Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Peer reviewe

Functional Changes during Hospital Stay in Older Patients Admitted to an Acute Care Ward: A Multicenter Observational Study

OBJECTIVES: Changes in physical performance during hospital stay have rarely been evaluated. In this study, we examined functional changes during hospital stay by assessing both physical performance and activities of daily living. Additionally, we investigated characteristics of older patients associated with meaningful in-hospital improvement in physical performance. METHODS: The CRiteria to assess appropriate Medication use among Elderly complex patients project recruited 1123 patients aged ≥65 years, consecutively admitted to geriatric or internal medicine acute care wards of seven Italian hospitals. We analyzed data from 639 participating participants with a Mini Mental State Examination score ≥18/30. Physical performance was assessed by walking speed and grip strength, and functional status by activities of daily living at hospital admission and at discharge. Meaningful improvement was defined as a measured change of at least 1 standard deviation. Multivariable logistic regression models predicting meaningful improvement, included age, gender, type of admission (through emergency room or elective), and physical performance at admission. RESULTS: Mean age of the study participants was 79 years (range 65-98), 52% were female. Overall, mean walking speed and grip strength performance improved during hospital stay (walking speed improvement: 0.04±0.20 m/s, p<0.001; grip strength improvement: 0.43±5.66 kg, p = 0.001), no significant change was observed in activities of daily living. Patients with poor physical performance at admission had higher odds for in-hospital improvement. CONCLUSION: Overall, physical performance measurements show an improvement during hospital stay. The margin for meaningful functional improvement is larger in patients with poor physical function at admission. Nevertheless, most of these patients continue to have poor performance at discharge

Dietary Arginine Supplementation Speeds Pulmonary VO2 Kinetics during Cycle Exercise

PURPOSE: To test the hypothesis that L-arginine (the substrate for nitric oxide synthase [NOS]) administration slows the VO2 kinetics at the onset of moderate-intensity exercise in humans. METHODS: Seven physically active males were randomly assigned to receive either placebo (lactose) or L-arginine hydrochloride capsules (7.2 g x d(-1)) for 14 d in a double-blind crossover design, with a 7-d washout period between the two conditions. On day 11 and day 14 of each condition, the subjects completed two consecutive 6-min bouts of cycle exercise at 80% of the ventilatory threshold with a 12-min rest interval. VO2 was measured on a breath-by-breath basis, and VO2 kinetics were determined with a single exponential model from the averaged data derived from four repetitions. Capillary and venous blood samples were taken to determine plasma [La] and serum [arginine], respectively. RESULTS: There were no differences in circulating lactate either before or during exercise. However, serum [arginine] was higher (P < 0.05) in the arginine condition at rest (119.0 +/- 12.6 vs 103.6 +/- 15.7 micromol x L(-1) in the control condition) and after exercise (113.3 +/- 26.0 vs 103.8 +/- 12.6 micromol x L(-1) in the control condition). With regard to the pulmonary VO2 kinetics, no significant difference was observed in the time at which the phase II response emerged or in the phase II amplitude between the two conditions. However, contrary to our hypothesis, the time constant was significantly reduced after arginine administration (i.e., 13.9 +/- 3.1 vs 15.8 +/- 2.6 s in the control condition, P < or = 0.014). CONCLUSION: Exogenous L-arginine administration speeds the phase II pulmonary VO2 response by 12% at the onset of moderate-intensity exercise in humans.status: publishe

Independent predictors of length of hospital stay.

<p>Analyses of length of hospital stay included number of drugs before admission, more than one hospital admission during the last year, comorbidity score, presence of heart failure, metastasized cancer, renal failure of infection, falls at home during the last year, pain, ADL score and walking speed category in a multivariate regression model with forward selection procedure and forced retention of centre, gender, age, and type of admission.</p><p>CI₉₅ = 95% confidence interval; ADL = Activities of Daily Living; BMI = Body Mass Index.</p><p>Independent predictors of length of hospital stay.</p

Characteristics of the study population (N = 1223).

<p>SD = Standard deviation; IQR = Interquartile range; BMI = Body Mass Index;</p><p>ADL = Activities of Daily Living.</p><p>Characteristics of the study population (N = 1223).</p