Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism.

Remarkably little is known about the postnatal cellular development of the human amygdala. It plays a central role in mediating emotional behavior and has an unusually protracted development well into adulthood, increasing in size by 40% from youth to adulthood. Variation from this typical neurodevelopmental trajectory could have profound implications on normal emotional development. We report the results of a stereological analysis of the number of neurons in amygdala nuclei of 52 human brains ranging from 2 to 48 years of age [24 neurotypical and 28 autism spectrum disorder (ASD)]. In neurotypical development, the number of mature neurons in the basal and accessory basal nuclei increases from childhood to adulthood, coinciding with a decrease of immature neurons within the paralaminar nucleus. Individuals with ASD, in contrast, show an initial excess of amygdala neurons during childhood, followed by a reduction in adulthood across nuclei. We propose that there is a long-term contribution of mature neurons from the paralaminar nucleus to other nuclei of the neurotypical human amygdala and that this growth trajectory may be altered in ASD, potentially underlying the volumetric changes detected in ASD and other neurodevelopmental or neuropsychiatric disorders

Neuroprotective efficacy of P7C3 compounds in primate hippocampus.

There is a critical need for translating basic science discoveries into new therapeutics for patients suffering from difficult to treat neuropsychiatric and neurodegenerative conditions. Previously, a target-agnostic in vivo screen in mice identified P7C3 aminopropyl carbazole as capable of enhancing the net magnitude of postnatal neurogenesis by protecting young neurons from death. Subsequently, neuroprotective efficacy of P7C3 compounds in a broad spectrum of preclinical rodent models has also been observed. An important next step in translating this work to patients is to determine whether P7C3 compounds exhibit similar efficacy in primates. Adult male rhesus monkeys received daily oral P7C3-A20 or vehicle for 38 weeks. During weeks 2-11, monkeys received weekly injection of 5'-bromo-2-deoxyuridine (BrdU) to label newborn cells, the majority of which would normally die over the following 27 weeks. BrdU+ cells were quantified using unbiased stereology. Separately in mice, the proneurogenic efficacy of P7C3-A20 was compared to that of NSI-189, a proneurogenic drug currently in clinical trials for patients with major depression. Orally-administered P7C3-A20 provided sustained plasma exposure, was well-tolerated, and elevated the survival of hippocampal BrdU+ cells in nonhuman primates without adverse central or peripheral tissue effects. In mice, NSI-189 was shown to be pro-proliferative, and P7C3-A20 elevated the net magnitude of hippocampal neurogenesis to a greater degree than NSI-189 through its distinct mechanism of promoting neuronal survival. This pilot study provides evidence that P7C3-A20 safely protects neurons in nonhuman primates, suggesting that the neuroprotective efficacy of P7C3 compounds is likely to translate to humans as well

Psychometric properties of leadership scales for health professionals : a systematic review

Background: The important role of leaders in the translation of health research is acknowledged in the implementation science literature. However, the accurate measurement of leadership traits and behaviours in health professionals has not been directly addressed. This review aimed to identify whether scales which measure leadership traits and behaviours have been found to be reliable and valid for use with health professionals. Methods: A systematic review was conducted. MEDLINE, EMBASE, PsycINFO, Cochrane, CINAHL, Scopus, ABI/ INFORMIT and Business Source Ultimate were searched to identify publications which reported original research testing the reliability, validity or acceptability of a leadership-related scale with health professionals. Results: Of 2814 records, a total of 39 studies met the inclusion criteria, from which 33 scales were identified as having undergone some form of psychometric testing with health professionals. The most commonly used was the Implementation Leadership Scale (n = 5) and the Multifactor Leadership Questionnaire (n = 3). Of the 33 scales, the majority of scales were validated in English speaking countries including the USA (n = 15) and Canada (n = 4), but also with some translations and use in Europe and Asia, predominantly with samples of nurses (n = 27) or allied health professionals (n = 10). Only two validation studies included physicians. Content validity and internal consistency were evident for most scales (n = 30 and 29, respectively). Only 20 of the 33 scales were found to satisfy the acceptable thresholds for good construct validity. Very limited testing occurred in relation to test-re-test reliability, responsiveness, acceptability, cross-cultural revalidation, convergent validity, discriminant validity and criterion validity. Conclusions: Seven scales may be sufficiently sound to be used with professionals, primarily with nurses. There is an absence of validation of leadership scales with regard to physicians. Given that physicians, along with nurses and allied health professionals have a leadership role in driving the implementation of evidence-based healthcare, this constitutes a clear gap in the psychometric testing of leadership scales for use in healthcare implementation research and practice

