Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non-genetic risk factors for Alzheimer's disease among Asian Americans and Canadians.

INTRODUCTION: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population. METHODS: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese. RESULTS: ACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception. DISCUSSION: ACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness. HIGHLIGHTS: The Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

Population-Based Pharmacodynamic Modeling of Omalizumab in Pediatric Patients with Moderate to Severe Persistent Inadequately Controlled Allergic Asthma.

Omalizumab is the first approved anti-immunoglobulin E (IgE) agent for the treatment of moderate to severe persistent inadequately controlled allergic asthma in adults and adolescents (≥ 12 years old). In 2016, it was approved in pediatric patients (6-11 years old). The objective of this study was to quantitatively characterize the relationship between serum free IgE and pulmonary function (as measured by forced expiratory volume in 1 s [FEV1]) in pediatrics using a population-based pharmacodynamic model. Data collected during the steroid-stable period (first 24 weeks) of an omalizumab trial with pediatric asthma patients (Study IA05) were used to build the pediatric IgE-FEV1 model. The previously developed population IgE-FEV1 model in adults/adolescents was adapted to characterize the FEV1 and IgE relationship in pediatrics with different magnitude and onset of response. The pediatric IgE-FEV1 model adequately characterized the IgE-FEV1 relationship in pediatrics, particularly at the extremes of the observed body weights (i.e., ≤ 30 kg) and IgE values at screening (i.e., > 700 IU/mL). The estimated sigmoidal free IgE-FEV1 curves were similar in shape and maximum effect, but the estimated free IgE concentration leading to 50% maximum effect (IC50) in pediatric patients (39.4, 95% confidence interval [CI] 24.3-63.9 ng/mL) was higher than estimated in adults (19.8, 95% CI 15.1-24.5 ng/mL). The model further confirmed that the current omalizumab dosing rationale based on the mean target free IgE level of 25 ng/ml was appropriate. The pediatric model can be used to predict population FEV1 response for omalizumab when combined with an omalizumab pharmacokinetic-IgE model.

Are equitable physical performance tests perceived to be fair? Understanding officer cadets' perceptions of fitness standards.

In the last few decades, the armed forces in Western countries such as Canada and the United States have accepted women into virtually all military occupations. Despite this, a growing body of research confirms that female service members face prejudiced treatment while conducting their work in these organizations that continue to be predominately masculine and male-dominated. In particular, women attending the Canadian Military Colleges (CMCs) experience gender-related conflicts arising from the dissimilar fitness test standards between male and female cadets. There have been, however, few studies that scrutinize the psychological mechanisms of these tensions. The aim of this study was to unpack the existing biased perceptions against women pertaining to physical fitness through ambivalent sexism, social dominance orientation, and right-wing authoritarianism. Officer and naval cadets (n = 167, 33.5% women) at the Royal Military College of Canada (RMC) completed survey measures. Indirect effect analyses showed that cadets who viewed the fitness standards to be unfair expressed more hostile rather than benevolent sexist outlooks against women, and these negative feelings were connected to greater levels of social dominance and right-wing authoritarianism. These results indicate that sexist beliefs, competitive worldviews, and authoritarianism are underlying attitudes that should be addressed by militaries striving to fully integrate women into their forces.

MRI predicts remission at 1 year in first-episode schizophrenia in females with larger striato-thalamic volumes.

BACKGROUND/AIMS: The Remission in Schizophrenia Working Group has defined remission as 'a low-mild symptom intensity level, maintained for a minimum of 6 months, where such symptoms do not affect an individual's behaviour' [Andreasen et al.: Am J Psychiatry 2005;162:441-449]. Since brain morphology relates to symptomatology, treatment and illness progression, MRI may assist in predicting remission. METHODS: Thirty-nine patients newly diagnosed with DSM-IV schizophrenia underwent MRI brain scan prior to antipsychotic exposure. The Global Assessment of Functioning (GAF) score was entered into a voxel-based analysis to evaluate its relationship with cerebral grey matter volume from the baseline MRI. We entered age, total intracranial volume and intake GAF score as co-variates. Males and females were analysed separately because gender is a potent determinant of outcome. RESULTS: Males had lower GAF scores than females, both at intake and at 1 year. Males comprised only 40% (12 out of 39) of the early remission group. For females only, early remission was strongly and positively correlated with bilateral lentiform and striatal volumes. For males, there was no such relationship. CONCLUSION: Larger striato-thalamic volume correlated with early remission in females only. These baseline MRI findings were unlikely to be confounded by antipsychotic treatment and chronicity. These brain morphological markers show gender dimorphism and may assist in the prediction of early remission in newly diagnosed schizophrenia.

A bayesian translational framework for knowledge propagation, discovery, and integration under specific contexts.

The immense corpus of biomedical literature existing today poses challenges in information search and integration. Many links between pieces of knowledge occur or are significant only under certain contexts-rather than under the entire corpus. This study proposes using networks of ontology concepts, linked based on their co-occurrences in annotations of abstracts of biomedical literature and descriptions of experiments, to draw conclusions based on context-specific queries and to better integrate existing knowledge. In particular, a Bayesian network framework is constructed to allow for the linking of related terms from two biomedical ontologies under the queried context concept. Edges in such a Bayesian network allow associations between biomedical concepts to be quantified and inference to be made about the existence of some concepts given prior information about others. This approach could potentially be a powerful inferential tool for context-specific queries, applicable to ontologies in other fields as well.

Frontal-subcortical protein expression following prenatal exposure to maternal inflammation.

BACKGROUND: Maternal immune activation (MIA) during prenatal life is a risk factor for neurodevelopmental disorders including schizophrenia and autism. Such conditions are associated with alterations in fronto-subcortical circuits, but their molecular basis is far from clear. METHODOLOGY/PRINCIPAL FINDINGS: Using two-dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry, with targeted western blot analyses for confirmation, we investigated the impact of MIA on the prefrontal and striatal proteome from an established MIA mouse model generated in C57B6 mice, by administering the viral analogue PolyI:C or saline vehicle (control) intravenously on gestation day (GD) 9. In striatum, 11 proteins were up-regulated and 4 proteins were down-regulated in the PolyI:C mice, while 10 proteins were up-regulated and 7 proteins down-regulated in prefrontal cortex (PFC). These were proteins involved in the mitogen-activated protein kinase (MAPK) signaling pathway, oxidation and auto-immune targets, including dual specificity mitogen-activated protein kinase kinase 1 (MEK), eukaryotic initiation factor (eIF) 4A-II, creatine kinase (CK)-B, L-lactate dehydrogenase (LDH)-B, WD repeat-containing protein and NADH dehydrogenase in the striatum; and guanine nucleotide-binding protein (G-protein), 14-3-3 protein, alpha-enolase, olfactory maker protein and heat shock proteins (HSP) 60, and 90-beta in the PFC. CONCLUSIONS/SIGNIFICANCE: This data fits with emerging evidence for disruption of critical converging intracellular pathways involving MAPK pathways in neurodevelopmental conditions and it shows considerable overlap with protein pathways identified by genetic modeling and clinical post-mortem studies. This has implications for understanding causality and may offer potential biomarkers and novel treatment targets for neurodevelopmental conditions.

A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia.

BACKGROUND: Anti-psychotic treatment appears to be associated with striatal volume increase, but how early this change occurs is still unknown. METHODS: A single prospective cohort of 20 anti-psychotic-naïve patients, newly diagnosed with schizophrenia, underwent magnetic resonance imaging brain scan at baseline. This was repeated following up to 8 weeks of anti-psychotic treatment. Ten patients had repeat scan within only 3 weeks. The choice of anti-psychotic medication was naturalistic, i.e., clinician-led. Well-matched healthy individuals were also scanned to control for non-specific changes over a 3-week period. RESULTS: After 3 weeks of anti-psychotic treatment, significant grey matter volume increase in the right caudate, superior and inferior frontal gyrus, precentral gyrus, and left inferior parietal lobule was noted. However, after 8 weeks of anti-psychotic treatment, volume increase in the right thalamus and bilateral cerebellum was observed. Significant grey matter reduction was detected in the left medial frontal gyrus at both 3- and 8-week intervals. CONCLUSIONS: Early increase in striatal volume change occurs as early as 3 weeks after anti-psychotic treatment, whilst thalamic volume increase is apparent later, by 8 weeks of treatment. We speculate that drug-mediated neuroplasticity may provide a biomarker for clinical recovery.