Role of the schizophrenia-linked gene complement component 4 in prefrontal cortex function in mice

Schizophrenia is a devastating mental illness characterized by a broad range of clinical manifestations including hallucinations, social cognitive impairments, and disordered thinking and behavior, all of which impair daily functioning. The immune molecule complement component 4 (C4), located in the major histocompatibility locus (MHC) on chromosome 6 in humans, is highly associated with schizophrenia such that specific structural variants and regulatory regions increase the expression of C4 and confer greater risk for this brain disorder. Besides their established role in brain immune defense, complement proteins play a role in various stages of brain development including neurogenesis, migration and synaptic development. However, C4 has never been experimentally upregulated to determine the impact of increased expression of this immune gene on brain development. Here, I study the role of C4 in layer 2/3 pyramidal neurons in the medial prefrontal cortex of mice to study the hypothesis that C4 overexpression causes circuit dysfunction by leading to the pathological elimination of synapses. Specifically, neuronal connectivity was assayed by measuring dendritic spine density using confocal microscopy and functional connectivity through whole-cell electrophysiology recordings. Additionally, the role of microglia in altering the developmental wiring of the brain was examined by quantifying microglia engulfment in the medial prefrontal cortex. Lastly, complement-induced changes to the prefrontal cortex were accompanied by deficits in social behavior in both juvenile and adult mice. Overall, these studies show that C4 affects brain connectivity by reducing dendritic spine density and excitatory drive through enhanced microglia-engulfment of synaptic material which was sufficient to cause lasting deficits in mouse social behavior

Discovering Perspectives on Health and Well-Being from Parents and Teachers of Preschool- Aged Children

Background: This study explores the concept of health and well-being as perceived by teachers and parents of preschool-aged children in the specific context of a child day care facility. The study also identifies the barriers parents and teachers encounter and the supports they require in promoting the health and well-being of preschool-aged children. Method: A qualitative phenomenological research design combined with a projective technique of Photovoice was used for data collection. A total of eight participants, four teachers and four parents of preschool-aged children from a child day care facility, participated in the study. Results: Several themes were identified related to barriers that parents and teachers face and the supports they require in promoting the health and well-being of preschool-aged children. Conclusions: This study discusses a potential role for occupational therapy practitioners in collaborating with administrators and teachers and parents of preschool-aged children to develop a program to promote the health and well-being of preschool-aged children

ErbB2 and p38γ MAPK Mediate Alcohol-Induced Increase in Breast Cancer Stem Cells and Metastasis

Background: Both epidemiological and experimental studies suggest that excessive alcohol exposure increases the risk for breast cancer and enhances metastasis/recurrence. We have previously demonstrated that alcohol enhanced the migration/invasion of breast cancer cells and cancer cells overexpressing ErbB2/HER2 were more sensitive to alcohol exposure. However, the underlying mechanisms remain unclear. This study was designed to investigate the mechanisms underlying alcohol-enhanced aggressiveness of breast cancer. Cancer stem cells (CSCs) play a critical role in cancer metastasis and recurrence. Methods: We evaluated the effect of chronic alcohol exposure on mammary tumor development/metastasis in MMTV-neu transgenic mice and investigated the cell signaling in response to alcohol exposure in breast cancer cells overexpressing ErbB2/HER2. Results and discussion: Chronic alcohol exposure increased breast cancer stem cell-like CSC population and enhanced the lung and colon metastasis in MMTV-neu transgenic mice. Alcohol exposure caused a drastic increase in CSC population and mammosphere formation in breast cancer cells overexpressing ErbB2/HER2. Alcohol exposure stimulated the phosphorylation of p38γ MAPK (p-p38γ) which was co-localized with phosphorylated ErbB2 and CSCs in the mammary tumor tissues. In vitro results confirmed that alcohol activated ErbB2/HER2 and selectively increased p-p38γ MAPK as well as the interaction between p38γ MAPK and its substrate, SAP97. However, alcohol did not affect the expression/phosphorylation of p38α/β MAPKs. In breast cancer cell lines, high expression of ErbB2 and p-p38γ MAPK was generally correlated with more CSC population. Blocking ErbB2 signaling abolished heregulin β1- and alcohol-stimulated p-p38γ MAPK and its association with SAP97. More importantly, p38γ MAPK siRNA significantly inhibited an alcohol-induced increase in CSC population, mammosphere formation and migration/invasion of breast cancer cells overexpressing ErbB2. Conclusions: p38γ MAPK is downstream of ErbB2 and plays an important role in alcohol-enhanced aggressiveness of breast cancer. Therefore, in addition to ErbB2/HER2, p38γ MAPK may be a potential target for the treatment of alcohol-enhanced cancer aggressiveness

Promoting Health and Wellness Among Preschool-Aged Children

Health and wellness are complex concepts which incorporate physical, social, and mental factors (Who.int, 2015). “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” (Who.int, 2015). According to the National Wellness Institute, wellness is “a conscious, self-directed and evolving process of achieving full potential.” It is important for children to learn about health and wellness at a young age. Preschool is a developmentally important stage, and knowledge learned in this stage may carry over throughout the lifespan. Thus, this is a crucial time period for children to become educated on health and wellness

Jazzing Up Virtual Interview Season With a Residency Program Information Portal for Interviewees

