Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype.

Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between ADNP and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype-specific episignature. A distinct episignature was shared by 15 individuals with BIS-causing SMARCA2 pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic ADNP variants. This represents first evidence of a sensitive phenotype-specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene-specific episignatures.

Which types of social support matter for Black sexual minority men coping with internalized homophobia? Findings from a mediation analysis.

Background: Minority stress theory views social support as a protective factor against the effects of minority-specific stressors like internalized homophobia (IH) on mental health in sexual minority populations. However, much of the empirical validation of this theory has been conducted within predominantly White samples, resulting in a limited understanding of how the theory applies to Black sexual minority individuals. Current examinations of social support fail to capture the nuances of how Black sexual minority men may access support systems differently, resulting in a need to investigate how social support, IH, and mental health operate for Black sexual minority men. This study examined relationships between IH, depression, and different types of social support (i.e., family, friends, Black community, gay community) using a mediation model. Methods: We used data from the POWER (Promoting Our Worth Equity and Resilience) Study, which recruited Black sexual minority men at Black Pride events across six cities in the United States from 2014 to 2017, to test four mediation pathways concurrently in Stata 17. Participants (N = 4,430) completed a questionnaire assessing a variety of health and life domains, including depression symptoms, internalized homophobia, and social support. Results: IH was positively associated with depression. Lower levels of family, friend, and Black community support were all positively associated with depression symptoms. Additionally, IH was positively associated with all types of support. Finally, family, friend, and Black community support partially mediated the relationship between IH and depression. Conclusions and implications: Results suggest that the relationship between social support and depression is complex for Black sexual minority men. Findings suggest family support is an important factor for clinical intervention efforts targeting depression, and that gay community support systems should assess how their environments can better support Black sexual minority men. Overall, findings demonstrate the necessity of future examination of how social support functions differently within Black sexual minority communities.

A Systematic Review of Conceptualizations and Operationalizations of Youth Polyvictimization.

Violence against youth is a global issue impacting millions each year. Increasingly, research has focused on studying those impacted by multiple forms of violence, or polyvictims. Evidence strongly suggests that polyvictimized youth tend to have worse physical and mental health outcomes than those who have experienced single forms of violence. Moreover, minoritized youth (i.e., racial and/or sexual minority youth, youth with disabilities) are more likely to experience polyvictimization, making this a social justice and equity concern. To date, there is no universal consensus on what exactly constitutes polyvictimization. This systematic review aims to examine the ways in which polyvictimization is being studied to inform both research and practice. As such, relevant databases were searched to amass the extant literature related to youth polyvictimization internationally. Empirical studies published since 2006 that focused on youth (under age 18) polyvictimization were included. After the review process, 264 studies met eligibility criteria, however 55 studies employed person-centered/finite mixture analyses and were removed for a separate review, resulting in 209 featured in the current systematic review. Results demonstrate that researchers are defining and operationalizing polyvictimization in different ways: (a) using individual victimization event counts; (b) employing domain-based counts; and (c) taking a "highest-victimized" percentage of their sample. The most used measurement tool was the Juvenile Victimization Questionnaire, though other validated tools and researcher-constructed questions were frequently utilized. Research on polyvictimization is burgeoning worldwide; however, this research is being conducted in disparate ways, making it difficult to compare findings and further advance the field.

Prenatal diagnosis of PORCN-related developmental syndrome in a fetus: A novel phenotype.

We report a case of a female fetus born to an unrelated couple with a complex fetal phenotype of a pleural effusion, a cardiac malformation, and syndactyly of the toes. Prenatal exome sequencing identified a variant of uncertain significance in the PORCN gene that was upgraded to likely pathogenic following postnatal clinical examination. The phenotype described in cases with variants in the PORCN gene is often associated with findings that cannot be prospectively diagnosed by ultrasonography. This is the first report of a prenatal phenotype involving a fetal effusion associated with variants in the PORCN gene, with skeletal findings identified later in gestation on ultrasonography. The diagnosis was confirmed on neonatal examination.

