Abstract Policymakers and accrediting bodies have recognized the importance of integrating public health, population health, and prevention into graduate medical education programs. The high ...prevalence of chronic illness, coupled with the impact of behavioral and societal determinants of health, necessitate an urgent call for family medicine residencies to prepare future leaders to meet these challenges. The University of Massachusetts Worcester Family Medicine Residency recently developed an integrated curriculum that strives to develop a culture of incorporating fundamental public health principles into everyday practice. This public health curriculum was designed to integrate new topics within the current residency structure through longitudinal and concentrated experiences. This strategy has substantially improved public health and prevention education without substantial impact on the already strained residency curricular structure. This paper describes the integration of public health and prevention education into a family medicine residency to help residents acquire the fundamental skills necessary to improve a population's health.
One application of nanocopper is as a wood-preserving pesticide in pressure treated lumber. Recent research has shown that pressure treated lumber amended with micronized copper azole (MCA), which ...contains nano-sized copper, releases copper under estuarine and marine conditions. The form of copper released (i.e., ionic, nanocopper (1 to 100 nm in size)) is not fully understood but will affect the bioavailability and toxicity of the metal. In this investigation, multiple lines of evidence, including size fractionation, ion selective electrode (ISE) electrochemistry, comparative toxicity, and copper speciation were used to determine the form of copper released from lumber blocks and sawdust. Results of all lines of evidence supported the hypothesis that ionic copper was released from MCA lumber and sawdust with little evidence that nanocopper was released. For example, copper concentrations in size fractionations of lumber block aqueous leachates including unfiltered, 0.1 μm and 3 kiloDaltons (kDa) were not significantly different suggesting the form of copper released was in the size range operationally-defined as dissolved. These results correlated with the ISE data which detects only ionic copper. In addition, comparative toxicity testing resulted in a narrow range of LC
50
s (i.e., 221 to 257 μg/L) for MCA lumber blocks and CuSO
4
. This investigation concluded ionic copper was released from the nanocopper pressure treated lumber under estuarine and marine conditions.
X-linked spinal and bulbar muscular atrophy (SBMA), Kennedy's disease, is a degenerative disease of the motor neurons that is associated with an increase in the number of CAG repeats encoding a ...polyglutamine stretch within the androgen receptor (AR). Recent work has demonstrated that the gene products associated with open reading frame triplet repeat expansions may be substrates for the cysteine protease cell death executioners, the caspases. However, the role that caspase cleavage plays in the cytotoxicity associated with expression of the disease-associated alleles is unknown. Here, we report the first conclusive evidence that caspase cleavage is a critical step in cytotoxicity; the expression of the AR with an expanded polyglutamine stretch enhances its ability to induce apoptosis when compared with the normal AR. The AR is cleaved by a caspase-3 subfamily protease at Asp146, and this cleavage is increased during apoptosis. Cleavage of the AR at Asp146 is critical for the induction of apoptosis by AR, as mutation of the cleavage site blocks the ability of the AR to induce cell death. Further, mutation of the caspase cleavage site at Asp146 blocks the ability of the SBMA AR to form perinuclear aggregates. These studies define a fundamental role for caspase cleavage in the induction of neural cell death by proteins displaying expanded polyglutamine tracts, and therefore suggest a strategy that may be useful to treat neurodegenerative diseases associated with polyglutamine repeat expansions.
Objectives: This study aimed to characterise the personality profiles of junior medical students most likely to choose psychiatry as a career, determine aspects of psychiatry that most attract ...potential recruits, and identify misperceptions about psychiatry that may dissuade students from pursuing this specialism.
Method: A total of 580 second-year medical students from the University of New South Wales, Australia completed a set of questionnaires that measured the likelihood with which various medical specialties were being considered as careers, personality traits using the NEO Five-Factor Inventory (NEO-FFI), and the degree to which students perceived each specialty as attractive across a number of parameters.
Results: Only 86 students (15%) indicated a strong likelihood of choosing psychiatry, compared to other specialties which attracted higher proportions of students (range 19–49%). These 86 students had significantly higher openness scores than those who indicated a lesser likelihood of pursuing psychiatry. Students who were highly interested in psychiatry ranked it as very attractive in respect to providing interesting and challenging subject matter, and relatively attractive in respect to financial reward, work enjoyment, good lifestyle, having a bright and interesting future, and association with colleagues. However, psychiatry remained less attractive with respect to prestige, perceived low effectiveness of treatments, degree to which it draws upon aspects of medical training, and lack of reliable scientific foundation. Within the entire sample, psychiatry was ranked most unattractive compared to the other specialties across eight of the 13 parameters assessed.
