Benefits of dual-release hydrocortisone treatment on central adiposity and health-related quality of life in secondary adrenal insufficiency.

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.

Idiopathic central diabetes insipidus in a large cohort of patients: the hypopituitarism ENEA rare observational (HEROS) study.

Central Diabetes Insipidus (CDI) is mainly associated with structural pathologies of the hypothalamic-pituitary area. Etiologies underlying CDI are identified in most patients, however idiopathic CDI is reported in 13-17% of cases after excluding other etiologies. The Hypopituitarism ENEA Rare Observational Study (HEROS study) retrospectively collected data of patients with idiopathic CDI from 14 pituitary centers in 9 countries. The cohort included 92 patients (59 females 64%), mean age at diagnosis was 35.4 ± 20.7 years, and a mean follow up of 19.1 ± 13.5 years following CDI diagnosis. In 6 women, diagnosis was related to pregnancy. Of 83 patients with available data on pituitary imaging, 40(48%) had normal sellar imaging, and 43(52%) had pathology of the posterior pituitary or the stalk, including loss of the bright spot, posterior pituitary atrophy or stalk enlargement. Anterior pituitary hormone deficiencies at presentation included hypogonadism in 6 (6.5%) patients (5 females), and hypocortisolism in one; during follow-up new anterior pituitary deficiencies developed in 6 patients. Replacement treatment with desmopressin was given to all patients except one, usually with an oral preparation. During follow up, no underlying disease causing CDI was identified in any patient. Patients with idiopathic CDI following investigation at baseline are stable with no specific etiology depicted during long-term follow-up.

Combining social network analysis and agent-based model for enabling nature-based solution implementation: The case of Medina del Campo (Spain).

Several barriers still hamper the effective implementation of Nature-Based Solutions (NBS). Among the others, this work focuses on collaboration barriers. NBS implementation claims for effective collaboration among different decision-agents. However, ambiguity in problem framings, which is ineradicable in multi-agents' decision environments, could create collaboration barriers. This work aims to demonstrate that collaboration barriers to NBS implementation can be overcome by enhancing the network of interactions among the decision-agents. An innovative method based on the integration between Social Network Analysis and hybrid Agent-Based Model/System Dynamic Model was adopted to this aim. The analysis results were used for designing networking interventions, i.e. efforts using social network characteristics that could enhance interactions mechanisms among decision-agents. The developed method was implemented in the Medina del Campo (Spain) case study. This area is characterised by one of the most critical groundwater bodies of the Duero River Basin. This work aims at supporting the implementation of suitable NBS to stop the degradation of the groundwater status and associated ecosystem services. The activities carried out within the framework of the NAIAD project showed that, by enhancing the interaction mechanisms, ambiguity in problem frames can still yield collective actions for NBS implementation.

Reference ranges of late-night salivary cortisol and cortisone measured by LC-MS/MS and accuracy for the diagnosis of Cushing's syndrome.

PURPOSE: International guidelines recommend salivary cortisol for the diagnosis of Cushing's syndrome. Despite mass spectrometry-based assays are considered the analytical gold-standard, there is still the need to define reference intervals and diagnostic accuracy of such methodology. METHODS: 100 healthy volunteers and 50 consecutive patients were enrolled to compare LC-MS/MS and electrochemiluminescence assay for the determination of late-night salivary cortisol and cortisone. Moreover, we aimed to determine reference intervals of salivary steroids in a population of healthy individuals and diagnostic accuracy in patients with suspected hypercortisolism and in a population including also healthy individuals. RESULTS: Method comparison highlighted a positive bias (51.8%) of immunoassay over LC-MS/MS. Reference intervals of salivary cortisol (0.17-0.97 µg/L), cortisone (0.84-4.85 µg/L) and ratio (0.08-0.30) were obtained. The most accurate thresholds of salivary cortisol for the diagnosis of hypercortisolism were 1.15 µg/L in the population with suspected hypercortisolism (AUC 1) and 1.30 µg/L in the population including also healthy individuals (AUC 1). Cut-off values of salivary cortisone (7.23 µg/L; Se 92.9%, Sp 97.2%, AUC 0.960 and Se 92.9%, Sp 99.1%, AUC 0.985 in suspected hypercortisolism and in overall population, respectively) and cortisol-to-cortisone ratio (0.20; Se 85.7%, Sp 80.6%, AUC 0.820 and Se 85.7%, Sp 85.5%, AUC 0.855 in suspected hypercortisolism and in overall population, respectively) were accurate and similar in both populations. CONCLUSION: LC-MS/MS is the most accurate analytical platform for measuring salivary steroids. Obtained reference intervals are coherent with previously published data and diagnostic accuracy for diagnosis of overt hypercortisolism proved highly satisfactory.

