Natasha Garfield

Strategies to optimize participation in diabetes prevention programs following gestational diabetes: a focus group study.

Objective We performed a qualitative study among women within 5 years of Gestational Diabetes (GDM) diagnosis. Our aim was to identify the key elements that would enhance participation in a type 2 diabetes (DM2) prevention program. Research Design and Methods Potential participants received up to three invitation letters from their GDM physician. Four focus groups were held. Discussants were invited to comment on potential facilitators/barriers to participation and were probed on attitudes towards meal replacement and Internet/social media tools. Recurring themes were identified through qualitative content analysis of discussion transcripts. Results Among the 1,201 contacted and 79 eligible/interested, 29 women attended a focus group discussion. More than half of discussants were overweight/obese, and less than half were physically active. For DM2 prevention, a strong need for social support to achieve changes in dietary and physical activity habits was expressed. In this regard, face-to-face interactions with peers and professionals were preferred, with adjunctive roles for Internet/social media. Further, direct participation of partners/spouses in a DM2 prevention program was viewed as important to enhance support for behavioural change at home. Discussants highlighted work and child-related responsibilities as potential barriers to participation, and emphasized the importance of childcare support to allow attendance. Meal replacements were viewed with little interest, with concerns that their use would provide a poor example of eating behaviour to children. Conclusions Among women within 5 years of a GDM diagnosis who participated in a focus group discussion, participation in a DM2 prevention program would be enhanced by face-to-face interactions with professionals and peers, provision of childcare support, and inclusion of spouses/partners.

Menin Missense Mutants Encoded by the MEN1 Gene that Are Targeted to the Proteasome: Restoration of Expression and Activity by CHIP siRNA

CONTEXT In multiple endocrine neoplasia type 1 (MEN1) characterized by tumors of parathyroid, enteropancreas, and anterior pituitary, missense mutations in the MEN1 gene product, menin, occur in a subset of cases. The mutant proteins are degraded by the proteasome. However, whether their expression and activity can be restored is not known. OBJECTIVE Our objective was to functionally characterize a panel of 16 menin missense mutants, including W423R and S443Y identified in new MEN1 families, with respect to protein stability, targeting to the proteasome and restoration of expression by proteasome inhibitors and expression and function by small interfering RNA technology. METHODS Flag-tagged wild-type (WT) and missense menin mutant expression vectors were transiently transfected in human embryonic kidney (HEK293) and/or rat insulinoma (Rin-5F) cells. RESULTS The majority of mutants were short-lived, whereas WT menin was stable. Proteasome inhibitors MG132 and PS-341 and inhibition of the chaperone, heat-shock protein 70 (Hsp70), or the ubiquitin ligase, COOH terminus of Hsp70-interacting protein (CHIP), by specific small interfering RNA, restored the levels of the mutants, whereas that of WT menin was largely unaffected. Inhibition of CHIP restored the ability of mutants to mediate normal functions of menin: TGF-β up-regulation of the promoters of its target genes, the cyclin-dependent kinase inhibitors p15 and p21 as well as TGF-β inhibition of cell numbers. CONCLUSION When the levels of missense menin mutants that are targeted to the proteasome are normalized they may function similarly to WT menin. Potentially, targeting specific components of the proteasome chaperone pathway could be beneficial in treating a subset of MEN1 cases.

Incidence and histopathological behavior of papillary microcarcinomas: Study of 429 cases

Objective We aim to present papillary microcarcinoma (PMC) incidence at a university teaching hospital, to compare characteristics of PMC in relation to size, and to assess for significant difference in PMC incidence among patients with non-PMC thyroid malignancies. Materials and Methods Pathology results were reviewed for consecutive total thyroidectomies between 2002 and 2007 (n = 860). Statistical significance was calculated using χ2 or, when unavailable, Fisher exact test. Results PMC was found in 429 cases, which is 49.9 percent of all total thyroidectomies. In PMC ≥5 mm, 25.1 percent had extrathyroidal extension vs 9.1 percent for <5 mm (P < 0.001). When 4 mm is used as a threshold, P value was 300–fold smaller. Incidence in patients with any non-PMC thyroid malignancy was 51.6 percent against 47.2 percent in all other patients (P = 0.203). Conclusions In this study, PMC was found in 49.9 percent of patients, which, to our knowledge, is higher than any other reported incidence. A threshold of ≥4 mm was more significant than 5 mm for carrying increased risk for extrathyroidal spread. There was no significant difference in PMC incidence in patients with malignant vs benign disease.

