Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life.

BACKGROUND: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). METHODS: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. RESULTS: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). CONCLUSIONS: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Cholesterol Lowering in Older Adults: Should We Wait for Further Evidence?

PURPOSE OF REVIEW: Current guidelines for primary and secondary prevention of cardiovascular events in adults up to age 75 years are well-established. However, recommendations for lipid-lowering therapies (LLT), particularly for primary prevention, are inconclusive after age 75. In this review, we focus on adults ≥ 75 years to assess low-density lipoprotein-cholesterol (LDL-C) as a marker for predicting atherosclerotic cardiovascular disease (ASCVD) risk, review risk assessment tools, highlight guidelines for LLT, and discuss benefits, risks, and deprescribing strategies. RECENT FINDINGS: The relationship between LDL-C and all-cause mortality and cardiovascular outcomes in older adults is complex and confounded. Current ASCVD risk estimators heavily depend on age and lack geriatric-specific variables. Emerging tools may reclassify individuals based on biologic rather than chronologic age, with coronary artery calcium scores gaining popularity. After initiating LLT for primary or secondary prevention, target LDL-C levels for older adults are lacking, and non-statin therapy thresholds remain unknown, relying on evidence from younger populations. Shared decision-making is crucial, considering therapy's time to benefit, life expectancy, adverse events, and geriatric syndromes. Deprescribing is recommended in end-of-life care but remains unclear in fit or frail older adults. After an ASCVD event, LLT is appropriate for most older adults, and deprescribing can be considered for those approaching the last months of life. Ongoing trials will guide statin prescription and deprescribing among older adults free of ASCVD. In the interim, for adults ≥ 75 years without a limited life expectancy who are free of ASCVD, an LLT approach that includes both lifestyle and medications, specifically statins, may be considered after shared decision-making.

Glial fibrillary acidic protein, neurofilament light, matrix metalloprotease 3 and fatty acid binding protein 4 as non-invasive brain tumor biomarkers.

BACKGROUND: Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival. METHODS: Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays. RESULTS: High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas. CONCLUSIONS: GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.

Distribution of Silent Cerebral Infarcts in Adults With Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: Previously we demonstrated that 90% of infarcts in children with sickle cell anemia occur in the border zone regions of cerebral blood flow (CBF). We tested the hypothesis that adults with sickle cell disease (SCD) have silent cerebral infarcts (SCIs) in the border zone regions, with a secondary hypothesis that older age and traditional stroke risk factors would be associated with infarct occurrence in regions outside the border zones. METHODS: Adults with SCD 18-50 years of age were enrolled in a cross-sectional study at 2 centers and completed a 3T brain MRI. Participants with a history of overt stroke were excluded. Infarct masks were manually delineated on T2-fluid-attenuated inversion-recovery MRI and registered to the Montreal Neurological Institute 152 brain atlas to generate an infarct heatmap. Border zone regions between anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA) were quantified using the Digital 3D Brain MRI Arterial Territories Atlas, and logistic regression was applied to identify relationships between infarct distribution, demographics, and stroke risk factors. RESULTS: Of 113 participants with SCD (median age 26.1 years, interquartile range [IQR] 21.6-31.4 years, 51% male), 56 (49.6%) had SCIs. Participants had a median of 5.5 infarcts (IQR 3.2-13.8). Analysis of infarct distribution showed that 350 of 644 infarcts (54.3%) were in 4 border zones of CBF and 294 (45.6%) were in non-border zone territories. More than 90% of infarcts were in 3 regions: the non-border zone ACA and MCA territories and the ACA-MCA border zone. Logistic regression showed that older participants have an increased chance of infarcts in the MCA territory (odds ratio [OR] 1.08; 95% CI 1.03-1.13; p = 0.001) and a decreased chance of infarcts in the ACA-MCA border zone (OR 0.94; 95% CI 0.90-0.97; p < 0.001). The presence of at least 1 stroke risk factor did not predict SCI location in any model. DISCUSSION: When compared with children with SCD, in adults with SCD, older age is associated with expanded zones of tissue infarction that stretch beyond the traditional border zones of CBF, with more than 45% of infarcts in non-border zone regions.

The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies.

BACKGROUND: Certain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case. METHODS: To elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed. RESULTS: GFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80. CONCLUSION: The 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG.

The Journey of Engaging With Web-Based Self-Harm and Suicide Content: Longitudinal Qualitative Study.