Supporting the Mental Health Needs of Community College Students.

The United States faces an unprecedented mental health crisis, with youth and young adults at the center. Even before the COVID-19 pandemic, nearly 50 percent of college students reported at least one mental health concern. The COVID-19 pandemic notably exacerbated these issues and underscored the urgent need to identify and implement ways to ameliorate the youth mental health crisis. In 2021, the National Academies of Sciences, Engineering, and Medicine called on the field of higher education to address growing concerns about student mental health by identifying and elevating emerging and promising approaches that offer a more holistic way to support students' mental health. Serving as the main entry point for more than 40 percent of students seeking a postsecondary degree, community colleges represent a tremendous and untapped opportunity to better address mental health in the United States, particularly for students who have been traditionally underserved (e.g., students of color, first-generation students, and low-income students). However, community colleges have limited evidence and guidance to inform the implementation of multilevel, holistic approaches to support students with varying mental health needs. To address this knowledge gap, this article shares a descriptive study of eight community colleges at the forefront of implementing multilevel approaches (a combination of prevention, early intervention, and treatment services) to support student mental health, as well as key facilitators for and barriers to their success.

Relationships between internalized stigma and depression and suicide risk among queer youth in the United States: a systematic review and meta-analysis.

Background: Queer youth experience high rates of depression and suicidality. These disparities stem from stigma-based stressors, including internalized stigma (i.e., negative social views that minoritized individuals internalize about their own identity). Given the importance of this factor in understanding mental health disparities among queer youth, we completed a systematic review and meta-analysis examining the relationships between internalized stigma and outcomes of depression and suicide risk (i.e., suicidal ideation, non-suicidal self-injury, and suicidal behavior). Methods: We followed the PRISMA standards. Six bibliographic databases were searched for studies in the United States from September 2008 to March 2022. Dual independent screening of search results was performed based on a priori inclusion criteria. Results: A total of 22 studies were included for data extraction and review. Most studies examined general internalized homophobia, with few examining internalized biphobia or transphobia. Many studies examined depression as an outcome, few studies examined suicidal ideation or behavior, and no studies examined non-suicidal self-injury. Meta-analyses model results show the association between general internalized queer stigma and depressive symptoms ranged r = 0.19, 95% CI [0.14, 0.25] to r = 0.24, 95% CI [0.19, 0.29], the latter reflecting more uniform measures of depression. The association between internalized transphobia and depressive outcomes was small and positive (r = 0.21, 95% CI [-0.24, 0.67]). General internalized queer stigma and suicidal ideation had a very weak positive association (r = 0.07, 95% CI [-0.27, 0.41]) and an even smaller, weaker positive association with suicide attempt (r = 0.02, 95% CI [0.01, 0.03]). Conclusion: Implications for clinical practice, policy, and future research are discussed.

Prenatal diagnosis of CLCN4-related neurodevelopmental disorder in fetuses with congenital brain anomalies.

We report two male fetuses born to a healthy unrelated couple, with agenesis of the corpus callosum identified on detailed 20-week ultrasound scans and confirmed by in-utero MRI. Whole-genome sequencing identified a likely pathogenic missense variant in the CLCN4 gene, establishing this as the causative gene in the family. Pathogenic variants in the CLCN4 gene cause a neurodevelopmental disorder (also called Raynaud-Claes syndrome) inherited in an X-linked pattern. The disorder is characterised by developmental delay, intellectual disability, autism spectrum disorder, epilepsy, mental health conditions, and significant feeding difficulties, predominantly, but not exclusively, affecting males. This is the first report of a prenatal phenotype associated with variants in the CLCN4 gene. The diagnosis of the CLCN4-related neurodevelopmental disorder in this family allowed accurate genetic counseling and discussion of reproductive choices. This leaves uncertainty about the possibility of a postnatal neurodevelopmental phenotype in heterozygous females, which we discuss.

