Review: the role of vitamin D in nervous system health and disease.

Vitamin D and its metabolites have pleomorphic roles in both nervous system health and disease. Animal models have been paramount in contributing to our knowledge and understanding of the consequences of vitamin D deficiency on brain development and its implications for adult psychiatric and neurological diseases. The conflation of in vitro, ex vivo, and animal model data provide compelling evidence that vitamin D has a crucial role in proliferation, differentiation, neurotrophism, neuroprotection, neurotransmission, and neuroplasticity. Vitamin D exerts its biological function not only by influencing cellular processes directly, but also by influencing gene expression through vitamin D response elements. This review highlights the epidemiological, neuropathological, experimental and molecular genetic evidence implicating vitamin D as a candidate in influencing susceptibility to a number of psychiatric and neurological diseases. The strength of evidence varies for schizophrenia, autism, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and is especially strong for multiple sclerosis.

Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting.

Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6-18 months between 2013 and 2015. Participants were supplemented with a wide range of vitamin D doses (1,000 - 15,000 IU/d) aimed at achieving serum 25-hydroxyvitamin D [25(OH)D] levels of at least 100 nmol/L. Serum 25(OH)D concentrations up to 300 nmol/L were achieved without perturbation of calcium homeostasis or incidence of toxicity. Hypercalcemia and hypercalciuria were not related to an increase in 25(OH)D concentrations nor vitamin D dose. To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for obese. Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe.

Adjuvant radiation therapy for low stage testicular seminoma: Diagnosis and therapy in evolution.

We performed a retrospective study to evaluate the clinical outcome of patients with early stage testicular seminoma who received adjuvant radiation therapy after orchiectomy over the past 15 years. During the 15 year period, 61 patients were treated with adjuvant radiation therapy for stages I, IIA, and IIB testicular seminoma. Patients received from 2,000 to 4,000 cGy delivered by a Cobalt machine and later by a linear accelerator. Our standard treatment protocol was modified in 13 patients: 7 secondary to abnormal lymphangiography (LAG) parameters and 6 due to abnormal computed tomography findings. We analyzed each patient's outcome for survival, recurrence, and complications. We then compared outcomes, looking for differing trends based on evolving evaluation or treatment techniques. The average follow-up is 75 months, with an overall survival rate of 93%. The cause specific survival is 100%. Four patients died from intercurrent diseases; at time of autopsy, one of these patients was noted to have a small focus of seminoma in a lateral inguinal node. He died from widely disseminated Hodgkin's disease. Three patients, including the aforementioned one, had recurrent disease outside of the radiation field, yielding a recurrence rate of 5%. No significant long term treatment complications were reported, although 24% of patients had one or more complications from LAG. Regardless the various changes in patient evaluation and radiation treatment techniques over the past 15 years, adjuvant radiation therapy remains effective in patients with early stage testicular seminoma.