Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice.

Background: glucocorticoids may play an important role in the formation of fear memory, which is relevant to the neurobiology of post-traumatic stress disorder (PTSD). In our previous study, we showed the glucocorticoid receptor (GR) forms a protein complex with FKBP51, which prevents translocation of GR into the nucleus to affect gene expression; this complex is elevated in PTSD patients and by fear-conditioned learning in mice, and disrupting this complex blocks the storage and retrieval of fear-conditioned memories. The timing of release of glucocorticoid relative to the formation of a traumatic memory could be important in this process, and remains poorly understood.

Regionally distinct GFAP promoter expression plays a role in off-target neuron expression following AAV5 transduction.

Astrocyte to neuron reprogramming has been performed using viral delivery of neurogenic transcription factors in GFAP expressing cells. Recent reports of off-target expression in cortical neurons following adeno-associated virus (AAV) transduction to deliver the neurogenic factors have confounded our understanding of the efficacy of direct cellular reprogramming. To shed light on potential mechanisms that may underlie the neuronal off-target expression of GFAP promoter driven expression of neurogenic factors in neurons, two regionally distinct cortices were compared-the motor cortex (MC) and medial prefrontal cortex (mPFC)-and investigated: (1) the regional tropism and astrocyte transduction with an AAV5-GFAP vector, (2) the expression of Gfap in MC and mPFC neurons; and (3) material transfer between astrocytes and neurons.

Procognitive and neurotrophic benefits of α5-GABA-A receptor positive allosteric modulation in a β-amyloid deposition mouse model of Alzheimer's disease pathology.

Reduced somatostatin (SST) and SST-expressing GABAergic neurons are well-replicated findings in Alzheimer's disease (AD) and are associated with cognitive deficits. SST cells inhibit pyramidal cell dendrites through α5-GABA-A receptors (α5-GABAA-R). α5-GABAAR positive allosteric modulation (α5-PAM) has procognitive and neurotrophic effects in stress and aging models.

A telerehabilitation program to improve visual perception in children and adolescents with hemianopia consecutive to a brain tumor: a single-arm feasibility and proof-of-concept trial.

Background: Brain tumor in children can induce hemianopia, a loss of conscious vision, profoundly impacting their development and quality of life, yet no effective intervention exists for this pediatric population. This study aimed to explore the feasibility, safety, and potential effectiveness of a home-based audiovisual stimulation in immersive virtual-reality (3D-MOT-IVR) to improve visual function and functional vision.

Methods: In a phase 2a, open-labeled, nonrandomized, single-arm study, conducted from July 2022 to October 2023 (NCT05065268), 10 children and adolescents with stable hemianopia were enrolled to perform 20-min sessions of 3D-MOT-IVR every other day for six weeks from home.

Examining the NEUROG2-lineage and associated-gene expression in human cortical organoids.

Proneural genes are conserved drivers of neurogenesis across the animal kingdom. How their functions have adapted to guide human-specific neurodevelopmental features is poorly understood. Here, we mined transcriptomic data from human fetal cortices and generated from human embryonic stem cell (hESC)-derived cortical organoids (COs) to show that NEUROG1 and NEUROG2 are most highly expressed in basal neural progenitor cells, with pseudotime trajectory analyses indicating that NEUROG1-derived lineages predominate early and NEUROG2 lineages later.

SARS-CoV-2 3CL (main protease) regulates caspase activation of gasdermin-D/E pores leading to secretion and extracellular activity of 3CL.

SARS-CoV-2 3C-like protease (3CL or M) cleaves the SARS-CoV-2 polyprotein and >300 intracellular host proteins to enhance viral replication. By lytic cell death following gasdermin (GSDM) pore formation in cell membranes, antiviral pyroptosis decreases 3CL expression and viral replication. Unexpectedly, 3CL and nucleocapsid proteins undergo unconventional secretion from infected cells via caspase-activated GSDMD/E pores in the absence of cell lysis.

Neuronal viability/astrocyte activity ratio in the dorsolateral prefrontal cortex as a biomarker of Alzheimer's dementia: a proton magnetic resonance spectroscopy study.

N-acetyl-aspartate (NAA) and myo-inositol (mI) are neurometabolites reflecting neuronal viability and astrocyte activity, respectively. These are quantified using proton magnetic resonance spectroscopy (1H-MRS) and may be biomarkers for Alzheimer's disease dementia (AD). Our objectives were: 1) Compare dorsolateral prefrontal cortex (DLPFC) NAA and mI levels between AD and cognitively healthy control participants (HC) 2) assess if NAA/mI ratio can distinguish groups, and 3) explore the relationship between metabolites and cognition.

Network connectivity differences in music listening among older adults following a music-based intervention.

Music-based interventions are a common feature in long-term care with clinical reports highlighting music's ability to engage individuals with complex diagnoses. While these findings are promising, normative findings from healthy controls are needed to disambiguate treatment effects unique to pathology and those seen in healthy aging. The present study examines brain network dynamics during music listening in a sample of healthy older adults before and after a music-based intervention.

Thermal optimization of robotic piezoelectric osteotomy motion in porcine trabecular bone.

Background: Piezoelectric osteotomy represents a potentially viable alternative to conventional techniques for preparing pilot holes for bone screws. However, piezoelectric osteotomes have demonstrated the potential to heat bone beyond 47 °C, which induces necrosis that could contribute to screw loosening, resulting in osteosynthetic material failure and pseudarthrosis. Thus, we sought to determine the working movements of a piezoelectric drill that resulted in the lowest maximum bone temperatures while ensuring that this optimal drilling motion resulted in temperatures below 47 °C.