Leadership Coaching in Surgical Residency: Reasons for Referral and Topics Addressed to Improve Nontechnical Skill.

PURPOSE: Professional coaching has been utilized in the military and private sector with a long track record of optimizing efficiency, improving high-functioning team performance, and creating greater satisfaction among the workforce. Recent studies in physician populations have suggested that coaching may protect healthcare providers from burnout and improve quality of life and resilience. The aims of the current study were to describe our single-institution experience with the introduction of a leadership coaching program among surgical residents and to characterize the nature of the common reasons for referral for coaching. METHODS: Upon identification by program faculty that a resident would benefit from coaching, an email was sent from the program director to the coach to establish contact between the coach and resident, with a brief synopsis of the factors that lead to the resident being referred for coaching. The study team obtained deidentified, simplified synopses of the initial email correspondences from program leadership reaching out to residents to refer them to coaching. Common recurring themes were quantified. Later, coaches reviewed their notes kept during coaching sessions and, in a similar fashion, identified topics discussed and skills developed in coaching sessions for each resident. Topics were summarized for each resident, and a deidentified list of residents and the themes reviewed in coaching were provided to the study team, who quantified these topics. Baseline demographic information on the resident cohort, including training level, gender, and number of repeat referrals were summarized to delineate differences in patterns of repeat referral and attrition. RESULTS: This study was conducted within the general surgery residency program at a single academic medical center, composed of 43 categorical and 8 preliminary residents. Over a 2.5-year period, 21 residents were referred: 5 chief, 8 senior, 5 midlevel, and 3 junior (1 preliminary) residents. Male residents represented 2/3 and female residents 1/3 of the total number of referrals. There were 3 repeat referrals, 2 male and 1 female. We identified 2 overarching reasons for which residents were referred for coaching: request for structured leadership training and request for communication training. Six themes were identified upon review of referrals for coaching. Among these were the need for improved communication, methods to improve team integration, tools to balance professional and personal responsibilities, and practices to improve confidence and assertiveness. Through the coaching relationship, residents reviewed deficits and received an individualized plan to address newly identified problem areas. Upon initiation of coaching, new themes like anxiety management, emotional intelligence, and cultural acclimatization were identified. During each coaching session, residents participate in exercises designed to build habits of effective listening, communication, and conflict resolution. CONCLUSIONS: Coaching in surgical residency provides a structured program for residents to develop skills in planning and orchestrating team operations, listening and communicating effectively, mitigating conflict, and managing professional and personal responsibilities. Follow-up studies will focus on the long-term effects of professional coaching, evaluating survey data from self-assessments and professional evaluations.

Improving outcomes of childhood and young adult non-Hodgkin lymphoma: 25 years of research and collaboration within the framework of the European Intergroup for Childhood Non-Hodgkin Lymphoma.

The European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) was established 25 years ago with the goal to facilitate clinical trials and research collaborations in the field both within Europe and worldwide. Since its inception, much progress has been made whereby major improvements in outcomes have been achieved. In this Review, we describe the different diagnostic entities of non-Hodgkin lymphoma in children and young adults describing key features of each entity and outlining clinical achievements made in the context of the EICNHL framework. Furthermore, we provide an overview of advances in biopathology with an emphasis on the role of biological studies and how they have shaped available treatments. Finally, for each entity, we describe future goals, upcoming clinical trials, and highlight areas of research that require our focus going forward.

Prenatal next-generation sequencing in the fetus with congenital malformations: how can we improve clinical utility?

Fetal malformations have a variable prognosis that may be influenced by the detection of an underlying monogenic etiology. The careful detection and selection of fetal phenotypes and the use of prenatal next-generation sequencing with robust bioinformatic pathways and variant selection have improved the clinical utility and impact of genetic testing.

The Postpandemic Nursing Workforce: Increasing Fill Rates and Reducing Workload Through a Generational Design of Workforce Layers.

