Prenatal SARS-CoV-2 infection results in neurodevelopmental and behavioral outcomes in mice.

Prenatal exposure to viral pathogens has been known to cause the development of neuropsychiatric disorders in adulthood. Furthermore, COVID-19 has been associated with a variety of neurological manifestations, raising the question of whether in utero SARS-CoV-2 exposure can affect neurodevelopment, resulting in long-lasting behavioral and cognitive deficits. Using a human ACE2-knock-in mouse model, we have previously shown that prenatal exposure to SARS-CoV-2 at later stages of development leads to fetal brain infection and gliosis in the hippocampus and cortex.

Knockdown of Lhx6 during embryonic development results in neurophysiological alterations and behavioral deficits analogous to schizophrenia in adult rats.

A decreased expression of specific interneuron subtypes, containing either the calcium binding protein parvalbumin (PV) or the neurotransmitter somatostatin (SST), are observed in the cortex and hippocampus of both patients with schizophrenia and rodent models used to study the disorder. Moreover, preclinical studies suggest that this loss of inhibitory function is a key pathological mechanism underlying the symptoms of schizophrenia. Interestingly, decreased expression of Lhx6, a key transcriptional regulator specific to the development and migration of PV and SST interneurons, is seen in human postmortem studies and following multiple developmental disruptions used to model schizophrenia preclinically.

Clinical research imperatives: principles and priorities from the perspective of Allied Health executives and managers.

Objective It is widely understood that a key means of improving health systems and patient outcomes is through research - accessing, understanding, generating and applying research evidence-based practice. To promote more targeted and strategic research in Allied Health practice, this study sought to establish the principles, areas and priorities for clinical research as perceived by Allied Health leaders in the South Australian public health system. Methods The study used a mixed-methods design (full, sequential and equal model).

Extrasynaptic localization is essential for α5GABA receptor modulation of dopamine system function.

Dopamine system dysfunction, observed in animal models with psychosis-like symptomatology, can be restored by targeting Gamma-Aminobutyric Acid type A receptors (GABAR) containing the α5, but not α1, subunit in the ventral hippocampus (vHipp). The reason for this discrepancy in efficacy remains elusive; however, one key difference is that α1GABARs are primarily located in the synapse, whereas α5GABARs are mostly extrasynaptic. To test whether receptor location is responsible for this difference in efficacy, we injected a small interfering ribonucleic acid (siRNA) into the vHipp to knock down radixin, a scaffolding protein that holds α5GABARs in the extrasynaptic space.

Risk predictors of race disparity in patients undergoing coronary artery bypass grafting: a propensity-matched analysis.

Objectives: The aim of this study was to compare long-term prognosis after isolated coronary artery bypass grafting between white and black patients and to investigate risk factors for poorer outcomes among the latest.

Methods: All consecutive 4766 black and white patients undergoing isolated coronary artery bypass grafting between May 2005 and June 2021 at our institution were included. Primary outcomes were long-term incidence of all-cause death and major adverse cardiovascular and cerebrovascular events in black versus white patients.

Conservation in a litre of air.

Since Ficetola et al. (2008) alerted ecologists and conservation biologists to the existence of environmental DNA (eDNA), the number of studies using eDNA has exploded, with a rapidly increasing diversity of research, monitoring, and management objectives. Initial applications focused on amphibians and fishes while today's taxonomic targets span the phylogenetic tree.

Discrete hippocampal projections are differentially regulated by parvalbumin and somatostatin interneurons.

People with schizophrenia show hyperactivity in the ventral hippocampus (vHipp) and we have previously demonstrated distinct behavioral roles for vHipp cell populations. Here, we test the hypothesis that parvalbumin (PV) and somatostatin (SST) interneurons differentially innervate and regulate hippocampal pyramidal neurons based on their projection target. First, we use eGRASP to show that PV-positive interneurons form a similar number of synaptic connections with pyramidal cells regardless of their projection target while SST-positive interneurons preferentially target nucleus accumbens (NAc) projections.

Environmental DNA reveals the genetic diversity and population structure of an invasive species in the Laurentian Great Lakes.

