Differential Association of Sex Hormones with Metabolic Parameters and Body Composition in Men and Women from the United States.

Sex hormones impact body composition. Data on the specific impact of each hormone on different body depots in men and women are scarce. The aim of this study is to evaluate the association between testosterone, estradiol and body fat distribution in the general population. This is a population-based cross-sectional study based on data from the 2013-2016 cycles of the National Health and Nutrition Examination Survey. Dual energy X-ray absorptiometry (DXA) and liquid chromatography tandem mass spectrometry were performed on participants aged 18-59 years to evaluate body composition and sex hormone levels, respectively. Weighted multivariable linear regression analyses were performed to evaluate the association between these parameters after adjustment for potential confounders. A total of 6655 participants (3309 males and 3346 females) was included in the analysis. Men with lower testosterone levels were older, had a higher body mass index (BMI) and had a generally unfavorable metabolic profile, while no specific trends were found in women. Among men, testosterone was positively associated with lean body mass and was negatively associated with fat mass and the android/gynoid (A/G) ratio, while an opposite trend was found for estradiol. Among women, testosterone did not impact body composition, while estradiol levels were positively associated with lean mass and were negatively associated with fat mass. Our results support the notion that the impact of different sex hormones on specific fat depots varies substantially between men and women.

Serum neurofilament light chain levels are associated with all-cause mortality in the general US population.

INTRODUCTION: Serum neurofilament light chain (sNfL) levels are biomarkers of neuro-axonal injury in multiple neurological diseases. Little is known on their potential role as prognostic markers in people without known neurological conditions. OBJECTIVE: The aim of this study is to evaluate the association between sNfL levels and all-cause mortality in a general population setting. METHODS: sNfL levels were measured in 2071 people aged 25-75 years from the general US population that participated in the 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES). Cognitive function was evaluated in a subset of participants aged 60-75 years using the Consortium to Establish a Registry for Alzheimer's Disease-Word Learning test, the Animal Fluency test and the Digit Symbol Substitution test. We applied Cox proportional hazard models adjusted for several potential confounders to evaluate the association between sNfL and all-cause mortality through December 2019 by linking NHANES data with data from the National Death Index. RESULTS: In a cross-sectional analysis, higher sNfL levels were associated with worse performance in all three cognitive function tests. Over a median follow-up of 6.1 years, 85 participants died. In a multivariable model adjusted for age, sex, race-ethnicity, diabetes, chronic kidney disease, harmful alcohol consumption, cigarette smoke and prevalent cardiovascular disease, higher sNfL levels were significantly and positively associated with all-cause mortality (HR per unit increase in log-transformed sNfL: 2.46, 95% CI 1.77-3.43, p < 0.001). Results were robust when analyses were stratified according to age, sex, body mass index and kidney function. CONCLUSION: We found a positive association between sNfL levels and mortality in the general US population. Further studies are needed to understand the biological mechanisms underlying this association.

Low 25 (OH) vitamin D levels are associated with increased prevalence of nonalcoholic fatty liver disease and significant liver fibrosis.

AIMS: Evidence on the role of 25-Hydroxyvitamin D (25(OH)D) in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) is conflicting and population-based data are scarce. Here, we assess the association between 25(OH)D levels, NAFLD and liver fibrosis in the general population. MATERIALS AND METHODS: This is an analysis of data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included adult participants with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median values of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. 25(OH)D was measured by high performance liquid chromatography-tandem mass spectrometry. RESULTS: A total of 3970 participants (1928 men and 2042 women) were included in the study. The prevalence of NAFLD (CAP ≥ 274 dB/m) and significant liver fibrosis (LSM ≥ 8 kPa) were 41.7% (95% CI 39.4-44.0) and 8.4% (95% CI 7.0-9.9), respectively, while 21.1% (95% CI 17.3-25.4) of participants had low 25(OH)D levels (<50 nmol/L). A multivariable logistic regression model adjusted for age, sex, race-ethnicity, body mass index, waist circumference, calendar period, diabetes, chronic kidney disease, and vitamin D supplementation showed that compared with participants with low 25(OH)D, those with optimal levels (≥75 nmol/L) had lower odds of both NAFLD (OR 0.73, 95% CI 0.55-0.98 p = 0.038) and significant liver fibrosis (OR 0.65, 95% CI 0.44-0.96, p = 0.033). CONCLUSIONS: An inverse relationship was found between 25(OH)D and NAFLD and fibrosis, suggesting a possible role of vitamin D in NAFLD occurrence and progression.

