Brownian regime of finite- N corrections to particle motion in the XY Hamiltonian mean field model

International audienceWe study the dynamics of the N-particle system evolving in the XY hamiltonian mean field (HMF) model for a repulsive potential, when no phase transition occurs. Starting from a homogeneous distribution, particles evolve in a mean field created by the interaction with all others. This interaction does not change the homogeneous state of the system, and particle motion is approximately ballistic with small corrections. For initial particle data approaching a waterbag, it is explicitly proved that corrections to the ballistic velocities are in the form of independent brownian noises over a time scale diverging not slower than N^(2/5) as N → ∞, which proves the propagation of molecular chaos. Molecular dynamics simulations of the XY-HMF model confirm our analytical findings

Is diabetes in Cushing's syndrome only a consequence of hypercortisolism?

OBJECTIVE: Diabetes mellitus (DM) is one of the most frequent complications of Cushing's syndrome (CS). The aim of this study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients. DESIGN: Cross-sectional study on 140 patients with CS. METHODS: A total of 113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7±15.7 years) and 27 men (19 with pituitary disease and eight with adrenal disease, aged 38.1±20.01 years) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes), and diabetes (CS/DM) groups. RESULTS: Seventy-one patients had CS/NGT (49.3%), 26 (18.5%) had CS/prediabetes and 43 (30.8%) had CS/DM. Significant increasing trends in the prevalence of family history of diabetes (P<0.001), metabolic syndrome (P<0.001), age (P<0.001) and waist circumference (P=0.043) and decreasing trends in HOMA-β (P<0.001) and oral disposition index (DIo) (P<0.002) were observed among the groups. No significant trends in fasting insulin levels, area under the curve for insulin (AUCINS), Matsuda index of insulin sensitivity (ISI-Matsuda) and visceral adiposity index were detected. CONCLUSIONS: Impairment of glucose tolerance is characterized by the inability of β-cells to adequately compensate for insulin resistance through increased insulin secretion. Age, genetic predisposition and lifestyle, in combination with the duration and degree of hypercortisolism, strongly contribute to the impairment of glucose tolerance in patients with a natural history of CS. A careful phenotypic evaluation of glucose tolerance defects in patients with CS proves useful for the identification of those at a high risk of metabolic complications

Clinical and metabolic effects of first-line treatment with somatostatin analogues or surgery in acromegaly: a retrospective and comparative study

To evaluate the metabolic effects of first-line somatostatin analogues or surgery in acromegaly. Retrospective, comparative, 12-month follow-up. Two hundred and thirty one patients (123 men, age 47.32 ± 14.63 years) with active acromegaly, first line treatments were somatostatin analogues in 151 (65.4%) and surgery in 80 (34.6%). Metabolic syndrome (MS) parameters, glucose, insulin and GH during oral glucose tolerance test, stimulated insulin sensitivity by insulin sensitivity index (ISI Matsuda), early and total insulin-secretion rate by insulinogenic index and AUC(INS), visceral adiposity function, expressed by visceral adipose index (VAI). Somatostatin analogues treatment improved all MS parameters and significantly reduced fasting glucose (P < 0.001), HbA1c (P = 0.014) and the prevalence of DM (P = 0.003) when disease control was achieved. Both somatostatin analogues and surgery improved ISI Matsuda (P < 0.001) and reduced AUC(INS) (P < 0.001) and VAI (P < 0.001 and P = 0.003, respectively). Only in controlled somatostatin analogues-treated patients a significant reduction in insulinogenic index (P = 0.010) was observed. ISI Matsuda showed a significant independent correlation with IGF-1 levels (β = -0.258; P = 0.001) and VAI score (β = -0.430; P < 0.001). VAI was independently correlated with IGF-1 (β = 0.183; P = 0.004). Both somatostatin analogues and surgery can safely be used as first-line therapy in acromegaly, without any untoward effects on glucose tolerance. The control of acromegaly is the main determinant of beneficial effects on general features of insulin sensitivity. VAI could represent an additional link between disease control and insulin sensitivity

Alteration of the growth hormone axis, visceral fat dysfunction, and early cardiometabolic risk in adults: the role of the visceral adiposity index

The aim of the study is to clarify the relationship between adipose tissue dysfunction, metabolic profile and growth hormone (GH)/insulin-like growth factor (IGF)-I secretion in healthy adult subjects. We investigated the metabolic profile in a cohort of 231 consecutive healthy subjects in relation to GH, IGF-I levels, and visceral adiposity index (VAI). Anthropometric measures, lipid profile, and glucose and insulin levels during oral glucose tolerance test, Homa-IR and ISI Matsuda, IGF-I and GH peak after GHRH plus Arginine test were analyzed. The subjects with high VAI showed lower GH peak (22.8 ± 11.1 vs. 42.2 ± 21.3 µg/L; p = 0.049) and lower IGF-I (presented as IGF-I under normal range, UNR) (0.54 ± 0.14 vs. 0.64 ± 0.12; p = 0.005) than group with normal VAI. ROC curve analysis identified the cut-off, able to detect subjects with high VAI, i.e., 31.8 µg/L for GH peak and 0.63 for IGF-1 UNR. The subjects with GH peak and IGF-I UNR under the cut-off showed significantly higher levels of VAI, systolic and diastolic blood pressure, glucose and insulin levels, Homa-IR, and lower ISI Matsuda, with a concomitant worse lipid profile (all p < 0.001). A strong relationship between GH axis, VAI and metabolic risk has been demonstrated. A percentage of apparently healthy subjects show a degree of visceral adipose dysfunction associated with GH and IGF-I levels that do not meet the criteria of overt GH deficiency (GHD). Long-term prospective studies could help to clarify and confirm whether a hypothetical condition of subclinical GHD could be taken into account as a new clinical entity

The Metabolic Profile in Active Acromegaly is Gender-Specific.

CONTEXT: The sexual dimorphism of the somatotroph axis has been documented, but whether the acromegaly-related metabolic alterations are gender-dependent has never been investigated. OBJECTIVE: The aim of the study was to evaluate the impact of gender on the metabolic parameters in acromegaly. DESIGN: We conducted a retrospective, comparative, multicenter study. PATIENTS: The 307 newly diagnosed acromegalic patients included in the study were grouped by gender: 157 men (aged 48.01 ± 14.28 yr), and 150 women (aged 48.67 ± 14.95 yr; of which 77 were premenopausal and 73 postmenopausal). OUTCOME MEASUREMENTS: We measured each component of the metabolic syndrome (MS), hemoglobin A1c, the areas under the curve (AUCs) of glucose and insulin during 2-h oral glucose tolerance test, basal insulin resistance using the homeostasis model assessment of the insulin resistance index, stimulated insulin sensitivity using the insulin sensitivity index, early insulin-secretion rate using the insulinogenic index, β-cell function relative to insulin sensitivity using the oral disposition index and the visceral adiposity index (VAI) as the surrogate of visceral fat function. RESULTS: Women showed a higher prevalence of MS (P &lt; 0.001), higher fasting insulin levels (P &lt; 0.001), AUC for insulin (P = 0.002), homeostasis model assessment of the insulin resistance index (P &lt; 0.001), and VAI (P &lt; 0.001) and a lower insulin sensitivity index (P = 0.002) than men, whereas no difference was found in fasting glucose, AUC for glucose, hemoglobin A1c, insulinogenic index, and oral disposition index. In women, fasting glucose and fasting insulin showed a significant trend toward increase (P &lt; 0.001) and decrease (P = 0.004), respectively, from the first to the fourth quartiles of age, whereas VAI showed a trend toward increase in both groups (P &lt; 0.001). A significantly higher prevalence of MS (P &lt; 0.001), increased waist circumference (P &lt; 0.001), low high-density lipoprotein cholesterol (P &lt; 0.001), and overt diabetes mellitus (P &lt; 0.001) was found in postmenopausal women compared with premenopausal women, as well as with men. CONCLUSIONS: The majority of metabolic features in acromegaly are gender-specific. Active acromegaly in women is strongly associated with higher visceral adiposity dysfunction, insulin resistance, and the features of MS. We suggest more accurate metabolic management in acromegalic women, especially in the postmenopausal years

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease

Background: Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Aims To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. Methods One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. Serum levels of TNF\u3b1, IL-6, adiponectin and leptin were also assessed. All biopsies were scored for NAFLD activity score (NAS) and its components, and for staging (Kleiner). Results By multiple linear regression analysis, VAI was independently associated with higher HOMA (P = 0.04), and fibrosis (P = 0.04). In addition, an independent association was found between higher VAI and lower adiponectin levels (P = 0.002). Higher HOMA (OR 1.149, 95% CI 1.003-1.316, P = 0.04), higher VAI (OR 1.446, 95% CI 1.023-2.043, P = 0.03), lobular inflammation (OR 3.777, 95% CI 1.771-8.051, P = 0.001), and ballooning (OR 2.884, 95% CI 1.231-6.757, P = 0.01) were correlated with significant fibrosis (F2-F4) on multiple logistic regression analysis. In particular, the prevalence of significant fibrosis progressively increased from patients with a VAI 64 2.1 and HOMA 64 3.4 (26%) to those with a VAI > 2.1 and HOMA > 3.4 (83%). Conclusions In NAFLD patients, visceral adiposity index is an expression of both qualitative and quantitative adipose tissue dysfunction and, together with insulin resistance, is independently correlated with significant fibrosis. \ua9 2011 Blackwell Publishing Ltd

Diagnosing silent cardiac dysautonomia via ambulatory blood pressure monitoring: early diagnosis shown by the lack of heart rate circadian rhythm in type 1 diabetes mellitus

Introduction. Diabetes mellitus (DM) can be complicated by an involvement of Neurovegetative System (NVS), conventionally and non-invasively diagnosed by the means of Ewing's test and Heart Rate Variability (HRV) analysis. It is well known that the NVS is physiologically responsible, via biological clocks, for the regulation of Circadian Rhythms (CR) characterizing the majority of biological functions. Therefore, this study is aimed at investigating the CR of Heart Rate (HR) and Blood Pressure (BP) in DM, postulating that the diagnosis of Silent Cardiac Dysautonomia (SCD) could be facilitated by detecting anomalous rhythmometric changes, including the worse one, i.e., the lose of a CR. Materials and Methods. The study has been performed on 30 clinically healthy subjects (CHS), 10 patients with DM1 and 30 patients with DM2, who underwent an ambulatory BP monitoring (ABPM) collecting data equidistantly every 30 minutes, under standardized conditions of lifestyle. The group specific monitored values of systolic (S), diastolic (D) BP, as well as HR have been analyzed via: 1. a conventional analysis of their intradiem variability; 2. a chronobiometric analysis (Cosinor method) of their CR. Results. The conventional analysis disclosed that in CHS, DM1 and DM2, both the HR and BP show an intradiem variability that is significant (p&lt;0.001). The chronobiological analysis showed that in CHS and DM2, both the HR and BP show a significant CR (p&lt;0.001), viceversa in DM1 HR is characterized by a non significant CR (p=0.124), notwithstanding that the SBP and DBP maintain a significant CR (p&lt;0.001). Conclusions. The disappearance of HR CR in DM1 reveals the involvement of neurovegetative biological clock that selectively controls the HR CR, as it is demonstrated by the pathophysiological finding of an internal desynchronization between the HR and BP CR. The selective lose of HR CR in DM1 leads to conclude that the ABPM, along with its Cosinor analysis, might be a practical, repeatable, low cost, low risk technique for diagnosing the SCD, at least in DM1. Clin Ter 2010; 161(1):e1-e1

The origin of ultra high energy cosmic rays

We briefly discuss some open problems and recent developments in the investigation of the origin and propagation of ultra high energy cosmic rays (UHECRs).Comment: Invited Review Talk at TAUP 2005 (Zaragoza - September 10-14, 2005). 7 page

Reduction in broad-spectrum antimicrobial prescriptions by primary care pediatricians following a multifaceted antimicrobial stewardship program

BackgroundSince 2016, following the Italian “National Plan to Contrast Antimicrobial Resistance”, Campania Region has implemented an antimicrobial stewardship program, including the obligation to associate an appropriate International Classification of Diseases-9 code to each antibiotic prescription, the publication of schemes for empirical antibiotic therapy and educational interventions.MethodsTo evaluate the impact of these interventions on the prescribing habits of family pediatricians, we conducted a retrospective cohort study (January 2016–December 2020), including all patients registered in an associate practice of Primary Care Pediatricians. We collected data on antibiotic prescriptions through a specific study management software; our primary outcomes were the annual prescription rates, calculated for both the number of patients in follow-up and the number of medical consultations, and the annual prescription rates for selected antibiotic classes and molecules. To investigate the hypothesis that chronic conditions would be associated with an increased rate of prescription, we also tested the association between underlying conditions and the number of antibiotics received.ResultsDuring the study period, 2,599 children received 11,364 antibiotic prescriptions (mean 4.37, SD 4.28). From 2016 to 2020 we observed a substantial reduction in both the annual prescription rate per 100 patients (9.33 to 3.39; R2 = 0.927, p = 0.009), and the annual prescription rate per 100 medical consultations (25.49 to 15.98; R2 = 0.996, p &lt; 0.01). The prescription rates of Amoxicillin-Clavulanate (50.25 to 14.21; R2 = 0.983, p = 0.001) and third generation Cephalosporins (28.43 to 5.43; R2 = 0.995, p &lt; 0.01) significantly decreased; we didn't find significant modifications in the prescription rates of Amoxicillin and Quinolones; finally, we observed a trend toward reduction in the prescription of Macrolides. No statistical association was found between antibiotics prescribing frequency and history of chronic diseases.DiscussionFollowing the implementation of the regional interventions on antimicrobial stewardship, we observed a substantial reduction in the overall antibiotic prescription per patients and per medical consultations, with a statistically significant reduction in the use of broad-spectrum molecules. Considering the results of our analysis, new guidance and training interventions addressed to specialists in the primary care sector should be implemented to further limit antibiotic resistance