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Skilled movements result from a mixture of feedforward and feedback mechanisms conceptualized by internal models. These mechanisms subserve both motor execution and motor imagery. Current research suggests that imagery allows updating feedforward mechanisms, leading to better performance in familiar contexts. Does this still hold in radically new contexts? Here, we test this ability by asking participants to imagine swinging arm movements around shoulder in normal gravity condition and in microgravity in which studies showed that movements slow down. We timed several cycles of actual and imagined arm pendular movements in three groups of subjects during parabolic flight campaign. The first, control, group remained on the ground. The second group was exposed to microgravity but did not imagine movements inflight. The third group was exposed to microgravity and imagined movements inflight. All groups performed and imagined the movements before and after the flight. We predicted that a mere exposure to microgravity would induce changes in imagined movement duration. We found this held true for the group who imagined the movements, suggesting an update of internal representations of gravity. However, we did not find a similar effect in the group exposed to microgravity despite the fact that the participants lived the same gravitational variations as the first group. Overall, these results suggest that motor imagery contributes to update internal representations of the considered movement in unfamiliar environments, while a mere exposure proved to be insufficient.

Parkinson's disease is a neurodegenerative disease, the etiology of which remains unknown, but some likely causes include oxidative stress, mitochondrial dysfunction and neuroinflammation. Peroxisome-proliferator-activated receptor (PPAR) agonists have been studied in animal models of Parkinson's disease and have shown neuroprotective effects. In this study, we aimed to (1) confirm the neuroprotective effects of PPAR-alpha agonist fenofibrate. To this end, male rats received fenofibrate (100 mg/kg) orally for 15 days, 5 days before the intraperitoneal injections of rotenone (2.5 mg/kg for 10 days). After finishing the treatment with rotenone and fenofibrate, animals were subjected to the open field, the forced swim test and the two-way active avoidance task. Subsequently, rats were euthanized for measurement of dopamine and metabolites levels in the striatum and quantification of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta (SNpc). In addition, we aimed to (2) evaluate the neuroprotective effects of fenofibrate on the accumulation of α-synuclein aggregates. Here, rats were treated for 5 days with fenofibrate continuing for over 28 days with rotenone. Then, animals were perfused for immunohistochemistry analysis of α-synuclein. The results showed that fenofibrate reduced depressive-like behavior and memory impairment induced by rotenone. Moreover, fenofibrate diminished the depletion of striatal dopamine and protected against dopaminergic neuronal death in the SNpc. Likewise, the administration of fenofibrate attenuated the aggregation of α-synuclein in the SNpc and striatum in the rotenone-lesioned rats. Our study confirmed that fenofibrate exerted neuroprotective effects because parkinsonian rats exhibited reduced behavioral, neurochemical and immunohistochemical changes, and importantly, a lower number of α-synuclein aggregates.

Background We present an uncommon cause of intracranial hemorrhage in a young adult. Tuberous sclerosis complex is a rare genetic disorder characterized by skin changes, benign systemic or central nervous system tumors [subependymal giant cell astrocytoma (SEGA)], mental retardation, or epilepsy. Hemorrhage into SEGA is exceedingly rare. Case presentation We evaluated a 21-year-old college student with migraine. Biopsy of numerous popular skin lesions on his nose revealed adenoma sebaceum. Magnetic resonance imaging brain showed a subependymal nodule near the foramen of Monro suspected to be SEGA. Genetic analysis identified a tuberous sclerosis complex-1 germ line mutation. Surveillance imaging was recommended for the subependymal tumor. Fourteen months later, he presented with spontaneous hemorrhage into the tumor. Hematoma evacuation and tumor resection revealed SEGA. The college graduate was able to return to full-time work. Conclusions We present an unusual cause of intracranial hemorrhage in a young adult. Thorough work-up and recognition of an underlying genetic predisposition can curtails diagnostic delay when life-threatening complications occur.

Although the primary cause of death in COVID-19 infection is respiratory failure, there is evidence that cardiac manifestations may contribute to overall mortality and can even be the primary cause of death. More importantly, it is recognized that COVID-19 is associated with a high incidence of thrombotic complications.Evaluate if the coronary artery calcium (CAC) score was useful to predict in-hospital (in-H) mortality in patients with COVID-19. Secondary end-points were needed for mechanical ventilation and intensive care unit admission.Two-hundred eighty-four patients (63, 25 years, 67% male) with proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who had a noncontrast chest computed tomography were analyzed for CAC score. Clinical and radiological data were retrieved.Patients with CAC had a higher inflammatory burden at admission (d-dimer, p = .002; C-reactive protein, p = .002; procalcitonin, p = .016) and a higher high-sensitive cardiac troponin I (HScTnI, p = .001) at admission and at peak. While there was no association with presence of lung consolidation and ground-glass opacities, patients with CAC had higher incidence of bilateral infiltration (p = .043) and higher in-H mortality (p = .048). On the other side, peak HScTnI200 ng/dl was a better determinant of all outcomes in both univariate (p = .001) and multivariate analysis (p = .001).The main finding of our research is that CAC was positively related to in-H mortality, but it did not completely identify all the population at risk of events in the setting of COVID-19 patients. This raises the possibility that other factors, including the presence of soft, unstable plaques, may have a role in adverse outcomes in SARS-CoV-2 infection.

Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy. Among 1625 patients with PA submitted to adrenal vein sampling in a multicenter multiethnic international study, 473 were ≤45 years of age; 231 of them had exhaustive imaging and follow-up data. Fifty-three percentage had a unilateral adrenal nodule, 43% had no nodules, and 4% bilateral nodules. Fifty-six percentage (n=131) received adrenalectomy and 128 were unambiguously diagnosed as unilateral PA. A unilateral adrenal nodule on imaging and hypokalemia were the strongest predictors of unilateral PA at regression analysis. Accordingly, imaging allowed correct identification of the responsible adrenal in 95% of the adrenalectomized patients with a unilateral nodule. The rate raised to 100% in the patients with hypokalemia, who comprised 29% of the total, but fell to 88% in those without hypokalemia. Therefore, a unilateral nodule and hypokalemia could be used to identify unilateral PA in patients ≤45 years of age if adrenal vein sampling is not easily available. However, adrenal vein sampling remains indispensable in 71% of the young patients, who showed no nodules/bilateral nodules at imaging and/or no hypokalemia. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01234220.

Between 6-20% of the cellular proteome is under circadian control and tunes mammalian cell function with daily environmental cycles. For cell viability, and to maintain volume within narrow limits, the daily variation in osmotic potential exerted by changes in the soluble proteome must be counterbalanced. The mechanisms and consequences of this osmotic compensation have not been investigated before. In cultured cells and in tissue we find that compensation involves electroneutral active transport of Na

OBJECTIVE To evaluate culture-independent procedures (immunochromatography and quantitative polymerase chain reaction [qPCR]) in the detection and susceptibility of Streptococcus pneumoniae directly from culture-negative pleural fluid (PF) in children. METHOD Detection of S. pneumoniae in PF of children with parapneumonic effusion and/or empyema by using two culture-independent methods: an immunochromatographic membrane test (IMT) which identifies the pneumococcal C antigen, and a real-time PCR test to detect pneumococcal genes lytA and pbp2b, a marker of susceptibility of β-lactam agents, in PF samples. RESULTS We tested 36 PF specimens and recorded the previous use of antimicrobials. In the final analysis, 34 samples were included. IMT and qPCR presented positive results in 23 (67.6%) and 24 (70.6%) of the samples, respectively, showing a moderate agreement (k = 0.518) between the two methods. From the 36 children included, 34 (94.4%) had antibiotic data available by the time when PFs were collected. Thirty-four (100%) children had been given treatment before PF sampling, with 33 (97%) receiving β-lactam antibiotics administered empirically. Of the 24 lytA real-time positive samples, 21 (87.5%) were also positive for pbp2b, a marker of β-lactam susceptibility. CONCLUSION The reduced sensitivity of culture for pneumococcal detection can be improved through the addition of IMT and qPCR analysis. The utility of qPCR combining detection of lytA and a marker of β-lactam susceptibility should be explored further.