Conclusions: Students interested in psychiatry are more likely to be ‘open’ and view the specialty as interesting and challenging. Such characteristics should be promoted more widely along with countering myths that as a specialty, psychiatry lacks a scientific foundation or is somehow different from mainstream medicine in terms of training and outcomes. Championing psychiatry in this manner may attract more recruits and enhance its prestige.
The prion protein (PrPC) has been suggested to operate as a scaffold/receptor protein in neurons, participating in both physiological and pathological associated events. PrPC, laminin, and ...metabotropic glutamate receptor 5 (mGluR5) form a protein complex on the plasma membrane that can trigger signaling pathways involved in neuronal differentiation. PrPC and mGluR5 are co-receptors also for β-amyloid oligomers (AβOs) and have been shown to modulate toxicity and neuronal death in Alzheimer's disease. In the present work, we addressed the potential crosstalk between these two signaling pathways, laminin-PrPC-mGluR5 or AβO-PrPC-mGluR5, as well as their interplay. Herein, we demonstrated that an existing complex containing PrPC-mGluR5 has an important role in AβO binding and activity in neurons. A peptide mimicking the binding site of laminin onto PrPC (Ln-γ1) binds to PrPC and induces intracellular Ca2+ increase in neurons via the complex PrPC-mGluR5. Ln-γ1 promotes internalization of PrPC and mGluR5 and transiently decreases AβO biding to neurons; however, the peptide does not impact AβO toxicity. Given that mGluR5 is critical for toxic signaling by AβOs and in prion diseases, we tested whether mGlur5 knock-out mice would be susceptible to prion infection. Our results show mild, but significant, effects on disease progression, without affecting survival of mice after infection. These results suggest that PrPC-mGluR5 form a functional response unit by which multiple ligands can trigger signaling. We propose that trafficking of PrPC-mGluR5 may modulate signaling intensity by different PrPC ligands.
The World Health Organization’s Tailoring Immunization Programmes approach was used to develop a new strategy to increase child vaccination coverage in a disadvantaged community in New South Wales, ...Australia, including reminders, outreach and home visiting. After 18 months, the strategy hasn’t been fully implemented. A process evaluation was conducted to identify barriers and facilitators for research translation. Participants included child health nurses, Population Health staff, managers and general practitioners. The Capability–Opportunity–Motivation model of behaviour change (COM-B) was used to develop questions. Twenty-four participants took part in three focus groups and four interviews. Five themes emerged: (i) designing and adopting new ways of working is time-consuming and requires new skills, new ways of thinking and changes in service delivery; (ii) genuine engagement and interaction across fields and institutions helps build capacity and strengthen motivation; (iii) implementation of a new strategy requires clarity; who’s doing what, when and how?; (iv) it is important not to lose sight of research findings related to the needs of disadvantaged families; and (v) trust in the process and perseverance are fundamental. There was strong motivation and opportunity for change, but a need to enhance service capability. Areas requiring support and resources were identified.
Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders caused by misfolding of a cellular protein PrP(C) into an infectious conformation PrP(Sc). Previously our group ...demonstrated induction of PrP(Sc)-specific antibodies with a SN6b vaccine that targets regions of the protein that are exposed upon misfolding. There are concerns that these antibodies could function as templates to promote misfolding and cause disease. To evaluate the consequences of prolonged exposure to PrP(Sc)-specific antibodies in a prion sensitized animal, tga20 mice were vaccinated with the SN6b vaccine. No clinical signs of disease were detected up to 255 d post-vaccination, and postmortem assay of brains and spleens revealed no proteinase-K resistant PrP. These results suggest that vaccinating against TSEs with the SN6b antigen is safe from the standpoint of prion disease induction.
Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders caused by misfolding of a cellular protein PrP
C
into an infectious conformation PrP
Sc
. Previously our group ...demonstrated induction of PrP
Sc
-specific antibodies with a SN6b vaccine that targets regions of the protein that are exposed upon misfolding. There are concerns that these antibodies could function as templates to promote misfolding and cause disease. To evaluate the consequences of prolonged exposure to PrP
Sc
-specific antibodies in a prion sensitized animal, tga20 mice were vaccinated with the SN6b vaccine. No clinical signs of disease were detected up to 255 d post-vaccination, and postmortem assay of brains and spleens revealed no proteinase-K resistant PrP. These results suggest that vaccinating against TSEs with the SN6b antigen is safe from the standpoint of prion disease induction.
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