Citations

The popular modern diet, characterized by an excess of animal protein and salt but insufficient in fruits, vegetables and water, is a poor fit for human physiological and homeostatic regulatory systems. Sustained net acid and sodium retention, coupled with an insufficient intake of cardiovascular protective potassium-rich foods and hydration in the modern diet can give rise to debilitating chronic organ dysfunction and ultimately, mortality. This holds true, especially in our aging population who are already facing inevitable decline in organ functional reserve. Importantly, in most cases, despite the mismatch and adverse effects to multiple organ systems, plasma electrolyte and acid-base parameters can, on the surface, be maintained within a “normal” reference range, primarily by activating (often maximally activating) compensatory homeostatic mechanisms. These diet-induced effects can thus be clinically silent for decades. Embodied in the chronic corrective homeostatic processes, however, are real risks for multiorgan damage. According to the Dietary Guideline Advisory Committee (DGAC), half of American adults have one or more chronic diseases that are preventable with dietary modification. Here, homeostasis of body fluid acid-base, sodium, potassium and water is examined. Our current dietary habits and their required regulatory adaptation, maladaptation and relevant physiology and pathophysiology are discussed. A framework of dietary modifications to avoid a propensity for maladaptation and thus lowers the risks of common modern diseases (primary prevention) and minimizes the risk of chronic and age-related disease progression (secondary prevention) is emphasized. Although there are other variables at play, a key to restoring the all-important dietary potassium to sodium ratio is greater consumption of vegetables/fruits and adopting salt temperance. Dietary and nutritional optimization is an under-emphasized area of health care that has an enormous potential to temper the epidemics of prevalent chronic diseases in modern society and improve population health.

Tendon injuries are among the most common and severe hand injuries with a high demand for functional recovery. Stem cells have been identified and isolated from different species and a variety of tissues for the sake of regenerative medicine. Recently, turkey has been suggested as a potential new large animal model for flexor tendon-related research. However, turkey tissue-specific stem cells have not been investigated. Here, we presented the isolation and verification of tendon-derived stem cells (TDSCs) from 6- to 8-month-old heritage-breed turkey. TDSCs were isolated from turkey flexor tendon by plating nucleated cells at the determined optimal density. Approximately 4% of the nucleated cells demonstrated clonogenicity, high proliferation rate, and trilineage differentiation potential after induction culturing. These cells expressed surface antigens CD90, CD105, and CD44, but did not express CD45. There was a high level of gene expression of tenogenic markers in TDSCs, including mohawk, collagen type I, tenascin C, and elastin. Turkey TDSCs also expressed transcription factorsPouV,Nanog, andSox2, which are critically involved in the regulation of stemness. The successful isolation of tendon-derived stem cells from turkey was beneficial for future studies in tendon tissue engineering and would help in the development of new treatment for tendon diseases using this novel animal model.

Key Points We conducted the first exome-wide association study between germ line variant genotype and survival outcomes after unrelated-donor BMT. A number of novel genes were found to significantly affect survival outcomes.

AbstractBackground: Prior studies have supported an inverse association between physical activity and colon cancer risk and suggest that higher physical activity may also improve cancer survival. Among participants in a phase III adjuvant trial for stage III colon cancer, we assessed the association of physical activity around the time of cancer diagnosis with subsequent outcomes.Methods: Before treatment arm randomization (FOLFOX or FOLFOX + cetuximab), study participants completed a questionnaire including items regarding usual daily activity level and frequency of participation in recreational physical activity (N = 1,992). Using multivariable Cox models, we calculated HRs for associations of aspects of physical activity with disease-free (DFS) and overall survival (OS).Results: Over follow-up, 505 participants died and 541 experienced a recurrence. Overall, 75% of participants reported recreational physical activity at least several times a month; for participants who reported physical activity at least that often (vs. once a month or less), the HRs for DFS and OS were 0.82 [95% confidence interval (CI), 0.69–0.99] and 0.76 (95% CI, 0.63–0.93), respectively. There was no evidence of material effect modification in these associations by patient or tumor attributes, except that physical activity was more strongly inversely associated with OS in patients with stage T3 versus T4 tumors (Pinteraction = 0.03).Conclusions: These findings suggest that higher physical activity around the time of colon cancer diagnosis may be associated with more favorable colon cancer outcomes.Impact: Our findings support further research on whether colon cancer survival may be enhanced by physical activity. Cancer Epidemiol Biomarkers Prev; 27(6); 696–703. ©2018 AACR.

Development of cell replacement therapies in diabetes requires understanding of the molecular underpinnings of β-cell maturation. The circadian clock regulates diverse cellular functions important for regulation of β-cell function and turnover. However, postnatal ontogenesis of the islet circadian clock and its potential role in β-cell maturation remain unknown. To address this, we studied wild-type Sprague-Dawley as well as Period1 luciferase transgenic (Per1:LUC) rats to determine circadian clock function, clock protein expression, and diurnal insulin secretion during islet development and maturation process. We additionally studied β-cell–specific Bmal1-deficient mice to elucidate a potential role of this key circadian transcription factor in β-cell functional and transcriptional maturation. We report that emergence of the islet circadian clock 1) occurs during the early postnatal period, 2) depends on the establishment of global behavioral circadian rhythms, and 3) leads to the induction of diurnal insulin secretion and gene expression. Islet cell maturation was also characterized by induction in the expression of circadian transcription factor BMAL1, deletion of which altered postnatal development of glucose-stimulated insulin secretion and the associated transcriptional network. Postnatal development of the islet circadian clock contributes to early-life β-cell maturation and should be considered for optimal design of future β-cell replacement strategies in diabetes.