Vitamin D Supplementation Improves Fasting Insulin Levels and HDL Cholesterol in Infertile Men.

CONTEXT: Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator. OBJECTIVE: This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men. METHODS: A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported. RESULTS: Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group. CONCLUSION: High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.

Communication between primary and secondary care: deficits and danger.

BACKGROUND: Timely and accurate communication between primary and secondary care is essential for delivering high-quality patient care. OBJECTIVE: The aim of this study is to evaluate the content contained in both referral and response letters between primary and secondary care and measure this against the recommended national guidelines. METHODS: Using an observational design, senior medical students and their general practice supervisors applied practice management software to identify 100 randomly selected adults, aged greater than 50 years, from a generated list of consults over a 2-year period (2013-2015). All data included in referral and response letters for these adults were examined and compared with the gold standard templates that were informed by international guidelines. RESULTS: Data from 3293 referral letters and 2468 response letters from 68 general practices and 17 hospitals were analysed. The median time that had elapsed between a patient being referred and receiving a response letter was 4 weeks, ranging from 1 week for Emergency Department referral letters to 7 weeks for orthopaedic surgery referral letters. Referral letters included the reason for referral (98%), history of complaint (90%) and current medications (82%). Less commonly included were management prior to referral (65%) and medication allergies (57%). The majority of response letters included information on investigations (73%), results (70%) and follow-up plan (85%). Less commonly, response letters included medication changes (30%), medication lists (33%) and secondary diagnoses (13%). CONCLUSIONS: Future research should be aimed at developing robust strategies to addressing communication gaps reported in this study.

A Mouse Model for Studying Nutritional Programming: Effects of Early Life Exposure to Soy Isoflavones on Bone and Reproductive Health.

Over the past decade, our research group has characterized and used a mouse model to demonstrate that "nutritional programming" of bone development occurs when mice receive soy isoflavones (ISO) during the first days of life. Nutritional programming of bone development can be defined as the ability for diet during early life to set a trajectory for better or compromised bone health at adulthood. We have shown that CD-1 mice exposed to soy ISO during early neonatal life have higher bone mineral density (BMD) and greater trabecular inter-connectivity in long bones and lumbar spine at young adulthood. These skeletal sites also withstand greater forces before fracture. Because the chemical structure of ISO resembles that of 17-ß-estradiol and can bind to estrogen receptors in reproductive tissues, it was prudent to expand analyses to include measures of reproductive health. This review highlights aspects of our studies in CD-1 mice to understand the early life programming effects of soy ISO on bone and reproductive health. Preclinical mouse models can provide useful data to help develop and guide the design of studies in human cohorts, which may, depending on findings and considerations of safety, lead to dietary interventions that optimize bone health.

Low birthweight, gestational age, need for surgical intervention and gram-negative bacteraemia predict intestinal failure following necrotising enterocolitis.

AIM: Necrotising enterocolitis (NEC) is associated with high morbidity and mortality. The aim of this study was to identify predictors of intestinal failure (IF), morbidity and mortality following NEC. METHODS: We performed a retrospective study of all neonates treated for NEC stage II or greater at a tertiary referral NICU between 2000 and 2009. Demographic data, need for surgery, residual bowel length and rates of bacteraemia, cholestasis, IF and mortality were analysed. RESULTS: During the 10-year period, 301 patients were referred with NEC and 152 had surgical intervention. Overall mortality was 32%. Of the 230 infants who survived >42 days, 97 (42%) had IF at 42 days, decreasing to 15% at >90 days. The rate of IF was significantly higher in the surgical group than the medical group (OR 2.04, 95% CI, 1.25-3.35, p < 0.004), but 23% of the medically treated infants with NEC also developed IF. There was a significant relationship between IF and gram-negative bacteraemia, the need for surgery, cholestasis, liver failure and mortality. CONCLUSION: Intestinal failure occurred in a significant proportion of infants with NEC. Predictors for IF among infants with NEC were low birthweight, low gestational age, need for surgical intervention and gram-negative bacteraemia.

Early life exposure to isoflavones adversely affects reproductive health in first but not second generation female CD-1 mice.

Soy-based infant formula (SBIF) can be a substantial source of soy isoflavones during early life. Because soy isoflavones have the capacity to mimic endogenous estrogen and thereby exert hormone-like effects, there is concern regarding reproductive health. The objectives were to determine if neonatal exposure to soy isoflavones altered reproductive health in females and, if so, whether such effects are transferred to subsequent generations. CD-1 mice were bred and F1 mouse offspring were cross-fostered at birth and randomized to 1 of 4 treatments: 7 mg soy isoflavones · kg body weight(-1) · d(-1) or corn oil from postnatal d (PND) 1 to 10 or from PND 1 to 21 (n = 8-13 females/group). Mice were subsequently bred to control males on PND 56 to obtain F2 females (n = 10-15/group). F1 mice that received isoflavones had ~15% greater body weight during wk 4-8 and markedly reduced fertility with a 55-60% success rate. Reduced fertility was associated with abnormal estrus cycles, fewer corpora lutea in ovaries, and increased incidence of hyperplasia and atypia in the uteri. Offspring (F2 mice) of isoflavone-treated F1 mice had ~15% higher body weight by wk 8 through 16 of age than controls and fertility was normal. In summary, early exposure to soy isoflavones resulting in serum isoflavone concentrations similar to human infants fed SBIF reduced fertility in F1 but not F2 mice and increased body weight in both generations of female offspring. Extrapolation of these findings to the human scenario are complex but can provide guidance for more fully understanding the implications for infants consuming SBIF.

Early exposure to soy isoflavones and effects on reproductive health: a review of human and animal studies.

Soy isoflavones are phytoestrogens with potential hormonal activity due to their similar chemical structure to 17-ß-estradiol. The increasing availability of soy isoflavones throughout the food supply and through use of supplements has prompted extensive research on biological benefits to humans in chronic disease prevention and health maintenance. While much of this research has focused on adult populations, infants fed soy protein based infant formulas are exposed to substantial levels of soy isoflavones, even when compared to adult populations that consume a higher quantity of soy-based foods. Infant exposure, through soy formula, primarily occurs from birth to one year of life, a stage of development that is particularly sensitive to dietary and environmental compounds. This has led investigators to study the potential hormonal effects of soy isoflavones on later reproductive health outcomes. Such studies have included minimal human data with the large majority of studies using animal models. This review discusses key aspects of the current human and animal studies and identifies critical areas to be investigated as there is no clear consensus in this research field.