Lithium iron phosphate is one of the most promising positive-electrode materials for the next generation of lithium-ion batteries that will be used in electric and plug-in hybrid vehicles. Lithium ...deintercalation (intercalation) proceeds through a two-phase reaction between compositions very close to LiFePO(4) and FePO(4). As both endmember phases are very poor ionic and electronic conductors, it is difficult to understand the intercalation mechanism at the microscopic scale. Here, we report a characterization of electrochemically deintercalated nanomaterials by X-ray diffraction and electron microscopy that shows the coexistence of fully intercalated and fully deintercalated individual particles. This result indicates that the growth reaction is considerably faster than its nucleation. The reaction mechanism is described by a 'domino-cascade model' and is explained by the existence of structural constraints occurring just at the reaction interface: the minimization of the elastic energy enhances the deintercalation (intercalation) process that occurs as a wave moving through the entire crystal. This model opens new perspectives in the search for new electrode materials even with poor ionic and electronic conductivities.
Food-induced thermogenesis is generally reported to be higher in the morning, although contrasting results exist because of differences in experimental settings related to the preceding fasting, ...exercise, sleeping and dieting. To definitively answer to this issue, we compared the calorimetric and metabolic responses to identical meals consumed at 0800 hours and at 2000 hours by healthy volunteers, after standardized diet, physical activity, duration of fast and resting.
Twenty subjects (age range 20-35 years, body mass index=19-26 kg m(-)(2)) were enrolled to a randomized cross-over trial. They randomly received the same standard meal in the morning and, 7 days after, in the evening, or vice versa. A 30-min basal calorimetry was performed; a further 60-min calorimetry was done 120-min after the beginning of the meal. Blood samples were drawn every 30-min for 180-min. General linear models, adjusted for period and carry-over, were used to evaluate the 'morning effect', that is, the difference of morning delta (after-meal minus fasting values) minus evening delta (after-meal minus fasting values) of the variables.
Fasting resting metabolic rate (RMR) did not change from morning to evening; after-meal RMR values were significantly higher after the morning meal (1916; 95% confidence interval (CI)=1792, 2041 vs 1756; 1648, 1863 kcal; P<0.001). RMR was significantly increased after the morning meal (90.5; 95% CI=40.4, 140.6 kcal; P<0.001), whereas differences in areas-under-the-curve for glucose (-1800; -2564,-1036 mg dl(-1) × h, P<0.001), log-insulin (-0.19; -0.30,-0.07 μU ml(-1) × h; P=0.001) and fatty free acid concentrations (-16.1;-30.0,-2.09 mmol l(-1) × h; P=0.024) were significantly lower. Delayed and larger increases in glucose and insulin concentrations were found after the evening meals.
The same meal consumed in the evening determined a lower RMR, and increased glycemic/insulinemic responses, suggesting circadian variations in the energy expenditure and metabolic pattern of healthy individuals. The timing of meals should probably be considered when nutritional recommendations are given.
Purpose
Patients with secondary adrenal insufficiency (SAI) have an increased morbidity and an impaired health-related quality of life (HRQoL), which seems to primarily depend on the sub-optimal ...replacement of hypoadrenalism with standard glucocorticoid (GC) therapy, and on the inadequate correction of other associated pituitary deficiencies. A dual-release hydrocortisone (DR-HC) formulation has shown to exert positive effects on morbidity and HRQoL, mainly in patients with primary adrenal insufficiency. We assessed the variations of anthropometric and metabolic parameters and HRQoL in patients with SAI after switching from cortisone acetate (CA) or hydrocortisone (HC) to DR-HC.
Methods
Twenty-one patients (17 M, 4 F) treated with CA (
n
= 16; 25 mg/day twice a day) or HC (
n
= 5; 20 mg/day three times a day), were evaluated for waist circumference, BMI, fasting glucose, HbA1c, insulin, HOMA-IR index, serum lipids, electrolytes, blood pressure and HRQoL at baseline, at 3, 6 and 12 months after switching from CA/HC to DR-HC.
Results
The study showed a significant reduction of waist circumference and BMI (
p
= 0.04, for both), after 3 and 6months of DR-HC treatment, respectively. No significant changes were observed for fasting glucose, insulin, HOMA-IR index, HbA1c, total cholesterol, triglycerides, LDL cholesterol, electrolytes, and blood pressure. However, HDL cholesterol significantly decreased (
p
= 0.003). An improvement of AddiQoL total score was observed during DR-HC treatment (
p
= 0.01), mainly for the category “emotions”. No predictors resulted for these changes.
Conclusion
DR-HC treatment provides some benefits in patients with SAI, reducing central adiposity and improving HRQoL; however, worsening of HDL cholesterol is observed during treatment with DR-HC.