Fathers stepping up? A cross-national comparison of fathers’ domestic labour and parents’ satisfaction with the division of domestic labour during the COVID-19 pandemic

The COVID-19 pandemic disrupted work and family life around the world. For parents, this upending meant a potential re-negotiation of the ‘status quo’ in the gendered division of labour. A comparative lens provides extended understandings of changes in fathers’ domestic work based in socio-cultural context–in assessing the size and consequences of change in domestic labour in relation to the type of work-care regime. Using novel harmonized data from four countries (the United States, Canada, the United Kingdom, and the Netherlands) and a work-care regime framework, this study examines cross-national changes in fathers’ shares of domestic labour during the early months of the pandemic and whether these changes are associated with parents’ satisfaction with the division of labour. Results indicate that fathers’ shares of housework and childcare increased early in the pandemic in all countries, with fathers’ increased shares of housework being particularly pronounced in the US. Results also show an association between fathers’ increased shares of domestic labour and mothers’ increased satisfaction with the division of domestic labour in the US, Canada, and the UK. Such comparative work promises to be generative for understanding the pandemic’s imprint on gender relations far into the future

Clinical practice guidelines on the evidenceâ based use of integrative therapies during and after breast cancer treatment

Answer questions and earn CME/CNEPatients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatmentâ related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapyâ induced nausea and vomiting, lymphedema, chemotherapyâ induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapyâ induced nausea and vomiting. Acetylâ Lâ carnitine is not recommended to prevent chemotherapyâ induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatmentâ related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mindâ body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194â 232. © 2017 American Cancer Society.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136746/1/caac21397_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136746/2/caac21397.pd

Electrophysiological resting state brain network and episodic memory in healthy aging adults

Recent studies have emphasized the changes in large-scale brain networks related to healthy aging, with the ultimate purpose to aid in differentiating normal neurocognitive aging from neurodegenerative disorders that also arise with age. Emerging evidence from functional Magnetic Resonance Imaging (fMRI) indicates that connectivity patterns within specific brain networks, especially the Default Mode Network (DMN), distinguish those with Alzheimer's disease from healthy individuals. In addition, disruptive alterations in the large-scale brain systems that support high-level cognition are shown to accompany cognitive decline at the behavioral level, which is commonly observed in the aging populations, even in the absence of disease. Although fMRI is useful for assessing functional changes in brain networks, its high costs and limited accessibility discourage studies that need large populations. In this study, we investigated the aging-effect on large-scale networks of the human brain using high-density electroencephalography and electrophysiological source imaging, which is a less costly and more accessible alternative to fMRI. In particular, our study examined a group of healthy subjects in the age range from middle- to older-aged adults, which is an under-studied range in the literature. Employing a high-resolution computation model, our results revealed age associations in the connectivity pattern of DMN in a consistent manner with previous fMRI findings. Particularly, in combination with a standard battery of cognitive tests, our data showed that in the posterior cingulate / precuneus area of DMN higher brain connectivity was associated with lower performance on an episodic memory task. The findings demonstrate the feasibility of using electrophysiological imaging to characterize large-scale brain networks and suggest that changes in network connectivity are associated with normal aging.This study was supported by National Science Foundation RII Track-2 FEC 1539068, Oklahoma Center for the Advancement of Science & Technology HR16–057, and Institute for Biomedical Engineering, Science, and Technology at University of Oklahoma. Financial support was provided by the University of Oklahoma Libraries’ Open Access Fund.Ye

AACAP 2006 Research Forum--Advancing research in early-onset bipolar disorder: barriers and suggestions

OBJECTIVE: The 2006 Research Forum addressed the goal of formulating a research agenda for early-onset bipolar disorder (EOBP) and improving outcome by understanding the risk and protective factors that contribute to its severity and chronicity. METHOD: Five work groups outlined barriers and research gaps in EOBP genetics, neuroimaging, prodromes, psychosocial factors, and pharmacotherapy. RESULTS: There was agreement that the lack of consensus on the definition and diagnosis of EOBP is the primary barrier to advancing research in BP in children and adolescents. Related issues included: the difficulties in managing co-morbidity both statistically and clinically; acquiring adequate sample sizes to study the genetics, biology, and treatment; understanding the EOBP\u27s developmental aspects; and identifying environmental mediators and moderators of risk and protection. Similarly, both psychosocial and medication treatment strategies for children with BP are hamstrung by diagnostic issues. To advance the research in EOBP, both training and funding mechanisms need to be developed with these issues in mind. CONCLUSIONS: EOBP constitutes a significant public health concern. Barriers are significant but identifiable and thus are not insurmountable. To advance the understanding of EOBP, the field must be committed to resolving diagnostic and assessment issues. Once achieved, with adequate personnel and funding resources, research into the field of EOBP will doubtless be advanced at a rapid pace

