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Functional properties of the resulting mutant α4β2-nAChR isoforms were compared to their wildtype counterparts. α4(R336H) subunit incorporation minimally affected single-channel amplitudes, whereas β2(V337G) subunit incorporation reduced them significantly in both isoforms. However, for both mutant subunits, increased function-per-receptor was predominantly caused by altered single channel kinetics. The α4(R336H) mutation primarily destabilizes desensitized states between openings. By contrast, the β2(V337G) mutation principally stabilizes receptor open states. The use of naturally-occurring and physiologically-impactful mutations has allowed us to define valuable new insights regarding the functional roles of nAChR intracellular domains. Further mechanistic context is provided by intracellular-domain structures recently published for other members of the Cys-loop receptor superfamily (α3β4-nAChR and 5-HT3AR).Several species of bears are known to rub deliberately against trees and other objects, but little is known about why bears rub. Patterns in rubbing behavior of male and female brown bears (Ursus arctos) suggest that scent marking via rubbing functions to communicate among potential mates or competitors. Using DNA from bear hairs collected from rub objects in southwestern Alberta from 2011-2014 and existing DNA datasets from Montana and southeastern British Columbia, we determined sex and individual identity of each bear detected. Using these data, we completed a parentage analysis. Deferiprone ic50 From the parentage analysis and detection data, we determined the number of offspring, mates, unique rub objects where an individual was detected, and sampling occasions during which an individual was detected for each brown bear identified through our sampling methods. Using a Poisson regression, we found a positive relationship between bear rubbing behavior and reproductive success; both male and female bears with a greater number of mates and a greater number of offspring were detected at more rub objects and during more occasions. Our results suggest a fitness component to bear rubbing, indicate that rubbing is adaptive, and provide insight into a poorly understood behaviour.

Adolescents living with HIV have poor treatment outcomes, including lower rates of viral suppression, than other age groups. Emerging evidence suggests a connection between improved mental health and increased adherence. Strengthening the focus on mental health could support increased rates of viral suppression. In sub-Saharan Africa clinical services for mental health care are extremely limited. Additional mechanisms are required to address the unmet mental health needs of this group. We consider the role that community-based peer supporters, a cadre operating at scale with adolescents, could play in the provision of lay-support for mental health.

We conducted qualitative research to explore the experiences of peer supporters involved in delivering a peer-led mental health intervention in Zimbabwe as part of a randomized control trial (Zvandiri-Friendship Bench trial). We conducted 2 focus group discussions towards the end of the trial with 20 peer supporters (aged 18-24) from across 10 intervention distgivers; and sustained investment in training and ongoing supervision.

Extending peer support to explicitly include a focus on mental health has enormous potential. From this empirical study we have developed a framework of core considerations and principles (the TRUST Framework) to guide the implementation of adequate supportive infrastructure in place to enhance the opportunities and mitigate risks.

Extending peer support to explicitly include a focus on mental health has enormous potential. From this empirical study we have developed a framework of core considerations and principles (the TRUST Framework) to guide the implementation of adequate supportive infrastructure in place to enhance the opportunities and mitigate risks.

Tuberculosis (TB) is a major cause of death worldwide. TB research draws heavily on clinical cohorts which can be generated using electronic health records (EHR), but granular information extracted from unstructured EHR data is limited. The St. Michael's Hospital TB database (SMH-TB) was established to address gaps in EHR-derived TB clinical cohorts and provide researchers and clinicians with detailed, granular data related to TB management and treatment.

We collected and validated multiple layers of EHR data from the TB outpatient clinic at St. Michael's Hospital, Toronto, Ontario, Canada to generate the SMH-TB database. SMH-TB contains structured data directly from the EHR, and variables generated using natural language processing (NLP) by extracting relevant information from free-text within clinic, radiology, and other notes. NLP performance was assessed using recall, precision and F1 score averaged across variable labels. We present characteristics of the cohort population using binomial proportions that includes a breadth of structured data derived from structured and unstructured EHR data by using NLP rulesets. The data are available for a variety of research applications, such as clinical epidemiology, quality improvement and mathematical modeling studies.

Motion preserving surgeries could be unsuccessful because of underestimation of deformities of the foot and knee in ankle osteoarthritis. This study aimed to investigate the concomitant deformities in medial ankle osteoarthritis and the difference between the two types, varus angulation and medial translation.

A retrospective study was conducted using medical records and radiographic data. Patients with medial ankle osteoarthritis that underwent weight-bearing X ray imaging and radiographic measurements including tibial plafond inclination (TPI), tibiotalar tilt angle (TT), lateral talo-first metatarsal angle, naviculo-cuboid overlap, and mechanical tibiofemoral angle (mTFA) were studied. The patients were categorized into two groups, the varus angulation group (TT ≥4°) and medial translation group (TT <4°). The radiographic measurements were compared between the two groups.

A total of 102 patients (male = 44; female = 58) were included; the mean age was 64.9 years (SD 8.3 years). The varus rotation group (N = 66) showed a significantly smaller lateral talo-first metatarsal angle (p<0.