Genetics and animal models of hypoparathyroidism

Hypoparathyroidism is a heterogeneous group of disorders with diverse etiologies. During the past decade, major advances have been made towards unraveling the precise cellular and molecular mechanisms that underlie the pathogenesis of this endocrinopathy. Studies of patients afflicted with the disease and of genetically altered mice with strategically engineered mutations have paved new and exciting avenues of investigation into its causes. While focusing on these discoveries, we review areas of controversy and discuss possible approaches for their resolution.

Carotid femoral pulse wave velocity in type 2 diabetes and hypertension: capturing arterial health effects of step counts

Objective: Optimal medication use obscures the impact of physical activity on traditional cardiometabolic risk factors. We evaluated the relationship between step counts and carotid-femoral pulse wave velocity (cfPWV), a summative risk indicator, in patients with type 2 diabetes and/or hypertension. Research design and methods: Three hundred and sixty-nine participants were recruited (outpatient clinics; Montreal, Quebec; 2011–2015). Physical activity (pedometer/accelerometer), cfPWV (applanation tonometry), and risk factors (A1C, Homeostatic Model Assessment–Insulin Resistance, blood pressure, lipid profiles) were evaluated. Linear regression models were constructed to quantify the relationship of steps/day with cfPWV. Results: The study population comprised 191 patients with type 2 diabetes and hypertension, 39 with type 2 diabetes, and 139 with hypertension (mean ± SD: age 59.6 ± 11.2 years; BMI 31.3 ± 4.8 kg/m2; 54.2% women). Blood pressure (125/77 ± 15/9 mmHg), A1C (diabetes: 7.7 ± 1.3%; 61 mmol/mol), and low-density lipoprotein cholesterol (diabetes: 2.19 ± 0.8 mmol/l; without diabetes: 3.13 ± 1.1mmol/l) were close to target. Participants averaged 5125 ± 2722 steps/day. Mean cfPWV was 9.8 ± 2.2 m/s. Steps correlated with cfPWV, but not with other risk factors. A 1000 steps/day increment was associated with a 0.1 m/s cfPWV decrement across adjusted models and in subgroup analysis by diabetes status. In a model adjusted for age, sex, BMI, ethnicity, immigrant status, employment, education, diabetes, hypertension, medication classes, the mean cfPWV decrement was 0.11 m/s (95% confidence interval −0.2, −0.02). Conclusions: cfPWV is responsive to step counts in patients who are well controlled on cardioprotective medications. This ability to capture the ‘added value’ of physical activity supports the emerging role of cfPWV in arterial health monitoring.

THE IMPACT OF PHARMACOTHERAPY ON LONG-TERM SURVIVAL AND STROKE AFTER HOSPITALIZATION FOR ATRIAL FIBRILLATION

We aim to evaluate the impact of several drugs on long-term all-cause mortality and risk of stroke or transient ischemic attack (TIA), in patients hospitalized for atrial fibrillation (AF). Using Quebec provincial health administrative databases, we conducted a retrospective cohort study of all

Sequential Thyroid Storm and Myxedema Coma: A Unique Case Report

Background and objective: Both thyroid storm and myxedema coma are rare life-threatening events and carry a high mortality rate. Our objective is to document a unique case of sequential thyroid storm and myxedema coma. Results: We report a very unusual case of a 46-year-old female patient who presented initially in 2002 with thyroid storm caused by a previously undiagnosed Graves’ disease. After two doses of radioactive iodine treatment, she developed hypothyroidism for which she was placed on l-thyroxine replacement therapy. She was lost to followup and, indeed, she failed to take her l-thyroxine medication and in the fall of 2010, she presented to our Emergency Department with myxedema coma, which was treated successfully. Conclusion: A careful and life-long follow-up is essential in patients who have received thyroid radioactive iodine ablation or total thyroidectomy to ensure that their thyroidal status remains stable. This constitutes the first step in the prevention of myxedema coma, a diagnosis which still carries an appreciable mortality rate.