Learning Objectives: To asynchronously connect interviewees to our residency program through a digital platform designed to recreate personalized knowledge-sharing.Background: Emergency medicine residency recruitment has continued in the virtual environment in 2021. Remote interviews limit the personalized exchange that occurs between program and applicant. Virtual interviews, while more equitable and financially feasible, result in applicants feeling less familiar with the program. To compensate, an emphasis on digital presence is needed. A well-curated website can provide foundational information about the program but typically lacks the personalized quality of an in-person on-site interview.Objectives: To asynchronously connect interviewees to our residency program through a digital platform designed to recreate personalized knowledge-sharing.Design: We created a website to convey personalized program information to 2021-2022 interviewees called the “Stanford Applicant Access Zone (SAAZ).” Through this private interviewee-only platform, we recreated many of the discussions and presentations that otherwise occur during an in-person interview. SAAZ contains interview logistics for the interview day, future engagement opportunities, videos highlighting unique features of the program, and a tour. We tracked the number of visits and page views to gauge use.Impact/Effectiveness: As of 11/23/21, there were 184 users of 210 invitees who account for 1506 page views. The peak usage was in the first week of November after invites were sent, with spikes in usage on a weekly basis thereafter, consistent with interview days. The average engagement time was 248 seconds. Apart from the welcome page, the most commonly viewed page was “Interviews” at 337 views (2.36/user), followed by “Engage” at 279 (2.18/user), “Meet the Team” at 207 (1.92/user), and “ACCEL” at 152(1.54/user). The interview day length decreased from 5 to 3 hours by relocating content to the website. SAAZ is a novel means to provide asynchronous program details while preserving personalized information sharing and shortening the virtual interview day

Fear of illness & virus evaluation (FIVE) COVID-19 scales for children-parent/caregiver-report development and validation

Commonly-used youth anxiety measures may not comprehensively capture fears, worries, and experiences related to the pervasive impact of the COVID-19 pandemic. This study described the development of the Fear of Illness and Virus Evaluation (FIVE) scales and validated the caregiver-report version. After initial development, feedback was obtained from clinicians and researchers, who provided suggestions on item content/wording, reviewed edits, and provided support for the updated FIVE’s content and face validity. Factor structure, measurement invariance, and psychometric properties were analyzed using data from a multi-site, longitudinal study of COVID-19-related effects on family functioning with 1599 caregivers from the United States and Canada. Confirmatory factor analyses indicated a hierarchical five-factor structure best fit the data, resulting in a 31-item measure with four lower-order subscales: (1) Fears about Contamination and Illness; (2) Fears about Social Distancing, (3) Avoidance Behaviors, and (4) Mitigation Behaviors, and a higher-order factor, (5) Total Fears, indicated by the two fear-related lower-order subscales. Measurement invariance by country of residence, child age, and child sex was found. All subscales demonstrated strong internal consistency, appropriate item-scale discrimination, and no floor or ceiling effects. The Total Fears subscale demonstrated appropriate test-retest reliability. Concurrent validity supported by strong correlation with a youth anxiety measure. The FIVE provides a psychometrically-sound measure of COVID-19-related fears and behaviors in youth in a caregiver-report format. Future research is necessary to evaluate correlates and longitudinal symptom patterns captured by the FIVE caregiver-report, as well as the validity and reliability of a youth self-report version of the FIVE. •A caregiver report of child and adolescent COVID-19 fears, worries, and associated behaviors.•Tested and validated in a sample of 1599 caregivers of children ages 5–17 years.•Face and content validity, structural validity, and internal consistency supported.•Psychometrically robust and useful tool

Fear of illness & virus evaluation (FIVE) COVID-19 scales for children-parent/caregiver-report development and validation.

ObjectiveCommonly-used youth anxiety measures may not comprehensively capture fears, worries, and experiences related to the pervasive impact of the COVID-19 pandemic. This study described the development of the Fear of Illness and Virus Evaluation (FIVE) scales and validated the caregiver-report version.MethodAfter initial development, feedback was obtained from clinicians and researchers, who provided suggestions on item content/wording, reviewed edits, and provided support for the updated FIVE's content and face validity. Factor structure, measurement invariance, and psychometric properties were analyzed using data from a multi-site, longitudinal study of COVID-19-related effects on family functioning with 1599 caregivers from the United States and Canada.ResultsConfirmatory factor analyses indicated a hierarchical five-factor structure best fit the data, resulting in a 31-item measure with four lower-order subscales: (1) Fears about Contamination and Illness; (2) Fears about Social Distancing, (3) Avoidance Behaviors, and (4) Mitigation Behaviors, and a higher-order factor, (5) Total Fears, indicated by the two fear-related lower-order subscales. Measurement invariance by country of residence, child age, and child sex was found. All subscales demonstrated strong internal consistency, appropriate item-scale discrimination, and no floor or ceiling effects. The Total Fears subscale demonstrated appropriate test-retest reliability. Concurrent validity supported by strong correlation with a youth anxiety measure.DiscussionThe FIVE provides a psychometrically-sound measure of COVID-19-related fears and behaviors in youth in a caregiver-report format. Future research is necessary to evaluate correlates and longitudinal symptom patterns captured by the FIVE caregiver-report, as well as the validity and reliability of a youth self-report version of the FIVE