Deterioration of neuroimmune homeostasis in Alzheimer's Disease patients who survive a COVID-19 infection.

Growing evidence has implicated systemic infection as a significant risk factor for the development and advancement of Alzheimer's disease (AD). With the emergence of SARS-CoV-2 (COVID-19) and the resultant pandemic, many individuals from the same aging population vulnerable to AD suffered a severe systemic infection with potentially unidentified long-term consequences for survivors. To study the impact of COVID-19 survival on the brain's intrinsic immune system in a population also suffering from AD, we profiled post-mortem brain tissue from patients in the UF Neuromedicine Human Brain and Tissue Bank with a diagnosis of AD who survived a COVID-19 infection (COVID-AD) and contrasted our findings with AD patients who did not experience a COVID-19 infection, including a group of brain donors who passed away before arrival of SARS-CoV-2 in the United States. We assessed disease-relevant protein pathology and microglial and astrocytic markers by quantitative immunohistochemistry and supplemented these data with whole tissue gene expression analysis performed on the NanoString nCounter® platform. COVID-AD patients showed slightly elevated Aß burden in the entorhinal, fusiform, and inferior temporal cortices compared to non-COVID-AD patients, while tau pathology burden did not differ between groups. Analysis of microglia revealed a significant loss of microglial homeostasis as well as exacerbated microgliosis in COVID-AD patients compared to non-COVID-AD patients in a brain region-dependent manner. Furthermore, COVID-AD patients showed reduced cortical astrocyte numbers, independent of functional subtype. Transcriptomic analysis supported these histological findings and, in addition, identified a dysregulation of oligodendrocyte and myelination pathways in the hippocampus of COVID-AD patients. In summary, our data demonstrate a profound impact of COVID-19 infection on neuroimmune and glial pathways in AD patients persisting for months post-infection, highlighting the importance of peripheral to central neuroimmune crosstalk in neurodegenerative diseases.

Apalutamide for High-Risk Localized Prostate Cancer Following Radical Prostatectomy (Apa-RP).

PURPOSE: Approximately 25% to 50% of patients with high-risk localized prostate cancer experience biochemical recurrence (BCR) within 2 years of radical prostatectomy. The Apa-RP study (NCT04523207) investigated whether adjuvant apalutamide plus androgen deprivation therapy (ADT) in high-risk patients who have undergone radical prostatectomy improved BCR-free survival. MATERIALS AND METHODS: Apa-RP was a multicenter, open-label, single-arm, phase 2 study conducted in community urology practices in the US. High-risk patients who had radical prostatectomy received 12 cycles of apalutamide (240 mg daily; 28-day cycles) plus ADT. The primary end point was BCR-free survival. Secondary end points included testosterone recovery (≥150 ng/dL) and safety. RESULTS: One hundred eight patients were enrolled; median age was 66.0 years (range 46.0-77.0 years). Median preoperative PSA and baseline testosterone were 7.6 ng/mL (range 2.2-62.7 ng/mL) and 340.0 ng/dL (range 43.0-939.0 ng/dL), respectively. The BCR-free rate at 24 months (12 months after completion of planned therapy) was 100% (90% CI 93-100). Serum testosterone recovery rate (≥50 and ≥150 ng/dL) 12 months after treatment completion was 96% (95% CI 88-98) and 77% (95% CI 66-85), respectively. Overall, 107 (99%) patients experienced treatment-emergent adverse events, with 24 (22%) experiencing grade 3 to 4 events. CONCLUSIONS: In Apa-RP, BCR-free survival was 100% with 77% of patients having testosterone recovery (≥150 ng/dL) within 12 months of actual treatment completion and a manageable safety profile. These results provide proof of concept that treatment intensification with 12 cycles of apalutamide plus ADT could become an option for patients with high-risk localized prostate cancer who have undergone radical prostatectomy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04523207.

Integrative proteomics identifies a conserved Aß amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid ß (Aß)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aß amyloid responsome. Proteins in the most conserved network (M42) accumulate in plaques, cerebrovascular amyloid (CAA), and/or dystrophic neuronal processes, and overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), increases the accumulation of Aß in plaques and CAA. M42 proteins bind amyloid fibrils in vitro, and MDK and PTN co-accumulate with cardiac transthyretin amyloid. M42 proteins appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD.

Infant versus noninfant formulas and cow's milk: Transition based on age or weight?