BACKGROUND: Self-harm and suicide are major public health concerns worldwide, with attention focused on the web environment as a helpful or harmful influence. Longitudinal research on self-harm and suicide-related internet use is limited, highlighting a paucity of evidence on long-term patterns and effects of engaging with such content. OBJECTIVE: This study explores the experiences of people engaging with self-harm or suicide content over a 6-month period. METHODS: This study used qualitative and digital ethnographic methods longitudinally, including one-to-one interviews at 3 time points to explore individual narratives. A trajectory analysis approach involving 4 steps was used to interpret the data. RESULTS: The findings from 14 participants established the web-based journey of people who engage with self-harm or suicide content. In total, 5 themes were identified: initial interactions with self-harm or suicide content, changes in what self-harm or suicide content people engage with and where, changes in experiences of self-harm or suicide behaviors associated with web-based self-harm or suicide content engagement, the disengagement-reengagement cycle, and future perspectives on web-based self-harm or suicide content engagement. Initial engagements were driven by participants seeking help, often when offline support had been unavailable. Some participants' exposure to self-harm and suicide content led to their own self-harm and suicide behaviors, with varying patterns of change over time. Notably, disengagement from web-based self-harm and suicide spaces served as a protective measure for all participants, but the pull of familiar content resulted in only brief periods of disconnection. Participants also expressed future intentions to continue returning to these self-harm and suicide web-based spaces, acknowledging the nonlinear nature of their own recovery journey and aiming to support others in the community. Within the themes identified in this study, narratives revealed that participants' behavior was shaped by cognitive flexibility and rigidity, metacognitive abilities, and digital expertise. Opportunities for behavior change arose during periods of cognitive flexibility prompted by life events, stressors, and shifts in mental health. Participants sought diverse and potentially harmful content during challenging times but moved toward recovery-oriented engagements in positive circumstances. Metacognitive and digital efficacy skills also played a pivotal role in participants' control of web-based interactions, enabling more effective management of content or platforms or sites that posed potential harms. CONCLUSIONS: This study demonstrated the complexity of web-based interactions, with beneficial and harmful content intertwined. Participants who demonstrated metacognition and digital efficacy had better control over web-based engagements. Some attributed these skills to study processes, including taking part in reflective diaries, showing the potential of upskilling users. This study also highlighted how participants remained vulnerable by engaging with familiar web-based spaces, emphasizing the responsibility of web-based industry leaders to develop tools that empower users to enhance their web-based safety.

Comparison of cerebral oxygen extraction fraction using ASE and TRUST methods in patients with sickle cell disease and healthy controls.

Abnormal oxygen extraction fraction (OEF), a putative biomarker of cerebral metabolic stress, may indicate compromised oxygen delivery and ischemic vulnerability in patients with sickle cell disease (SCD). Elevated OEF was observed at the tissue level across the brain using an asymmetric spin echo (ASE) MR method, while variable global OEFs were found from the superior sagittal sinus (SSS) using a T2-relaxation-under-spin-tagging (TRUST) MRI method with different calibration models. In this study, we aimed to compare the average ASE-OEF in the SSS drainage territory and TRUST-OEF in the SSS from the same SCD patients and healthy controls. 74 participants (SCD: N = 49; controls: N = 25) underwent brain MRI. TRUST-OEF was quantified using the Lu-bovine, Bush-HbA and Li-Bush-HbS models. ASE-OEF and TRUST-OEF were significantly associated in healthy controls after controlling for hematocrit using the Lu-bovine or the Bush-HbA model. However, no association was found between ASE-OEF and TRUST-OEF in patients with SCD using either the Bush-HbA or the Li-Bush-HbS model. Plausible explanations include a discordance between spatially volume-averaged oxygenation brain tissue and flow-weighted volume-averaged oxygenation in SSS or sub-optimal calibration in SCD. Further work is needed to refine and validate non-invasive MR OEF measurements in SCD.

Exploring the factors affecting classification and reporting of uncertain prenatal microarray findings, using a "virtual fetus" model-a pilot study.

OBJECTIVE: Significant discrepancy exists between laboratories in classification and reporting of copy number variants (CNVs). Studies exploring factors affecting prenatal CNV management are rare. Our "virtual fetus" pilot study examines these factors. METHOD: Ten prenatally diagnosed CNVs of uncertain significance (VUS) > 1Mb, encompassing OMIM-morbid genes, inherited from healthy parents, were classified by 15 MD geneticists from laboratory, prenatal, and preimplantation genetic testing (PGT) units. Geneticists addressed factors affecting classification, obligation to report, and recommendation for invasive testing or PGT. RESULTS: CNVs were classified likely benign (10.7%), VUS (74.7%), likely pathogenic (8.7%), or pathogenic (6.0%). Classification discrepancy was higher for losses versus gains. Classifying pathogenic/likely pathogenic was more common for losses (adjusted odds ratio [aOR] 10.9, 95% CI 1.55-76.9), and geneticists specializing in gynecology (aOR 4.9, 95% CI 1.03-23.3). 84.0% of respondents would report CNVs, depending on classification and family phenotype. Invasive testing in pregnancies was recommended for 29.3% of CNVs, depending on the classification and geneticist's specialization. PGT was recommended for 32.4%, depending on classification, experience years, and family's phenotype (38.0% for patients undergoing in vitro fertilization irrespectively, 26.7% otherwise). CONCLUSION: Factors affecting CNV classification/reporting are mainly dosage, family phenotype, geneticist specialization and experience. Understanding factors from our pilot study may facilitate developing an algorithm for clinical consensus and optimal management.

Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy.

The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile). In patient-derived fibroblasts, bi-allelic SNF8 variants cause loss of ESCRT-II subunits. Snf8 loss of function in zebrafish results in global developmental delay and altered embryo morphology, impaired optic nerve development, and reduced forebrain size. In vivo experiments corroborated the pathogenicity of the tested SNF8 variants and their variable impact on embryo development, validating the observed clinical heterogeneity. Taken together, we conclude that loss of ESCRT-II due to bi-allelic SNF8 variants is associated with a spectrum of neurodevelopmental/neurodegenerative phenotypes mediated likely via impairment of the autophagic flux.

Laboratory Evolution of Metalloid Reductase Substrate Recognition and Nanoparticle Product Size.

Glutathione reductase-like metalloid reductase (GRLMR) is an enzyme that reduces selenodiglutathione (GS-Se-SG), forming zerovalent Se nanoparticles (SeNPs). Error-prone polymerase chain reaction was used to create a library of ∼10,000 GRLMR variants. The library was expressed in BL21Escherichia coli in liquid culture with 50 mM of SeO32- present, under the hypothesis that the enzyme variants with improved GS-Se-SG reduction kinetics would emerge. The selection resulted in a GRLMR variant with two mutations. One of the mutations (D-E) lacks an obvious functional role, whereas the other mutation is L-H within 5 Šof the enzyme active site. This mutation places a second H residue within 5 Šof an active site dicysteine. This GRLMR variant was characterized for NADPH-dependent reduction of GS-Se-SG, GSSG, SeO32-, SeO42-, GS-Te-SG, and TeO32-. The evolved enzyme demonstrated enhanced reduction of SeO32- and gained the ability to reduce SeO42-. This variant is named selenium reductase (SeR) because of its emergent broad activity for a wide variety of Se substrates, whereas the parent enzyme was specific for GS-Se-SG. This study overall suggests that new biosynthetic routes are possible for inorganic nanomaterials using laboratory-directed evolution methods.

Neural control of reproduction in reptiles.

Reptiles display considerable diversity in reproductive behavior, making them great models to study the neuroendocrine control of reproductive behavior. Many reptile species are seasonally breeding, such that they become reproductively active during their breeding season and regress to a nonreproductive state during their nonbreeding season, with this transition often prompted by environmental cues. In this review, we will focus on summarizing the neural and neuroendocrine mechanisms controlling reproductive behavior. Three major areas of the brain are involved in reproductive behavior: the preoptic area (POA), amygdala, and ventromedial hypothalamus (VMH). The POA and VMH are sexually dimorphic areas, regulating behaviors in males and females respectively, and all three areas display seasonal plasticity. Lesions to these areas disrupt the onset and maintenance of reproductive behaviors, but the exact roles of these regions vary between sexes and species. Different hormones influence these regions to elicit seasonal transitions. Circulating testosterone (T) and estradiol (E2) peak during the breeding season and their influence on reproduction is well-documented across vertebrates. The conversion of T into E2 and 5α-dihydrotestosterone can also affect behavior. Melatonin and corticosterone have generally inhibitory effects on reproductive behavior, while serotonin and other neurohormones seem to stimulate it. In general, there is relatively little information on the neuroendocrine control of reproduction in reptiles compared to other vertebrate groups. This review highlights areas that should be considered for future areas of research.

COVID-19 Recovery: Consistent Absence of Cerebrospinal Fluid Biomarker Abnormalities in Patients With Neurocognitive Post-COVID Complications.

