Evoked mid-frontal activity predicts cognitive dysfunction in Parkinson’s disease

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A history of repeated alcohol intoxication promotes cognitive impairment and gene expression signatures of disease progression in the 3xTg mouse model of Alzheimer’s diseaseThe impact of alcohol abuse on Alzheimer’s disease (AD) is poorly understood. Here, we show that the onset of neurocognitive impairment in a mouse model of AD is hastened by repeated alcohol intoxication through exposure to alcohol vapor, and we provide a comprehensive gene expression dataset of the prefrontal cortex by the single-nucleus RNA sequencing of 113,242 cells. We observed a broad dysregulation of gene expression that involves neuronal excitability, neurodegeneration, and inflammation, including interferon genes. Several genes previously associated with AD in humans by genome-wide association studies were differentially regulated in specific neuronal populations. Gene expression patterns of AD mice with a history of alcohol intoxication were more similar to gene expression signatures of older AD mice with more advanced disease and cognitive impairment than those of younger AD mice with prodromic disease, suggesting that alcohol promotes transcriptional changes consistent with AD progression. Our gene expression dataset at the single-cell level provides a unique resource for investigations of the molecular bases of the detrimental role of excessive alcohol intake in AD. Significance statement Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Many efforts have been geared toward the identification of environmental and genetic risk factors. However, alcohol has received limited attention as a potential risk factor for AD. We explored effects of the interaction of a history of alcohol intoxication with genetic AD susceptibility on cognitive performance and gene expression at the single-cell level. We found that a history of repeated alcohol intoxication promotes the emergence of spatial learning and memory impairments in pre-symptomatic triple transgenic AD (3xTg-AD) mice. We also show that a history of repeated alcohol intoxication induces prefrontal cortex transcriptional changes associated with AD progression.
Source: medical_xpress - 🏆 101. / 51 Read more »

Infusing wellness opportunities into integrated youth services - BMC PsychiatryBackground Appropriate health services and health promotion strategies for young people with mental health and substance use (MHSU) concerns are critical for recovery. Foundry, an integrated youth services (IYS) initiative for young people ages 12-24 in British Columbia (BC), Canada, has recently added leisure and recreational activities (referred to as the Wellness Program) into its services. The objectives of this study were to: (1) describe how the Wellness Program was implemented over a two-year period into IYS (2) provide an overview of what the Wellness Program is, who accessed the program since inception and initial evaluation results. Methods This study was part of the developmental evaluation of Foundry. A phased approach was used to implement the program at nine centres. Data was accessed from Foundry’s centralized platform ‘Toolbox’ and included activity type, number of unique youth and visits, additional services sought, information about how youth found out about the centre, and demographics. Qualitative data was also accessed from focus groups (n=2) conducted with young people (n=9). Results Over the two-year period, 355 unique youth accessed the Wellness Program, with 1319 unique visits. Almost half (40%) of youth identified the Wellness Program as the first point of access to Foundry. A total of 384 different programs were offered targeting five wellness domains (physical, mental/emotional, social, spiritual, and cognitive/intellectual). The majority of youth identified as young girls/women (58.2%), 22.6% as gender diverse, and 19.2% as young men/boys. The mean age was 19 years, and most participants were between the ages of 19-24 years (43.6%). From the thematic analysis of focus groups, we found young people enjoyed the social aspect of the program with peers and facilitators, and identified program improvements that are being considered as the program grows. Conclusions This study provides insight into the development and implementation of leisure
Source: BioMedCentral - 🏆 22. / 71 Read more »

Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity - Nature CommunicationsLooking at genes that are differentially responsive to pathogens depending on the genetic background may help in the identification of therapeutic targets in personalized medicine. Here, using challenge of monocytes with three pathogens the authors identified eQTL that are shared between pathogens and loci that are pathogen specific.
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Systemic aspergillosis in a patient with interferon gamma receptor 1 deficiency; a case report - BMC PediatricsBackground Interferon-gamma receptor deficiency is a heterogeneous spectrum of disease which involves mutations in IFNGR1, IFNGR2 genes, and the downstream signaling proteins such as STAT1. These mutations are associated with immunodeficiency 27 A and 27B, making the patient prone to mycobacterial infections. Patients with this condition are also at increased risk for affliction with viral and bacterial infections, such as with the Herpesviridae family, Listeria, and Salmonella. Moreover, SH2B3 mutation is associated with autoimmune and lymphoproliferative conditions. Case presentation the patient was a 19-month-old infant girl who presented with a two-week history of fever. She had near-normal flowcytometry with high IgM and IgE. She had pneumonic infiltration in her chest and right hilar and para-aortic lymphadenopathy. PCR of whole blood for Aspergillus fumigatus came back positive. In her Whole Exome Sequencing she had IFNGR1 and SH2B3 mutations. Conclusion systemic fungal infections such as Aspergillosis can occur in patients with interferon-gamma receptor one deficiency. This type of immunodeficiency should be considered in treating patients with systemic Aspergillosis.
Source: BioMedCentral - 🏆 22. / 71 Read more »