Background/objectives: The aim of the present study was to validate a short questionnaire on habitual dietary salt intake, to quickly and easily identify individuals whose salt consumption exceeds recommended levels. Subjects/methods: A total of 1131 hypertensive subjects participating in the MINISAL-SIIA study were included in the analysis. Anthropometric indexes, blood pressure, and 24-h urinary sodium excretion (NaU) were measured. A fixed-sequence questionnaire on dietary salt intake was administered. Results: NaU was significantly associated with scores, with a linear association across categories (p for trend 85 mmol/day) and “very high NaU” (NaU > 170 mmol/day) was 86 and 35%, respectively. The score of the questionnaire had a significant ability to detect both “high NaU”—with a specificity of 95% at the score of 10 points—and “very high NaU”—with a specificity of 99.6% at score of 13 points. Conclusions: The main results of the study indicates that a higher score of this short questionnaire is distinctive of habitual high salt consumption in hypertensive patients.

to investigate the role of gender, age, province of residence, and nursing home residency on the risk of death for residents in the Friuli Venezia Giulia (FVG) Region (Northern Italy) tested positive for Covid-19, considering recovery as a competing event. The secondary objective is to describe the impact of the Covid-19 epidemic in FVG and in the Regions of Northern and Central Italy in terms of incidence and mortality compared to the national data.retrospective cohort study.resident population in FVG in the period between 29 February and 25 June 2020.in order to describe the impact of the Covid-19 outbreak in FVG, in terms of incidence and mortality compared to the national data, the standardized incidence (SIR) and mortality (SMR) ratios and their respective 95% confidence intervals (95%CI) were calculated compared to the Italian population for the northern and central Regions of Italy and the autonomous Provinces (PA) of Trento and Bolzano. A retrospective cohort study was conducted on subjects residing in FVG to whom at least one naso-oropharyngeal swab (hereafter, named swab) resulted positive for Covid-19. For each subject included in the cohort, the observation period started with the first positive swab and ended with the first of the following events: death, recovery or censored, which means that at the end of the observation period the subject was still alive and positive. The cause of death was assigned to Covid-19 if a subject had not yet recovered at the time when the event occurred. Cohort members were considered recovered after two negative consecutive swabs. The sub-hazard ratio (SHR) was estimated by applying the regression model of competing risks by Fine and Gray, in which the event of interest was the death caused by Covid-19 and the competing event was recovery. The explanatory variables included in the multiple models are: gender, age at the beginning of the observation period, the Province of residence, and nursing home residency. The cause-specific hazard was estimated using Cox proportional hazard regression.during the observation period, 3,305 cases and 345 deaths were recorded in FVG; SIR and SMR resulted, respectively, equal to 0.64 (95%CI 0.61-0.68) and 0.43 (95%CI 0.37-0.50). The FVG was the Northern Region one with the lowest incidence and mortality. The cohort consisted of 3,121 residents in FVG with at least one swab with a positive Covid-19 result during the study period. The SHR of dying for Covid-19 is equal to 16.13 (95%CI 9.73-26.74) for people with age 70-79 years and 35.58 (95%CI 21.77-58.15) with age=80 years respect those with age70 years. It is higher in males (SHR 1.71; 95%CI 1.34-2.17). There is no evidence that being resident in a nursing home affects the SHR (SHR 0.91 and 95%CI 0.69-1.20). As regards the province as an explanatory variable, the sub-hazard of death in the province of Trieste appears to overlap to the sub-hazard of Pordenone used as a reference; for the provinces of Udine and Gorizia the sub-hazards seem lower than the reference.while other Northern Regions and autonomous Provinces show higher standardized incidence and mortality compared with Italy, FVG and Veneto do not. In FVG, male gender and age are important determinants of death while there is no evidence that the condition of guest in a nursing home increases the sub-hazard of death.

Context Adrenal gland imaging is recommended by the current guidelines for the workup of primary aldosteronism (PA). However, its diagnostic performance has not been established in large, multiethnic cohorts of patients who undergo adrenal vein sampling (AVS) and adrenalectomy. Objective This work aims to assess the diagnostic accuracy of cross-sectional adrenal imaging. Methods This international multicenter study took place in tertiary referral centers. A total of 1625 PA patients seeking surgical cure were enrolled in an international study involving 19 centers in North America, Europe, Asia, and Australia. Of these, 1311 (81%) had imaging data available and 369 (23%), who received a final diagnosis of surgically cured unilateral PA, were examined. Patients underwent AVS and imaging by computed tomography and/or magnetic resonance imaging. The accuracy of detection of unilateral PA at imaging was estimated by the area under the receiver operator characteristics curve using cure (biochemical and/or full clinical success) as the reference at follow-up after unilateral adrenalectomy. Results In the cohort of 1311 patients with imaging data available, 34% and 7% of cases showed no detectable or bilateral nodules, respectively. Imaging did not detect the culprit adrenal in 28% of the surgically cured unilateral PA patients. Moreover, the clinical outcome did not differ significantly between the imaging-positive and imaging-negative patients. Conclusion Cross-sectional imaging did not identify a lateralized cause of disease in around 40% of PA patients and failed to identify the culprit adrenal in more than one-fourth of patients with unilateral PA.

Introduction:Breast milk is nutritionally adequate and is related to the reduction of various health problems in childhood. Its offer is widely recommended in health guidelines.Objective:To estimate the prevalence and obstacles to breastfeeding in patients with CHD in southern Brazil.Methods:Cross-sectional study of patients with CHD between 2 and 18 years of age. Patients with genetic syndromes and patients whose mothers had died were excluded from the analysis. The variables on breastfeeding in the first 2 years of life were collected through a phone call to the mothers, which was conducted by trained evaluators. Prevalence was described in proportions and the continuous variables as means and standard deviation. Bivariate analyses were evaluated using a chi-square test to measure the association between the variables and the outcome.Results:A total of 351 patients with CHD were analysed. There was a predominance of males (53%) and a mean age of 9.54 ± 4.52 years. Breastfeeding up to the sixth month was present in 40% of the cases.Conclusion:The mothers of babies with CHD face great challenges to maintain the supply of breast milk, whether inherent to the practice of breastfeeding or related to CHD.