Infant formulas are meant to be used until 1 year of age, at which point children are transitioned to non-infant formulas or cow's milk, depending on their remaining dietary intake. Noninfant formulas and cow's milk are appropriate for children who have an average weight at that 1-year mark (9-9.5 kg); however, can contribute significant protein and/or electrolytes to children who are underweight for age, particularly if they still rely heavily on formula feeding for their caloric intake. In this short communication, we present several cases of patients who received excessive amounts of nutrients for age following the formula transition at the 1-year mark. We also provide recommendations for clinicians to consider when faced with underweight infants who are meant to be transitioning off infant formulas.

Health Resource Utilization and Cost Impact of Integrative Medicine Services for Newly Diagnosed Chronic Pain Patients.

Background: Integrative medicine (IM) is the healing-oriented practice of medicine that emphasizes the relationship between practitioner and patient. It considers the whole person, their environment, lifestyle, and social and cultural factors. It is evidence based and makes use of all appropriate therapies, conventional and complimentary. Objective: To evaluate the impact of IM services on health outcomes and care costs of chronic pain management patients compared with standard care. Methods: This article uses University of New Mexico hospital billing data from 10/2016 to 09/2019 to identify patients with nervous system or musculoskeletal pain. A total of 1,304 patients were matched using propensity scores into IM services (treatment: 652) and standard care (control: 652) cohorts for difference-in-differences analysis. The patients were matched based on age, sex, race, zip code, insurance type, ICD-10s, prescriptions, health care events, and medical claim costs. Results: Patients who used IM services had better health outcomes and lower costs at 3-month, 6-month, and 12-month follow-up. At the 12-month follow-up, the IM group showed a 19% decrease in utilization of inpatient care, a 37% decrease in Emergency Department utilization, and an 11.3% reduction in claim costs compared with the control group. Conclusion: Patients who utilize IM services as part of chronic pain management have overall lower health care costs and better health outcomes. Unfortunately, in the health system studied, less than 3% of patients utilize these services. Promotion of and education about IM services should be aimed at both patients and their providers.

Impact of a rash management guide in patients receiving apalutamide for high-risk localized prostate cancer in the Apa-RP study.

BACKGROUND/OBJECTIVES: Based on the SPARTAN and TITAN studies, apalutamide is approved for patients with nonmetastatic castration-resistant and metastatic castration-sensitive prostate cancer. Skin rash was a common adverse reaction across indications. We hypothesized that earlier identification and intervention could improve rash outcomes. SUBJECTS/METHODS: A prespecified rash management guide outlining recommended skin care practices was provided to all patients enrolled in Apa-RP (NCT04523207). Rash-related safety data from Apa-RP were compared descriptively with data from SPARTAN and TITAN. RESULTS: Patients in Apa-RP experienced improved rash-related outcomes vs those in SPARTAN and TITAN. CONCLUSIONS: Increased vigilance and proactive management may reduce the incidence, severity, and duration of rash during apalutamide treatment.

Diabetes Basic Training Program: Empowering Veterans for Wellness.

Background: Diabetes impacts 1 in 4 patients in the Veterans Health Administration and is associated with serious negative health consequences in addition to high health care system utilization and cost. The Cincinnati Veterans Affairs Medical Center developed Diabetes Basic Training, a 9-week intervention that blends medical consultation with group support and training in self-management strategies for enhancing patient motivation and empowerment. Observations: Diabetes Basic Training combined 3 monthly shared medical appointments and 6 Diabetes Self-Management Program sessions led in part by trained peers with diabetes. Diabetes Self-Management Program sessions focus on educating patients on diabetes and self-management tools and encourage active practice in building self-management skills and confidence. During shared medical appointments, a clinical psychologist or psychology postdoctoral fellow skilled in motivational interviewing facilitated the group to enhance patient motivation and empowerment for improved diabetes self-management. Conclusions: This novel program combined 2 types of group appointments to provide veterans with access to health care professionals and education on diabetes self-management. Preliminary results suggest the need for larger studies and that these programs may be beneficial in a veteran population.

Oligomeric amyloid beta prevents myelination in a clusterin-dependent manner.