Environmental DNA (eDNA) has been established as a noninvasive and efficient approach to sample genetic material from aquatic environments. Although most commonly used to determine species presence and measure biodiversity, eDNA approaches also hold great potential to obtain population-level genetic information from water samples. In this study, we sequenced a panel of multiallelic microsatellite markers from filtered water and fish tissue samples to uncover patterns of intraspecific diversity in the freshwater Round Goby () across their invaded range in the Laurentian Great Lakes region.

α5-GABAA Receptor Modulation Reverses Behavioral and Neurophysiological Correlates of Psychosis in Rats with Ventral Hippocampal Alzheimer's Disease-like Pathology.

Of the 35 million people in the world suffering from Alzheimer's Disease (AD), up to half experience comorbid psychosis. Antipsychotics, used to treat psychosis, are contraindicated in elderly patients because they increase the risk of premature death. Reports indicate that the hippocampus is hyperactive in patients with psychosis and those with AD.

GL-II-73, a Positive Allosteric Modulator of α5GABA Receptors, Reverses Dopamine System Dysfunction Associated with Pilocarpine-Induced Temporal Lobe Epilepsy.

Although seizures are a hallmark feature of temporal lobe epilepsy (TLE), psychiatric comorbidities, including psychosis, are frequently associated with TLE and contribute to decreased quality of life. Currently, there are no defined therapeutic protocols to manage psychosis in TLE patients, as antipsychotic agents may induce epileptic seizures and are associated with severe side effects and pharmacokinetic and pharmacodynamic interactions with antiepileptic drugs. Thus, novel treatment strategies are necessary.

Extrasynaptic localization is essential for α5GABA receptor modulation of dopamine system function.

Unlabelled: Dopamine system dysfunction, observed in animal models with psychosis-like symptomatology, can be restored by targeting Gamma-Aminobutyric Acid type A receptors (GABA R) containing the α5, but not α1, subunit in the ventral hippocampus (vHipp). The reason for this discrepancy in efficacy remains elusive; however, one key difference is that α1GABA Rs are primarily located in the synapse, whereas α5GABA Rs are mostly extrasynaptic. To test whether receptor location is responsible for this difference in efficacy, we injected a small interfering ribonucleic acid (siRNA) into the vHipp to knock down radixin, a scaffolding protein that holds α5GABA Rs in the extrasynaptic space.

Congenital blindness does not protect against a schizophrenia-related phenotype in rodents.

Background: In 1950, Drs. Chevigny and Braverman authored a book about people's attitudes and prejudices toward the blind, noting that out of the thousands of schizophrenia patients they and others had treated, not one was blind. This led some to the intriguing hypothesis that congenital blindness may provide protection against schizophrenia.

Detecting and analysing intraspecific genetic variation with eDNA: From population genetics to species abundance.

Advancements in environmental DNA (eDNA) approaches have allowed for rapid and efficient species detections in diverse environments. Although most eDNA research is focused on leveraging genetic diversity to identify taxa, some recent studies have explored the potential for these approaches to detect within-species genetic variation, allowing for population genetic assessments and abundance estimates from environmental samples. However, we currently lack a framework outlining the key considerations specific to generating, analysing and applying eDNA data for these two purposes.

Aberrant Dopamine System Function in the Ferrous Amyloid Buthionine (FAB) Rat Model of Alzheimer's Disease.

Antipsychotics increase the risk of death in elderly patients with Alzheimer's disease (AD). Thus, there is an immediate need for novel therapies to treat comorbid psychosis in AD. Psychosis has been attributed to a dysregulation of the dopamine system and is associated with aberrant regulation by the hippocampus.

Environment and shipping drive environmental DNA beta-diversity among commercial ports.

The spread of nonindigenous species by shipping is a large and growing global problem that harms coastal ecosystems and economies and may blur coastal biogeographical patterns. This study coupled eukaryotic environmental DNA (eDNA) metabarcoding with dissimilarity regression to test the hypothesis that ship-borne species spread homogenizes port communities. We first collected and metabarcoded water samples from ports in Europe, Asia, Australia and the Americas.

Long-term macrophyte and snail community responses to population declines of invasive rusty crayfish (Faxonius rusticus).