Background Portal vein thrombosis (PVT) is the most common thrombotic complication in cirrhosis; however, local risk factors involved in its pathogenesis are still not fully investigated. The aim of the study was to evaluate hemostasis and endothelial damage in the portal vein in patients with cirrhosis and portal hypertension.Methods Adult cirrhotics undergoing transjugular intrahepatic portosystemic shunt were consecutively enrolled. Rotational thromboelastometry (ROTEM), dosage of total circulating glycosaminoglycans (GAGs), and endotoxemia levels (lipopolysaccharide [LPS]), along with evaluation of endothelial dysfunction by quantification of circulating endothelial microparticles (MPs), were performed on citrated peripheric and portal venous blood samples from each enrolled patient.Results Forty-five cirrhotics were enrolled. ROTEM analysis revealed the presence of a significant heparin-like effect in portal blood (median ɑ angle NATEM 50° vs. HEPTEM 55°, p = 0.027; median coagulation time NATEM 665 s vs. HEPTEM 585 s, p = 0.006), which was not detected in peripheral blood, and was associated with a higher concentration of circulating GAGs. Even though total annexin V-MP circulating MPs were less concentrated in the splanchnic district, the proportion of MPs of endothelial origin, with respect to annexin V-MP, was significantly increased in the portal district (p = 0.036). LPS concentration was higher in portal (197 pg/mL) compared with peripheral blood (165 pg/mL) (p Conclusion Evidences of a damage of glycocalyx along with increased concentration of endothelial MPs suggest the presence of a significant endothelial alteration in the portal vein with respect to peripheral veins. Portal site-specific endothelial damage could hamper its antithrombotic properties and may represent an important local risk factor in the pathogenesis of PVT.

Background ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. Methods This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. Results There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1–100), intravenous 94.4% (78–100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p

CDKL5 deficiency disorder (CDD) is a rare X-linked neurodevelopmental disorder that is characterised by early-onset seizures, intellectual disability, gross motor impairment, and autistic-like features. CDD is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene that encodes a serine/threonine kinase with a predominant expression in the brain. Loss of CDKL5 causes neurodevelopmental alterations in vitro and in vivo, including defective dendritic arborisation and spine maturation, which most likely underlie the cognitive defects and autistic features present in humans and mice. Here, we show that treatment with epigallatocathechin-3-gallate (EGCG), the major polyphenol of green tea, can restore defects in dendritic and synaptic development of primary Cdkl5 knockout (KO) neurons. Furthermore, defective synaptic maturation in the hippocampi and cortices of adult Cdkl5-KO mice can be rescued through the intraperitoneal administration of EGCG, which is however not sufficient to normalise behavioural CDKL5-dependent deficits. EGCG is a pleiotropic compound with numerous cellular targets, including the dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) that is selectively inhibited by EGCG. DYRK1A controls dendritic development and spine formation and its deregulation has been implicated in neurodevelopmental and degenerative diseases. Treatment with another DYRK1A inhibitor, harmine, was capable of correcting neuronal CDKL5-dependent defects; moreover, DYRK1A levels were upregulated in primary Cdkl5-KO neurons in concomitance with increased phosphorylation of Tau, a well-accepted DYRK1A substrate. Altogether, our results indicate that DYRK1A deregulation may contribute, at least in part, to the neurodevelopmental alterations caused by CDKL5 deficiency., Highlights • Epigallocatechin-3-gallate (EGCG) restores CDKL5-dependent synaptic defects in vitro; • Epigallocatechin-3-gallate (EGCG) restores CDKL5-dependent synaptic defects in vitro; • DYRK1A levels and activity is increased in CDKL5 deficient neurons

Background: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. Methods: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. Results: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). Conclusions: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. Trial registration: ClinicalTrials.gov, NCT01360346. Registered on 25 March 2011.

The pulsatile secretion of adrenocortical hormones and a stress reaction occurring when starting adrenal vein sampling (AVS) can affect the selectivity and also the assessment of lateralization when sequential blood sampling is used. We therefore tested the hypothesis that a simulated sequential blood sampling could decrease the diagnostic accuracy of lateralization index for identification of aldosterone-producing adenoma (APA), as compared with bilaterally simultaneous AVS.In 138 consecutive patients who underwent subtyping of primary aldosteronism, we compared the results obtained simultaneously bilaterally when starting AVS (t-15) and 15 min after (t0), with those gained with a simulated sequential right-to-left AVS technique (R ⇒ L) created by combining hormonal values obtained at t-15 and at t0. The concordance between simultaneously obtained values at t-15 and t0, and between simultaneously obtained values and values gained with a sequential R ⇒ L technique, was also assessed. We found a marked interindividual variability of lateralization index values in the patients with bilaterally selective AVS at both time point. However, overall the lateralization index simultaneously determined at t0 provided a more accurate identification of APA than the simulated sequential lateralization indexR ⇒ L (P = 0.001). Moreover, regardless of which side was sampled first, the sequential AVS technique induced a sequence-dependent overestimation of lateralization index. While in APA patients the concordance between simultaneous AVS at t0 and t-15 and between simultaneous t0 and sequential technique was moderate-to-good (K = 0.55 and 0.66, respectively), in non-APA patients, it was poor (K = 0.12 and 0.13, respectively).Sequential AVS generates factitious between-sides gradients, which lower its diagnostic accuracy, likely because of the stress reaction arising upon starting AVS.

Background We previously showed that low-dose computed tomography (LDCT) screening in asbestos-exposed workers is effective in detecting lung cancer (LC) at an early stage. Here, we evaluate whether LDCT screening could reduce mortality from LC in such a high-risk population. Methods Within a cohort of 2433 asbestos-exposed men enrolled in an Occupational Health surveillance programme, we compared mortality between the participants in the ATOM002 study (LDCT-P, N = 926) and contemporary non-participants (LDCT-NP, N = 1507). We estimated standardized mortality ratios for the LDCT-P and LDCT-NP populations using regional and national rates (SMR_FVG and SMR_ITA, respectively). We compared survival for all causes, all neoplasms, LC and malignant neoplasm of pleura (MNP) between LDCT-P and LDCT-NP using Cox proportional hazard models adjusted for age, smoking history, asbestos exposure level and comorbidities. Results A reduction in mortality from LC was observed in the LDCT-P group compared with regional and national figures (SMR_FVG = 0.55, 95% confidence interval (CI) 0.24-1.09; SMR_ITA = 0.51, 95% CI 0.22-1.01); this was not the case for the LDCT-NP group (SMR_FVG = 2.07, 95% CI 1.53-2.73; SMR_ITA = 1.98, 95% CI 1.47-2.61). A strong reduction in LC mortality was observed for the LDCT-P compared with the LDCT-NP [hazard ratio (HR) = 0.41, 95% CI 0.17-0.96]. Mortality was also reduced for all causes (HR = 0.61, 95% CI 0.44-0.84), but not for all neoplasms (HR = 0.97, 95% CI 0.62-1.50) and MNP (HR = 0.86, 95% CI 0.31-2.41) within the LDCT-P population. Conclusions In our cohort, participation in the LDCT screening study was associated with reduced mortality from LC. This finding supports the use of LDCT in surveillance programmes for asbestos-exposed workers.

Objectives The need for a central venous catheter has limited the widespread use of ultrafiltration in daily clinical practice for the treatment of acute heart failure (AHF) with overt fluid overload. We evaluated the feasibility of a new ultrafiltration device, the CHIARA (Congestive Heart Impairment Advanced Removal Approach) system, that utilizes a single-lumen cannula (17G, multi-hole) inserted in a peripheral vein of the arm. Methods In this multicenter, prospective, feasibility study, consecutive ultrafiltration treatments (lasting ≥6 hours and with an ultrafiltration rate ≥100ml/h) with the CHIARA device and a single peripheral venous approach were performed at 6 Italian hospitals. For each session, we evaluated the performance of the venous access, the ultrafiltrate volume removed, and the cause of its interruption. Results One-hundred-three ultrafiltration sessions were performed in 55 patients with AHF (average 1.9±1.7 treatment/patient). The overall median length of ultrafiltration treatment was 14h (interquartile range 7–21) with removal of 3266±3088ml of fluid (183±30ml/hour). The treatment was successfully completed in 92 (89%) sessions and in 80% of patients. The mean suction flow rate from the vein was 70±20ml/min, while the mean re-injection flow rate was 98±26ml/min. There were no clinically relevant complications related to the venous access and/or to the anticoagulant therapy with heparin. Conclusions The study demonstrated that the CHIARA system satisfies clinical applicability and efficacy criteria in the treatment of AHF, in terms of adequate fluid removal through a single peripheral venous access.

