees well with the actual droplets calculated from known dried particles. The method allows direct visualization and measurement of droplets by light or electron microscopy, but it is limited to particles smaller than 2 μm in diameter. Further work is required to improve the fixation chamber design and sampling technique to ensure complete fixation and collection of droplets greater than 2 μm in diameter before the method can be used to characterize the polydisperse aerosol droplets from nebulizers. © 1979.

Objective: Suicidal individuals experience ambivalent states where they simultaneously consider death and the continuation of their lives. But we have little understanding of how suicidal individuals, particularly youth, mentally construct their future lives. To address this knowledge gap, we aimed to examine episodic future thinking and the related cognitive process of episodic memory among suicidal and nonsuicidal adolescents., Method: We administered a performance-based measure of episodic future thinking to community-based adolescents ( N  = 176, 15-19 years; 69.3% female at birth, 57.1% identifying with a racial minoritized group) and examined the concurrent and predictive validity of details generated within an imagined future event in relation to suicidal ideation (SI; ranging from passive desire of wanting to be dead to active desire to kill oneself)., Results: Greater difficulty imagining discrete actions within an imagined positive future event was associated with past and subsequent SI, although these associations were largely accounted for by depressive symptoms. In contrast, greater difficulty imagining action-related details tied to either positive or negative future events predicted SI 6 months later controlling for symptoms of both anxiety and depression, SI history, and narrative style., Conclusions: Findings from this study offer an initial glimpse into how suicidal adolescents imagine their future and may inform the design of interventions intended to promote a stronger desire for life than death.

Objective: The purpose of this study was to explore the experiences of cultural competence and humility among patients of the lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA+) community in physical therapy. Researchers sought to understand the perspectives of adults over 18 years old who have received physical therapy and identify as a member of the LGBTQIA+ community., Methods: A phenomenological qualitative approach was utilized for this study. Patients were recruited through social media and LGBTQIA+ advocacy organizations across the United States. Twenty-five patients agreed to participate in the study. Focus groups and individual interviews were conducted using a semi-structured interview guide informed by Campinha-Bacote domains of cultural competence (cultural awareness, skill, knowledge, encounter, and desire) to collect individual experiences, discussions, thoughts, perceptions, and opinions., Results: Three central themes and subthemes emerged from the data and were categorized according to cultural acceptance (societal impact, implicit and explicit bias), power dynamics between the in-group and out-group (out-group hyperawareness of their otherness), and participant solutions (policy, training, education)., Conclusion: An LGBTQIA+ patient's experience is influenced by the provider cultural acceptance, and the resulting power dynamics that impact LGBTQIA+ patients' comfort, trust, and perceptions of care. Enhanced patient experiences were found more prevalent with providers that possessed elevated levels of education or experience with this community, supporting Campinha-Bacote assumption that there is a direct relationship between level of competence in care and effective and culturally responsive service., Impact: Awareness of the underlying issues presented in these themes will assist in the development of effective solutions to improve LGBTQIA+ cultural competence among physical therapists and physical therapist assistants on a systemic level., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The purpose of this perspective is to discuss the imperative for curricular change that focuses on the utilization of structural competency to promote excellence in physical therapist professional education, transform society, and achieve health equity. Pedagogy centered around biomedical and social determinants of health (SDOH) models are limited in that they lack self-reflexivity, encode social identities like race and gender as risk factors for poor health, fail to examine structural causes of health inequity, conflate SDOH and the structural forces that shape their unequal distribution, and overlook instances of injustice. Promoting health equity will require structural competency, an approach that considers drivers of health beyond the individual and their conditions of daily living (ie, SDOH). Utilizing this approach in physical therapist professional education will help learners understand the evolving needs of society in a deeper, more holistic way: one that considers structural determinants of health as the primary drivers of health equity and inequity., Impact: This paper provides a perspective on how physical therapist professional education can promote health equity for all by embracing an equity-focused, structurally competent pedagogy/approach., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Suicide screening is critical in pediatric emergency departments (EDs). Behavioral measures of suicide risk may complement self-report measures. The current study examines suicide-specific behavioral measures and tests their potential short-term within-person effects among respondents, ability to discriminate future suicide attempt from suicidal ideation, and translation into interpretable categorical composite scores. The sample included 167 youth (10-17 years), presenting for suicide-related reasons to a pediatric psychiatric ED. During their ED visit, participants completed the Death/Life Implicit Association Test (IAT) and the Suicide Stroop Task. Recurrent suicidal thoughts and attempts were assessed within 6 months of the ED visit via medical records and email surveys. Youth displayed a decrease in the levels of distress and self-injurious desires (negative mood, desire to hurt themselves, and desire to die) after completing the behavioral tasks. The Death/Life IAT prospectively differentiated with 68% accuracy between youth who attempted suicide after their ED visit and those who had suicidal ideation but no attempt, p = 0.04, OR = 5.65, although this effect became marginally significant after controlling for self-report and demographic covariates. Neither the Suicide Stroop Task, nor the categorical composite scores predicted suicide attempts, ps = 0.08-0.87, ORs = 0.96-3.95. Behavioral measures of suicide risk administered in the ED do not appear to increase distress or self-injurious desires. They may be able to distinguish those who go on to attempt suicide (vs. consider suicide) within six months after discharge., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Identify feeding supports required among infants with neonatal encephalopathy and determine growth trajectories to 3 years., Study Design: Single-center retrospective cohort study of 120 infants undergoing therapeutic hypothermia. Logistic regression and stratified analyses identified whether clinical factors, EEG-determined encephalopathy severity, and MRI-based brain injury predict feeding supports (nasogastric tube, oral feeding compensations) and growth., Results: 50.8% of infants required feeding supports in the hospital, decreasing to 14% at discharge. Moderate-to-severe encephalopathy and basal ganglia injury predicted feeding support needs. Yet, 35% of mildly encephalopathic infants required gavage tubes. Growth trajectories approximated expected growth of healthy infants., Conclusion: Infants with neonatal encephalopathy-even if mild-frequently experience feeding difficulties during initial hospitalization. With support, most achieve full oral feeds by discharge and adequate early childhood growth. Clinical factors may help identify infants requiring feeding support, but do not detect all at-risk infants, supporting routine screening of this high-risk population., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p -values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older ( p = 0.021), not born in Canada ( p = 0.043), visible minorities ( p = 0.01) and have a lower attained education ( p < 0.0001) and perceived fair/poor health ( p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities ( p = 0.009) and have a lower attained education ( p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened.