BACKGROUND: To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC). METHODS: Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination, lumbar puncture, and venipuncture ≥3 months after COVID-19 symptom onset. Healthy volunteers were included. CSF and plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike antigen (N-Ag, S-Ag), and CSF biomarkers of immune activation and neuronal injury were analyzed. RESULTS: SARS-CoV-2 N-Ag or S-Ag were undetectable in all samples and no participant had pleocytosis. We detected no significant differences in CSF and plasma cytokine concentrations, albumin ratio, IgG index, neopterin, ß2M, or in CSF biomarkers of neuronal injury and astrocytic damage. Furthermore, principal component analysis (PCA1) analysis did not indicate any significant differences between the study groups in the marker sets cytokines, neuronal markers, or anti-cytokine autoantibodies. CONCLUSIONS: We found no evidence of ongoing viral replication, immune activation, or CNS injury in plasma or CSF in patients with neurocognitive PCC compared with COVID-19 controls or healthy volunteers, suggesting that neurocognitive PCC is a consequence of events suffered during acute COVID-19 rather than persistent viral CNS infection or residual CNS inflammation.

Acute glomerulonephritis with concurrent suspected bacterial pneumonia - is it the tip of the iceberg?

BACKGROUND: Post infectious glomerulonephritis is the most common glomerulopathy in children, occurring several weeks after nephritogenic streptococcal throat or skin infection. Reports of acute glomerulonephritis (AGN) occurring during active bacterial pneumonia in children are rare. The aim of this study was to evaluate the incidence of AGN concurrent with bacterial pneumonia in children. METHODS: We reviewed records of all children admitted with a diagnosis of pneumonia to the pediatric department in a single tertiary medical center between January 2015 and April 2023. Patients with bacterial pneumonia and concurrent glomerulonephritis were included. RESULTS: Eleven (0.98%) of 1,123 patients with bacterial pneumonia had concurrent AGN. All were males with a median age of 2.7 years (range 1-13). Mean time from bacterial pneumonia onset to acute glomerulonephritis symptoms was 2.7 ± 1.5 days. Five (45%) patients had evidence of pneumococcal infection. Hypertension was found in 10 (91%) patients. Mean trough eGFR was 43.5 ± 21.4 ml/min/1.73 m2 (range 11-73). Ten patients (91%) had low C3 levels. Median urinary protein-to-creatinine ratio was 2.5 mg/mg (IQR 2.15-14.75). All patients fully recovered. Microscopic hematuria was the last finding to normalize after a median of 29.5 days (IQR 17.25-38). CONCLUSION: AGN during bacterial pneumonia may be more frequent than previously recognized. Kidney prognosis was excellent in all patients. Prospective studies are needed to evaluate the impact of this condition.

Validity of Clinical Severity Scores for Respiratory Syncytial Virus: A Systematic Review.

BACKGROUND: Respiratory syncytial virus (RSV) is a widespread respiratory pathogen, and RSV-related acute lower respiratory tract infections are the most common cause of respiratory hospitalization in children <2 years of age. Over the last 2 decades, a number of severity scores have been proposed to quantify disease severity for RSV in children, yet there remains no overall consensus on the most clinically useful score. METHODS: We conducted a systematic review of English-language publications in peer-reviewed journals published since January 2000 assessing the validity of severity scores for children (≤24 months of age) with RSV and/or bronchiolitis, and identified the most promising scores. For included articles, (1) validity data were extracted, (2) quality of reporting was assessed using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis checklist (TRIPOD), and (3) quality was assessed using the Prediction Model Risk Of Bias Assessment Tool (PROBAST). To guide the assessment of the validity data, standardized cutoffs were employed, and an explicit definition of what we required to determine a score was sufficiently validated. RESULTS: Our searches identified 8541 results, of which 1779 were excluded as duplicates. After title and abstract screening, 6670 references were excluded. Following full-text screening and snowballing, 32 articles, including 31 scores, were included. The most frequently assessed scores were the modified Tal score and the Wang Bronchiolitis Severity Score; none of the scores were found to be sufficiently validated according to our definition. The reporting and/or design of all the included studies was poor. The best validated score was the Bronchiolitis Score of Sant Joan de Déu, and a number of other promising scores were identified. CONCLUSIONS: No scores were found to be sufficiently validated. Further work is warranted to validate the existing scores, ideally in much larger datasets.

The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies.

Background: Certain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case. Methods: To elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed. Results: GFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80. Conclusion: The 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG.

Parenting and family self-sufficiency services contribute to impacts of Early Head Start for children and families.

Introduction: There is evidence that two-generation early childhood programs, those that strive to support not only child development, but also optimal parenting and family wellbeing, help to foster resilience for young children and their families in the face of adversity. Methods: Using data from a large experimental evaluation, the Early Head Start Research and Evaluation Project, this paper explores how parenting and family self-sufficiency services embedded in Early Head Start (EHS), a federally funded, nationally implemented two-generation early childhood program for low-income families lasting from pregnancy and until children are three, contribute to the impacts of the program for both the children and their families. Results: Parenting support in any modality (home visiting, case management or parent education) contributed to program impacts on important child and family outcomes, but not parent employment. Somewhat surprisingly, family receipt of employment services did not lead to any of the impacts of the program, while education and job training services did. When EHS parents received education or job training services, it led to impacts not only on mother employment, but also on other important family and child outcomes. Discussion: These findings validate and reinforce the two-generation approach of EHS, specifically supporting the focus on parenting and parent education and job training.

