Effect of Metformin on the High-Density Lipoprotein Proteome in Youth with Type 1 Diabetes

Background: Youth with type 1 diabetes (T1D) have normal or elevated High-Density Lipoprotein Cholesterol (HDL-C), however, the function of HDL, partly mediated by the HDL proteome, may be impaired. Metformin can be used as an adjunct therapy in youth with T1D, but its effects on the HDL proteome are unknown. Objective: To determine the effect of metformin on the HDL proteome. Subjects: Youth (12-20 years old) with T1D who had a BMI \u3e 90th percentile, HbA1c \u3e 8.0% and Tanner stage 5. Methods: Double-blinded, placebo-controlled randomized sub-study. We examined the effects of metformin (n = 25) or placebo (n = 10) after 6 months on HDL proteome. Changes in HDL proteins were measured by data-independent acquisition (DIA) mass spectrometry and compared between treatment groups. As a secondary outcome, associations between proteins of interest and the most studied function of HDL, the cholesterol efflux capacity (CEC), was examined. Results: The relative abundance of 84 HDL-associated proteins were measured. Two proteins were significantly affected by metformin treatment, peptidoglycan recognition protein 2 (PGRP2; +23.4%, p = .0058) and alpha-2-macroglobulin (A2MG; +29.8%, p = .049). Metformin did not significantly affect CEC. Changes in affected HDL proteins did not correlate with CEC. Conclusions: Despite having little effect on HDL-C, metformin increased PGRP2 and A2MG protein on HDL in youth with T1D, but had no significant effect on CEC. Further studies are needed to understand the impact of PGRP2 and A2MG on other HDL functions

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The First Physical Therapy Summit on Global Health: Implications and Recommendations for the 21st century

The First Physical Therapy Summit on Global Health was convened at the 2007 World Confederation for Physical Therapy (WCPT) Congress to vision practice in the 21st century and, in turn, entry-level education and research, as informed by epidemiological indicators, and consistent with evidence-based noninvasive interventions, the hallmark of physical therapy. The Summit and its findings were informed by WHO data and validated through national databases of the countries of the five WCPT regions. The health priorities based on mortality were examined in relation to proportions of physical therapists practicing in the areas of regional priorities and of the curricula in entry-level programs. As a validation check and to contextualize the findings, input from members of the 800 Summit participants was integrated and international consultants refined the recommendations. Lifestyle-related conditions (ischemic heart disease, smoking-related conditions, hypertension, stroke, cancer, and diabetes) were leading causes of premature death across regions. Contemporary definitions of physical therapy support that the profession has a leading role in preventing, reversing, as well as managing lifestyle-related conditions. The proportions of practitioners practicing primarily in these priority areas and of the entry-level curricula based on these priorities were low. The proportions of practitioners in priority areas and entry-level curricula devoted to lifestyle-related conditions warrant being better aligned with the prevalence of these conditions across regions in the 21st century. A focus on clinical competencies associated with effective health education and health behavior change formulates the basis for The Second Physical Therapy Summit on Global Health. © Informa Healthcare USA, Inc