Background: White matter loss is a well-documented phenomenon in Alzheimer's disease (AD) patients that has been recognized for decades. However, the underlying reasons for the failure of oligodendrocyte progenitor cells (OPCs) to repair myelin deficits in these patients remain elusive. A single nucleotide polymorphism (SNP) in Clusterin has been identified as a risk factor for late-onset Alzheimer's disease and linked to a decrease in white matter integrity in healthy adults, but its specific role in oligodendrocyte function and myelin maintenance in Alzheimer's disease pathology remains unclear. Methods: To investigate the impact of Clusterin on OPCs in the context of Alzheimer's disease, we employed a combination of immunofluorescence and transmission electron microscopy techniques, primary culture of OPCs, and an animal model of Alzheimer's disease. Results: Our findings demonstrate that Clusterin, a risk factor for late-onset AD, is produced by OPCs and inhibits their differentiation into oligodendrocytes. Specifically, we observed upregulation of Clusterin in OPCs in the 5xFAD mouse model of AD. We also found that the phagocytosis of debris, including amyloid beta (Aß), myelin, and apoptotic cells leads to the upregulation of Clusterin in OPCs. In vivo experiments confirmed that Aß oligomers stimulate Clusterin upregulation and that OPCs are capable of phagocytosing Aß. Furthermore, we discovered that Clusterin significantly inhibits OPC differentiation and hinders the production of myelin proteins. Finally, we demonstrate that Clusterin inhibits OPC differentiation by reducing the production of IL-9 by OPCs. Conclusion: Our data suggest that Clusterin may play a key role in the impaired myelin repair observed in AD and could serve as a promising therapeutic target for addressing AD-associated cognitive decline.

Song and genetic divergence within a subspecies of white-crowned sparrow (Zonotrichia leucophrys nuttalli).

Animal culture evolves alongside genomes, and the two modes of inheritance-culture and genes-interact in myriad ways. For example, stable geographic variation in culture can act as a reproductive barrier, thereby facilitating genetic divergence between "cultural populations." White-crowned sparrows (Zonotrichia leucophrys) are a well-established model species for bird song learning and cultural evolution, as they have distinct, geographically discrete, and culturally transmitted song types (i.e., song dialects). In this study, we tested the hypothesis that divergence between culturally transmitted songs drives genetic divergence within Nuttall's white-crowned sparrows (Z. l. nuttalli). In accordance with sexual selection theory, we hypothesized that cultural divergence between mating signals both preceded and generated genetic divergence. We characterized the population structure and song variation in the subspecies and found two genetically differentiated populations whose boundary coincides with a major song boundary at Monterey Bay, California. We then conducted a song playback experiment that demonstrated males discriminate between songs based on their degree of divergence from their local dialect. These results support the idea that discrimination against non-local songs is driving genetic divergence between the northern and southern populations. Altogether, this study provides evidence that culturally transmitted bird songs can act as the foundation for speciation by sexual selection.

IL-1ra gene therapy in equine osteoarthritis improves physiological, anatomical, and biological outcomes of joint degeneration.

OBJECTIVE: To evaluate the effects of a gene transfer approach to IL-1ß inhibition in an equine osteochondral chip fragment model of joint injury using a self-complementary adeno-associated virus with interleukin receptor antagonist transgene cassette (scAAVIL-1ra), as posttraumatic osteoarthritis in horses, similar to people, is a significant clinical problem. ANIMALS: 16 horses were utilized for the study. METHODS: All horses had an osteochondral chip fragment induced arthroscopically in one middle carpal joint while the contralateral joint was sham operated. Eight horses received either scAAVIL-1ra or saline in the osteoarthritis joint. Horses were evaluated over 70 days clinically (lameness, imaging, and biomarker analysis) and euthanized at 70 days and evaluated grossly, with imaging and histopathology. RESULTS: The following findings were statistically significant. Injection of scAAVIL-1ra resulted in high synovial fluid levels of IL-1ra (0.5 to 9 µg/mL) throughout the duration of the experiment (70 days). Over the duration, we observed scAAVIL-1ra to improve lameness (lameness score relative improvement of 1.2 on a scale of 0 to 5), cause suppression of prostaglandin E2 (a relative decline of 30 pg/mL), and result in histological improvement in articular cartilage (decreased chondrocyte loss and chondrone formation) and subchondral bone (less osteochondral splitting and osteochondral lesions). Within the synovial membrane of scAAVIL-1ra-treated joints, we also observed perivascular infiltration with CD3-positive WBCs, suggesting lymphocytic T-cell perivascular infiltration commonly observed with viral transduction. CLINICAL RELEVANCE: These data provide support for further evaluation and optimization of scAAVIL-1ra gene therapy to treat equine osteoarthritis.