Development of a Brief Intervention for Emergency Department Attendees Presenting With Self-Harm and Co-Occurring Substance Use Problems.

Background: People who present to the emergency department with self-harm and co-occurring substance use problems often have difficulty accessing effective care. Aims: To develop a brief psychosocial intervention for this population, which would be suitable for testing in a future randomized controlled trial. Methods: A modified Delphi method was used. A 34-item, 3-round, online Delphi survey was informed by a literature review and stakeholder telephone discussions (n = 17). Two panels consisting of people with lived experience (PWLE: n = 15) and people with occupational experience (PWOE: n = 21) participated in the survey. The threshold for consensus was a pooled agreement rate across the two panels of 80% or more. Results: Expert consensus was achieved for 22 items. The new intervention consists of weekly follow-up phone calls for up to 1 month, delivered by Liaison Psychiatry practitioners, in which both self-harm and substance use problems are explored and addressed, and patients are supported in accessing community services. Limitations: Some stakeholder ideas regarding intervention components could not be included as survey options due to anticipated difficulties with implementation. Conclusions: The key elements of a brief psychosocial intervention for self-harm and co-occurring substance use problems have been agreed. Feasibility testing is currently underway.

Mindfulness, coping, and disruptions as predictors of college student distress at the beginning of the COVID-19 pandemic.

Objective: This research examined how stressors experienced by college students within the first month of the COVID-19 pandemic were associated with their reports of psychological distress, mindfulness, and coping strategies. Participants: Students attending 11 universities in the U.S. (N = 464, M age = 20.72, SD = 3.90, 91% female, 61% White, and 77% non-Hispanic) in early childhood education, child development, and family science classes participated.Methods: Students completed an online survey about pandemic-related disruptions, depressive symptoms, mindfulness, coping, and demographics.Results: Students whose families had more financial difficulties reported more disruptions. Depression and avoidant coping were positively correlated with distress, while mindfulness was inversely correlated with distress and depression. Disruptions, family financial status, depressive symptoms, mindfulness, and avoidant coping significantly predicted distress, controlling for university site and student sex, age, race, and ethnicity in multiple regression analyses. Avoidant coping significantly moderated (amplified) the effect of disruptions on distress. Conclusions: College student well-being can be supported through Campus programming that includes mindfulness practices and alternatives to avoidant strategies for coping with stress.

Diagnostic Utility of Exome Sequencing Among Israeli Children With Kidney Failure.

Introduction: Genetic etiologies are estimated to account for a large portion of chronic kidney diseases (CKD) in children. However, data are lacking regarding the true prevalence of monogenic etiologies stemming from an unselected population screen of children with advanced CKD. Methods: We conducted a national multicenter prospective study of all Israeli pediatric dialysis units to provide comprehensive "real-world" evidence for the genetic basis of childhood kidney failure in Israel. We performed exome sequencing and assessed the genetic diagnostic yield. Results: Between 2019 and 2022, we recruited approximately 88% (n = 79) of the children on dialysis from all 6 Israeli pediatric dialysis units. We identified genetic etiologies in 36 of 79 (45%) participants. The most common subgroup of diagnostic variants was in congenital anomalies of the kidney and urinary tract causing genes (e.g., EYA1, HNF1B, PAX2, COL4A1, and NFIA) which together explain 28% of all monogenic etiologies. This was followed by mutations in genes causing renal cystic ciliopathies (e.g., NPHP1, NPHP4, PKHD1, and BBS9), steroid-resistant nephrotic syndrome (e.g., LAGE3, NPHS1, NPHS2, LMX1B, and SMARCAL1) and tubulopathies (e.g., CTNS and AQP2). The genetic diagnostic yield was higher among Arabs compared to Jewish individuals (55% vs. 29%) and in children from consanguineous compared to nonconsanguineous families (63% vs. 29%). In 5 participants (14%) with genetic diagnoses, the molecular diagnosis did not correspond with the pre-exome diagnosis. Genetic diagnosis has a potential influence on clinical management in 27 of 36 participants (75%). Conclusion: Exome sequencing in an unbiased Israeli nationwide dialysis-treated kidney failure pediatric cohort resulted in a genetic diagnostic yield of 45% and can often affect clinical decision making.