Human milk oligosaccharides (HMOs) are bioactive factors that benefit neonatal health, but little is known about effects on growth in very preterm infants (<32 weeks' gestation). We aimed to quantify HMO concentrations in human milk fed to very preterm infants during the neonatal hospitalization and investigate associations of HMOs with infant size and body composition at term-equivalent age. In 82 human-milk-fed very preterm infants, we measured HMO concentrations at two time points. We measured anthropometrics and body composition with air displacement plethysmography at term-equivalent age. We calculated means of individual and total HMOs, constructed tertiles of mean HMO concentrations, and assessed differences in outcomes comparing infants in the highest and intermediate tertiles with the lowest tertile using linear mixed effects models, adjusted for potential confounders. The mean (SD) infant gestational age was 28.2 (2.2) weeks, and birthweight was 1063 (386) grams. Exposure to the highest (vs. lowest) tertile of HMO concentrations was not associated with anthropometric or body composition z-scores at term-corrected age. Exposure to the intermediate (vs. lowest) tertile of 3FL was associated with a greater head circumference z-score (0.61, 95% CI 0.15, 1.07). Overall, the results do not support that higher HMO intakes influence growth outcomes in this very preterm cohort.

Background: Despite increased attention on treatment and prevention for suicidal adolescents, we know little about potential intervention targets. Episodic future thinking-the ability to imagine detailed, personal, and future-oriented events-is a modifiable cognitive process that has been linked with suicidal ideation (SI) in adolescents. However, until now its modifiability has only been tested in adults., Method: Adolescents ( N  = 176, ages 15-19; 71% SI) completed performance-based measures of episodic future thinking (i.e., Experimental Recombination Paradigm) and memory immediately before and after an Episodic Specificity Induction (ESI)., Results: Adolescents produced a greater number of future episodic details after (vs. before) the ESI but showed no change in non-episodic details (e.g., semantic information). Patterns of change in episodic future thinking were not moderated by SI history. Adolescents overall did not demonstrate change in past episodic detail counts after the ESI. However, there were select moderating effects of SI history on this effect., Conclusion: Results show that episodic future thinking can change immediately following an episodic specificity induction among adolescents, regardless of whether they have previously experienced SI. This demonstration of within-person change constitutes a foundational first step in examining malleability of episodic future thinking in adolescents and offers preliminary evidence of a cognitive mechanism that may be leveraged in service of reducing adolescents' SI., Competing Interests: The authors have declared they have no competing or potential conflicts of interest., (© 2024 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Objective: The purpose of this study was to understand the lesbian, gay, bisexual, transgender, queer, intersex, agender, and other gender and sexually diverse identities (LGBTQIA+) health care experience and associated cultural competence from the physical therapist perspective (physical therapist and physical therapist assistant)., Methods: An exploratory qualitative approach implementing semi-structured focus groups and private interviews was utilized. To further anonymity, researchers allowed subjects to keep their camera off on Zoom. An interview protocol included questions guided by Campinha-Bacote domains of cultural competence (cultural awareness, skill, knowledge, encounter, and desire) to collect individual experiences, stories, discussions, thoughts, and opinions. Physical therapist clinicians were recruited from the clinical education affiliation lists of Regis University and Thomas Jefferson University. Seventy-one practicing physical therapists from the USA agreed to be part of the study., Results: Themes were organized using the Social Ecological Model Framework. Themes are in parentheses following each level of the Social Ecological Model and include intrapersonal level (psychological stress and implicit and explicit biases), interpersonal (acceptance and competency), organizational (experience), community (advocacy), and society and policy (explicit biases and policy)., Conclusion: Cultural competence in physical therapy is influenced by intrapersonal, interpersonal, organizational, community, and social and policy factors. Themes of psychological stress, limited awareness, decreased acceptance, and competency as well as limited exposure and experience, and a lack of advocacy and broader societal and policy issues prevent adequate LGBTQIA+ cultural competency of physical therapist providers. Further research in the physical therapist profession is needed to elaborate on the student, educator, and patient perspectives and how this information informs the LGBTQIA+ cultural competence of clinicians., Impact: This project may have a significant impact on suggestions for the delivery of content for health profession education to best impact health equity goals and save lives. Implementation of this content may have a direct impact on health disparities in LGBTQIA+ populations by reducing stigma and discrimination from health care providers, thus improving quality of health care and decreasing rates of patient mortality for LGBTQIA+ individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Youth experiencing suicidal thoughts and/or behaviors (STBs) frequently present to emergency departments for acute psychiatric care. These settings offer a transitory yet pivotal opportunity to assess, intervene on, and plan continued care for STBs. This study examined a clinically relevant, understudied aspect of psychological functioning among youth experiencing STBs in the emergency department: episodic future thinking, or the ability to imagine discrete autobiographical future events. A sample of 167 youths (10-17 years) presenting to a pediatric psychiatric emergency department for STBs completed a performance-based measure of episodic future thinking