Public experiences and perspectives of primary care in Canada: results from a cross-sectional survey.

Background: Through medicare, residents in Canada are entitled to medically necessary physician services without paying out of pocket, but still many people struggle to access primary care. We conducted a survey to explore people's experience with and priorities for primary care.

Methods: We conducted an online, bilingual survey of adults in Canada in fall 2022.

An education resource for human papillomavirus oropharyngeal cancer patients: think-aloud interviews.

Purpose: The human papillomavirus (HPV) is well recognised as a factor in developing oropharyngeal cancer (OPC). A booklet for HPV-OPC patients aimed to deliver evidence-based messages in everyday language, in a way to minimise negative psychological impacts on patients. Our study explored the suitability of the booklet for use.

A three-pronged approach that leans on Indigenous knowledge for northern fish monitoring and conservation.

Investigating whether changes within fish populations may result from harvesting requires a comprehensive approach, especially in more data-sparse northern regions. Our study took a three-pronged approach to investigate walleye population change by combining Indigenous knowledge (IK), phenotypic traits, and genomics. We thank Larson et al.

Loss of tyrosine hydroxylase, motor deficits and elevated iron in a mouse model of phospholipase A2G6-associated neurodegeneration (PLAN).

Phospholipase A2G6-associated neurodegeneration (PLAN) is a rare early-onset monogenic neurodegenerative movement disorder which targets the basal ganglia and other regions in the central and peripheral nervous system; presenting as a series of heterogenous subtypes in patients. We describe here a B6.C3-Pla2g6 mouse model of PLAN which presents with early-onset neurodegeneration at 90 days which is analogous of the disease progression that is observed in PLAN patients.

Size reductions and genomic changes within two generations in wild walleye populations: associated with harvest?

The extent and rate of harvest-induced genetic changes in natural populations may impact population productivity, recovery, and persistence. While there is substantial evidence for phenotypic changes in harvested fishes, knowledge of genetic change in the wild remains limited, as phenotypic and genetic data are seldom considered in tandem, and the number of generations needed for genetic changes to occur is not well understood. We quantified changes in size-at-age, sex-specific changes in body size, and genomic metrics in three harvested walleye () populations and a fourth reference population with low harvest levels over a 15-year period in Mistassini Lake, Quebec.

One‑carbon metabolism factor MTHFR variant is associated with saccade latency in Spinocerebellar Ataxia type 2.

Background: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder due to a CAG-repeat expansion. This work is intended to identify modifiers of the clinical phenotype in SCA2, following up on recent genome-wide association analyses that demonstrated the prominent role of DNA-damage repair and methylation for the severity and progression of polyglutamine diseases. In particular, we assessed the impact of MTHFR as rate-limiting enzyme in DNA methylation pathways, which modulates cerebellar neurotransmission and motor neuron atrophy.

Basolateral amygdala - nucleus accumbens circuitry regulates optimal cue-guided risk/reward decision making.

Maladaptive decision making is a characteristic feature of substance use disorder and pathological gambling. Studies in humans and animals have implicated neural circuits that include the basolateral amygdala (BLA) and nucleus accumbens (NAc) in facilitating risk/reward decision making. However, the preclinical literature has focussed primarily on situations where animals use internally-generated information to adapt to changes in reward likelihood, whereas many real-life situations require the use of external stimuli to facilitate context-appropriate behavior.

Validation of the 8 edition UICC/AJCC TNM staging system for HPV associated oropharyngeal cancer patients managed with contemporary chemo-radiotherapy.

Background: To compare outcomes of high-risk human papilloma virus-related oropharyngeal squamous cell carcinoma (HPV OPSCC) treated with modern radiation treatment (RT) and daily image-guidance, staged with the 7 versus the 8 Edition (Ed) Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM staging systems.

Methods: All eligible patients with HPV OPSCC treated definitively over a 10-year period (2007-2016) at a single institution were included. Protocols consisting of either RT or chemo-radiation (CRT) (weekly cisplatin or cetuximab) +/- neoadjuvant chemotherapy for those with bulky disease were used.

Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of -related disorders.

Background: Chitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified.

Methods And Results: We identified three unrelated families with a total of six affected patients with the clinical manifestations of Chitayat-Hall syndrome.

Compound heterozygous TRPV4 mutations in two siblings with a complex phenotype including severe intellectual disability and neuropathy.

TRPV4 encodes a polymodal calcium-permeable plasma membrane channel. Dominant pathogenic mutations in TRPV4 lead to a wide spectrum of abnormal phenotypes. This is the first report of biallelic TRPV4 mutations and we describe two compound heterozygous siblings presenting with a complex phenotype including severe neuromuscular involvement.