Auditory P50 Sensory Gating Alterations in Major Depressive Disorder and their Relationship to Clinical Symptoms.

Cognitive deficits in depression are pervasive and include impairments in attention and higher-order functions but the degree to which low-level sensory processes are affected is unclear. The present work examined event-related potential (P50 and N100) features of auditory sensory gating (i.e., the ability to inhibit P50/N100 responses to redundant stimuli) and their relationship to depressive symptoms, including ruminations and dysfunctional attitudes. In 18 patients with major depressive disorder (MDD) and 18 healthy volunteers, auditory sensory gating was measured using a paired-stimulus paradigm yielding ratio (rP50, rN100) and difference (dP50, dN100) gating indices, which reflected amplitude reductions from first (S1) to second (S2) stimulus. Patients with MDD exhibited diminished rP50 and dP50 gating scores and delayed S1-N100 latencies compared to healthy volunteers. These measures were positively associated with ruminative thoughts, negative attitudes and degree of depression. Study findings implicate aberrant sensory processing in depressed patients that is related to severity of maladaptive thinking.

Disease and brain region specific immune response profiles in neurodegenerative diseases with pure and mixed protein pathologies.

The disease-specific accumulation of pathological proteins has long been the major focus of research in neurodegenerative diseases (ND), including Alzheimer's disease (AD) and related dementias (RD), but the recent identification of a multitude of genetic risk factors for ND in immune-associated genes highlights the importance of immune processes in disease pathogenesis and progression. Studies in animal models have characterized the local immune response to disease-specific proteins in AD and ADRD, but due to the complexity of disease processes and the co-existence of multiple protein pathologies in human donor brains, the precise role of immune processes in ND is far from understood. To better characterize the interplay between different extracellular and intracellular protein pathologies and the brain's intrinsic immune system in ND, we set out to comprehensively profile the local immune response in postmortem brain samples of individuals with "pure" beta-Amyloid and tau pathology (AD), "pure" α-Synuclein pathology in Lewy body diseases (LBD), as well as cases with Alzheimer's disease neuropathological changes (ADNC) and Lewy body pathology (MIX). Combining immunohistochemical profiling of microglia and digital image analysis, along with deep immunophenotyping using gene expression profiling on the NanoString nCounter® platform and digital spatial profiling on the NanoString GeoMx® platform we identified a robust immune activation signature in AD brain samples. This signature is maintained in persons with mixed pathologies, irrespective of co-existence of AD pathology and Lewy body (LB) pathology, while LBD brain samples with "pure" LB pathology exhibit an attenuated and distinct immune signature. Our studies highlight disease- and brain region-specific immune response profiles to intracellular and extracellular protein pathologies and further underscore the complexity of neuroimmune interactions in ND.

A Pilot Randomized Controlled Trial of Motivation-Based Social Skills Group Treatment with Parent Training.

Despite the popularity of social skills groups, there remains a need for empirical investigation of treatment effects, especially when targeting pivotal aspects of social functioning such as initiations to peers. The goal of the present study was to conduct a randomized controlled trial of a 12-week social intervention (SUCCESS), which combined an inclusive social group with a parent education program. Twenty-five 4- to 6-year-olds with Autism Spectrum Disorder (ASD) were randomized to SUCCESS (N = 11) or to treatment as usual (N = 14). Combining a peer group model with a parent training program, the SUCCESS intervention used naturalistic behavioral techniques (e.g., environmental arrangement, natural reinforcement) to increase social initiations to peers. After 12 weeks, children participating in the SUCCESS program made more frequent initiations to peers than children in the treatment-as-usual group, including more prompted and unprompted initiations to request. Additional gains in clinician-rated social functioning were observed in children randomized to SUCCESS, while differential treatment effects were not detected in parent-rated measures. However, lower baseline social motivation was associated with greater parent-reported initiation improvement. This study provides preliminary support for the efficacy of a naturalistic, behavioral social skills intervention to improve peer initiations for children with ASD. The findings suggest that using a motivation-based social skills group was effective in increasing both prompted and spontaneous initiations to peers, and highlights the need for further research into the role of baseline social motivation in predicting social skills treatment response.

Proactive case finding of alcohol-related liver disease in high-risk populations: A systematic review.