Enhancing nature-based solutions acceptance through stakeholders' engagement in co-benefits identification and trade-offs analysis.

Nature-based solutions (NBS) are increasingly recognized as a valid alternative to grey infrastructures - i.e. hard, human-engineered structures - as measures for reducing climate-related risks. Increasing evidences demonstrated that NBS can reduce risks to people and property as effectively as traditional grey infrastructures, but potentially offering many additional benefits, e.g. improving the natural habitat for wildlife, enhancing water and air quality, improving socio-cultural conditions of communities. The growing attention on the NBS, triggered an increasing interest in developing integrated and multi-disciplinary frameworks for assessing NBS effectiveness accounting for the co-benefits production. Starting from the analysis of the existing frameworks, this work claims for a more direct engagement of stakeholders - i.e. co-benefits beneficiaries - in developing NBS assessment framework. This work aims at demonstrating that differences in co-benefits perception and valuation might lead to trade-offs and, thus, to potential conflicts. An innovative methodology using a quasi-dynamic Fuzzy Cognitive Map approach based on multiple-time-steps was developed in order to assess NBS effectiveness, and to detect and analyze trade-offs among stakeholders due to differences in co-benefits perception. The developed methodology was implemented in the Lower Danube case study. The trade-off analysis among stakeholders shows that they are quite low in the short term. Most of the potential conflicts can be detected in the long term, involving mainly the stakeholders that assigned a high value to the agricultural productivity variable. The results demonstrated that accounting for the different stakeholders' perception of the co-benefits is key for reducing trade-offs and enhance NBS acceptability.

Towards the tailoring of glucocorticoid replacement in adrenal insufficiency: the Italian Society of Endocrinology Expert Opinion.

CONTEXT: Glucocorticoid (GC) replacement therapy in patients with adrenal insufficiency (AI) is life saving. After over 50 years of conventional GC treatment, novel formulations are now entering routine clinical practice. METHODS: Given the spectrum of medications currently available and new insights into the understanding of AI, the authors reviewed relevant medical literature with emphasis on original studies, prospective observational data and randomized controlled trials performed in the past 35 years. The Expert Opinion of a panel of selected endocrinologists was sought to answer specific clinical questions. The objective was to provide an evidence-supported guide, for the use of GC in various settings from university hospitals to outpatient clinics, that offers specific advice tailored to the individual patient. RESULTS: The Panel reviewed available GC replacement therapies, comprising short-acting, intermediate and long-acting oral formulations, subcutaneous formulations and the novel modified-release hydrocortisone. Advantages and disadvantages of these formulations were reviewed. CONCLUSIONS: In the Panel's opinion, achieving the optimal GC timing and dosing is needed to improve the outcome of AI. No-single formulation offers the best option for every patients. Recent data suggest that more emphasis should be given to the timing of intake. Tailoring of GS should be attempted in all patients-by experts-on a case-by-case basis. The Panel identified specific subgroups of AI patients that could be help by this process. Long-term studies are needed to confirm the short-term benefits associated with the modified-release GCs. The impact of GC tailoring has yet to be proven in terms of hospitalization rate, morbidity and mortality.