Inequities between nursing workforce supply and demand continue to challenge nurse executives in creating the vision for a postpandemic nursing workforce. Health system's workforce redesign strategies must prioritize the changing needs of the multigenerational workforce to maximize the available supply of nurses willing to remain in the workforce. A test of a newly designed flexible workforce framework, aimed to meet the needs of the multigenerational workforce, resulted in increased fill rates and decreased costs of labor.

An Effective Response to Healthcare Disparities Begins With a Strategic Plan.

For too long, healthcare disparities have negatively affected underrepresented groups in urban areas throughout the United States. Disparities in care and outcomes related to social determinants were known, and efforts were made to address them. Effective change for all moved up to top priority in the wake of COVID-19's arrival, police brutality, social unrest, and the murders of Black Americans, including George Floyd. Henry Ford Health (HFH), working with leading local community organizations, immediately pledged to address social and racial injustices. Unfortunately, many neighborhoods still suffer disproportionately from maternal and infant mortality, food insecurity, and other social vulnerabilities. HFH's commitment to equity includes creatively meeting the needs of the underserved. HFH has developed innovative ways to address the social, economic, and educational challenges to the health of Metro Detroit. Through thoughtful consideration and passionate leadership, HFH is strategically creating authentic and scalable social change to address racism and discrimination in healthcare.

Next Generation Sequencing after Invasive Prenatal Testing in Fetuses with Congenital Malformations: Prenatal or Neonatal Investigation.

Congenital malformations diagnosed by ultrasound screening complicate 3-5% of pregnancies and many of these have an underlying genetic cause. Approximately 40% of prenatally diagnosed fetal malformations are associated with aneuploidy or copy number variants, detected by conventional karyotyping, QF-PCR and microarray techniques, however monogenic disorders are not diagnosed by these tests. Next generation sequencing as a secondary prenatal genetic test offers additional diagnostic yield for congenital abnormalities deemed to be potentially associated with an underlying genetic aetiology, as demonstrated by two large cohorts: the 'Prenatal assessment of genomes and exomes' (PAGE) study and 'Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study' performed at Columbia University in the US. These were large and prospective studies but relatively 'unselected' congenital malformations, with little Clinical Genetics input to the pre-test selection process. This review focuses on the incremental yield of next generation sequencing in single system congenital malformations, using evidence from the PAGE, Columbia and subsequent cohorts, with particularly high yields in those fetuses with cardiac and neurological anomalies, large nuchal translucency and non-immune fetal hydrops (of unknown aetiology). The total additional yield gained by exome sequencing in congenital heart disease was 12.7%, for neurological malformations 13.8%, 13.1% in increased nuchal translucency and 29% in non-immune fetal hydrops. This demonstrates significant incremental yield with exome sequencing in single-system anomalies and supports next generation sequencing as a secondary genetic test in routine clinical care of fetuses with congenital abnormalities.

WFS1 protein expression correlates with clinical progression of optic atrophy in patients with Wolfram syndrome.

BACKGROUND: Wolfram syndrome (WFS) is a rare disorder characterised by childhood-onset diabetes mellitus and progressive optic atrophy. Most patients have variants in the WFS1 gene. We undertook functional studies of WFS1 variants and correlated these with WFS1 protein expression and phenotype. METHODS: 9 patients with a clinical diagnosis of WFS were studied with quantitative PCR for markers of endoplasmic reticulum (ER) stress and immunoblotting of fibroblast protein extracts for WFS1 protein expression. Luciferase reporter assay was used to assess ATF-6 dependent unfolded protein response (UPR) activation. RESULTS: 6 patients with compound heterozygous nonsense mutations in WFS1 had no detectable WFS1 protein expression; 3 patients with missense variants had 4%, 45% and 48% WFS1 protein expression. One of these also had an OPA1 mutation and was reclassified as autosomal dominant optic atrophy-plus syndrome. There were no correlations between ER stress marker mRNA and WFS1 protein expression. ERSE-luciferase reporter indicated activation of the ATF6 branch of UPR in two patients tested. Patients with partial WFS1 expression showed milder visual acuity impairment (asymptomatic or colour blind only), compared with those with absent expression (registered severe vision impaired) (p=0.04). These differences remained after adjusting for duration of optic atrophy. CONCLUSIONS: Patients with WFS who have partial WFS1 protein expression present with milder visual impairment. This suggests a protective effect of partial WFS1 protein expression on the severity and perhaps progression of vision impairment and that therapies to increase residual WFS1 protein expression may be beneficial.