BACKGROUND: Alcohol-related liver disease (ARLD) is often diagnosed at a late stage when mortality is unacceptably high. Earlier identification of ARLD may lead to reduced alcohol intake, participation in hepatocellular carcinoma surveillance and reduction in liver-related morbidity and mortality. People with alcohol use disorder (AUD) are at highest risk of ARLD. The aim of this systematic review was to understand the yield of proactive screening for ARLD amongst high-risk groups. METHODS: Embase, Medline, Scopus and grey literature were searched for studies describing proactive assessment for alcohol-related liver disease in people with a history of alcohol excess or diagnosed AUD. Outcomes of interest were fibrosis and cirrhosis detection rates, clinical outcomes, portal hypertension evaluation, attendance at follow-up and cost-effectiveness. RESULTS: Fifteen studies were identified for inclusion from 1115 returned by the search. Four key settings for patient engagement were identified as inpatient addiction services, outpatient addiction services, general acute hospital admissions and community outreach. Of these, acute hospital admissions were the highest yield for cirrhosis at 10.8%-29.6% and community outreach the lowest was 1.2%-2.3%. CONCLUSIONS: Targeted fibrosis assessment of high-risk populations for ARLD is feasible to conduct and identifies a proportion of patients at risk of advanced liver disease. The highest yield is amongst inpatients admitted with AUD. Prospective work is needed to establish which are the most effective and acceptable screening methods and the impact on long-term outcomes.

Physician Leadership and Burnout: The Need for Agency; a Qualitative Study of an Academic Institution.

Purpose: Organizational approaches to physician burnout are limited. Training physician leaders to influence the organizational environment is a growing area of study. This study explored perceived physician leadership behaviors in response to burnout from the viewpoint of faculty physicians not in formal leadership positions. Understanding physician leadership behaviors from the viewpoint of those faculty being led can inform organizational strategy and leadership training to address physician burnout. Subjects and Methods: Interview requests were sent to 70 randomly identified faculty physicians from a roster containing all 1145 physician faculty that excluded the Pediatric Department, at an academic health care institution in Southern California. The first ten respondents were asked to participate in a 30-to-40-minute semi-structured virtual interview via Zoom. The interviewees were asked two questions pertaining to burnout and their perception of how leadership responded. The two questions were "What has leadership done to address burnout?" and "If you had five minutes to advise your leaders on burnout, what would you say?" The recorded interviews were transcribed, redacted, and then sent to two reviewers. Thematic analysis through iterative coding was completed, and categories were constructed that aligned with the two interview questions. Results: Overall, five themes were identified. These themes were organized according to the interview questions and broadly categorized as physician leadership behaviors observed that corresponded to the interview question of what leadership had done to address burnout and physician leadership behaviors desired corresponding to the second interview question of what advice should be given. Leadership behaviors observed in the context of burnout included three themes; referral to individual wellness programs, increased number of meetings and events, and a lack of agency in addressing wellness issues. The two themes of leadership behaviors desired were the obtainment of more resources and the granting of greater appreciation and recognition for work done through enhanced communication. Conclusion: This small study of faculty physician perceptions of leadership behaviors identified several themes that had been identified in previous studies of leadership and burnout; need for relationship building through communication, need for resources to address work issues, and referral to wellness programs. However, the identification of a lack of agency in addressing factors in the wellness environment has not been identified in the previous burnout and physician leadership literature. Further study into the causes of this perceived lack of agency should be explored. Understanding the root causes of physician leaders' lack of agency can further inform physician leadership education as an organizational approach to burnout.

Inspiring diverse researchers in Virginia: Cultivating research excellence through a career-building program.

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, and intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the "inspiring Diverse Researchers in Virginia" (iDRIV) program. This yearlong program provided education, coaching, mentoring, and sponsorship for underrepresented early career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% as Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

Weight bias and stigma in healthcare: What are we doing about it?

Weight bias and weight stigma is present in healthcare settings negatively affecting people with obesity. Healthcare professionals should be aware of how their potential bias and stigma may be impacting clients with obesity. With obesity projected to rise among the world, the healthcare environment needs to be more accepting and accommodating.

Neonatal epidermolysis bullosa: a clinical practice guideline.

