Vitamin D deficiency in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder affecting, among others, the endocrine system, with derangement of steroid hormones functions. Vitamin D is a steroid recognized for its role in calcium homeostasis. In addition, vitamin D influences muscle metabolism by genomic and non-genomic actions, including stimulation of the insulin-like-growth-factor 1 (IGF1), a major regulator of muscle trophism. To verify the presence of vitamin D deficit in DM1 and its possible consequences, serum 25-hydroxyvitamin D (25(OH)D), calcium, parathormone (PTH), and IGF1 levels were measured in 32 DM1 patients and in 32 age-matched controls. Bone mineral density (BMD) and proximal muscle strength were also measured by DXA and a handheld dynamometer, respectively. In DM1 patients, 25(OH)D levels were reduced compared to controls, and a significant decrease of IGF1 was also found. 25(OH)D levels inversely correlated with CTG expansion size, while IGF1 levels and muscle strength directly correlated with levels of 25(OH)D lower than 20 and 10 ng/ml, respectively. A significantly higher percentage of DM1 patients presented hyperparathyroidism as compared to controls. Calcium levels and BMD were comparable between the two groups. Oral administration of cholecalciferol in 11 DM1 patients with severe vitamin D deficiency induced a normal increase of circulating 25(OH)D, ruling out defects in intestinal absorption or hepatic hydroxylation. DM1 patients show a reduction of circulating 25(OH)D, which correlates with genotype and may influence IGF1 levels and proximal muscle strength. Oral supplementation with vitamin D should be considered in DM1 and might mitigate muscle weakness.     

Temperature-Acclimated Brown Adipose Tissue Modulates Insulin Sensitivity in Humans

In rodents, brown adipose tissue (BAT) regulates cold- and diet-induced thermogenesis (CIT; DIT). Whether BAT recruitment is reversible and how it impacts on energy metabolism have not been investigated in humans. We examined the effects of temperature acclimation on BAT, energy balance, and substrate metabolism in a prospective crossover study of 4-month duration, consisting of four consecutive blocks of 1-month overnight temperature acclimation (24°C [month 1] → 19°C [month 2] → 24°C [month 3] → 27°C [month 4]) of five healthy men in a temperature-controlled research facility. Sequential monthly acclimation modulated BAT reversibly, boosting and suppressing its abundance and activity in mild cold and warm conditions (P < 0.05), respectively, independent of seasonal fluctuations (P < 0.01). BAT acclimation did not alter CIT but was accompanied by DIT (P < 0.05) and postprandial insulin sensitivity enhancement (P < 0.05), evident only after cold acclimation. Circulating and adipose tissue, but not skeletal muscle, expression levels of leptin and adiponectin displayed reciprocal changes concordant with cold-acclimated insulin sensitization. These results suggest regulatory links between BAT thermal plasticity and glucose metabolism in humans, opening avenues to harnessing BAT for metabolic benefits.     

Beyond Open Big Data: Addressing Unreliable Research

The National Institute of Health invests US $30.9 billion annually in medical research. However, the subsequent impact of this research output on society and the economy is amplified dramatically as a result of the actual medical treatments, biomedical innovations, and various commercial enterprises that emanate from and depend on these findings. It is therefore a great concern to discover that much of published research is unreliable. We propose extending the open data concept to the culture of the scientific research community. By dialing down unproductive features of secrecy and competition, while ramping up cooperation and transparency, we make a case that what is published would then be less susceptible to the sometimes corrupting and confounding pressures to be first or journalistically attractive, which can compromise the more fundamental need to be robustly correct.     

Lumbar spine MRI in upright position for diagnosing acute and chronic low back pain: statistical analysis of morphological changes

Background

Patients with low back pain frequently demonstrate recumbent magnetic resonance imaging (MRI) alterations not always related to homogeneous clinical symptoms. The purpose of this study was to evaluate and quantify the statistical significance of variations of some anatomical parameters of the lumbosacral spine and reveal occult disc pathologies from recumbent to upright position in patients with acute and chronic low back pain.

Materials and methods

Fifty-seven patients complaining of low back pain (27 women, 30 men) underwent dynamic lumbosacral MRI with a 0.25-T tilting system (G-scan Esaote). We settled five parameters for which variations have been evaluated: lumbosacral angle, lordosis angle, L3–L4 intersomatic disc height, L3–L4 interspinous processes distance, and widest anteroposterior dural sac diameter. Images were obtained in both recumbent and upright positions.

Results

Statistically significant differences [one-way analysis of variance (ANOVA), p = 0.0043] were found between each pair of values of parameters sampled in recumbent and upright positions. In 70 % of patients, on visual qualitative analysis only, an increment of disc protrusions and/or spondylolisthesis was found in the upright position; in three cases, in the upright position only, an interarticular pseudocyst was found.

Conclusions

Dynamic MRI with an open-configuration, low-field tilting MRI system is a feasible and promising tool to study degenerative pathology of the spine. Moreover, in cases of low back pain with negative MRI in the recumbent position or in patients with pain in the upright position only, tilting MRI permits visualization of occult spine and disc pathologies in patients with acute or chronic low back pain.     

Lack of evidence of premature atherosclerosis in untreated severe isolated growth hormone (GH) deficiency due to a GH-releasing hormone receptor mutation

BACKGROUND: GH deficiency (GHD) acquired at adult age as a result of pathological processes of the pituitary gland or the hypothalamus causes changes that are associated with worsening cardiovascular risk. They include increase in abdominal obesity, total and low- density lipoprotein cholesterol, and C-reactive protein. GHD adults also have thickening of the carotid arteries. It has been postulated that GHD is the link between hypopituitarism and the increase in cardiovascular and cerebrovascular mortality observed in hypopituitarism. However, several confounding factors exist, such as associated pituitary deficits and replacement of other hormones or surgical or radiological therapies used to treat the underlying pituitary of hypothalamic pathologies. OBJECTIVE: The aim of this study was to determine the consequences of lifetime isolated GHD (IGHD) on the metabolic and cardiovascular status of adult members of a large Brazilian cohort with severe IGHD due to a homozygous mutation in the GHRH receptor gene. DESIGN: Twenty-two GH naive adult dwarfs (10 men and 12 women; aged 44 +/- 12 yr) were compared with 22 healthy volunteers (10 men and 12 women; aged 45 +/- 12 yr) living in the same area. RESULTS: GHD subjects had increased abdominal obesity, higher total and low-density lipoprotein cholesterol, and higher C-reactive protein than controls. They did not have an increase in carotid wall thickness, and there was no evidence of premature atherosclerosis as evaluated by exercise echocardiography. CONCLUSIONS: In this homogeneous cohort residing in a rural area of Brazil, lifetime, untreated severe IGHD is not associated with evidence of premature atherosclerosis despite unfavorable cardiovascular risk profile.