Movements rely on a mixture of feedforward and feedback mechanisms. With experience, the brain builds internal representations of actions in different contexts. Many factors are taken into account in this process among which is the immutable presence of gravity. Any displacement of a massive body in the gravitational field generates forces and torques that must be predicted and compensated by appropriate motor commands. The insular cortex is a key brain area for graviception. However, no attempt has been made to address whether the same internal representation of gravity is shared between feedforward and feedback mechanisms. Here, participants either mentally simulated (only feedforward) or performed (feedforward and feedback) vertical movements of the hand. We found that the posterior part of the insular cortex was engaged when feedback was processed. The anterior insula, however, was activated only in mental simulation of the action. A psychophysical experiment demonstrates participants’ ability to integrate the effects of gravity. Our results point toward a dual internal representation of gravity within the insula. We discuss the conceptual link between these two dualities.

The aim of this study was to evaluate the safety and the effectiveness of polydioxanone-made biodegradable biliary stent placement for the treatment of post-transplant benign, refractory biliary anastomotic strictures. This was a retrospective observational study on all adult liver transplant recipients who developed a clinically significant anastomotic stricture between January 2014 and June 2017. Percutaneous transhepatic cholangioplasty with balloon dilation was performed as therapeutic approach in selected patients after multidisciplinary evaluation. Refractory strictures (defined as stricture persistence after two interventional procedures) were managed with placement of polydioxanone-made biodegradable biliary stent (SX-Ella biliary stent, Czech Republic). Patency of the common bile duct was calculated using Kaplan–Meier analysis. Eighteen adult liver transplant recipients who developed a refractory biliary anastomotic stricture [males/females 13/5, median (IQR) 58.2 (9.3) years] underwent biodegradable biliary stent placement after 10.4 (32) months from liver transplantation. All procedures except one were uneventful. After a median (IQR) follow-up time of 27.2 (22) months, complete resolution of anastomotic stricture was achieved in 72% of patients, with significant improvement on liver enzymes. Polydioxanone-made biodegradable biliary stent might be a safe and effective therapeutic option for the difficult-to-treat benign biliary anastomotic stricture after liver transplantation.

Background Clinical experience is limited for primary central nervous system (CNS) lymphoma that arises from the dura mater, which is denoted with the term primary dural lymphoma (PDL). This study was aimed at determining the relative incidence, presentation, and outcomes of PDL. Methods The institutional databases of the Divisions of Neuro-Oncology at the Massachusetts General Hospital and the Yale School of Medicine were retrospectively searched for patients with primary CNS lymphoma. Patients with pathologically confirmed dural lymphoma and no evidence of primary cerebral or systemic involvement were identified. Clinical data, diagnostic findings, treatments, and outcomes were recorded. Results A total of 20 patients with PDL were identified, and they represented 6.3% of the individuals with primary CNS lymphomas (20 of 316). Histopathological examination of PDL revealed the following underlying subtypes: diffuse large B-cell lymphoma (10 of 20 patients), marginal zone lymphoma (6 of 20), follicular lymphoma (2 of 20), undefined B-cell non-Hodgkin lymphoma (1 of 20), and T-cell non-Hodgkin lymphoma (1 of 20). On imaging, all tumors appeared as extra-axial masses with avid contrast enhancement and mostly mimicked meningioma. The median apparent diffusion coefficient value was 667 ± 26 mm2 /s. Cerebrospinal fluid analyses and symptoms were nonspecific, and the diagnosis rested on tissue analysis. Therapeutic approaches included surgery, radiotherapy, and chemotherapy. The median overall survival was not reached after 5 years. Three patients were deceased at database closure because of tumor progression. The extent of tumor resection correlated positively with overall survival (P = .044). Conclusions PDL is a rare variant of primary CNS lymphoma that can be radiographically mistaken for meningioma. The outcome is excellent with multimodality treatment, and aggressive surgery may convey a survival advantage in select cases.

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are responsible for the onset of CDKL5 Deficiency Disorder (CDD), a neurological pathology characterised by severe infantile seizures, intellectual disability, impairment of gross motor skills, sleep and gastrointestinal disturbances. CDKL5 is a serine/threonine kinase the molecular network of which is not yet fully understood. Loss of CDKL5 both in vitro and in vivo leads to altered neuronal morphology including axon specification and outgrowth, dendritic arborisation and spine morphology suggesting a link between CDKL5 and the regulation of proper cytoskeleton functioning. Recently, we found that CDKL5 regulates the binding of CLIP170 to microtubules (MT). CLIP170 is a MT-plus end tracking protein (+TIP) that associates with MTs when present in its open, active conformation. Here we present evidence suggesting CLIP170 contributes to neuronal CDKL5-dependent defects and that it represents an important novel druggable target for CDD; indeed, CLIP170 is directly targeted by the neuroactive steroid pregnenolone (PREG), which induces the active conformation of the protein thus promoting MT-dynamics. We here show that PREG and a synthetic derivative pregnenolone-methyl-ether (PME) can restore the MT association of CLIP170 and revert morphological and molecular defects in Cdkl5-KO neurons at different stages of maturation. All together, these findings identify CLIP170 as possible novel druggable target for CDKL5 related disorders providing an intriguing prospective for future disease-modifying drug-based therapies.

Recent evidence suggests that 2-week treatment with the non-psychotomimetic cannabinoid cannabidivarin (CBDV) could be beneficial towards neurological and social deficits in early symptomaticThe aim of this study was to provide further insights into the efficacy of CBDV inCBDV 0.2, 2, 20 and 200 mg/kg/day was administered toCBDV rescues recognition memory deficits inCBDV administration exerts an enduring rescue of memory deficits in

Immunodeficiency is a major risk factor for primary central nervous system lymphoma (PCNSL), but data on the disease in immunocompromised hosts are scarce. We aimed to define clinical and imaging features and determine prognostic factors for immunodeficiency-associated PCNSL.All PCNSL cases seen at Yale-New Haven Hospital between 2002 and 2017 were retrospectively screened for immunodeficiency. For patients with immunosuppression, biopsies were evaluated and clinical data were collected. Predictors of survival were identified using Kaplan-Meier survival analysis and log-rank test. p values 0.05 were considered significant.23 patients with immunodeficiencies were identified: eleven on immunosuppressants after solid organ transplantation, seven with human immunodeficiency virus infection, and five on immunosuppressive treatment due to various autoimmune disorders. PCNSL cases were largely Epstein-Barr-Virus positive (78%), histologically classified as diffuse large B cell lymphomas (87%), and showed peripheral contrast enhancement (81%) and corresponding heterogeneous diffusion-weighted imaging patterns (DWI) on magnetic resonance imaging (MRI) (71%). Median overall survival was 31 months. Age 60 years at diagnosis (p 0.01), peripheral enhancement of the mass on MRI (p = 0.04), heterogeneous DWI patterns (p = 0.04), and clonal immunoglobulin heavy chain gene rearrangement (IgHR) (p = 0.03) were found to be negative prognostic markers.Immunodeficiency-associated PCNSL presents with similar clinical, pathological and imaging features. Age 60 years, clonal IgHR, heterogeneous DWI pattern and peripheral enhancement on MRI may serve as predictors of less favorable outcome.