assessing richness in detail and subjective characteristics of imagined future events. STB recurrence was assessed 6 months later. Immediately following a suicide-related crisis, youth demonstrated mixed abilities to imagine their future: they generated some concrete future event details but did not subjectively perceive these events as being very detailed or likely to occur. Older adolescents (i.e., 15-17) generated more episodic details than pre-/younger adolescents (i.e., 10-14), particularly those pertaining to actions or sensory perceptions. There was no evidence linking less detailed episodic future thinking and greater likelihood of STBs following the emergency department visit; instead, hopelessness was a more robust risk factor. Findings underscore the importance and clinical utility of better understanding the psychological state of youth during or immediately following a suicide-related crisis. In particular, assessing youths' future thinking abilities in the emergency department may directly inform approaches to acute care delivery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Abstract: This study examined the differences in negative beliefs about disclosing suicidal thoughts and behaviors (STBs) between US Veterans and non-Veterans, and between Veterans who are and are not enrolled in Veterans Health Administration (VHA) care. Participants included 495 adults with a history of suicide ideation who completed an online self-report questionnaire inquiring about history of STBs, STB disclosure, and beliefs about STB disclosures. Group differences in STB disclosure beliefs were analyzed. Results showed that Veterans (vs. non-Veterans) more strongly believed that STB disclosure would result in firearm confiscation. VHA-enrolled (vs. non-VHA enrolled) Veterans reported stronger beliefs that STB disclosures result in involuntary hospitalization. Among VHA-enrolled Veterans, stronger beliefs regarding providers' interest regarding true STB experiences and others' comfort with STB disclosures were associated with lower STB disclosure likelihood. Findings highlight that educating Veterans on the benefits of STB disclosure and limiting misinformation regarding its consequences is paramount, specifically through improved suicide-related communication within the VHA and stigma reduction campaigns., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The present study aimed to expand the literature on single-item assessments for suicidal thoughts and behaviors (STBs) by examining measurement invariance of commonly used single-item assessments of suicidal ideation (SI), planning (SP), and attempts (SA) with respect to race and ethnicity. Predictive invariance with respect to depression, and multi-item measures of passive and active SI were also explored. Measurement invariance was examined across (a) Black and White respondents and (b) Hispanic/Latinx and non-Hispanic/-Latinx respondents. Participants ( N = 1,624; 51.66% male) were recruited from Mechanical Turk and Prime Panels. Participants were administered four distinct single-item measures each for SI, SP, and SA across three timeframes (past month, past year, lifetime). Items were drawn from well-known large-scale studies (e.g., National Comorbidity Survey) and common suicide risk assessments. Multiple group confirmatory factor analysis was used to examine measurement invariance; regression with group by measure interactions were used to evaluate predictive invariance. Measurement invariance was observed for both Black ( N = 534) and White ( N = 1,089) respondents as well as Hispanic/Latinx ( N = 335) and non-Hispanic/-Latinx ( N = 1,288) respondents across single-item outcomes. Thus, SI, SP, and SA rates can be defensibly compared between Black and White and Hispanic/Latinx and non-Hispanic/-Latinx respondents within studies; however, comparison of SI and SP rates across studies with differing assessment prompts should be met with caution. Multiple single-item STB measures demonstrated predictive bias across race and ethnicity suggesting potential differential screening capabilities. Elevated SI, SP, and SA rates for Hispanic/Latinx individuals were also observed. Findings reiterate the importance of minor language differences in single-item STB assessments. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Introduction: The aim of this study was to adapt and validate the Belongingness Scale-Clinical Placement Experience (BES-CPE) for Doctor of Physical Therapy (DPT) students in the United States., Review of Literature: Belongingness is vital to one's mental, emotional, and physical health. Research has shown that belongingness is positively correlated with students' academic performance and achievement. An absence of belongingness may hinder students' full participation in clinical experiences and compromise clinical achievement., Subjects: Respondents were current or former DPT students at least 18 years of age who had either completed the midterm evaluation of their final terminal full-time clinical education experience (TCE) in their DPT program or were no more than 1 year from the completion of their final TCE., Methods: The BES-CPE was adapted for DPT students, and the scale was completed electronically by those who met the inclusion criteria. Principal component analysis with promax rotation and Cronbach's α were used to determine construct validity and reliability., Results: One hundred fifty-nine respondents completed all items on the BES-CPE and demographic survey. A 3-component structure was identified (esteem, connectedness, and efficacy), which was aligned to the original BES-CPE scale. One item was discarded, and the final version of the BES-CPE for DPT students is a 33-item scale with satisfactory internal consistency., Discussion and Conclusion: This study adapted and provided evidence for validity of the first known scale to measure belongingness in DPT students during their clinical education experiences (CEEs) in the United States. The 33-item BES-CPE provided valid and reliable measures of belongingness in DPT students during CEEs that can be used to provide a better understanding of the student experience in the clinical learning environment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Academy of Physical Therapy Education, APTA.)