Red blood cell alloimmunization in transfused patients with hereditary hemorrhagic telangiectasia: A single centre retrospective study.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a genetic blood vessel disorder which may lead to chronic bleeding and red blood cell (RBC) transfusions. Data on transfusion requirements and complications in HHT patients are sparse.

Study Design And Methods: Retrospective chart review was conducted at St.

Quality of life, clinical outcomes and cost utilization of endoscopic therapy in patients with Barrett's esophagus and early esophageal cancer-an 8-year Canadian experience.

Background And Aims: Endoscopic treatment is a definitive and cost-effective management strategy for early neoplasia in Barrett's oesophagus (BE). However, little is known of its impact on quality of life (QoL). This study reports outcomes of endoscopic eradication treatment (EET), focusing on QoL and costs in a Canadian tertiary referral centre.

Quantifying the magnitude of the general contextual effect in a multilevel study of SARS-CoV-2 infection in Ontario, Canada: application of the median rate ratio in population health research.

Background: Regional variations in SARS-CoV-2 infection were observed in Canada and other countries. Studies have used multilevel analyses to examine how a context, such as a neighbourhood, can affect the SARS-CoV-2 infection rates of the people within it. However, few multilevel studies have quantified the magnitude of the general contextual effect (GCE) in SARS-CoV-2 infection rates and assessed how it may be associated with individual- and area-level characteristics.

Vascular injury derived apoptotic exosome-like vesicles trigger autoimmunity.

According to a central tenet of classical immune theory, a healthy immune system must avoid self-reactive lymphocyte clones but we now know that B cells repertoire exhibit some level of autoreactivity. These autoreactive B cells are thought to rely on self-ligands for their clonal selection and survival. Here, we confirm that healthy mice exhibit self-reactive B cell clones that can be stimulated by agonists of toll-like receptor (TLR) 1/2, TLR4, TLR7 and TLR9 to secrete anti-LG3/perlecan.

Predictors of Change in Vaccination Decisions Among the Vaccine Hesitant: Examining the Roles of Age and Intolerance of Uncertainty.

Background: Vaccine hesitancy and resistance pose significant threats to controlling pandemics and preventing infectious diseases. In a group of individuals unvaccinated against the disease caused by the SARS-CoV-2 coronavirus (COVID-19), we investigated how age, intolerance of uncertainty (IU), and their interaction affected the likelihood of having changed one's vaccination decision a year later. We hypothesized that higher IU would increase the likelihood of becoming vaccinated, particularly among individuals of younger age.

Education and Training in Global Neurosurgery: Current State and Path Toward a Uniform Curriculum.

Education is a sustainable long-term measure to address the global burden of neurosurgical disease. Neurosurgery residencies in high-income countries are accredited by a regional governing body and incorporate various educational activities. Few opportunities for training may be present in low-income and middle-income countries due to a lack of neurosurgery residency programs, tuition, and health care workforce reductions.

Canadian health care providers' and education workers' hesitance to receive original and bivalent COVID-19 vaccines.

Background: The demand for COVID-19 vaccines has diminished as the pandemic lingers. Understanding vaccine hesitancy among essential workers is important in reducing the impact of future pandemics by providing effective immunization programs delivered expeditiously.

Method: Two surveys exploring COVID-19 vaccine acceptance in 2021 and 2022 were conducted in cohorts of health care providers (HCP) and education workers participating in prospective studies of COVID-19 illnesses and vaccine uptake.

Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms.

Mutations in methyl-CpG binding protein 2 (MeCP2), such as the T158M, P152R, R294X, and R306C mutations, are responsible for most Rett syndrome (RTT) cases. These mutations often result in altered protein expression that appears to correlate with changes in the nuclear size; however, the molecular details of these observations are poorly understood. Using a C2C12 cellular system expressing human MeCP2-E1 isoform as well as mouse models expressing these mutations, we show that T158M and P152R result in a decrease in MeCP2 protein, whereas R306C has a milder variation, and R294X resulted in an overall 2.

Offshore wind and wave energy can reduce total installed capacity required in zero-emissions grids.

As the world races to decarbonize power systems to mitigate climate change, the body of research analyzing paths to zero emissions electricity grids has substantially grown. Although studies typically include commercially available technologies, few of them consider offshore wind and wave energy as contenders in future zero-emissions grids. Here, we model with high geographic resolution both offshore wind and wave energy as independent technologies with the possibility of collocation in a power system capacity expansion model of the Western Interconnection with zero emissions by 2050.

Effect of hyperglycemia and empagliflozin on markers of cardiorenal injury and inflammation in patients with type 1 diabetes.

Aims: To investigate the effect of hyperglycemia and empagliflozin on cardiorenal injury and inflammation in patients with uncomplicated type 1 diabetes (T1D).

Methods: Serum cardiac (sST2, Gal-3, cTnT), kidney injury (KIM-1, NGAL), inflammatory (sTNFR1, sTNFR2), and hemodynamic (NT-proBNP, EPO) markers were assessed post-hoc in two separate T1D cohorts. The glycemic clamp trial (NCT02344602) evaluated 49 adults with T1D and 27 controls under euglycemic and acute hyperglycemic conditions.

Structural connectivity changes in unilateral hearing loss.

Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome.