Quality of Life in Childhood Onset Growth Hormone-Deficient Patients in the Transition Phase from Childhood to Adulthood

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O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis

Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia in mammals. Protein O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis. Mechanistically, O-GlcNAcylation on specific threonine residues increased the catalytic efficiency for ammonia of carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme in ureagenesis. Pharmacological inhibition of O-GlcNAcase, the enzyme removing O-GlcNAc from proteins, resulted in clinically relevant reductions of systemic ammonia in both genetic (hypomorphic mouse model of propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models of liver diseases. In conclusion, by fine-tuned control of ammonia entry into ureagenesis, hepatic O-GlcNAcylation of CPS1 increases ammonia detoxification and is a novel target for therapy of hyperammonemia in both genetic and acquired diseases

Outcome after acute ischemic stroke (AIS) in older patients: Effects of age, neurological deficit severity and blood pressure (BP) variations

The goal of this study was to examine the relationship between BP variations and neurological deficit outcome in old-old patients after AIS. Fifty-four patients (66-96 years), admitted consecutively for stroke were assessed, using a non-invasive BP monitoring (NIBPM), measuring mean systolic (SBP) and diastolic (DBP) blood pressure and their variation between days 1 and 7. Neurological assessment and cognitive function were evaluated using the NIH stroke Scale (NIHSS) and the short portable mental status Questionnaire (SPMSQ), respectively. Functional status was assessed using the modified Rankin scale (RS) and the Barthel index (BI). NIHSS on the 1st day positively correlated with SPMSQ score and with BI on day 21. The NIHSS variation (\u394NIHSS) between days 21 and 1 negatively correlated with mean 24-h BP change between days 7 and 1 (r=-0.59 for DBP and r=-0.54 for SBP; p<0.001). Age, severity of stroke at admission, history of hypertension, atrial fibrillation (AF) and BP levels at admission were not correlated to \u394NIHSS. An inverse correlation between the decrease of 24-h BP within the first week and \u394NIHSS suggests prudence in lowering BP in the acute phase of stroke in elderly

Prevalence of Metabolic Syndrome in Adult Hypopituitary Growth Hormone (GH)-Deficient Patients Before and After GH Replacement.

Context and Objective: Metabolic and body compositional consequences of GH deficiency (GHD) in adults are associated with a phenotype similar to the metabolic syndrome (MetS). Patients: We assessed MetS prevalence in adult GHD patients (n = 2531) enrolled in the Hypopituitary Control and Complications Study. Prevalence was assessed at baseline and after 3 yr of GH replacement in a subset of 346 adult-onset patients. Results: Baseline MetS crude prevalence was 42.3%; age-adjusted prevalence in the United States and Europe was 51.8 and 28.6% (P < 0.001), respectively. In the United States, age-adjusted prevalence was significantly higher (P < 0.001) than in a general population survey. Increased MetS risk at baseline was observed for age 40 yr or older (adjusted relative risk 1.34, 95% confidence interval 1.17-1.53, P < 0.001), females (1.15, 1.05-1.25, P = 0.002), and adult onset (1.77, 1.44-2.18, P < 0.001). In GH-treated adult-onset patients, MetS prevalence was not changed after 3 yr (42.5-45.7%, P = 0.172), but significant changes were seen for waist circumference (62.1-56.9%, P = 0.008), fasting glucose (26.0-32.4%, P < 0.001), and blood pressure (59.8-69.7%, P < 0.001). Significantly increased risk of MetS at yr 3 was associated with baseline MetS (adjusted relative risk 4.09, 95% confidence interval 3.02-5.53, P < 0.001) and body mass index 30 kg/m(2) or greater (1.53, 1.17-1.99, P = 0.002) and increased risk (with a P value < 0.1) for GH dose 600 mug/d or greater (1.18, 95% confidence interval 0.98-1.44, P = 0.088). Conclusion: MetS prevalence in GHD patients was higher than in the general population in the United States and higher in the United States than Europe. Prevalence was unaffected by GH replacement, but baseline MetS status and obesity were strong predictors of MetS after GH treatment

Prevalence and incidence of diabetes mellitus in adult patients on growth hormone replacement for growth hormone deficiency: A surveillance database analysis

Context: GH replacement in adult GH-deficient patients may cause insulin resistance, raising concerns of potential increased risk of developing diabetes mellitus (DM). Objective: Our objective was to assess DM prevalence and incidence in the international Hypopituitary Control and Complications Study (HypoCCS) surveillance database. Design and Participants: GH-treated patients enrolled into HypoCCS (2922 U. S. and 3709 European patients) were assessed for DM, defined as recorded on the clinical report form, reported as adverse events, fasting glucose at least 7 mmol/liter recorded at least twice, or insulin treatment reported. Results: DM prevalence was 8.2% [95% confidence interval (CI) = 7.6-8.9] overall, 11.3% in the United States and 5.7% in Europe. Incidence (n/1000 patient-years) was 9.7 (95% CI = 8.4-10.9) overall, 14.1 (11.5-16.7) in the United States, and 7.0 (5.6-8.3) in Europe. Overall incidence was 2.1 (0.9-3.3) for patients with body mass index (BMI) below 25 kg/m(2) increasing to 16.4 (13.7-19.1) for BMI over 30 kg/m(2). Obesity (BMI > 30 kg/m(2)) prevalence was higher in the United States than Europe and higher in U. S. patients than a U.S. reference population. After age, gender, and BMI adjustment, U. S. HypoCCS DM incidence was 10.6 (8.1-13.0), compared with 7.1 (6.0-8.1) in the National Health Interview Survey. In Europe, incidence for French and German patients was comparable to reference populations; for Sweden, the point estimate was higher than the reference population, but 95% CI overlapped. GH dose was not correlated with DM incidence. Conclusions: The present analysis showed no evidence for increased DM incidence in GH-treated adult hypopituitary patients. However, those more prone to develop DM exhibited a higher than normal prevalence of obesity. (J Clin Endocrinol Metab 96: 2255-2261, 2011

Enhancing energy awareness through the analysis of thermal energy consumption

Energy efficiency by means of reduction in wasteful energy consumption is a growing policy priority for many countries. Innovative systems should be designed to continuously monitor a smart city environment and provide all stakeholders the tools to improve energy efficiency. This paper presents the EDEN platform, designed to collect and analyze thermal energy consumption of residential and public building heating systems. EDEN is being deployed in a major Italian city and collects energy consumption measurements through an extensive smart metering grid involving thousands of buildings. EDEN also collects and analyzes indoor climate conditions, and user feedbacks, such as their thermal comfort perception, by means of an ad-hoc social network. Collected data are further enriched with temporal and spatial information at different abstraction levels and meteorological data available as an open source data set. Several technical Key Performance Indicators (KPIs) have been defined to inform users on their building thermal energy consumption, while user-friendly KPIs present energy savings or over-consumptions in an informative fashion