Background: Preterm birth adversely impacts brain development and contributes to neurodevelopmental impairment; the temporal lobe may be particularly vulnerable to the impact of very preterm (VP) birth. Yet, no prior magnetic resonance imaging (MRI) scoring system incorporated a method to quantify temporal lobe size in VP infants., Methods: We developed and applied three metrics (temporal lobe length, extra-axial space, and temporal horn width) to quantify temporal lobe structure on term-equivalent brain MRIs obtained from 74 VP and 16 term infants. We compared metrics between VP and term infants and explored associations of each metric with perinatal risk factors., Results: All metrics had excellent reliability (intra-class correlation coefficient 0.62-0.98). VP infants had lower mean temporal lobe length (76.8 mm versus 79.2 mm, p = 0.02); however, the difference attenuated after correction for postmenstrual age. VP infants had larger temporal horn widths compared with term infants (2.6 mm versus 1.8 mm, p < 0.001). Temporal lobe length was positively associated with gestational age, birth weight, and male sex, and negatively associated with the duration of parenteral nutrition., Conclusions: The proposed metrics are reliable and sensitive in distinguishing differences in temporal lobe development between VP and full-term infants., Impact: We developed a novel method for quantifying temporal lobe size among very preterm infants at term equivalent using simple metrics performed on brain MRI. Temporal lobe metrics were reliable, correlated with brain volume from volumetric analysis, and were sensitive in identifying differences in temporal lobe development among preterm compared with term infants, specifically larger temporal horn size in preterm infants. This temporal lobe metric system will enable future work to delineate the perinatal and postnatal factors that impact temporal lobe growth, and better understand the relationship between temporal lobe disturbance and neurodevelopment in very preterm infants., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Genetic testing for hereditary cancer susceptibility has advanced over time due to the discovery of new risk genes, improved technology and decreased cost. In the province of Ontario, testing eligibility criteria were initially developed to include hereditary breast, ovarian and colorectal cancer syndromes. The rapid evolution of genetic technologies has facilitated the ability to interrogate a large number of genes concurrently. This, coupled with new knowledge about risk genes, necessitated a coordinated approach to expanding the scope of genes and indications tested and synchronisation of access and test utilisation across the province as required in a publicly funded universal healthcare system., Methods: Ontario Health-Cancer Care Ontario convened expert working groups to develop a standardised and comprehensive cancer gene list for adults and accompanying hereditary cancer testing (HCT) criteria using an evidence-based framework and broad laboratory and clinical genetics engagement., Results: A standardised 76-cancer-gene panel, organised into 13 larger disease site panels and 25 single/small gene panels, was developed and endorsed by the working groups. Provincial genetic testing eligibility criteria were updated to align with the new panels and to guide clinical decision-making. In the first year following the implementation of these changes, 10 564 HCT panels were performed with an overall mutation detection rate of 12.2%., Conclusion: Using an evidence framework and broad clinical engagement to develop and endorse an updated guidance document, cancer genetic testing for adults in Ontario is now standardised and coordinated across the province., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE., (© 2023. The Author(s).)

Introduction: The goal of clinical and translational science (CTS) is to fill gaps in medical knowledge toward improving human health. However, one of our most pressing challenges does not reside within the biological map we navigate to find sustainable cures but rather the moral compass to recognize and overcome racial and ethnic injustices that continue to influence our society and hinder diverse research rigor. The Georgetown-Howard Universities Center for Clinical and Translational Science includes an inter-institutional TL1-funded training program for predoctoral/postdoctoral trainees in Translational Biomedical Science (TBS)., Methods: In the fall of 2020, the TBS program responded to the national social justice crisis by incorporating a curriculum focused on structural racism in biomedical research. Educational platforms, including movie reviews, Journal Clubs, and other workshops, were threaded throughout the curriculum by ensuring safe spaces to discuss racial and ethnic injustices and providing trainees with practical steps to recognize, approach, and respond to these harmful biases in the CTS. Workshops also focused on why individuals underrepresented in science are vital for addressing and closing gaps in CTS., Results: Paring analysis using REDCap software de-identified participants after invitations were sent and collected in the system to maintain anonymity for pre- and post-analysis. The Likert scale evaluated respondents' understanding of diverse scientific circumstances. The pre/Fall and post/Spring surveys suggested this curriculum was successful at raising institutional awareness of racial and ethnic biases. Evaluating the effectiveness of our program with other training Clinical and Translational Science Awards (CTSA) consortiums will strengthen both the academic and professional TBS programs., (© The Author(s) 2022.)