DEBRA International is undertaking a long-term initiative to develop clinical practice guidelines (CPGs) for epidermolysis bullosa (EB), to -improve the clinical care of people living with EB. Current neonatal care is based on evidence, clinical expertise and trial and error, with collaboration between the EB specialist team, parent or carer and patient, and is dependent on the neonate's individual presentation and type of EB. Early intervention based on research and clinical practice is needed to establish a foundation of knowledge to guide international practitioners to create and improve standards of care and to be able to work effectively with those newly diagnosed with EB. This CPG was created by an international panel with expertise working with persons with EB. The CPG focuses on neonatal care using a systematic review methodology covering four key areas: (i) diagnosis and parental psychosocial support; (ii) hospital management: medical monitoring, wound care and pain; (iii) feeding and nutrition; and (iv) discharge planning and EB education. These four areas highlight the importance of a multidisciplinary team approach, to provide a patient-specific holistic care model that incorporates the needs and wishes of the parents and carers. The Hospital Implementation Tool included promotes transfer of theory to clinical practice.

A Twin Study of Altered White Matter Heritability in Youth With Autism Spectrum Disorder.

OBJECTIVE: White matter alterations are frequently reported in autism spectrum disorder (ASD), yet the etiology is currently unknown. The objective of this investigation was to examine, for the first time, the impact of genetic and environmental factors on white matter microstructure in twins with ASD compared to control twins without ASD. METHOD: Diffusion-weighted MRIs were obtained from same-sex twin pairs (6-15 years of age) in which at least 1 twin was diagnosed with ASD or neither twin exhibited a history of neurological or psychiatric disorders. Fractional anisotropy (FA) and mean diffusivity (MD) were examined across different white matter tracts in the brain, and statistical and twin modeling were completed to assess the proportion of variation associated with additive genetic (A) and common/shared (C) or unique (E) environmental factors. We also developed a novel Twin-Pair Difference Score analysis method that produces quantitative estimates of the genetic and environmental contributions to shared covariance between different brain and behavioral traits. RESULTS: Good-quality data were available from 84 twin pairs, 50 ASD pairs (32 concordant for ASD [16 monozygotic; 16 dizygotic], 16 discordant for ASD [3 monozygotic; 13 dizygotic], and 2 pairs in which 1 twin had ASD and the other exhibited some subthreshold symptoms [1 monozygotic; 1 dizygotic]) and 34 control pairs (20 monozygotic; 14 dizygotic). Average FA and MD across the brain, respectively, were primarily genetically mediated in both control twins (A = 0.80, 95% CI [0.57, 1.02]; A = 0.80 [0.55, 1.04]) and twins concordant for having ASD (A = 0.71 [0.33, 1.09]; A = 0.84 [0.32,1.36]). However, there were also significant tract-specific differences between groups. For instance, genetic effects on commissural fibers were primarily associated with differences in general cognitive abilities and perhaps some diagnostic differences for ASD because Twin-Pair Difference-Score analysis indicated that genetic factors may have contributed to ∼40% to 50% of the covariation between IQ scores and FA of the corpus callosum. Conversely, the increased impact of environmental factors on some projection and association fibers were primarily associated with differences in symptom severity in twins with ASD; for example, our analyses suggested that unique environmental factors may have contributed to ∼10% to 20% of the covariation between autism-related symptom severity and FA of the cerebellar peduncles and external capsule. CONCLUSION: White matter alterations in youth with ASD are associated with both genetic contributions and potentially increased vulnerability or responsivity to environmental influences. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. The author list of this paper includes contributors from the location and/or community where the research was conducted and they participated in the data collection, design, analysis, and/or interpretation of the work.

The Utility of the Level of Personality Functioning Scale in Maternal Samples: A Brief Report.

Maternal personality plays a role in how a mother parents her children and adolescents. Current trait-based measures of personality are acceptable for use in maternal samples, but the presence or absence of given personality traits might not be enough to describe how personality relates to parenting. The Level of Personality Functioning Scale (LPFS) could serve as a solution, as it was designed to capture level of dysfunction in personality without being reliant on specific personality traits. Research, however, has yet to demonstrate the LPFS as a useful measure of personality in maternal samples, thus the goal of this study. A sample of 123 mothers reported on behavioral problems in their adolescent-aged children and their own personality using both a trait-based measure and the LPFS. Our data showed that maternal reports on the LPFS were associated with maternal perceptions of adolescent behavioral problems, in addition to being an acceptable measure of personality in our maternal sample. We also provide support for incremental validity of the LPFS in our sample, as the LPFS uniquely predicted maternal perceptions of adolescent behavioral problems even after controlling for maternal personality traits. Our results are discussed in light of the limitations of the extant work on maternal personality and add to the literature by demonstrating that the LPFS is an acceptable and ubiquitous measure of personality in maternal samples.