Where do we aspire to publish? A position paper on scientific communication in biochemistry and molecular biology.

The scientific publication landscape is changing quickly, with an enormous increase in options and models. Articles can be published in a complex variety of journals that differ in their presentation format (online-only or in-print), editorial organizations that maintain them (commercial and/or society-based), editorial handling (academic or professional editors), editorial board composition (academic or professional), payment options to cover editorial costs (open access or pay-to-read), indexation, visibility, branding, and other aspects. Additionally, online submissions of non-revised versions of manuscripts prior to seeking publication in a peer-reviewed journal (a practice known as pre-printing) are a growing trend in biological sciences. In this changing landscape, researchers in biochemistry and molecular biology must re-think their priorities in terms of scientific output dissemination. The evaluation processes and institutional funding for scientific publications should also be revised accordingly. This article presents the results of discussions within the Department of Biochemistry, University of São Paulo, on this subject.

Where do we aspire to publish? A position paper on scientific communication in biochemistry and molecular biology

The scientific publication landscape is changing quickly, with an enormous increase in options and models. Articles can be published in a complex variety of journals that differ in their presentation format (online-only or in-print), editorial organizations that maintain them (commercial and/or society-based), editorial handling (academic or professional editors), editorial board composition (academic or professional), payment options to cover editorial costs (open access or pay-to-read), indexation, visibility, branding, and other aspects. Additionally, online submissions of non-revised versions of manuscripts prior to seeking publication in a peer-reviewed journal (a practice known as pre-printing) are a growing trend in biological sciences. In this changing landscape, researchers in biochemistry and molecular biology must re-think their priorities in terms of scientific output dissemination. The evaluation processes and institutional funding for scientific publications should also be revised accordingly. This article presents the results of discussions within the Department of Biochemistry, University of São Paulo, on this subject.

Computed Tomography Findings of Bronchiectasis in Different Respiratory Phases Correlate with Pulmonary Function Test Data in Adults.

OBJECTIVE: To investigate bronchiectasis variations in different computed tomography (CT) respiratory phases, and their correlation with pulmonary function test (PFT) data, in adults. METHODS: Retrospective data analysis from 63 patients with bronchiectasis according to CT criteria selected from the institution database and for whom PFT data were also available. Bronchiectasis diameter was measured on inspiratory and expiratory phases. Its area and matched airway-vessel ratios in both phases were also calculated. Finally, PFT results were compared with radiological measurements. RESULTS: Bronchiectatic airways were larger on inspiration than on expiration (mean cross-sectional area, 69.44 vs. 40.84 mm2; p < 0.05) as were airway-vessel ratios (2.1 vs. 1.4; p < 0.05). Cystic bronchiectasis cases showed the least variation in cross-sectional area (48%). Mean predicted values of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were 81.5 and 77.2%, respectively, in the group in which bronchiectasis could not be identified on expiratory images, and 58.3 and 56.0%, respectively, in the other group (p < 0.05). Variation in bronchiectasis area was associated with poorer lung function (r = 0.32). CONCLUSION: Bronchiectasis detection, diameter, and area varied significantly according to CT respiratory phase, with non-reducible bronchiectasis showing greater lung function impairment.

Usefulness of an ad hoc questionnaire (Acro-CQ) for the systematic assessment of acromegaly comorbidities at diagnosis and their management at follow-up.