Body composition analysis to distinguish between fat mass and fat-free mass is an established research approach to assess nutritional status. Within neonatal medicine, preterm infant body composition is linked with later health outcomes including neurodevelopment and cardiometabolic health. Mounting evidence establishing fat-free mass as an indicator of nutritional status, coupled with the availability of testing approaches that are feasible to use in preterm infants, have enhanced interest in measuring body composition in the neonatal intensive care unit (NICU) setting. In this paper, we use the concept of clinical utility-the added value of a new methodology over current standard care-as a framework for assessing several existing body composition methodologies with potential for clinical application to preterm neonates. We also use this framework to identify remaining knowledge gaps and prioritize efforts to advance our understanding of clinically-oriented body composition testing in the NICU., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: The present study sought to determine the relationship between self-reported cannabis use dosage in grams per day with (1) objective sleep outcomes: sleep efficiency (SE), sleep onset latency SOL and number of night-time awakenings (NWAK) (2) if objective and subjective sleep measures, using the PSQI, differed between cannabis users and non-cannabis users., Methods: Our sample included 178 participants, aged 18-35 years. We collected demographic information, cannabis use in dosage per day and frequency of use, depressive symptoms through the CESD, and subjective sleep reports using the PSQI. After the survey assessment, we monitored sleep using the Phillips Actiwatch Spectrum watch for a minimum of 5 nights., Results: The amount of cannabis consumed per day was inversely related to SOL and SE, and positively related to NWAK. After controlling for covariates, regression models were statistically significant for predicting SOL (β = -0.369, p <.001), SE (β = -0.232, p <.05) and NWAK, (β = -0.318, p <.001), indicating cannabis dosage per day is the strongest predictor for the sleep parameters. Subjective sleep measures did not differ from cannabis users versus non-cannabis users., Conclusion: Recreational cannabis use is beneficial for SOL but may be detrimental to SE as those who reported increased cannabis use also had more NWAK. Cannabis may be useful for sleep onset, results suggest that increased use does not aid in sleep maintenance., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To determine associations between body composition and concurrent measures of brain development including (1) Tissue-specific brain volumes and (2) White matter microstructure, among very preterm infants at term equivalent age., Design: Prospective observational study., Setting: Single-centre academic level III neonatal intensive care unit., Patients: We studied 85 infants born <33 weeks' gestation., Methods: At term equivalent age, infants underwent air displacement plethysmography to determine body composition, and brain MRI from which we quantified tissue-specific brain volumes and fractional anisotropy (FA) of white matter tracts. We estimated associations of fat and lean mass Z-scores with each brain outcome, using linear mixed models adjusted for intrafamilial correlation among twins and potential confounding variables., Results: Median gestational age was 29 weeks (range 23.4-32.9). One unit greater lean mass Z-score was associated with larger total brain volume (10.5 cc, 95% CI 3.8 to 17.2); larger volumes of the cerebellum (1.2 cc, 95% CI 0.5 to 1.9) and white matter (4.5 cc, 95% CI 0.7 to 8.3); and greater FA in the left cingulum (0.3%, 95% CI 0.1% to 0.6%), right uncinate fasciculus (0.2%, 95% CI 0.0% to 0.5%), and right posterior limb of the internal capsule (0.3%, 95% CI 0.03% to 0.6%). Fat Z-scores were not associated with any outcome., Conclusions: Lean mass-but not fat-at term was associated with larger brain volume and white matter microstructure differences that suggest improved maturation. Lean mass accrual may index brain growth and development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acid-suppressing medications (ASMs) are commonly prescribed in the neonatal intensive care unit (NICU), in particular among preterm infants, despite well-established adverse effects and little evidence to support efficacy., Local Problem: We sought to develop an initiative to reduce ASM exposure in our predominantly inborn level III NICU. Our specific aim was to reduce the number of nonindicated ASM prescriptions by 50% within a 12-month period., Methods: Our multidisciplinary team developed an evidence-based guideline defining indications for ASM prescription in a level III NICU. Plan-do-study-act cycles included staff education, formal clinical practice guideline implementation, and implementation of standardized documentation tools in the electronic health record (EHR). Outcome measures were the number of nonindicated and total inpatient prescriptions started per month, duration of ASM prescription, and number of prescriptions continued after NICU discharge. Balancing measures were the number of patients started on thickened feeds and number of patients discharged home on nasogastric tube feeds. We used statistical process control and Pareto charts to assess these measures over a 12-month baseline period, 9-month implementation period, and 19-month post-implementation period spanning September 2017-December 2020., Results: Nonindicated ASM prescriptions decreased from median 3 to 0 per month from the baseline to post-implementation period. Simultaneously, the median number of ASM prescriptions at discharge declined from 2 to 0 per month. The median duration of inpatient prescriptions declined from 23 to 7 days. Rates of patients started on thickened feeds and patients discharged home on nasogastric tube feeds remained stable throughout the study., Conclusion: Enactment of an evidence-based guideline was associated with a substantial decline in nonindicated ASM use in our NICU and a decline in duration of exposure to ASM's when prescribed. Our interventions proved effective in altering clinical practice and could be applied to other NICUs with similar patient populations aiming to reduce ASM use., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Adolescents and their parents do not always see eye to eye. This principle applies to multi-informant reports of adolescents' self-injurious thoughts and behaviors. Although prior work has revealed the presence of parent-adolescent discrepant reports, we have little insight into exactly who is most likely to display such discrepancies. To address this knowledge gap, the present investigation examines demographic correlates of parent-adolescent reports of adolescents' self-injurious thoughts and behaviors, with a focus on race and ethnicity., Method: The sample included 45 dyads of adolescents ( M  = 15.79 years, SD  = 1.42) and their parents reporting on adolescents' history of suicide ideation, suicide plan, suicide gesture, suicide attempt, and nonsuicidal self-injury (NSSI)., Results: Greater discrepancies in reports of adolescents' suicide ideation and NSSI were observed among racial minority parent-adolescent dyads (Black, Asian, Multiracial, Other) relative to White dyads. Racial minority parents tended to report less suicide ideation and NSSI observed in their adolescents compared to adolescents' self-report. Moreover, Hispanic parents tended to report less NSSI relative to adolescents' self-report. Parent-adolescent discrepancies did not consistently correspond with other characteristics such as age and sexual orientation., Conclusion: Racial minority parent-adolescent dyads, relative to White parent-adolescent dyads, are less likely to see eye to eye on adolescents' suicidal and nonsuicidal self-harming tendencies.