Purpose The body behaves as a global system with many interconnected subsystems. While the effects of a gravitational change on body responses have been extensively studied in isolation, we are not aware of any study that has examined these two types of body responses concurrently. Here, we examined how the cognitive and cardiovascular systems respond during application of varying gravito-inertial stressors in men and women. Methods Ten men and nine women underwent three 5-min centrifugation sessions (2.4 g at the feet, 1.5 g at the heart) in which participants rhythmically moved a hand-held object for 20 s. Grip force and hemodynamic responses were continuously measured during centrifugation and rest periods. Result Men optimized the modulation between grip force and the destabilizing load force, but not women. Exposure to artificial gravity induced higher heart rate and mean arterial pressure in both sexes compared to baseline. However, during artificial gravity exposure, only women decreased heart rate across sessions. Interestingly, we found that finishers of the protocol (mostly men) and Non-finishers (mostly women) exhibited divergent patterns of hemodynamic responses. Conclusion We speculate that the lack of grip force adaptation reported in women could be linked to the challenged hemodynamic responses during artificial gravity. By deriving a simple model to predict failure to complete the protocol, we found that mean arterial pressure—and not sex of the participant—was the most relevant factor. As artificial gravity is being proposed as a countermeasure in long-term manned missions, the observed effects in grip force adaptation and hemodynamic responses during varying gravito-inertial stressors application are particularly important.

Background: The coastal area of Friuli Venezia Giulia (FVG) region, north-eastern Italy, was characterized by work activities in which asbestos was used until the early 1990s, particularly in shipbuilding. A public health sur- veillance program (PHSP) for asbestos-exposed workers was established, although limited evidence exists about the efficacy of such programs in reducing disease occurrence and mortality. Objectives: To compare mortality in a cohort of 2,488 men occupationally exposed to asbestos, enrolled in a PHSP in FVG between the early 1990s and 2008, with that of the general population of FVG and Italy. Methods: Standardized Mortality Ratios (SMR), with 95% Con- fidence Interval (95% CI), for all causes, all cancers, lung (LC) and pleural cancer (PC) were estimated in the cohort and in subgroups of workers with the first hire in shipbuilding that caused asbestos exposure (

Background/aim In the last years, the use of Image Guided Stereotactic Radiotherapy (IG-SBRT) in patients with metastatic prostate cancer has increased. In this study, we aimed to assess the role of IG-SBRT in terms of local control and safety in patients with metastatic prostate cancer. Materials and methods Primary and secondary endpoints of this prospective observational study were local control and safety related to IG-SBRT. All lesions were treated with 24 Gy as a single fraction or 27 Gy in 3 fractions. After SBRT, Systemic therapies were administered only after the occurrence of more than three synchronous active lesions in oligometastatic patients (patients with less than 4 active synchronous lesions) or new lesions occurrence in patients with more than 3 synchronous lesions. Results From April 2011 to June 2017, 78 metastatic lesions (32 bone and 46 node) from 51 patients with prostate cancer were treated. After a median follow-up of 18.5 months (range=3-103 months), only 2 lesions (4%) relapsed inside the radiation field. All local recurrences were located on the bone. Estimated 12 and 24 months local control ratios were 98.7 and 97.4%, respectively. Except for one case, toxicity greater than G2 was not recorded. Conclusion IG-SBRT is safe and can be considered as a valid therapy in patients with metastatic prostate cancer requiring a long-lasting metastases control.

Objectives. To compare a local cohort of 2,488 men occupationally exposed to asbestos and enrolled in a public health surveillance program with the 1995 – 2009 cancer incidence of the general population of Friuli Venezia Giulia (FVG) region, Northeast Italy, we conducted a historical cohort study. Methods. Standardized incidence ratios (SIRs), with 95% confidence interval (95%CI), for specific cancer sites were estimated in the cohort and in subgroups of workers employed in shipbuilding between 1974-1994. For internal comparisons, we estimated incidence rate ratios (IRRs) for all cancers, lung cancer and mesothelioma, by level of exposure to asbestos and sector of employment adjusted for smoking habits and age at start of follow-up. Results. Among cohort members the SIR was 8.82 (95%CI 5.95-12.61) for mesothelioma and 1.61 (95%CI 1.26-2.04) for lung cancer. In subgroup analyses, the SIR for lung cancer in subjects hired in shipbuilding between 1974-1984 was 2.09 (95%CI 1.32-3.13). In the overall cohort, a borderline increased incidence was also found for stomach cancer (SIR=1.53 95%CI 0.96-2.31). Internal comparisons within the cohort show that among men with high asbestos exposure level the relative risk was almost three-fold for lung cancer (IRR=2.94 95%CI 1.01-8.57). Conclusions. This cohort experienced an excess in the incidence of both mesothelioma and lung cancer, showing increasing incidence rates at higher level of asbestos exposure. For lung cancer, the relative incidence was highest among workers hired in shipbuilding between 1974-1984.

We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients. AVS was successful in 80.1% of all cases but allowed identification of unilateral PA in only 45.5% by the criteria in use at each center. Adrenalectomy was performed in 41.8% of all patients and cured arterial hypertension in 19.6% of the patients, 2-fold more frequently in women than men ( P P =0.027). Compared with surgical cases, patients treated medically needed more antihypertensive medications ( P P The low rate of adrenalectomy and cure of hypertension in PA patients seeking surgical cure indicates suboptimal AVS use, possibly related to issues in patient selection, technical success, and AVS data interpretation. Given the better outcomes of AVS-guided adrenalectomy, these results call for actions to improve the diagnostic use of this test that is necessary for detection of surgical PA candidates. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01234220.

Adrenal vein sampling (AVS) is the key test for subtyping patients with primary aldosteronism (PA) before referring those with unilateral disease for laparoscopic unilateral adrenalectomy. However, it is still not systematically used, despite guidelines recommendations, because it is still considered as an invasive, risky, and challenging procedure. Simultaneous bilateral catheterization is believed to add technical difficulties inherent with attempting to catheterize both adrenal veins at the same time, but can be useful to minimize differences between the sides due to timing. We herein report on the protocol for routine clinical use. Tips for preparation of the patient as well as optimal catheterization of adrenal veins and sampling are provided to propose a protocol that is easy, safe, and reliable. Key Points • Adrenal vein sampling is the reference standard in the case of primary aldosteronism to detect the hyper-functioning side and allow subsequent treatment. • Simultaneous bilateral adrenal vein sampling avoids bias related to sampling timing. • Some technical suggestions concerning patient preparation and catheterization are proposed to make simultaneous adrenal vein sampling easier and safer.