A central focus of invasive species research has been on human efforts to eradicate invaders or reduce their abundance to mitigate the worst of their impacts. In some cases, however, populations of invasive species decline without human intervention, which may inform management responses to these invaders. Such is the case of the invasive rusty crayfish (Faxonius rusticus) in northern Wisconsin, USA, where systematic population monitoring since 1975 has revealed population declines in approximately half of the lakes surveyed.

Hippocampal α5-GABA Receptors Modulate Dopamine Neuron Activity in the Rat Ventral Tegmental Area.

Background: Aberrant dopamine neuron activity is attributable to hyperactivity in hippocampal subfields driving a pathological increase in dopamine neuron activity, which is positively correlated with psychosis in humans. Evidence indicates that hippocampal hyperactivity is due to loss of intrinsic GABAergic (gamma-aminobutyric acidergic) inhibition. We have previously demonstrated that hippocampal GABAergic neurotransmission can be modulated by targeting α5-GABA receptors, which are preferentially expressed in hippocampal regions.

Increased Presynaptic Dopamine Synthesis Capacity Is Associated With Aberrant Dopamine Neuron Activity in the Methylazoxymethanol Acetate Rodent Model Used to Study Schizophrenia-Related Pathologies.

Aberrant dopamine system function is thought to contribute to the positive symptoms of schizophrenia. Clinical imaging studies have demonstrated that the largest dopamine abnormality in patients appears to be an increase in presynaptic dopamine activity. Indeed, studies utilizing positive emission tomography reliably report increases in presynaptic dopamine bioavailability in patients and may serve as a biomarker for treatment response.

A Preconditioning Paradox: Contrasting Effects of Initial Phyllosphere and Early Leaf Decomposer Microfungi on Subsequent Colonization by Leaf Decomposing Non-Unit-Restricted Basidiomycetes.

Fungal interactions during leaf decomposition can facilitate or inhibit other fungi. This experiment focused on whether preconditioning of leaf litter by microfungi that were confined to one leaf (Unit-Restricted) made leaf litter less likely to be colonized and decomposed by basidiomycetes that bind litter into mats (Non-Unit-Restricted) than non-preconditioned litter. Leaves of in litterbags were preconditioned by incubating them for 0, 1, 2 or 3 months in flat litter/seed rain baskets 10 cm above the forest floor to avoid colonization by basidiomycete fungi.

Time of day influences stress hormone response to ketamine.

Over 50% of depressed patients show hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Conventional therapy takes weeks to months to improve symptoms. Ketamine has rapid onset antidepressant effects.

Gestational buprenorphine exposure disrupts dopamine neuron activity and related behaviors in adulthood.

Opioid misuse among pregnant women is rapidly increasing in the United States. The number of maternal opioid-related diagnoses increased by 131% in the last ten years, resulting in an increased number of infants exposed to opioids and a subsequent increase in infants developing neonatal abstinence syndrome (NAS). The most prescribed treatment to combat maternal opioid use disorder is buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist.

Positive Allosteric Modulation of α5-GABAA Receptors Reverses Stress-Induced Alterations in Dopamine System Function and Prepulse Inhibition of Startle.

Background: Up to 64% of patients diagnosed with posttraumatic stress disorder (PTSD) experience psychosis, likely attributable to aberrant dopamine neuron activity. We have previously demonstrated that positive allosteric modulators of α5-GABAARs can selectively decrease hippocampal activity and reverse psychosis-like physiological and behavioral alterations in a rodent model used to study schizophrenia; however, whether this approach translates to a PTSD model remains to be elucidated.

Methods: We utilized a 2-day inescapable foot shock (IS) procedure to induce stress-related pathophysiology in male Sprague-Dawley rats.

Buprenorphine Exposure Alters the Development and Migration of Interneurons in the Cortex.

The misuse of opioids has reached epidemic proportions over the last decade, with over 2.1 million people in the United States suffering from substance use disorders related to prescription opioid pain relievers. This increase in opioid misuse affects all demographics of society, including women of child-bearing age, which has led to a rise in opioid use during pregnancy.