Clinicopathological and molecular characterisation of “multiple classifier” endometrial carcinomas

Endometrial carcinoma (EC) molecular classification based on four molecular subclasses identified in The Cancer Genome Atlas (TCGA) has gained relevance in recent years due to its prognostic utility and potential to predict benefit from adjuvant treatment. While most ECs can be classified based on a single classifier (POLE exonuclease domain mutations - POLEmut, MMR deficiency - MMRd, p53 abnormal - p53abn), a small but clinically relevant group of tumours harbour more than one molecular classifying feature and are referred to as 'multiple-classifier' ECs. We aimed to describe the clinicopathological and molecular features of multiple-classifier ECs with abnormal p53 (p53abn). Within a cohort of 3518 molecularly profiled ECs, 107 (3%) tumours displayed p53abn in addition to another classifier(s), including 64 with MMRd (MMRd-p53abn), 31 with POLEmut (POLEmut-p53abn), and 12 with all three aberrations (MMRd-POLEmut-p53abn). MMRd-p53abn ECs and POLEmut-p53abn ECs were mostly grade 3 endometrioid ECs, early stage, and frequently showed morphological features characteristic of MMRd or POLEmut ECs. 18/28 (60%) MMRd-p53abn ECs and 7/15 (46.7%) POLEmut-p53abn ECs showed subclonal p53 overexpression, suggesting that TP53 mutation was a secondary event acquired during tumour progression. Hierarchical clustering of TCGA ECs by single nucleotide variant (SNV) type and somatic copy number alterations (SCNAs) revealed that MMRd-p53abn tumours mostly clustered with single-classifier MMRd tumours (20/23) rather than single-classifier p53abn tumours (3/23), while POLEmut-p53abn tumours mostly clustered with single-classifier POLEmut tumours (12/13) and seldom with single-classifier p53abn tumours (1/13) (both p ≤ 0.001, chi-squared test). Finally, the clinical outcome of patients with MMRd-p53abn and POLEmut-p53abn ECs [stage I 5-year recurrence-free survival (RFS) of 92.2% and 94.1%, respectively] was significantly different from single-classifier p53abn EC (stage I RFS 70.8%, p = 0.024 and p = 0.050, respectively). Our results support the classification of MMRd-p53abn EC as MMRd and POLEmut-p53abn EC as POLEmut. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Comparing the frequency of common genetic variants and haplotypes between carriers and non-carriers of BRCA1 and BRCA2 deleterious mutations in Australian women diagnosed with breast cancer before 40 years of age

BACKGROUND: BRCA1 and BRCA2 mutations are found in a proportion of families with multiple early-onset breast cancers. There are a large number of different deleterious mutations in both genes, none of which would be detectable using standard genetic association studies. Single common variants and haplotypes of common variants may capture groups of deleterious mutations since some low prevalence haplotypes of common variants occur more frequently among chromosomes that carry rare, deleterious mutations than chromosomes that do not. METHODS: DNA sequence data for BRCA1 and BRCA2 was obtained from 571 participants from the Australian Breast Cancer Family Study. Genetic variants were classified as either deleterious mutations or common genetic variants. Variants tagging common polymorphisms were selected and haplotypes resolved using Haploview. Their frequency was compared to those with and without deleterious mutations using a permutation test. RESULTS: A common genetic variant in BRCA1 (3232A > G) was found to be over-represented in deleterious mutation carriers (p = 0.05), whereas a common genetic variant in BRCA2 (1342A > C) occurred less frequently in deleterious mutation carriers (p = 0.04). All four of the common BRCA1 variants used to form haplotypes occurred more frequently in the deleterious mutation carriers when compared to the non-carriers, but there was no evidence of a difference in the distributions between the two groups (p = 0.34). In BRCA2, all four common variants were found to occur less frequently in the deleterious mutation carriers when compared to non-carriers, but the evidence for difference in the distribution between the two groups was weak (p = 0.16). Several less common haplotypes of common BRCA1 variants were found to be over-represented among deleterious mutation carriers but there was no evidence for this at the population level. In BRCA2, only the most common haplotype was found to occur more frequently in deleterious mutation carriers, with again no evidence at the population level. CONCLUSIONS: We observed differences in the frequency of common genetic variants of the BRCA1 and BRCA2 and their haplotypes between early-onset breast cancer cases who did and did not carry deleterious mutations in these genes. Although our data provide only weak evidence for a difference in frequencies at the population level, the number of deleterious mutation carriers was low and the results may yet be substantiated in a larger study using pooled data