Diabetes Mellitus is Associated With Higher Serum Neurofilament Light Chain Levels in the General US Population.

CONTEXT: Serum neurofilament light chain (sNfL) levels are biomarkers of neuroaxonal injury in multiple neurological diseases. OBJECTIVE: Given the paucity of data on the distribution of sNfL levels in the general population, in the present study we identified predictors of sNfL levels in a community setting and investigated the association between diabetes and sNfL. METHODS: sNfL levels were measured in 2070 people aged 20 to 75 years from the general US population (275 with and 1795 without diabetes) that participated in the 2013-2014 cycle of the National Health and Nutrition Examination Survey. We evaluated the association between diabetes and sNfL levels after adjustment for age, sex, race-ethnicity, alcohol use, and kidney function using a multivariable linear regression model. Cognitive function was evaluated in a subset of participants aged 60 to 75 years using the Consortium to Establish a Registry for Alzheimer's Disease-Word Learning test, the Animal Fluency test, and the Digit Symbol Substitution test. RESULTS: The weighted prevalence of diabetes was 10.4% (95% CI, 9.0-11.9). In each age stratum, patients with diabetes exhibited higher sNfL levels compared with nondiabetic participants. Age, proportion of males, prevalence of diabetes, and homeostatic model of insulin resistance increased progressively across quartiles of sNfL levels in the overall population, whereas estimated glomerular filtration rate (eGFR) showed an opposite trend. In the multivariable model, age, sex, eGFR, alcohol use and diabetes were significantly associated with sNfL levels. Moreover, higher sNfL levels were associated with worse performance in all 3 cognitive function tests. CONCLUSION: Diabetes is associated with higher sNfL. Further large-scale and prospective studies are needed to replicate our results and evaluate the ability of sNfL to predict the incidence of neuropathy and dementia in this patient population.

NT-ProBNP and mortality across the spectrum of glucose tolerance in the general US population.

BACKGROUND: Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels. METHODS: Serum NT-ProBNP levels were measured in 5502 people aged 45-79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015. RESULTS: After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP < 100 pg/ml, those with levels 100-300 pg/ml and ≥ 300 pg/ml had a higher incidence of both all-cause mortality (HR 1.61, 95% CI 1.12-2.32, p = 0.012 and HR 2.96, 95% CI 1.75-5.00, p < 0.001, respectively) and cardiovascular mortality (HR 1.57, 95% CI 1.17-2.10, p = 0.011 and HR 2.08, 95% CI 1.47-2.93, p < 0.001, respectively). The association was consistent in subgroup analyses based on glycemic status, obesity, age and sex. CONCLUSIONS: Elevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.

Seasonal variation in estimated cardiovascular risk in patients with type 2 diabetes.

BACKGROUND AND AIMS: Seasonal variations in several risk factors for cardiovascular events (CVD) were described. Here, we evaluate the impact of seasonal variations in blood pressure (BP), lipid profile and glycemic control on estimated CVD risk in patients with type 2 diabetes (T2D). METHODS AND RESULTS: Retrospective monocentric study of patients with T2D who were visited at least once in the winter period and once in the summer period, less than 8 months apart, for which data related to systolic (S) BP, diastolic (D) BP, body mass index, glycosylated hemoglobin (HbA1c), total cholesterol, HDL cholesterol and smoking habit were available on both occasions. The 10-year CVD risk was calculated using the UKPDS risk engine and the ASCVD risk estimator. As many as 411 patients were included in the study. Significant within-patient differences between summer and winter were found for the absolute risk of events assessed with both calculators (Δs-w UKPDS-CHD: -1.33%, Δs-w UKPDS-Stroke: -0.84%, Δs-w ASCVD: -2.21%). The seasonal change in SBP was the main responsible for the change in risk estimated with both the UKPDS-Stroke (r2 = 0.43) and the ASCVD (r2 = 0.50) scores, while the change in total cholesterol was the main determinant of the change in risk for the UKPDS-CHD (r2 = 0.34). A significant correlation was identified between changes in temperature and changes in SBP (ρ = 0.130, p = 0.008), but not in other risk factors. CONCLUSIONS: Seasonal variations in the classic CVD risk factors influence the risk estimated using validated calculators.