Iatrogenic injuries of the renal artery include pseudoaneurysms (PSA) and pseudoaneurysms with arteriovenous fistula (PSA + AVF). They can cause hematuria, anemization and flank pain. Endovascular treatment is recommended due to its effectiveness. To assess the potential difference between the embolization of iatrogenic renal PSA and iatrogenic renal PSA + AVF, in terms of technical and clinical success rate, procedure complexity and impact on the renal function. We retrospectively reviewed 30 embolization procedures of iatrogenic renal PSA and renal PSA + AVF in 27 patients in two centers between December 2006 and February 2017, comparing technical and clinical success rate, total procedural time, creatinine before and after the procedure and parenchymal ischemic area after the procedure. All patients underwent CT before embolization procedure and different embolization materials were used. We identified 15 iatrogenic renal PSA and 15 iatrogenic renal PSA + AVF (causes: 23 nephron-sparing surgery, 2 nephrostomies, 1 lithotripsy, 1 ureteroscopic pyelolithotomy, 1 renal biopsy). Microcoils were used in 21 cases, microcoils and Spongostan in 3 cases, microcoils and controlled-release microcoils in 4 cases and controlled-release microcoils in 1 case. No significant statistical differences were found in the comparison of technical and clinical success rate, total procedural time, creatinine and parenchymal ischemic area after the procedure. Transarterial embolization can be considered as the first-line treatment for renal artery iatrogenic lesions, considering its effectiveness. No statistical significant differences were found in the comparison of the embolization procedures of iatrogenic renal PSA and PSA + AVF.

Laparoscopic sleeve gastrectomy (LSG) is considered safe and effective even as conversion procedure after primary bariatric operations. The correlation between gastric pouch volumes and patients weight loss remains unclear. To assess a correlation between the gastric remnant size and the weight loss, we reviewed 49 consecutive barium swallow UGS performed at our institute from August 2012 through May 2014 in LSG patients with symptoms and/or unsatisfactory weight loss. The anteroposterior (AP), laterolateral (LL) and vertical (CC) diameters of the gastric pouch were measured to calculate the volume by the formula of the ellipsoid (AP × LL × CC × 0.5). Patients were divided in two groups: group 1 without gastric pouch (n = 36) and group 2 with gastric pouch (n = 13). Correlation between pouch volume and weight loss data was calculated with t Student’s and Fisher tests to compare the percent excess body mass index (BMI) and percent excess body mass loss (EBL) between two groups, and P

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

Cardiac CT (CCT) is an imaging modality that is becoming a standard in clinical cardiology. We evaluated indications, safety, and impact on patient management of routine CCT in a multicenter national registry. MATERIALS AND METHODS: During a period of 6 months, 47 centers in Italy enrolled 3,455 patients. RESULTS: CCT was performed mainly with 64-slice CT scanners (73.02 %). Contrast agents were administrated in 3,185 patients (92.5 %). Mean DLP changes with type of scanner and was lower in >64 row detector scanner. The most frequent indication for CCT was suspected CAD (44.8 %), followed by calcium scoring (9.6 %), post-angioplasty/stenting (8.3 %), post-CABGs (7.5 %), study of cardiac anatomy (4.22 %) and assessment in patients with known CAD (4.1 %) and acute chest pain (1.99 %). Most of the CCTs were performed in outpatient settings (2,549; 74 %) and a minority in inpatient settings (719, 20.8 %). Adverse clinical events (mild-moderate) occurred in 26 examinations (0.75 %). None of them was severe. In 45.3 % of the cases CCT findings impacted patient management. CONCLUSION: CCT is performed with different workloads in participating centers. It is a safe procedure and its results have a strong impact on patient management.

Background: Schools have become a key figure for the promotion of health and obesity interventions, bringing the development of critical awareness to the construction and promotion of a healthy diet, physical activity, and the monitoring of the nutritional status in childhood and adolescence. Objectives: To describe a study protocol to evaluate the effectiveness of an intervention designed to improve knowledge of food choices in the school environment. Methods: This is a cluster-randomized, parallel, two-arm study conducted in public elementary and middle schools in Brazil. Participants will be children and adolescents between the ages of 5 and 15 years, from both genders. The interventions will be focusing on changes in lifestyle, physical activities and nutritional education. Intervention activities will occur monthly in the school’s multimedia room or sports court. The control group arm will receive usual recommendations by the school. The primary outcome variable will be anthropometric measures, such as body mass index percentiles and levels of physical activity by the International Physical Activity Questionnaire. Results: We expect that after the study children will increase the ingestion of fresh food, reduce excessive consumption of sugary and processed foods, and reduce the hours of sedentary activities. Conclusion: The purpose of starting the dietary intervention at this stage of life is to develop a knowledge that will enable for healthy choices, providing opportunities for a better future for this population. Resumo Fundamento: As escolas tornaram-se essenciais para a promoção de saúde e de intervenções para obesidade, propiciando o desenvolvimento de consciência crítica para a construção e promoção de dieta saudável, atividade física e monitoramento do status nutricional na infância e adolescência. Objetivos: Descrever um protocolo de estudo para avaliar a eficiência de uma intervenção projetada para aprimorar o conhecimento sobre escolhas alimentares no ambiente escolar. Métodos: Estudo clínico randomizado em cluster, paralelo, de dois braços, conduzido em escolas públicas de ensino fundamental e médio no Brasil. Os participantes serão crianças e adolescentes entre 5 e 15 anos de idade, dos dois sexos. As intervenções se concentrarão em mudanças de estilo de vida, atividade física e educação nutricional. As atividades de intervenção ocorrerão mensalmente na sala de multimídia ou quadra de esportes das escolas. O grupo controle receberá as recomendações usuais através da escola. O desfecho primário será a mudança nas medidas antropométricas, como índice de massa corporal e os níveis de atividade física conforme o Questionário Internacional de Atividade Física. Resultados: Esperamos que, após o estudo, as crianças aumentem o consumo de alimentos frescos, reduzam o consumo excessivo de alimentos açucarados e processados, e reduzam as horas gastas em atividades sedentárias. Conclusão: O propósito de iniciar a intervenção dietética nessa fase da vida é desenvolver o conhecimento que permitirá escolhas saudáveis, propiciando oportunidades para um melhor futuro para essa população.

Purpose To correlate radiation dose to the risk of severe radiologically-evident radiation-induced lung injury (RRLI) using voxel-by-voxel analysis of the follow-up computed tomography (CT) of patients treated for lung cancer with hypofractionated helical Tomotherapy. Methods and materials The follow-up CT scans from 32 lung cancer patients treated with various regimens (5, 8, and 25 fractions) were registered to pre-treatment CT using deformable image registration (DIR). The change in density was calculated for each voxel within the combined lungs minus the planning target volume (PTV). Parameters of a Probit formula were derived by fitting the occurrences of changes of density in voxels greater than 0.361 g cm −3 to the radiation dose. The model’s predictive capability was assessed using the area under receiver operating characteristic curve (AUC), the Kolmogorov-Smirnov test for goodness-of-fit, and the permutation test (P test ). Results The best-fit parameters for prediction of RRLI 6 months post RT were D 50 of 73.0 (95% CI 59.2.4–85.3.7) Gy, and m of 0.41 (0.39–0.46) for hypofractionated (5 and 8 fractions) and D 50 of 96.8 (76.9–123.9) Gy, and m of 0.36 (0.34–0.39) for 25 fractions RT. According to the goodness-of-fit test the null hypothesis of modeled and observed occurrence of RRLI coming from the same distribution could not be rejected. The AUC was 0.581 (0.575–0.583) for fractionated and 0.579 (0.577–0.581) for hypofractionated patients. The predictive models had AUC>upper 95% band of the P test . Conclusions The correlation of voxel-by-voxel density increase with dose can be used as a support tool for differential diagnosis of tumor from benign changes in the follow-up of lung IMRT patients.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The etiology and pathogenesis of PD are still unknown, however, many evidences suggest a prominent role of oxidative stress, inflammation, apoptosis, mitochondrial dysfunction and proteosomal dysfunction. The peroxisome proliferator-activated receptor (PPAR) ligands, a member of the nuclear receptor family, have anti-inflammatory activity over a variety of rodent's models for acute and chronic inflammation. PPAR-α agonists, a subtype of the PPAR receptors, such as fenofibrate, have been shown a major role in the regulation of inflammatory processes. Animal models of PD have shown that neuroinflammation is one of the most important mechanisms involved in dopaminergic cell death. In addition, anti-inflammatory drugs are able to attenuate toxin-induced parkinsonism. In this study we evaluated the effects of oral administration of fenofibrate 100mg/kg 1h after infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the SNpc. First, we assessed the motor behavior in the open field for 24h, 7, 14 and 21 days after MPTP. Twenty-two days after surgery, the animals were tested for two-way active avoidance and forced swimming for evaluation regarding cognitive and depressive parameters, respectively. Twenty-three days after infusion of the toxin, we quantified DA and turnover and evaluated oxidative stress through the measurement of GSH (glutathione peroxidase), SOD (superoxide dismutase) and LOOH (hydroperoxide lipid). The data show that fenofibrate was able to decrease hypolocomotion caused by MPTP 24h after injury, depressive-like behavior 22 days after the toxin infusion, and also protected against decreased level of DA and excessive production of reactive oxygen species (ROS) 23 days after surgery. Thus, fenofibrate has shown a neuroprotective effect in the MPTP model of Parkinson's disease.