Objective: The present study sought to evaluate the psychometric properties and inter-informant agreement of the Self-Injurious Thoughts and Behaviors Interview-Revised ( SITBI-R ) in adolescents and their parents., Method: Suicidal and nonsuicidal adolescents from the community ( N = 206), ages 12-19 years, were administered the SITBI-R during a lab visit. Approximately half of the adolescents' parents opted to complete a parent assessment, including the SITBI-R, on behalf of their child. Inter-rater reliability, convergent validity, and inter-informant agreement were assessed., Results: The SITBI-R exhibited overall excellent inter-rater reliability and good convergent validity in adolescents. Parent-adolescent agreement ranged from fair to poor across most outcomes, with parents tending not to report past self-injurious thoughts and behaviors endorsed by their children., Conclusions: The present study suggests that the SITBI-R can be extended for use with adolescents. Future research should evaluate moderators and implications of parent-adolescent disagreement, particularly with regard to suicide risk.

Point-of-care human milk analysis is now feasible in the neonatal intensive care unit (NICU) and allows accurate measurement of macronutrient delivery. Higher macronutrient intakes over this period may promote brain growth and development. In a prospective, observational study of 55 infants born at <32 weeks’ gestation, we used a mid-infrared spectroscopy-based human milk analyzer to measure the macronutrient content in repeated samples of human milk over the NICU hospitalization. We calculated daily nutrient intakes from unfortified milk and assigned infants to quintiles based on median intakes over the hospitalization. Infants underwent brain magnetic resonance imaging at term equivalent age to quantify total and regional brain volumes and fractional anisotropy of white matter tracts. Infants in the highest quintile of energy intake from milk, as compared with the lower four quintiles, had larger total brain volume (31 cc, 95% confidence interval [CI]: 5, 56), cortical gray matter (15 cc, 95%CI: 1, 30), and white matter volume (23 cc, 95%CI: 12, 33). Higher protein intake was associated with larger total brain (36 cc, 95%CI: 7, 65), cortical gray matter (22 cc, 95%CI: 6, 38) and deep gray matter (1 cc, 95%CI: 0.1, 3) volumes. These findings suggest innovative strategies to close nutrient delivery gaps in the NICU may promote brain growth for preterm infants.

Several barriers exist to routine assessment of suicidal ideation (SI) in adolescents across settings, including insufficient time, tools, and training. Such barriers often result in the use of brief or even single-item assessments of SI, which may result in misclassification. The present study sought to compare single- and multi-item assessment of SI in adolescents, and to examine factors associated with different response profiles. Adolescents (n =206) were recruited from the community and completed a lab visit including a single and multi-item assessment for SI. Results suggest that two thirds of adolescents with passive SI go undetected when relying solely on a single-item screener, yet they present a similar clinical profile to those with passive SI who endorse the screener question. The present study provides support for the notion that multi-item assessment paints a more accurate, nuanced picture of SI among adolescents and may be an important component of routine screening.

Background: Noninfectious complications are the greatest cause of morbidity and mortality in common variable immunodeficiency (CVID), but their pathogenesis remains poorly defined., Objective: Using high-throughput approaches, we aimed to identify, correlate, and determine the significance of immunologic features of CVID with noninfectious complications (CVIDc)., Methods: We simultaneously applied proteomics, RNA sequencing, and mass cytometry to a large cohort with primary antibody deficiency., Results: CVIDc is differentiated from uncomplicated CVID, other forms of primary antibody deficiency, and healthy controls by a distinct plasma proteomic profile. In addition to confirming previously reported elevations of 4-1BB, IL-6, IL-18, and IFN-γ, we found elevations of colony-stimulating factor 1, IL-12p40, IL-18R, oncostatin M, TNF, and vascular endothelial growth factor A to differentiate CVIDc. This cytokine dysregulation correlated with deficiency of LPS-specific antibodies and increased soluble CD14, suggesting microbial translocation. Indicating potential significance of reduced LPS-specific antibodies and resultant microbial-induced inflammation, CVIDc had altered LPS-induced gene expression matching plasma proteomics and corresponding with increased CD14 + CD16 - monocytes, memory T cells, and tissue inflammation ameliorated by T-cell-targeted therapy. Unsupervised machine learning accurately differentiated subjects with CVIDc and supported cytokine dysregulation, antibody deficit, and T-cell activation as defining and convergent features., Conclusions: Our data expand understanding of CVIDc proteomics, establish its link with deficiency of IgA and LPS-specific antibodies, and implicate altered LPS-induced gene expression and elevated monocytes and T cells in this cytokine dysregulation. This work indicates that CVIDc results when insufficient antibody neutralization of pathogen-associated molecular patterns, like LPS, occurs in those with a heightened response to these inflammatory mediators, suggesting a 2-hit model of pathogenesis requiring further exploration., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Non-celiac gluten sensitivity is often clinically indistinguishable from celiac disease, and patients show improvement or resolution of their symptoms with a gluten-free diet. In contrast to celiac disease, the effects of gluten on the skin and hair in the context of non-celiac gluten sensitivity are not as clear. This review aims to describe the impact of gluten on the skin and hair in patients with non-celiac gluten sensitivity and those without a definitive celiac disease diagnosis. A literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guidelines for systematic reviews. Forty-two publications met inclusion criteria with five studies describing the skin manifestations of non-celiac gluten sensitivity. Trials identifying the impact of a gluten-free diet on skin disease, as well as dermatologic conditions and their associations with antigliadin antibodies were also identified. Dermatologic manifestations in patients with non-celiac gluten sensitivity vary and may be non-specific. It may be appropriate for some of these patients with skin manifestations to trial a gluten-free diet. Dermatologic conditions that may respond positively to a gluten-free diet include psoriasis, atopic dermatitis, vitiligo, and palmoplantar pustulosis, while linear IgA disease does not appear to improve with this dietary change.