Metabolic and Psychological Features are Associated with Weight Loss 12 Months After Sleeve Gastrectomy.

CONTEXT: Laparoscopic sleeve gastrectomy (LSG) is a recognized effective procedure of bariatric surgery, but a poor response in weight loss may still represent a clinical problem. To date there are no validated predictors useful to better perform patient selection. OBJECTIVE: To establish the association of baseline anthropometric, metabolic, and psychologic features with the percent total weight loss (%TWL) and percent excess weight loss (%EWL) 12 months after surgery. DESIGN: Retrospective longitudinal analysis of a set of data about obese patients attending the outpatient service of a single obesity center from June 2016 to June 2019. PATIENTS: A total of 106 obese patients underwent LSG with presurgery evaluation and follow-up at 12 months after surgery. MAIN OUTCOME: Weight loss 12 months after LSG. RESULTS: Patients who achieved a %TWL higher than the observed median (≥34%) were younger, with a lower fasting plasma glucose and glycated hemoglobin, with a lower prevalence of hypertension and with a lower score in the impulsiveness scale, compared with patients with a %TWL < 34%. Similar findings were found when %EWL was considered. Multivariable stepwise regression analysis showed that younger age, lower impulsiveness, higher-than-normal urinary free cortisol, and lower HbA1c were associated with higher %TWL, explaining about 31.5% of the weight loss. CONCLUSION: Metabolic and psychologic features at baseline were independently associated with weight loss and explained a non-negligible effect on the response to LSG. These data suggest that careful metabolic and psychologic profiling could help in sharper indications and personalized pre- and postsurgical follow-up protocols in candidates for LSG.

Hypercortisolism and altered glucose homeostasis in obese patients in the pre-bariatric surgery assessment.

AIMS: Hypothalamus-pituitary-adrenal (HPA) axis hyperactivity was suggested to be associated with the metabolic syndrome (MS), obesity and diabetes. The aim of this study was to test whether hypercortisolism was associated with altered glucose homeostasis and insulin resistance, hypertension and dyslipidemia in a homogeneous population of obese patients. MATERIALS/METHODS: In retrospective analysis of a set of data about obese patients attending the outpatient service of a single obesity centre between January 2013 and January 2020, 884 patients with BMI >30 kg/m2 were segregated in two subgroups: patients with urinary free cortisol (UFC) higher than normal (UFC+; n = 129) or within the normal range (UFC-; n = 755). RESULTS: The overall prevalence of UFC+ was 14.6% and double test positivity (morning cortisol >1.8 mcg/dL following overnight dexamethasone suppression test, ODST) was detected in 1.0% of patients. Prediabetes (OR 1.74; 95%CI 1.13-2.69; p = 0.012) and diabetes (OR 2.03; 95%CI 1.21-3.42; p = 0.008) were associated with higher risk of UFC+ when analysis was adjusted for confounding variables. Conversely, hypertension and dyslipidemia were not related to UFC+. Within the individuals with normal FPG and HbA1c, those with higher estimated insulin resistance (HOMA2-IR) maintained a higher risk of UFC+ (OR 2.84, 95%CI 1.06-7.63; p = 0.039) and this relationship was weakened only when the body fat percentage was included into the model. CONCLUSIONS: In obese patients, hypercortisolism was more frequent across the entire spectrum of altered glucose homeostasis including the very early stages; this relation could not be detected for the other criteria of the MS, as waist, hypertension and atherogenic dyslipidemia.

Baseline TSH levels and short-term weight loss after different procedures of bariatric surgery.

BACKGROUND: Bariatric surgery is a valuable therapeutic option in the treatment of obesity but the outcomes show a large subject-to-subject variability yet to be explained. Thyroid function may represent an involved factor and we have only few controversial data about its influence. SUBJECTS/METHODS: We retrospectively assessed using a longitudinal approach the relation between baseline TSH levels and short-term (6 and 12 months) weight loss in 387 euthyroid patients who underwent laparoscopic gastric banding (LAGB; n = 187) or sleeve gastrectomy (SG; n = 200). RESULTS: After LAGB, patients with low-normal TSH levels (0.40-1.40 mUI/L) had higher percent total weight loss, ∆BMI and percent excess weight loss when compared to patients with normal (1.41-2.48 mUI/L) and high-normal (2.49-4.00 mUI/L) TSH (p < 0.05). Conversely, no association was detected after SG (p = 0.17). The multivariable regression analysis showed that also baseline BMI (6-12 months) and HOMA2-IR (only at 6 months) were independently associated with the outcomes. CONCLUSIONS: TSH levels may influence the short-term weight loss response after LAGB. The lack of association after SG suggests that the influence of baseline endocrine and metabolic factors may not be relevant for procedures with greater and more immediate calorie intake restriction.

Visit-to-visit blood pressure variability in patients with type 2 diabetes with and without previous history of cardiovascular disease.

OBJECTIVE: Visit-to-visit variability in SBP is a risk factor for cardiovascular disease (CVD) in type 2 diabetes (T2DM) but little is known on whether in T2DM this differs according to presence or absence of previous CVD. METHODS: We retrospectively assessed the coefficient of variation (standard deviation/mean) of mean SBP (SBP-CV) in 970 patients (44% with established CVD) attending at least four times our secondary care diabetes clinic in 2015-2016 to estimate their risk of CVD-related events using the 10-year UKPDS Risk Engine. RESULTS: Patients with established CVD had a higher SBP-CV (10.3 ±â€Š4.8%) than patients without CVD (8.9 ±â€Š4.3%; P < 0.001) as confirmed by the progressively higher prevalence of established CVD in tertiles of SBP-CV (36.6, 46.1, and 52.0%; P < 0.001), in association with more aggressive and complex drug regimens. On the basis of the 10-year UKPDS Risk Engine, higher SBP-CV values were associated with increased risks of the CVD outcomes regardless of the previous history of CVD in multivariate models. CONCLUSION: Visit-to-visit variability of SBP was greater in T2DM patients with that in those without previous history of CVD, and maintained an independent association with higher estimated risk of CVD-related events regardless of the history of CVD, suggesting that its prognostic significance is relevant in the entire CVD continuum of patients with T2DM.

Resting Whole Body Energy Metabolism in Class 3 Obesity; from Preserved Insulin Sensitivity to Overt Type 2 Diabetes.

CONTEXT: Insulin resistance and diabetes may influence separately or in combination whole body energy metabolism. OBJECTIVE: To assess the impact of insulin resistance and/or overt type 2 diabetes on resting energy expenditure (REE) in class 3 obese individuals. DESIGN AND SETTING: Retrospective, cross-sectional analysis of a set of data about individuals attending the outpatients service of a single center of bariatric surgery between January 2015 and December 2017. PATIENTS: We screened 382 patients in which abnormal thyroid function was excluded, and segregated them in three groups of subjects: patients with type 2 diabetes (T2DM; n=70), non-diabetic insulin-resistant patients with HOMA-IR ≥ 3 (n=236), non-diabetic insulin-sensitive patients with HOMA-IR < 3 (n=75). MAIN OUTCOME MEASURE: Resting energy expenditure (REE), body composition and insulin resistance assessed using indirect calorimetry, bioimpedance and HOMA-IR. RESULTS: Non-diabetic insulin-sensitive patients resulted to be younger, with lower BMI and higher prevalence of female subjects; meanwhile, non-diabetic but insulin-resistant patients and T2DM patients were not different in terms of anthropometric parameters. REE was higher in T2DM than in non-diabetic insulin-resistant and insulin-sensitive individuals when expressed as percent of the predicted REE (based on Harris Benedict equation) (p<0.0001) or when adjusted for kg of free fat mass (p<0.0001) and was found to be higher also in insulin-resistant vs insulin-sensitive patients (p<0.001). The respiratory quotient was different between groups (0.87±0.11, 0.86±0.12 and 0.91±0.14 in T2DM, insulin-resistant and insulin-sensitive patients, respectively; p<0.03). Regression analysis confirmed that HOMA-IR was independently associated with the REE (R2=0.110, p<0.001). CONCLUSION: Class 3 obese patients with normal insulin sensitivity are characterized by reduced fasting REE in comparison to insulin-resistant obese patients and obese patients with short duration of diabetes supporting the hypothesis that down-regulation of nutrients' oxidative disposal may represent an adaptation of energy metabolism in obese individuals with preserved insulin sensitivity.

Resting Energy Expenditure in Obese Women with Primary Hypothyroidism and Appropriate Levothyroxine Replacement Therapy.

CONTEXT: Growing evidence suggests that appropriate levothyroxine (LT4) replacement therapy may not correct the full set of metabolic defects afflicting individuals with hypothyroidism. OBJECTIVE: To assess whether obese subjects with primary hypothyroidism are characterized by alterations of the resting energy expenditure (REE). DESIGN: Retrospective analysis of a set of data about obese women attending the outpatients service of a single obesity center from January 2013 to July 2019. PATIENTS: A total of 649 nondiabetic women with body mass index (BMI) > 30 kg/m2 and thyrotropin (TSH) level 0.4-4.0 mU/L were segregated into 2 groups: patients with primary hypothyroidism taking LT4 therapy (n = 85) and patients with normal thyroid function (n = 564). MAIN OUTCOMES: REE and body composition assessed using indirect calorimetry and bioimpedance. RESULTS: REE was reduced in women with hypothyroidism in LT4 therapy when compared with controls (28.59 ±â€…3.26 vs 29.91 ±â€…3.59 kcal/kg fat-free mass (FFM)/day), including when adjusted for age, BMI, body composition, and level of physical activity (P = 0.008). This metabolic difference was attenuated only when adjustment for homeostatic model assessment of insulin resistance (HOMA-IR) was performed. CONCLUSIONS: This study demonstrated that obese hypothyroid women in LT4 therapy, with normal serum TSH level compared with euthyroid controls, are characterized by reduced REE, in line with the hypothesis that standard LT4 replacement therapy may not fully correct metabolic alterations related to hypothyroidism. We are not able to exclude that this feature may be influenced by the modulation of insulin sensitivity at the liver site, induced by LT4 oral administration.

Screening for non-alcoholic fatty liver disease in type 2 diabetes using non-invasive scores and association with diabetic complications.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with type 2 diabetes. Here, we estimate the proportion of patients with type 2 diabetes that should be referred to hepatologists according to the European Association for the Study of the Liver (EASL)-European Association for the Study of Diabetes (EASD)-European Association for the Study of Obesity (EASO) Guidelines and evaluate the association between non-invasive biomarkers of steatosis and fibrosis and diabetic complications. RESEARCH DESIGN AND METHODS: This is a retrospective analysis of type 2 diabetes patients who attended on a regular basis our diabetes clinic between 2013 and 2018 (n=2770). Steatosis was assessed using Fatty Liver Index (FLI), Hepatic Steatosis Index and NAFLD Ridge Score and fibrosis using NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI) and AST/alanine aminotransferase (ALT) ratio. Outcome measures were altered albumin excretion rate (AER), chronic kidney disease (CKD) and cardiovascular disease (CVD). RESULTS: The prevalence of advanced fibrosis varied from 1% (APRI) to 33% (NFS). The application of the guidelines using a sequential combination of FLI and FIB-4 would lead to referral of 28.3% of patients when using standard FIB-4 cut-offs, while this number dropped to 13.4% when age-adjusted FIB-4 thresholds were applied. A higher prevalence of altered AER was associated with liver steatosis (FLI: OR: 3.49; 95% CI 2.05 to 5.94, p<0.01), whereas liver fibrosis was associated with CKD (FIB-4: OR: 6.39; 95% CI 4.05 to 10.08, p<0.01) and CVD (FIB-4: OR: 2.62; 95% CI 1.69 to 4.04, p<0.01). CONCLUSIONS: While specific fibrosis scores identify different proportion of patients with advanced fibrosis, the use of age-adjusted FIB-4 cut-offs leads to a drop in gray-zone results, making referrals to hepatologists more sustainable. Interestingly non-invasive biomarkers were consistently associated with a different pattern of diabetic complications.