Summary
Ghrelin, an acylated peptide produced predominantly by the stomach, has been discovered to be a natural ligand of the growth hormone secretagogue receptor type 1a (GHS‐R1a). Ghrelin has ...recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts several other neuroendocrine, metabolic and also nonendocrine actions that are explained by the widespread distribution of ghrelin and GHS‐R expression. The likely existence of GHS‐R subtypes and evidence that the neuroendocrine actions, but not all the other actions, of ghrelin depend on its acylation in serine‐3 revealed a system whose complexity had not been completely explored by studying synthetic GHS. Ghrelin secretion is mainly regulated by metabolic signals and, in turn, the modulatory action of ghrelin on the control of food intake and energy metabolism seems to be among its most important biological actions. However, according to a recent study, ghrelin‐null mice are neither anorectics nor dwarfs and this evidence clearly depicts a remarkable difference from leptin null mice. Nevertheless, the original and fascinating story of ghrelin, as well as its potential pathophysiological implications in endocrinology and internal medicine, is not definitively cancelled by these data as GHS‐R1a null aged mice show significant alterations in body composition and growth, in glucose metabolism, cardiac function and contextual memory. Besides potential clinical implications for natural or synthetic ghrelin analogues acting as agonists or antagonists, there are several open questions awaiting an answer. How many ghrelin receptor subtypes exist? Is ghrelin ‘the’ or just ‘a’ GHS‐R ligand? That is, are there other natural GHS‐R ligands? Is there a functional balance between acylated and unacylated ghrelin forms, potentially with different actions? Within the next few years suitable answers to these questions will probably be found, making it possible to gain a better knowledge of ghrelin's potential clinical perspectives.
Background
When evaluating a patient for central adrenal insufficiency (CAI), there is a wide range of morning cortisol values for which no definite conclusion on hypothalamus–pituitary–adrenal (HPA) ...axis function can be drawn; in these cases, a stimulation test is required. Aim of this study was to develop an integrated model for CAI prediction when morning cortisol is in the grey zone, here defined as 40.0–160.0 μg/L.
Methods
Overall, 119 patients with history of sellar tumour which underwent insulin tolerance test (ITT) for the evaluation of HPA axis were enrolled. Supervised regression techniques were used for model development.
Results
An integrated predictive model was developed and internally validated, and showed a significantly better diagnostic performance than morning cortisol alone (AUC 0.811 vs 0.699,
p
= 0.003). A novel predictive score (CAI-score) was retrieved, on a 5.5-point scale, by considering morning cortisol (0 points if 130.1–160.0 μg/L, 1 point if 100.1–130.0 μg/L, 1.5 points if 70.1–100.0 μg/L, 2.5 points if 40.0–70.0 μg/L), other pituitary deficits (2 points if ≥ 3 deficits), and sex (1 point if male). A diagnostic algorithm integrating CAI-score and ITT was finally proposed, with an overall accuracy of 99%, and the possibility to avoid the execution of stimulation tests in 25% of patients.
Conclusions
This was the first study that proposed an integrated score for the prediction of CAI when morning cortisol is in the grey zone. This score might be helpful to reduce the number of patients who need a stimulation test for the assessment of HPA axis function.
To evaluate long-term morphological, functional, and clinical outcome in adrenal incidentalomas.
A total of 118 patients (77 F and 47 M; age 62.3+/-1.0 years) with adrenal incidentalomas were ...evaluated at baseline and followed-up for median 3 years (range 1-10 years) by clinical, biochemical, hormonal, and morphological evaluation. Among them, six patients with diagnosis of subclinical Cushing's syndrome (SCS) underwent surgery.
At entry, 86% (n=102) of tumors were nonfunctioning (NF) and 14% (n=16) showed SCS. Comparing NF with SCS patients, a significantly higher percentage of dyslipidemia was found in the group of SCS patients (50 vs 23%, P=0.033). During follow-up, adrenal function remained normal in all NF patients, none of them developed subclinical or overt endocrine disease. The cumulative risk of mass enlargement was globally low (25%), but progressive up to 8 years. SCS was confirmed in all patients, and none of them shifted to overt Cushing's syndrome. The cumulative risk of developing metabolic-cardiovascular abnormalities was globally low (22%), but progressive up to 8 years and new diseases were recorded in the group of NF patients only (three patients with dyslipidemia, four with impaired fasting glucose/impaired glucose tolerance, and three with diabetes mellitus). SCS patients who underwent surgery did not show any significant clinical improvement.
The risk of mass enlargement, hormonal, and metabolic impairment over time is globally low. Conservative management seems to be appropriate, but further prospective studies are needed to establish the long-term outcome of such patients, especially for metabolic status, cardiovascular risk profile and their relationship with endocrine function.
Introduction
The proportion of patients with low GH response to provocative tests increases with the number of other pituitary hormone deficiencies, reason why in panhypopituitary patients GH ...stimulation tests may be unnecessary to diagnose GH deficiency (GHD)
Purpose
To re-evaluate the diagnostic cut-offs of GH response to GHRH + arginine (ARG) test related to BMI, considering the patients’ pituitary function as the gold standard for the diagnosis of GHD.
Methods
The GH responses to GHRH + ARG were studied in 358 patients with history of hypothalamic-pituitary disease. GHD was defined by the presence of at least 3 other pituitary deficits (n = 223), while a preserved somatotropic function was defined by the lack of other pituitary deficits and an IGF-I SDS ≥ 0 (n = 135). The cut-off with the best sensitivity (SE) and specificity (SP), was identified for each BMI category using the ROC curve analysis. To avoid over-diagnosis of GHD we subsequently searched for the cut-offs with a SP ≥ 95%.
Results
The best GH cut-off was 8.0 μg/l (SE 95%, SP 100%) in lean, 7.0 μg/l (SE 97.3%, SP 82.8%) in overweight, and 2.8 μg/l (SE 84.3%, SP 91.7%) in obese subjects. The cut-off with a SP ≥ 95% was 2.6 μg/l (SE 68.5%, SP 96.6%) in overweight and 1.75 μg/l (SE 70.0%, SP 97.2%) in obese subjects.
Conclusions
This is the first study that evaluates the diagnostic cut-offs of GH response to GHRH + ARG related to BMI using a clinical definition of GHD as gold standard. Our results suggest that with this new approach, the GHRH + ARG cut-offs should be revised to avoid GHD over-diagnosis.
Cardiometabolic disorders have been associated with primary hyperparathyroidism (PHPT), while the relationship of cardiovascular risk score (CRS) and metabolic syndrome (MS) with different clinical ...presentation of PHPT remains undefined. Our aim was to evaluate CRS, MS and its components in PHPT looking for their correlation to different clinical forms. In 68 consecutive PHPT patients and 68 matched controls, CRS, MS and its components were assessed to perform an observational case–control study at an ambulatory referral center for Bone Metabolism Diseases. Patients were stratified in symptomatic and asymptomatic PHPT; these latter were divided in high-risk and low-risk subgroups for end-organ damage. An increased proportion of PHPT patients had intermediate-high CRS and MS (mean, 95 % Confidence Interval (CI) 51.5 %, 39.6–63.3 and 20.6 %, 11.0–30.2, respectively,
p
< 0.02 vs. controls). Intermediate-high CRS was prevalent both in symptomatic and low-risk asymptomatic PHPT while MS resulted prevalent in low-risk asymptomatic but not in symptomatic PHPT. Type 2 DM, IFG, mixed dyslipidemia, hypertriglyceridemia, HDL-hypocholesterolemia, and LDL-hypercholesterolemia predominated in low-risk asymptomatic, while only LDL-hypercholesterolemia prevailed also in symptomatic PHPT. In patients and controls without cardiometabolic risk factors, HOMA-IR index was significantly increased in PHPT vs. controls (
p
< 0.03) and associated to total calcium (
R
= 0.73;
p
< 0.001). By multivariate analysis low-risk asymptomatic PHPT predicted MS after adjusting for age, sex, and BMI. Our data show an increased frequency of intermediate-high CRS both in symptomatic and low-risk asymptomatic PHPT while MS prevails in low-risk asymptomatic PHPT, supporting the potential for cardiovascular morbidity and mortality also in this form.
Purpose
Uncertainties exist about the predictors of the severity of the clinical picture of GH deficiency (GHD) syndrome. Aim of the study was to evaluate, in adult patients with GHD, the predictors ...of the development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis.
Methods
We retrospectively studied 327 adult patients (age 47.1 ± 17.1 years) with untreated severe GHD (mean follow-up 110.9 ± 56.8 months). GHD was defined by GHRH + arginine test using BMI cut-offs. The possible development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis was investigated by Kaplan–Meier survival analysis. For each clinical outcome, either a univariate or multivariate analysis according to the Cox proportional-hazards model was performed to identify those factors that were associated with the development of the event.
Results
GH secretion parameters were not associated with the outcomes. Hypercholesterolemia was positively and negatively predicted by a BMI ≥ 30 kg/m
2
(HR 2.50,
p
0.00) and the dose of l-thyroxine possibly in place (HR 0.98,
p
0.02), respectively. Hypertension was positively predicted by a BMI ≥ 30 kg/m
2
(HR 2.64, p 0.00) and IGF-I SDS values (HR 2.26,
p
0.00). Diabetes mellitus was positively predicted by hypertension (HR 11.76,
p
0.01). Osteoporosis was positively and negatively predicted by hypercholesterolemia (HR 3.25,
p
0.01) and hypertension (HR 0.21,
p
0.00), respectively.
Conclusions
The severity of the impairment of GH secretion does not predict the development of the clinical picture of GHD syndrome: untreated adult GHD does not increase the development of metabolic risk factors in hypopituitaric patients.
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