Introduction : Estimates of the prevalence of comorbid depression vary, ranging from 9 and 62%. Deterioration of mental health may emerge as a result of psoriasis; however, it is theorized that depression alone may independently predispose patients to new-onset psoriasis. Areas covered : The aim of this brief review is to explore the impact of depression on psoriasis treatment. Expert opinion : The two studies that directly assess the role of depression in psoriasis treatment outcomes are important, as unaddressed depression can undermine the success of a given treatment. This may reflect the notion that depressed individuals are less likely to be adherent. Thus, it may be valuable for clinicians to not only screen for depression, but to ensure that it is adequately treated. Our knowledge of treatment preferences in psoriasis patients with comorbid depression is limited. Expanding our understanding of preferences may allow providers to better align their recommendations to ultimately increase adherence. Additionally, given that many psoriasis treatments have an impact on depression, it may be beneficial for clinicians to evaluate patients for psychiatric risk factors to optimize the treatment regimen.

The entorhinal cortex alvear pathway is a major excitatory input to hippocampal CA1, yet nothing is known about its physiological impact. We investigated the alvear pathway projection and innervation of neurons in CA1 using optogenetics and whole cell patch clamp methods in transgenic mouse brain slices. Using this approach, we show that the medial entorhinal cortical alvear inputs onto CA1 pyramidal cells (PCs) and interneurons with cell bodies located in stratum oriens were monosynaptic, had low release probability, and were mediated by glutamate receptors. Optogenetic theta burst stimulation was unable to elicit suprathreshold activation of CA1 PCs but was capable of activating CA1 interneurons. However, different subtypes of interneurons were not equally affected. Higher burst action potential frequencies were observed in parvalbumin-expressing interneurons relative to vasoactive-intestinal peptide-expressing or a subset of oriens lacunosum-moleculare (O-LM) interneurons. Furthermore, alvear excitatory synaptic responses were observed in greater than 70% of PV and VIP interneurons and less than 20% of O-LM cells. Finally, greater than 50% of theta burst-driven inhibitory postsynaptic current amplitudes in CA1 PCs were inhibited by optogenetic suppression of PV interneurons. Therefore, our data suggest that the alvear pathway primarily affects hippocampal CA1 function through feedforward inhibition of select interneuron subtypes., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Common variable immunodeficiency (CVID) is the most frequently diagnosed primary antibody deficiency. About half of CVID patients develop chronic non-infectious complications thought to be due to intrinsic immune dysregulation, including autoimmunity, gastrointestinal disease, and interstitial lung disease (ILD). Multiple studies have found ILD to be a significant cause of morbidity and mortality in CVID. Yet, the precise mechanisms underlying this complication in CVID are poorly understood. CVID ILD is marked by profound pulmonary infiltration of both T and B cells as well as granulomatous inflammation in many cases. B cell depletive therapy, whether done as a monotherapy or in combination with another immunosuppressive agent, has become a standard of therapy for CVID ILD. However, CVID is a heterogeneous disorder, as is its lung pathology, and the precise patients that would benefit from B cell depletive therapy, when it should administered, and how long it should be repeated all remain gaps in our knowledge. Moreover, some have ILD recurrence after B cell depletive therapy and the relative importance of B cell biology remains incompletely defined. Developmental and functional abnormalities of B cell compartments observed in CVID ILD and related conditions suggest that imbalance of B cell signaling networks may promote lung disease. Included within these potential mechanisms of disease is B cell activating factor (BAFF), a cytokine that is upregulated by the interferon gamma (IFN-γ):STAT1 signaling axis to potently influence B cell activation and survival. B cell responses to BAFF are shaped by the divergent effects and expression patterns of its three receptors: BAFF receptor (BAFF-R), transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA). Moreover, soluble forms of BAFF-R, TACI, and BCMA exist and may further influence the pathogenesis of ILD. Continued efforts to understand how dysregulated B cell biology promotes ILD development and progression will help close the gap in our understanding of how to best diagnose, define, and manage ILD in CVID., 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 © 2021 Matson, Abyazi, Bell, Hayes and Maglione.)