Fasting Whole-Body Energy Homeostasis and Hepatic Energy Metabolism in Nondiabetic Humans with Fatty Liver.

BACKGROUND: Fatty liver is believed to be sustained by a higher than normal adipose-derived NEFA flux to the liver. Also, hepatic energy metabolism may be a rate-limiting step of intrahepatic fat (IHF) accumulation. AIMS: To assess whole-body energy metabolism and hepatic high-energy phosphates (HEPs) in individuals with fatty liver. METHODS: We studied 22 individuals with fatty liver and 22 control individuals matched for anthropometric features by means of (1) hepatic 1H-magnetic resonance spectroscopy (MRS) to measure the IHF content, (2) hepatic 31P-MRS to assess the relative content of HEPs (phosphomonoesters, phosphodiesters, inorganic phosphorus, and ATP), and (3) indirect calorimetry to assess whole-body resting energy expenditure and substrate oxidation. RESULTS: Patients with newly diagnosed fatty liver and controls were not different for anthropometric parameters. Based on HOMA2%-S, individuals with fatty liver were more insulin resistant than controls. Resting energy expenditure and the pattern of substrate oxidation were not different between groups. Relative content of HEPs was not different between groups; in particular, the Pi/γ-ATP ratio, the most important signals in terms of monitoring energy homeostasis, was not different even if it was associated with indirect calorimetry-derived parameters of oxidative substrate disposal. CONCLUSIONS: These data demonstrate that fasting whole-body energy metabolism and the relative content of HEPs in nondiabetic patients with fatty liver are not different than those in controls when they are matched for anthropometric features.

Legal issues in governing genetic biobanks: the Italian framework as a case study for the implications for citizen's health through public-private initiatives.

This paper outlines some of the challenges faced by regulation of genetic biobanking, using case studies coming from the Italian legal system. The governance of genetic resources in the context of genetic biobanks in Italy is discussed, as an example of the stratification of different inputs and rules: EU law, national law, orders made by authorities and soft law, which need to be integrated with ethical principles, technological strategies and solutions. After providing an overview of the Italian legal regulation of genetic data processing, it considers the fate of genetic material and IP rights in the event of a biobank's insolvency. To this end, it analyses two case studies: a controversial bankruptcy case which occurred in Sardinia, one of the first examples of private and public partnership biobanks. Another case study considered is the Chris project: an example of partnership between a research institute in Bolzano and the South Tyrolean Health System. Both cases seem to point in the same direction, suggesting expediency of promoting and improving public-private partnerships to manage biological tissues and biotrust to conciliate patent law and public interest.

The asthma-anxiety connection.