Idiopathic Parkinson's disease is a neurodegenerative disorder that affects approximately 1 % of the population over 55 years of age. The disease manifests itself through motor and nonmotor symptoms induced mainly by the neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The possible mechanisms involved in this pathology include mitochondrial dysfunction, neuroinflammation, and oxidative stress. The present study evaluated the effects of the nonselective cyclooxygenase inhibitor ibuprofen on motor and depressive-like behavior induced by rotenone in rats. Rotenone (2.5 mg/kg, i.p., for 10 days) decreased tyrosine hydroxylase immunoreactivity in the SNpc, and ibuprofen treatment (15 mg/kg, p.o., for 22 days) blocked this impairment. We also found that rotenone-induced motor deficits (hypolocomotion) and depressive-like behavior, and ibuprofen was able to reverse these deficits. In addition to motor and nonmotor behaviors, we evaluated oxidative stress induced by rotenone. Rotenone administration depleted glutathione levels in the hippocampus and reduced catalase activity in both the hippocampus and striatum. Post treatment with ibuprofen blocked the depletion of glutathione induced by rotenone and increased the basal levels of this antioxidant in the striatum. Ibuprofen also restored catalase activity. The neuroprotective effects of ibuprofen against toxicity induced by rotenone appear to be attributable to its antioxidant properties, in addition to cyclooxygenase inhibition.

The incidence of mesothelioma in Italy shows wide geographical variation, with the highest incidence rates in Genoa and Friuli Venezia Giulia (FVG). For mesothelioma, national standard incidence rates are not available prior to the calendar year 2006.

Background: The prevalence of hypertension among children and adolescents is estimated to range between 1% and 13%. Excess weight and central obesity are related to blood pressure levels in adults, and may be important in the early pathogenesis of SH when present in childhood. Objectives: To study the association between anthropometric variables and blood pressure levels in schoolchildren from the 5th and 8th grades, and to identify which parameter was more strongly correlated with blood pressure levels. Methods: Contemporary cross-sectional study with probabilistic population-based cluster sampling of schoolchildren enrolled from the 5th to the 8th grades in public elementary schools of Porto Alegre. Data on familial risk factors and anthropometry were collected. Statistical analysis included correlations and cluster-adjusted confidence intervals. Results: The mean age of participants was 12.57 (± 1.64) years, and 55.2% of them were females. Abnormal blood pressure levels were found in 11.3% of the sample and borderline values, in 16.2%. Among the anthropometric variables analyzed, hip circumference was the one with the strongest correlation with increased blood pressure (r = 0.462, p < 0.001), followed by waist circumference (r = 0.404, p < 0.001) and abdominal skinfold (r = 0.291, p < 0.001). Conclusion: We observed an association of waist circumference and skinfolds with increased blood pressure levels in the schoolchildren of the sample. Therefore, it is of the utmost importance that early measurements of blood pressure, and waist and hip circumferences become a routine in health services in order to prevent this condition.

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the injury site and prevents neuronal damage after an MPTP infusion could be considered as a potential treatment for PD during the early stage of disease development.

Objective To assess the effectiveness of educational interventions including behavioral modification, nutrition and physical activity to prevent or treat childhood obesity through a systematic review and meta-analysis of randomized trials. Method A search of databases (PubMed, EMBASE and Cochrane CENTRAL) and references of published studies (from inception until May 2012) was conducted. Eligible studies were randomized trials enrolling children 6 to 12 years old and assessing the impact of educational interventions during 6 months or longer on waist circumference, body mass index (BMI), blood pressure and lipid profile to prevent or treat childhood obesity. Calculations were performed using a random effects method and pooled-effect estimates were obtained using the final values. Results Of 22.852 articles retrieved, 26 trials (23.617 participants) were included. There were no differences in outcomes assessed in prevention studies. However, in treatment studies, educational interventions were associated with a significant reduction in waist circumference [− 3.21 cm (95%CI − 6.34, − 0.07)], BMI [− 0.86 kg/m 2 (95%CI − 1.59, − 0.14)] and diastolic blood pressure [− 3.68 mmHg (95%CI − 5.48, − 1.88)]. Conclusions Educational interventions are effective in treatment, but not prevention, of childhood obesity and its consequences.

BackgroundThe prevalence of overweight in children with CHD is about 26.9%. Increase in adipose tissue is related to the secretion of proinflammatory markers such as C-reactive protein. Assuming that children with CHD are exposed to other inherent risk factors for heart disease, our objective was to evaluate the correlation between levels of C-reactive protein and body mass index in children and adolescents with CHD.MethodsA cross-sectional study with 377 children and adolescents with CHD in a clinical setting of a reference hospital was carried out. C-reactive protein data were collected after 12 hours of fasting. Nutritional status was classified according to body mass index. The patients were divided into three groups: cyanotic, acyanotic, and minimal heart defects (controls).ResultsThe mean age was 9.9±4.2 years, and 53.6% of the sample included males. The cyanotic group represented 22.3%, acyanotic 42.2%, and minimal defects 35.5% of the sample. The average body mass index percentile was 57.23±32.06. The median values of C-reactive protein were as follows: cyanotic 0.340, acyanotic with clinical repercussion 0.203, and minimal defects 0.128. There was a significant difference between the minimal defects and the cyanotic groups (p=0.023). There was a significant correlation between C-reactive protein and body mass index percentile (r=0.293, pConclusionThe correlation between body mass index percentile and C-reactive protein was confirmed in this population. The prevention of overweight is paramount to avoid overlapping modifiable risk factors to those already inherent to the CHD.

