AAV9/SLC6A1 gene therapy rescues abnormal EEG patterns and cognitive behavioral deficiencies in Slc6a1-/- mice.

The SLC6A1 gene encodes the gamma-aminobutyric acid (GABA) transporter GAT-1, the deficiency of which is associated with infantile encephalopathy with intellectual disability. We designed two AAV9 vectors, with either the JeT or MeP promoter, and conducted preclinical gene therapy studies using heterozygous and homozygous Slc6a1 KO mice at different developmental ages and various routes of administration. Neonatal intracerebroventricular administration of either vector resulted in significantly normalized EEG patterns in Slc6a1-/- or Slc6a1+/- mice, as well as improvement in several behavioral phenotypes of Slc6a1-/- mice.

Pilot feasibility randomised controlled trial of cognitive-behavioural therapy for functional cognitive disorder after concussion.

Background: Functional cognitive disorder (FCD) may be common after a concussion, and no evidence-based treatment options are available. The current study evaluated the feasibility of a novel cognitive-behavioural therapy (CBT) protocol tailored to FCD after concussion.

Methods: Participants were randomised to CBT (n=11) or the current standard of care, cognitive rehabilitation (n=13).

Graded exposure therapy for adults with persistent symptoms after mTBI: A historical comparison study.

Fear avoidance behaviour is associated with slow recovery from mild traumatic brain injury (mTBI). This study is a preliminary evaluation of graded exposure therapy (GET), which directly targets fear avoidance behaviour, for reducing post-concussion symptoms (PCS) and disability following mTBI. In a historical comparison design, we compared two groups from independent randomized trials.

Connect-ROD - development and qualitative evaluation of a community-based group intervention to support well-being in patients with a rare or orphan disease.

Background: Patients living with various rare or orphan diseases (ROD) experience common psychosocial difficulties. Those need emerge from a combination of factors, such as the large variety of patients and the rarity of resources, as well as concentrated efforts on physical health needs that yielded increases in life expectancy and quality in patients. A gap is therefore rising in the consideration of psychosocial needs of patients, such as coping with the impacts of physical limitations, reducing social isolation and distress.

Concurrent Crystallization Mechanism Leading to Low Temperature Percolation of LAGP Glass-Ceramic Electrolyte.

Sintering of ceramic electrolytes (CE) is the most efficient way to obtain a dense, all ceramic solid-state battery with oxide-based materials. However, the high temperature required for this process leads to detrimental reactivity between CE and the active material. Crystalline ceramics are necessary for highly conductive oxide materials.

Perception of Paternal Postpartum Depression among Healthcare Professionals: A Qualitative Study.

The pathway to parenthood constitutes a fundamental and transformative stage in every individual's life. While postpartum depression in mothers has been increasingly studied and acknowledged, paternal postpartum depression (PPD) has garnered only moderate research attention. This study aims to delve into the comprehension and knowledge of healthcare professionals who may encounter men suffering from postpartum depression.

Catastrophizing is associated with excess cognitive symptom reporting after mild traumatic brain injury.

Objective: Persistent cognitive symptoms after mild traumatic brain injury (mTBI) often do not correlate with objective neuropsychological performance. Catastrophizing (i.e.

Wastewater-based epidemiology: the crucial role of viral shedding dynamics in small communities.

Background: Wastewater surveillance (WWS) of pathogens is a rapidly evolving field owing to the 2019 coronavirus disease pandemic, which brought about a paradigm shift in public health authorities for the management of pathogen outbreaks. However, the interpretation of WWS in terms of clinical cases remains a challenge, particularly in small communities where large variations in pathogen concentrations are routinely observed without a clear relation to clinical incident cases.

Methods: Results are presented for WWS from six municipalities in the eastern part of Canada during the spring of 2021.

Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B.

Dominantly inherited GAA repeat expansions in FGF14 are a common cause of spinocerebellar ataxia (GAA-FGF14 ataxia; spinocerebellar ataxia 27B). Molecular confirmation of FGF14 GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories. We developed and validated a strategy to detect FGF14 GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing.

Emplacement of the Franklin large igneous province and initiation of the Sturtian Snowball Earth.