BACKGROUND: The literature reports a significant association between various mental disorders and asthma, in particular depression and/or anxiety, with some more robust data regarding anxiety disorders. However, the nature of this association remains largely unclear. OBJECTIVES: (1) To test the hypothesis of a specific association of anxiety and depressive disorder (according to the DSM-IV) with asthma and (2) to test the bidirectional hypothesis of causality between asthma and psychiatric disorders. METHODS: Ninety-six adults were compared with 96 control subjects matched according to main socio-demographic variables (i.e., gender, age, marital status, cohabiting/non-cohabiting, and BMI). Subjects with asthma were divided according to GINA and ACT classifications. All subjects underwent Structured Clinical Interviews for DSM-IV Axis I (SCID-I) diagnosis. RESULTS: Significant association between asthma and lifetime anxiety disorders emerged (OR 3.03; p = 0.003); no significant association with other psychiatric diagnosis emerged. Moreover, lifetime and current anxiety were associated with asthma severity levels (p < 0.01 and p = 0.001 based on age). Asthma preceded anxiety in 48% of cases; in 52% of cases, anxiety preceded asthma, without significant group differences. The risk of asthma, particularly of severe, uncontrolled forms (p < 0.01), resulted higher in lifetime anxiety disorder patients (p = 0.003 and p = 0.001 based on age at onset). Current anxiety increased the risk of asthma, and that of an uncontrolled form (p < 0.05). Asthma increased the risk of lifetime anxiety disorders (p = 0.002 and p = 0.018 using ages). Intermittent asthma increased the risk of lifetime and current anxiety disorders (p < 0.01). CONCLUSIONS: Anxiety disorders, in particular Lifetime Anxiety Disorders, represent the only psychiatric disorder significantly associated with asthma, with a possible bidirectional, anxiety-asthma relationship, each of which can be caused or result from the other.

The legal fate of biobanks between privacy, IPRs and crisis of a firm. A preliminary study on the case of bio-bankruptcy"

In the case of biobank bankruptcy, the current legal framework is not suitable to protect the rights of research subjects. In the paper we identify such a gap in protection and suggest some remedies to address it (AU)

En caso de quiebra del biobanco, el marco jurídico actual no parece adecuado para garantizar los derechos de los sujetos de investigación. En este artículo se identifica esa brecha en la protección y se sugieren algunos remedios para hacerla frente (AU)

Comparison of objective Bayes factors for variable selection in parametric regression models for survival analysis.

This paper considers the problem of selecting a set of regressors when the response variable is distributed according to a specified parametric model and observations are censored. Under a Bayesian perspective, the most widely used tools are Bayes factors (BFs), which are undefined when improper priors are used. In order to overcome this issue, fractional (FBF) and intrinsic (IBF) BFs have become common tools for model selection. Both depend on the size, Nt , of a minimal training sample (MTS), while the IBF also depends on the specific MTS used. In the case of regression with censored data, the definition of an MTS is problematic because only uncensored data allow to turn the improper prior into a proper posterior and also because full exploration of the space of the MTSs, which includes also censored observations, is needed to avoid bias in model selection. To address this concern, a sequential MTS was proposed, but it has the drawback of an increase of the number of possible MTSs as Nt becomes random. For this reason, we explore the behaviour of the FBF, contextualizing its definition to censored data. We show that these are consistent, providing also the corresponding fractional prior. Finally, a large simulation study and an application to real data are used to compare IBF, FBF and the well-known Bayesian information criterion.

TH17 cells are increased in the peripheral blood of patients with SAPHO syndrome.

To assess whether the immune derangement previously observed in SAPHO syndrome could be linked to variations in blood TH1, TH2 or TH17 lymphocytes frequency. Seven SAPHO patients with a protracted course of the disease were studied ex-vivo for intracellular cytokines production by means of flow-cytometry and compared with matched groups of Psoriatic Arthritis patients and healthy controls. The Kruskal-Wallis test on the median of the three categories showed that there is a significant association between the TH17 levels and the category (p value = 0.02474). The mean and variance for the proportion of IL-17 producing CD4+ cells were compared between groups showing significant differences between SAPHO versus PsA subgroup (p = 0.05) and SAPHO versus healthy controls (p = 0.008). Interestingly, activation of TH17 axis, but not of TH1 and TH2, has been found, and can be observed both in patients with different activity of the disease or treated with different drugs. The TH17 increase in peripheral blood of our SAPHO subjects resembles the one recently found in patients with different AIDs. Novel therapeutic options in these patients may therefore include IL-17 blockade.

The legal fate of biobanks between privacy, IPRs and crisis of a firm. A preliminary study on the case of "bio-bankruptcy" .

In the case of biobank bankruptcy, the current legal framework is not suitable to protect the rights of research subjects. In the paper we identify such a gap in protection and suggest some remedies to address it.