COVID-19 has affected many people worldwide. Beyond the physical symptoms brought on by this virus, it has adversely affected those without the illness through isolation, social distancing, and changes in job and housing security. Clinicians are trying to address the mental health needs of millions of strained Americans with and without COVID-19 and are operating without a systematic strategy. Informed by the authors' experiences during the pandemic, this Open Forum attempts to answer two questions: What are the specific considerations in working with economically compromised Hispanic/Latino and Black/African American populations with mental illness? How can mental health providers and researchers best help?

Objective: This article reviews clinical trials to assess the efficacy, safety, and clinical application of trifarotene 0.005% cream (Aklief)., Data Sources: A systematic review of the literature was performed using the terms trifarotene OR Aklief OR CD5789 in MEDLINE (PubMed) and EMBASE databases. Articles prior to May 2020 were considered for inclusion. Bibliographies and ClinicalTrials.gov were also searched to identify further studies., Study Selection and Data Extraction: Relevant English language and human studies related to pharmacology, clinical trials, and safety were considered., Data Synthesis: In the 52-week phase III trial, treatment success rates for facial acne (Investigator Global Assessment [IGA] rating of no or almost no acne) and truncal acne (Physician's Global Assessment [PGA] rating of no or almost no acne) were 65.1% and 66.9%, respectively. Overall success rates (IGA and PGA success in the same patient) were 57.9%; 52.8% of patients had a Dermatology Quality of Life Index score of 0 or 1, compared with 22.6% at baseline. Trifarotene was well tolerated, with pruritus, irritation, and sunburn as the most common adverse effects., Relevance to Patient Care and Clinical Practice: Trifarotene is a newly Food and Drug Administration-labeled fourth-generation topical retinoid that shows particular promise in the treatment of facial and truncal acne vulgaris. It is an effective and safe addition to currently available retinoids., Conclusion: Trifarotene is effective and safe for treatment of facial and truncal acne. Future trials should compare its efficacy and tolerability with that of the older, clinically established retinoids. Despite efficacy, cost may be a prohibitive factor.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by erythematous lesions, pruritus, and a skin barrier defect. Long-term treatment in children is challenging, as there is only one Food and Drug Administration-approved systemic medication. Current treatments may have limited efficacy or serious side effects in children. With a deeper understanding of AD pathogenesis and the advent of target-specific medications, several biologics are undergoing clinical trials for future use in pediatric AD., Areas Covered: This article reviews the current and emerging biologic therapies for treatment of pediatric AD. It allows for comprehensive comparison of medications and their clinical trials to help providers optimize patient treatment plans while providing expert insight into upcoming advancements in the treatment of pediatric AD., Expert Opinion: Treating pediatric AD is complicated given the variety of disease severity, psychosocial impact, and relative lack of approved medications for severe disease. Given the safety data on dupilumab, newer biologics will likely be second-line. We do not yet understand the long-term impact of newer biologics on an immature immune system, nor do we fully understand their risks and toxicities. We should proceed optimistically, yet cautiously, with the study of biologics in children.

Objective: To assess the association of very preterm infants' brain size at term-equivalent age with physical growth from birth to term and body composition at term., Study Design: We studied 62 infants born at <33 weeks of gestation. At birth and term, we measured weight and length and calculated body mass index. At term, infants underwent air displacement plethysmography to determine body composition (fat and fat-free mass) and magnetic resonance imaging to quantify brain size (bifrontal diameter, biparietal diameter, transverse cerebellar distance). We estimated associations of physical growth (Z-score change from birth to term) and body composition with brain size, adjusting for potential confounders using generalized estimating equations., Results: The median gestational age was 29 weeks (range, 24.0-32.9 weeks). Positive gains in weight and body mass index Z-score were associated with increased brain size. Each additional 100 g of fat-free mass at term was associated with larger bifrontal diameter (0.6 mm; 95% CI, 0.2-1.0 mm), biparietal diameter (0.7 mm; 95% CI, 0.3-1.1 mm), and transverse cerebellar distance (0.3 mm; 95% CI, 0.003-0.5 mm). Associations between fat mass and brain metrics were not statistically significant., Conclusions: Weight and body mass index gain from birth to term, and lean mass-but not fat-at term, were associated with larger brain size. Factors that promote lean mass accrual among preterm infants may also promote brain growth., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Erwinia amylovora is a plant pathogen from the Erwiniaceae family and a causative agent of the devastating agricultural disease fire blight. Here we characterize eight lytic bacteriophages of E. amylovora that we isolated from the Wasatch front (Utah, United States) that are highly similar to vB&#95;EamM&#95;Ea35-70 which was isolated in Ontario, Canada. With the genome size ranging from 271 to 275 kb, this is a novel jumbo family of bacteriophages. These jumbo bacteriophages were further characterized through genomic and proteomic comparison, mass spectrometry, host range and burst size. Their proteomes are highly unstudied, with over 200 putative proteins with no known homologs. The production of 27 of these putative proteins was confirmed by mass spectrometry analysis. These bacteriophages appear to be most similar to bacteriophages that infect Pseudomonas and Ralstonia rather than Enterobacteriales bacteria by protein similarity, however, we were only able to detect infection of Erwinia and the closely related strains of Pantoea .