PURPOSE: To determine the validity of a self-administered questionnaire (Acro-CQ) developed to systematically assess the presence, type and time of onset of acromegaly comorbidities. METHODS: This is a cross-sectional study; 105 acromegaly patients and 147 controls with other types of pituitary adenoma, referred to a specialized Italian Center, autonomously compiled Acro-CQ in an outpatient clinical setting. To test its reliability in a different setting, Acro-CQ was administered via mail to 78 patients with acromegaly and 100 with other pituitary adenomas, referred to a specialized US Center. Data obtained from questionnaires in both settings were compared with medical records (gold standard). RESULTS: Demographics of patients and controls from both countries were similar. In both settings, >95 % of the questionnaires were completely filled; only one item was missed in the others. Concordance with medical record was excellent (k > 0.85) for most of the items, independently from the way of administration, patient age, gender and nationality, pituitary adenoma type and disease activity. CONCLUSIONS: Acro-CQ is an inexpensive, highly accepted from patients and reliable tool recommended to expedite systematic collection of relevant clinical data in acromegaly at diagnosis, to be replicated at follow-ups. This tool may guide a targeted, cost-effective management of complications. Moreover, it could be applied to retrieve data for survey studies in both acromegaly and other pituitary adenomas, as information is easily and rapidly accessible for statistical analysis.

Optimization of the Production of Inactivated Clostridium novyi Type B Vaccine Using Computational Intelligence Techniques.

Clostridium novyi causes necrotic hepatitis in sheep and cattle, as well as gas gangrene. The microorganism is strictly anaerobic, fastidious, and difficult to cultivate in industrial scale. C. novyi type B produces alpha and beta toxins, with the alpha toxin being linked to the presence of specific bacteriophages. The main strategy to combat diseases caused by C. novyi is vaccination, employing vaccines produced with toxoids or with toxoids and bacterins. In order to identify culture medium components and concentrations that maximized cell density and alpha toxin production, a neuro-fuzzy algorithm was applied to predict the yields of the fermentation process for production of C. novyi type B, within a global search procedure using the simulated annealing technique. Maximizing cell density and toxin production is a multi-objective optimization problem and could be treated by a Pareto approach. Nevertheless, the approach chosen here was a step-by-step one. The optimum values obtained with this approach were validated in laboratory scale, and the results were used to reload the data matrix for re-parameterization of the neuro-fuzzy model, which was implemented for a final optimization step with regards to the alpha toxin productivity. With this methodology, a threefold increase of alpha toxin could be achieved.

Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception.

BACKGROUND AND PURPOSE: Depression is common amongst subjects with multiple sclerosis (MS), and several investigations have explored different determinants of this condition, including physical disability, psychological and psychosocial factors. The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with depression. The aim of this study was to analyze the influence of disease-related factors, BDNF Val66Met polymorphism and perception of disease on the severity of depression in MS. METHOD: In total, 136 MS patients (88 women) were recruited and genotyped for BDNF rs6265 polymorphism at nucleotide 196 (G/A) using 'high resolution melting'. Depressive symptoms were assessed by the Multiple Sclerosis Depression Rating Scale. Perception of health status was assessed using the SF-36 questionnaire. RESULTS: A multivariable linear regression model showed that the best predictors of depression were the SF-36 General health (ß = -0.209; P = 0.013), Mental health (ß = -0.410; P < 0.001) and Social activity (ß = -0.195; P = 0.035) scores; physical disability (assessed by the Extended Disability Status Scale score) was directly correlated to depression severity on univariate analysis, but it was not a relevant predictor of depression on multivariate analysis; other variables directly related to the disease (treatment, annual relapsing rate) and the BDNF Val66Met polymorphism were not significantly associated with depression. CONCLUSION: Perception of the health status is the principal predictor of depressive symptoms in our sample. This result supports the hypothesis that the subjective interpretation of the disease's consequences is one of the main factors in determining depression in MS.

Multidetector Computed Tomography Findings in Pulmonary Hamartomas: A New Fat Detection Threshold.