During the Cryogenian (720 to 635 Ma ago) Snowball Earth glaciations, ice extended to sea level near the equator. The cause of this catastrophic failure of Earth's thermostat has been unclear, but previous geochronology has suggested a rough coincidence of glacial onset with one of the largest magmatic episodes in the geological record, the Franklin large igneous province. U-Pb geochronology on zircon and baddeleyite from sills associated with the paleo-equatorial Franklin large igneous province in Arctic Canada record rapid emplacement between 719.

Attachment and Clinical Outcomes Among Treatment-Seeking Adults With Persistent Symptoms After Mild Traumatic Brain Injury.

Objective: Interpersonal attachment influences the development and course of disease. Overreliance on insecure attachment strategies may increase risk for poor disease outcomes. This study aimed to investigate largely unexplored relationships between attachment strategies and clinical outcomes among adults with persistent symptoms after mild traumatic brain injury (mTBI).

Oral anticoagulation use in non-valvular atrial fibrillation patients in rural setting.

Background: The 2019 ACC/AHA/HRS guidelines established direct oral anticoagulants (DOACs) as first line therapy over warfarin for non-valvular atrial fibrillation (AF).

Methods: Ambulatory clinic patients with non-valvular AF or atrial flutter seen between 10/1/2019-7/12/2020 included. High-risk AF defined as males CHADS-VASc score ≥2 and females ≥3.

A novel stress-based intervention reduces cigarette use in non-treatment seeking smokers.

Tobacco use is the leading cause of preventable mortality worldwide. Since current smoking cessation aids show only modest efficacy, new interventions are needed. Given the evidence that stress is a potent trigger for smoking, the present randomized clinical trial tested whether stress could augment the effects of a memory updating (retrieval-extinction) intervention.

After the virus has cleared-Can preclinical models be employed for Long COVID research?

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) can cause the life-threatening acute respiratory disease called COVID-19 (Coronavirus Disease 2019) as well as debilitating multiorgan dysfunction that persists after the initial viral phase has resolved. Long COVID or Post-Acute Sequelae of COVID-19 (PASC) is manifested by a variety of symptoms, including fatigue, dyspnea, arthralgia, myalgia, heart palpitations, and memory issues sometimes affecting between 30% and 75% of recovering COVID-19 patients. However, little is known about the mechanisms causing Long COVID and there are no widely accepted treatments or therapeutics.

Group intervention programs and their impact on well-being and quality-of-life for adults living with a rare or orphan disease - realist review of literature.

Purpose: Adults living with a rare or orphan diseases (ROD) experience common psychosocial difficulties that are often poorly addressed in usual care. This realist literature review aims to inform the development, evaluation and implementation of evidence based group therapy programs adapted to shared needs of patients living with various ROD.

Method: The review is based on an analysis of Context-Mechanism-Outcome configurations.

Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Here we investigated the impact of male sex and age comparing sex-matched or age-matched ferrets infected with SARS-CoV-2. Differences in temperature regulation was identified for male ferrets which was accompanied by prolonged viral replication in the upper respiratory tract after infection.

The Intersection of Age and Influenza Severity: Utility of Ferrets for Dissecting the Age-Dependent Immune Responses and Relevance to Age-Specific Vaccine Development.

Many factors impact the host response to influenza virus infection and vaccination. Ferrets have been an indispensable reagent for influenza virus research for almost one hundred years. One of the most significant and well-known factors affecting human disease after infection is host age.

Reduced anterior hippocampal and ventromedial prefrontal activity when repeatedly retrieving autobiographical memories.

Research has reported that repeatedly retrieving a novel or imagined event representation reduces activity within brain regions critical for constructing mental scenarios, namely the anterior hippocampus and ventromedial prefrontal cortex (vmPFC). The primary aim of this investigation was to test if this pattern reported for imagined events would be found when repeatedly recollecting autobiographical memories. Twenty-four participants retrieved 12 pre-selected autobiographical memories four times while undergoing an fMRI scan.

The Power of First Impressions: Can Influenza Imprinting during Infancy Inform Vaccine Design?

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system, and lack of previous exposure to the virus is thought to synergistically play a role in the increased disease severity in younger age groups. No influenza vaccines are available for those under six months, although maternal influenza immunization is recommended.