The roles of low-voltage-activated (T-type) calcium channels in brain diseases have been studied extensively. Less is known regarding the involvement of T-type channels in cognition and behavior. Sensory integration (SI) is a cognitive process whereby the brain uses unimodal or multimodal sensory features to create a comprehensive representation of the environment. The multisensory object oddity (MSO) task assesses SI using combinations of sensory features of objects, either in the same or different sensory modalities. The regulation of SI involves the orbitofrontal cortex (OFC), an area which shows high levels of T-type calcium channel expression. We tested the effects of blocking T-type calcium channels on the MSO task with the selective T-type antagonist, Z944 (5 mg/kg; i.p. systemic; 100 or 500 µM OFC infusion), in male Long Evans rats. With systemic treatment, Z944 impaired the visual and visual-olfactory versions of the task. Infusion of 100 and 500 µM Z944 produced deficits in the olfactory version of the task. In addition, only vehicle-infused, but not Z944-infused, rats showed significant performance above chance for all task variants. Thus, the present results suggest that T-type calcium channels in OFC are involved in SI of features in an oddity task. Given that unimodal SI was disrupted by OFC infusions of Z944, the deficits in the multimodal task must be interpreted with caution. As SI is disrupted in psychiatric disorders, further investigations elucidating the brain regions implicated in SI regulation by T-type calcium channels may help inform therapeutic development for those suffering from SI impairments.
Introduction:The serine-threonine kinase AKT2 is a critical mediator of insulin's anabolic effects, particularly cellular glucose uptake. The gain-of-function c.49G>A, p.(Glu17Lys)AKT2 variant results in hypoketotic hypoglycemia with suppressed insulin and free fatty acid levels due to constitutive activation of the insulin signaling cascade. Although biochemical similarities exist amongst the eight individuals identified to date, the associated phenotype varies considerably. Treatment of these patients remains challenging, consisting primarily of frequent feeds with uncooked cornstarch.Case Presentation: We describe a female with hemihypertrophy, developmental delay, and dysmorphic features who presented to our center with hypoglycemic seizures at age 6-months. Critical sample revealed hypoketotic hypoglycemia, undetectable insulin, and suppressed free fatty acids. Molecular testing confirmed a pathogenic c.49G>A, p.(Glu17Lys) AKT2 mutation. Glycemic control was initially difficult to establish, with recurrent hypoglycemia despite high glucose infusion rates. Following in-hospital administration of Posted on
Our understanding of the neural substrates underlying the cognitive symptoms of schizophrenia remains limited, contributing to a lack of pharmaceuticals effective in treating these deficits. Cognitive impairment is the main source of disability in schizophrenia. Thus, research endeavours involving the identification of therapeutic targets can vastly improve the lives of affected individuals. Compared to previously employed techniques, optogenetics has accelerated such endeavours by allowing for manipulations of neuronal activity to occur with an unprecedented combination of cellular and temporal specificity. Research using this technique has united multiple, once tangentially-related, streams of evidence suggesting dysfunctional fast-spiking parvalbumin (PV) containing interneurons are a common substrate underlying the cognitive aberrations documented in schizophrenia. This review summarizes relevant optogenetic studies and identifies areas for future research, using this emerging technique.
Background In response to the COVID-19 pandemic, jurisdictions around the world implemented policies to reduce COVID-19 transmission through public masking, travel restrictions, and closure of non-essential businesses. Collectively known as non-pharmaceutical interventions (NPI), these strategies reliably reduce the spread of COVID-19. International data suggests NPI also reduce hospitalizations for pediatric respiratory infections and their consequences, particularly asthma exacerbation. However, few Canadian studies have examined the impact of NPI on hospitalizations for common causes of pediatric respiratory distress. Objectives This study describes the impact of NPI on admissions for bronchiolitis, pneumonia, and asthma at a Canadian pediatric tertiary care centre. Design/Methods A retrospective chart review was conducted including all pediatric patients <18 years admitted to the general pediatric and pediatric intensive care units with bronchiolitis, pneumonia, or asthma. Data regarding diagnosis, length of hospitalization, and mortality were collected before (September 2016-March 2020) and in the 6 months after provincial NPI implementation (March 2020-September 2020). NPI were present throughout this period, however, specific measures varied due to evolving public health orders. Chi-squared testing was conducted to describe the impact of NPI on number of admissions, length of hospitalization, and mortality. Results Participants (n=1631) included 111 (6.8%) patients <1 month, 878 (53.8%) patients 1-23 months, 331 (20.3%) patients 24 months-4 years, and 311 (19.1%) patients ≥5 years. A mean of 205 patients were admitted every 6 months with respiratory distress (bronchiolitis, pneumonia, and/or asthma) prior to NPI implementation. During this timeframe, the 6-month mean admissions due to asthma, pneumonia, and bronchiolitis were 48, 56, and 101, respectively. In the 6 months following NPI implementation, there were 56 admissions for respiratory distress, including 15 for asthma, 19 for pneumonia, and 22 for bronchiolitis. Mean length of stay increased following the implementation of NPI from 8.49 to 11.68 days, whereas 6-month mean mortality decreased from two to zero deaths. Results did not attain statistical significance (p>0.05). Conclusion Results suggest NPI reduce hospitalizations and mortality from bronchiolitis, pneumonia, and asthma. Given the similar seasonality of these conditions, periodic use of NPI beyond the COVID-19 pandemic may reduce pediatric morbidity and mortality from common causes of respiratory distress. However, additional research is needed to describe the relationship between NPI and length of hospitalization. Future studies should also examine the impact of NPI on other pediatric infectious diseases to better characterize their utility.
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