Decontamination of metals from firefighter turnout gear.

Firefighters are exposed to many different contaminants during structural fires. Moreover, if their protective gear is not successfully decontaminated, firefighters are at risk of being repeatedly exposed to contaminants from previous fires. Thus, the successful removal of contaminants from firefighter turnout gear is necessary to prevent or reduce repeated exposure risks. Laundering methods can reduce the probability of re-exposure to contaminants, such as heavy metals, thus reducing repeated exposure risks. In this study, the efficiencies of heavy metal removal from the firefighter turnout gear outer textile by Decon7 cleaning solution and a standard reference detergent were compared. Nitric acid digests were used to extract metals from textile samples, which were cut from small sections of firefighter jackets, before and after their laundering with either cleaning solution. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to determine metal contents, including arsenic (As), antimony (Sb), cadmium (Cd), chromium (Cr), and lead (Pb) concentrations. Results from multiplicate samples indicated that, on average, Decon7 was significantly more efficient than a standard detergent in decreasing the concentrations of the five metals studied herein.

An Integrated Conceptual Model to Understand Suicidality among Queer Youth to Inform Suicide Prevention.

In this article, we apply and combine elements from four theoretical frameworks (i.e., Minority Stress Theory, Person-in-Environment and Risk and Resilience Framework, Interpersonal-Psychological Theory of Suicide, and Intersectionality) to explain the problem of queer youth suicide through our integrated conceptual model, Queer Prevention of Youth Suicidality Model (Queer-PRYSM). The need for this conceptual model is based on the current state of the literature, including mixed empirical findings on factors related to queer youth suicidality, no scholarly consensus on specific contributing factors regarding high rates of suicidality among queer youth (including queer youth subgroups), and the absence of a unifying theory to explain the queer youth suicide risk. To address these limitations in theory, evidence, and scholarship explaining suicidality among queer youth we present our integrated model with growing, current, relevant research with queer youth. Queer-PRYSM includes minority stressors specific to queer youth, mental health problems, interpersonal-psychological factors, socioecological factors (i.e., family, school, peers, and community), and intersectionality concepts. Queer-PRYSM is essential to understanding the relationship of distal and proximal risk and protective factors in queer youth suicide and developing evidence-informed suicide preventive interventions that can be incorporated into practice, policy, and system structures.

Suicide Postvention in Schools: What Evidence Supports Our Current National Recommendations?

Suicide is a leading cause of death for school-aged preteens and adolescents and a growing risk for younger children. Schools are the ubiquitous institutional context serving this age group. These trends suggest a need for knowledge and guidance related to school postvention efforts, yet the available research is limited. Focusing on postvention, or the period after a peer suicide occurs, is critical to youth suicide prevention because this is a time of elevated suicide risk for youth. Targeted postvention interventions in schools can mitigate youth suicide risk and limit contagion within a school's student body. This article explores the scientific literature related to school-based suicide postvention, describing the strength and limits of research supporting common recommendations for suicide postvention in schools. It identifies widespread recommendations for school postvention that have only preliminary supportive evidence and notes several areas in need of additional research. With clearer postvention best practices to guide their suicide crisis preparedness plans and postvention procedures, schools can better support students, families, and the community as a whole in order to prevent further tragedies.

Bacteria Associated with Healthcare-Associated Infections on Environmental Samples Obtained from Two Fire Departments.