Association of glutathione S-transferase omega polymorphism and spinocerebellar ataxia type 2.

Background: Spinocerebellar ataxia type 2 is a neurodegenerative disorder caused by a CAG repeat expansion in ATXN2 gene. There is high clinical variability among affected patients suggesting the occurring of modifier genes influencing the clinical phenotype.

Objective: The objective is to assess the association of GSTO1 rs4925 and GSTO2 rs2297235 SNPs on the clinical phenotype in SCA2 patients.

From Function to Phenotype: Impaired DNA Binding and Clustering Correlates with Clinical Severity in Males with Missense Mutations in MECP2.

Mutations in the MECP2 gene cause Rett syndrome (RTT). MeCP2 binds to chromocentric DNA through its methyl CpG-binding domain (MBD) to regulate gene expression. In heterozygous females the variable phenotypic severity is modulated by non-random X-inactivation, thus making genotype-phenotype comparisons unreliable.

A preliminary study of dopamine D2/3 receptor availability and social status in healthy and cocaine dependent humans imaged with [(11)C](+)PHNO.

Background: Previous work in healthy non-human primates and humans has shown that social status correlates positively with dopamine 2/3 receptor (D2/3R) availability imaged with antagonist radioligands and positron emission tomography (PET). Further work in non-human primates suggests that this relationship is disrupted by chronic cocaine administration. This exploratory study examined the relationship between social status and D2/3R availability in healthy (HH) and cocaine dependent (CD) humans using the D3-preferring, agonist radioligand, [(11)C](+)PHNO.

Large normal and intermediate alleles in the context of SCA2 prenatal diagnosis.

In 2001 a program for predictive testing of Spinocerebellar Ataxia type 2 was developed in Cuba, based on the detection of an abnormal CAG trinucleotide repeat expansion in the ATXN2 gene. A descriptive study was designed to assess the implications of ATXN2 large normal and intermediate alleles in the context of the SCA2 Prenatal Diagnosis Program. Four clinical scenarios were selected based upon the behaviour of large normal and intermediate alleles when passing from one generation to the next, showing expansions, contractions, or stability in the CAG repeat size.

Detection of rarely identified multiple mutations in MECP2 gene do not contribute to enhanced severity in Rett syndrome.

The objective of our study was to characterize the influence of multiple mutations in the MECP2 gene in a cohort of individuals with Rett syndrome. Further analysis demonstrated that nearly all resulted from de novo in cis mutations, where the disease severity was indistinguishable from single mutations. Our methods involved enrolling participants in the RTT Natural History Study (NHS).

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum.

Background: Mutations in SACS, leading to autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), have been identified as a frequent cause of recessive early-onset ataxia around the world. Here we aimed to enlarge the spectrum of SACS mutations outside Quebec, to establish the pathogenicity of novel variants, and to expand the clinical and imaging phenotype.

Methods: Sequencing of SACS in 22 patients with unexplained early-onset ataxia, assessment of novel SACS variants in 3.

Psychological well-being and family satisfaction levels five years after being confirmed as a carrier of the Machado-Joseph disease mutation.

The present study on long-term outcome of presymptomatic testing for Machado-Joseph disease (MJD) aimed to evaluate the psychological well-being and the familial satisfaction of subjects that 5 years prior received an unfavorable result in the predictive testing (PT). The study included 47 testees of Azorean origin (23 from the island of Flores and 24 from S. Miguel) that completed the fourth evaluation session of the MJD protocol, and undertook a neurological examination at the moment of participation in the study.

The longitudinal elderly person shadowing program: outcomes from an interprofessional senior partner mentoring program.

The University of Saskatchewan's Longitudinal Elderly Person Shadowing (LEPS) is an interprofessional senior mentors program (SMP) where teams of undergraduate students in their first year of medicine, pharmacy, and physiotherapy; 2nd year of nutrition; 3rd year nursing; and 4th year social work partner with community-dwelling older adults. Existing literature on SMPs provides little information on the sustainability of attitudinal changes toward older adults or changes in interprofessional attitudes. LEPS students completed Polizzi's Aging Semantic Differential and the Interdisciplinary Education Perception Scale.

Uncommon features in Cuban families affected with Friedreich ataxia.

This report describes two families who presented with autosomal recessive ataxia. By means of Polymerase Chain Reaction (PCR) molecular testing we identified expansions in the gene encoding Frataxin (FTX) that is diagnostic of Friedreich ataxia. A history of reproductive loss in the two families, prominent scoliosis deformity preceding the onset of ataxic gait, the presence of a sensitive axonal neuropathy, as well as the common origin of ancestors are unusual features of these families.