PURPOSE: The aim of the study was to determine the accuracy of multidetector computed tomography in the evaluation of histologically confirmed pulmonary hamartomas (PHs), with a special focus on fat detection. MATERIALS AND METHODS: Data from 55 patients who had received a histologically confirmed diagnosis of PH and had undergone 64-slice thoracic MDCT were retrospectively evaluated. RESULTS: PHs manifested predominantly as peripheral pulmonary nodules with lobulated margins. The average lesion diameter was 1.51 cm (SD 0.6 cm). Histologic analyses identified fat content in 43/55 (78.2%) surgical specimens. The accuracy, sensitivity, and specificity of fat detection at a density threshold of -40 HU were 83.7%, 100%, and 87.2%, respectively. A threshold of -33 HU yielded better results (95.3%, 100%, and 96.3%, respectively). Popcorn-like calcifications were found in only 12/55 (21.8%) PHs and were the only imaging feature suggestive of PH in 7.2% of cases. Most (66%) lesions with popcorn-like calcifications also contained fat. CONCLUSIONS: The adoption of a new threshold for fat content (<-33 HU) can lead to further improvements in the overall ability to detect PHs by CT.

The acute effect of a mineralocorticoid receptor agonist on corticotrope secretion in Addison's disease.

PURPOSE: Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA) axis, mediating the ''proactive'' feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addison's disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated. METHODS: Ten patients affected by autoimmune Addison's disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy. RESULTS: H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone. CONCLUSIONS: Our study showed a lack of FC effect on corticotrope secretion in Addison's disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.

Addition of metal ions to a (hemi)cellulolytic enzymatic cocktail produced in-house improves its activity, thermostability, and efficiency in the saccharification of pretreated sugarcane bagasse.

High activity and stability are essential for (hemi)cellulolytic enzymes used in biomass conversion, while non-productive binding of cellulases to lignin reduces saccharification efficiency and needs to be avoided. One potential strategy is the addition of inexpensive metal ions. This paper describes the influence of divalent metal ions on the activity, thermostability, and saccharification efficiency of (hemi)cellulolytic enzymes produced in-house by Aspergillus niger under solid-state fermentation (SSF). The use of Mn(2+) provided the best (hemi)cellulolytic activity and stability, with an increase in endoglucanase activity of up to 57%. The use of Mn(2+) was then investigated in the saccharification of sugarcane bagasse submitted to acid, steam-explosion, and hydrothermal pretreatments. The addition of Mn(2+) ions at 10mM in the saccharification of acid-pretreated bagasse resulted in a 34% increase in glucose release. These positive effects appeared to be due to a reduction in non-productive enzyme adsorption. The findings suggest that the addition of inexpensive metal ions can help to improve activity, thermostability, and saccharification efficiency of (hemi)cellulolytic enzymes.

Computed tomographic pulmonary changes in patients with chronic rhinosinusitis.

OBJECTIVE: To investigate whether patients with a diagnosis of chronic rhinosinusitis (CRS) show characteristic pulmonary changes on chest CT compared with a control group without sinusopathy. METHODS: This retrospective, observational study included patients with and without a diagnosis of CRS who underwent CT examination of the lungs between 2012 and 2014. Two radiologists, who were blinded for the presence of CRS, reviewed the scans for the presence of any abnormalities consensually. The χ(2) test was used for correlative analysis, with a significance level of 0.05. RESULTS: A total of 123 CT series (51.2% from male patients, mean age 41 ± 16 years) were reviewed, including those from 59 (48%) patients with a diagnosis of CRS. Patients with CRS were more likely than the control group to exhibit atelectasis, bronchiolectasis, centrilobular nodules and ground-glass opacities (all p < 0.05), with a significant predilection for middle lobe and lingular involvement observed (p < 0.001). Other abnormalities, such as bronchial wall thickening and air trapping, did not differ between groups. CONCLUSION: Atelectatic changes, ground-glass opacities, bronchiolectasis and centrilobular nodules are the most frequent abnormalities associated with CRS, with peculiar middle lobe and lingular involvement observed on chest CT examinations. ADVANCES IN KNOWLEDGE: CRS is a frequent disorder that displays typical pulmonary changes at CT. The recognition of such findings can prevent patients with this condition from undergoing unnecessary investigations that might be based on the presence of the aforementioned radiological features.