Midbrain dopamine neurons play critical roles in reward- and aversion-driven associative learning. However, it is not clear whether they do this by a common mechanism or by separate mechanisms that can be dissociated. In the present study we addressed this question by testing whether a partial lesion of the dopamine neurons of the rat SNc has comparable effects on conditioned place preference (CPP) learning and conditioned place aversion (CPA) learning. Partial lesions of dopamine neurons in the rat substantia nigra pars compacta (SNc) induced by bilateral intranigral infusion of 6-hydroxydopamine (6-OHDA, 3μg/side) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 200μg/side) impaired learning of conditioned place aversion (CPA) without affecting conditioned place preference (CPP) learning. Control experiments demonstrated that these lesions did not impair motor performance and did not alter the hedonic value of the sucrose and quinine. The number of dopamine neurons in the caudal part of the SNc positively correlated with the CPP scores of the 6-OHDA rats and negatively correlated with CPA scores of the SHAM rats. In addition, the CPA scores of the 6-OHDA rats positively correlated with the tissue content of striatal dopamine. Insomuch as reward-driven learning depends on an increase in dopamine release by nigral neurons, these findings show that this mechanism is functional even in rats with a partial lesion of the SNc. On the other hand, if aversion-driven learning depends on a reduction of extracellular dopamine in the striatum, the present study suggests that this mechanism is no longer functional after the partial SNc lesion.

As metoclopramide stimulates aldosterone secretion, we tested its usefulness in the assessment of lateralization of primary aldosteronism by adrenal vein sampling (AVS).Prospective within-patient study in consecutive patients undergoing AVS for primary aldosteronism subtyping.We compared the diagnostic accuracy of baseline and postmetoclopramide lateralization index and relative (to cortisol) aldosterone secretion indices (RASI) for each adrenal gland with aldosterone-producing adenoma (APA) determined by the four corners criteria as the reference diagnosis.We recruited 93 consecutive patients (mean age: 52 years; women 31%). Metoclopramide increased plasma aldosterone in the inferior vena cava and in both adrenal veins. The postmetoclopramide lateralization index was accurate in identifying APA, but did not increase diagnostic accuracy over baseline lateralization index, because the RASI increased similarly in both sides. Conversely, metoclopramide raised RASI to values more than 0.90 bilaterally in non-APA patients allowing accurate identification of factitious aldosterone suppression. In contrast, RASI was 0.90 or less in 48% contralateral to the tumor in APA patients. Regression analysis showed the APA patients with persistent suppression of RASI contralaterally showed a more florid primary aldosteronism phenotype.Metoclopramide does not enhance lateralization of aldosterone excess in APA, but consistently increased the value of RASI in non-APA cases, thus unmasking potentially misleading suppression of aldosterone. Postmetoclopramide RASI may therefore allow a more precise diagnosis when AVS can be achieved only unilaterally.

The incidence of mesothelioma in Italy shows wide geographical variation, with the highest incidence rates in Genoa and Friuli Venezia Giulia (FVG). For mesothelioma, national standard incidence rates are not available prior to the calendar year 2006.To estimate the Standardized Incidence rate Ratio (SIR) of mesothelioma in a cohort of former workers undergoing health surveillance because of previous asbestos exposure, when sex-, age-, and calendar year-specific rates of the national standard are not available and the number of expected cases calculated from the regional rates is biased by the size of the study cohort.We conducted a sensitivity analysis in a cohort of 2,488 men. We considered every Italian cancer registry available with complete data in the period 1995-2007 (N=14). We calculated, for each year and age group, the corresponding weighted mean rate of 10 registries of North-Italy (Mean W10), the weighted mean rate of all 14 registries available (Mean W14) and considered FVG standard rate.During the period 1995-2007, we observed 25 incident cases of mesothelioma with expected cases that varied between 2.00 (Mean W14) and 2.56 (FVG standard rate), with a SIR of 12.49 (CI95% 8.08-18.48) and 9.76 (CI95% 6.32-14.45) respectively.Our results show that the use of FVG rates as standard does not lead to significant distortions in the calculation of the expected cases. However, distortion is remarkable in the SIRs estimation. Using a weighted mean standard incidence rate may be a valid alternative for SIR estimate when national standard rates are not available.

Rotenone exposure in rodents provides an interesting model for studying mechanisms of toxin-induced dopaminergic neuronal injury. However, several aspects remain unclear regarding the effects and the accuracy of rotenone as an animal model of Parkinson's disease (PD). In order to counteract these limitations, this study characterized a precise neurotoxin-delivery strategy employing the bilateral intranigral administration protocol of rotenone as a reliable model of PD. We performed bilateral intranigral injections of rotenone (12 μg) and subsequent general activity (1, 10, 20, and 30 days after rotenone) and cognitive (7, 8, 15, and 30 days after rotenone) evaluations followed by neurochemical and immunohistochemical tests. We have observed that rotenone was able to produce a remarkable reduction on the percentage of tyrosine hydroxylase immunoreactive neurons (about 60%) within the substantia nigra pars compacta. Dopamine (DA) was severely depleted at 30 days after rotenone administration, similarly to its metabolites. In addition, an increase in DA turnover was detected at the same time-point. In parallel, striatal serotonin and its metabolite were found to be increased 30 days after the neurotoxic insult, without apparent modification in the serotonin turnover. Besides, motor behavior was impaired, mainly 1 day after rotenone. Furthermore, learning and memory processes were severely disrupted in different time-points, particularly at the training and test session (30 days). We now provide further evidence of a time-dependent neurodegeneration associated to cognitive impairment after the single bilateral intranigral administration of rotenone. Thus, it is proposed that the current rotenone protocol provides an improvement regarding the existing rotenone models of PD.

The present study investigated the neurochemical, motor and cognitive effects of pioglitazone in a rat model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the first experiment, we administered MPTP, and 1 h later administered a single oral dose of pioglitazone (5, 15 and 30 mg/kg). The following day, we performed the open-field test and neurochemical dose response curve. We demonstrated that 30 mg/kg of pioglitazone was capable of restoring striatal dopamine (DA) concentrations and motor behaviors. A second experiment was conducted to test the effects of two protocols (acute and chronic) of pioglitazone (30 mg/kg) administration in the open-field test, two-way active avoidance task and in the DA and metabolites levels. The acute protocol consisted of a single oral administration 1 h after MPTP, whereas the chronic protocol was performed with daily administrations starting 1 h after MPTP and ending 22 days after that. Results showed that neither protocol was able to reverse the cognitive impairment promoted by MPTP. We also demonstrated that acute treatment generated some level of neuroprotection, as confirmed by the absence of DA reduction in the group treated with pioglitazone in comparison to the sham group. By contrast, chronic treatment leaded to a reduction of striatal DA, close to MPTP administration alone. These findings suggest that acute administration of pioglitazone (30 mg/kg) was more efficient in generating beneficial effects on motor behaviors and in striatal DA levels. Nevertheless, we failed to demonstrate that pioglitazone administration improved performance on a dopamine-related cognitive task after MPTP.

ObjectiveTo estimate the prevalence of overweight, obesity and nutritional habits in schoolchildren aged 10–18 years.MethodsContemporary, cross-sectional, population-based study, with a stratified probabilistic sample of secondary schools in Porto Alegre comprising a total of 511 schoolchildren. Data on family risk factors, anthropometrics and eating habits were collected.ResultsThe prevalence of excess weight was 27·6 % among the schoolchildren, with 17·8 % being overweight (BMI ≥ 85th and sd1·14)v. 4·22 (sd1·01) meals/d for students with normal weight). The mean weekly intake of unhealthy foods was 3·25 times for soft drinks, 2·91 for fried foods and 4·01 for sweets. The intake of skimmed milk (38·9 %) and diet soft drinks (20·9 %) was greater among obese children.ConclusionOverweight and obesity are increasing even in developing countries such as Brazil. Although many families are already taking measures towards healthier health habits, preventive actions must be considered a priority, with an emphasis on education, in order to avoid the need to treat obesity and its significant burden in the near future.