(1) Background: Firefighters spend about 64% of their time responding to medical emergencies and providing medical care without a patient history, which can render them vulnerable to healthcare-associated infections (HAI). Infection prevention, control, and surveillance systems have been instituted at hospitals. However, the prevalence of firefighters' exposure to HAI is unknown. The objective of this study was to document evidence of HAI on surfaces in fire stations and engines to inform disinfection procedures and identify which pathogens might contribute to occupational exposures. (2) Methods: High-touch or high-use surfaces of two fire departments were sampled during five separate occasions. One fire station from one fire department was sampled over a 4-week period, whereas four fire stations were sampled from a different fire department only once. Sampled surfaces included: entryway floor, washing machine, medical bag, back seat of engine, keyboard of reporting computer, engine console, and uniform pants. (3) Results: Multiple statistical models determined that bacterial contamination was similar between the two fire departments and their stations. Keyboards were the most contaminated surface for all fire stations and departments, E. coli was the most common bacteria detected, and C. difficile was the least detected bacteria. Adjustments for rates of contamination found that contamination rates varied between fire stations. (4) Conclusions: Comprehensive environmental sampling and clinical studies are needed to better understand occupational exposures of firefighters to HAI.

The prenatal exome - a door to prenatal diagnostics?

Introduction: Prenatal exome sequencing (ES) allows parents the opportunity to obtain arapid molecular diagnosis of monogenic etiology when their fetus is found to have structural anomalies detected on prenatal ultrasound. Such information can improve antenatal and neonatal counseling, decision-making and management, and expand reproductive options in subsequent pregnancies.Areas covered: This review appraises the evidence, from acomprehensive search of bibliographic databases, for the introduction of ES into the fetal medicine care pathway when investigating congenital malformations. The perspectives of clinical geneticists, clinical scientists, fetal medicine specialists, and patients are explored in relation to the novel investigation and the benefits and challenges of its use in ongoing pregnancies with particular reference to UK medical practice.Expert opinion: ES provides agenetic diagnosis for more than 1 in 10 fetuses with structural differences on ultrasound and normal conventional tests (karyotype or chromosomal microarray) in carefully selected cases. The diagnostic rate increases for certain phenotypes and can range between 6% and 80% where conventional cytogenetics have not detected adiagnosis. Expert oversight is required to ensure that patients receive high-quality, evidence-based care and accurate counseling, supported by amultidisciplinary team familiar with the test and its implications.

Redesign of hydrophobic quantum dots mitigates ligand-dependent toxicity in the nematode C. elegans.

Surface properties of engineered nanomaterials (ENMs) have been shown to influence their interaction with biological systems. However, studies to date have largely focused on hydrophilic materials, likely due to biocompatibility concerns and aqueous exposure conditions necessary for many model systems. Therefore, a knowledge gap exists in nanotoxicity literature for impacts of hydrophobic ENMs, with studies of hydrophobic materials largely limited to carbon ENMs. Here we demonstrate testing of hydrophobic quantum dots (QDs) using the nematode C. elegans, a model soil organism cultured on solid media and amenable to hydrophobic exposures. To evaluate the influence of hydrophobicity, we compared CdSe/ZnS QDs functionalized with hydrophobic trioctylphosphine oxide (TOPO) to identical QDs functionalized with hydrophilic dihydrolipoic acid-polyethylene glycol (DHLA-PEG) and alternative hydrophobic CdSe/ZnS QDs functionalized with oleic acid (OA). Results show that hydrophobic TOPO QDs are significantly more toxic than hydrophilic DHLA-PEG QDs, and substitution of TOPO with OA yields relatively non-toxic hydrophobic QDs. Fluorescence microscopy shows TOPO QDs loosely associated with the organism's cuticle, but atomic force microscopy shows no difference in cuticle structure from exposure. Importantly, TOPO ligand alone is as toxic as TOPO QDs, and our data suggests that TOPO may impact neuromuscular function, perhaps upon displacement from the QD surface. This study demonstrates the importance of examining ligand-specific impacts of hydrophobic ENMs and indicates OA-functionalized QDs as a potential alternative to TOPO QDs for reduced toxicity.