Initial evaluation of the "Trauma surgery course"

BACKGROUND: The consequence of the low rate of penetrating injuries in Europe and the increase in non-operative management of blunt trauma is a decrease in surgeons' confidence in managing traumatic injuries has led to the need for new didactic tools. The aim of this retrospective study was to present the Corso di Chirurgia del Politrauma (Trauma Surgery Course), developed as a model for teaching operative trauma techniques, and assess its efficacy. METHOD: the two-day course consisted of theoretical lectures and practical experience on large-sized swine. Data of the first 126 participants were collected and analyzed. RESULTS: All of the 126 general surgeons who had participated in the course judged it to be an efficient model to improve knowledge about the surgical treatment of trauma. CONCLUSION: A two-day course, focusing on trauma surgery, with lectures and life-like operation situations, represents a model for simulated training and can be useful to improve surgeons' confidence in managing trauma patients. Cooperation between organizers of similar initiatives would be beneficial and could lead to standardizing and improving such courses

Involvement of PPAR\u3b3 in the anticonvulsant activity of EP-80317, a ghrelin receptor antagonist

Ghrelin, des-acyl ghrelin and other related peptides possess anticonvulsant activities. Although ghrelin and cognate peptides were shown to physiologically regulate only the ghrelin receptor, some of them were pharmacologically proved to activate the peroxisome proliferator-activated receptor gamma (PPAR\u3b3) through stimulation of the scavenger receptor CD36 in macrophages. In our study, we challenged the hypothesis that PPAR\u3b3 could be involved in the anticonvulsant effects of EP-80317, a ghrelin receptor antagonist. For this purpose, we used the PPAR\u3b3 antagonist GW9662 to evaluate the modulation of EP-80317 anticonvulsant properties in two different models. Firstly, the anticonvulsant effects of EP-80317 were studied in rats treated with pilocarpine to induce status epilepticus (SE). Secondly, the anticonvulsant activity of EP-80317 was ascertained in the repeated 6-Hz corneal stimulation model in mice. Behavioral and video electrocorticographic (ECoG) analyses were performed in both models. We also characterized levels of immunoreactivity for PPAR\u3b3 in the hippocampus of 6-Hz corneally stimulated mice. EP-80317 predictably antagonized seizures in both models. Pre-treatment with GW9662 counteracted almost all EP-80317 effects both in mice and rats. Only the effects of EP-80317 on power spectra of ECoGs recorded during repeated 6-Hz corneal stimulation were practically unaffected by GW9662 administration. Moreover, GW9662 alone produced a decrease in the latency of tonic-clonic seizures and accelerated the onset of SE in rats. Finally, in the hippocampus of mice treated with EP-80317 we found increased levels of PPAR\u3b3 immunoreactivity. Overall, these results support the hypothesis that PPAR\u3b3 is able to modulate seizures and mediates the anticonvulsant effects of EP-80317

Non-alcoholic fatty liver disease is associated with early left ventricular dysfunction in childhood acute lymphoblastic leukaemia survivors.

Background: Childhood acute lymphoblastic leukaemia (ALL) survivors have an increased risk of metabolic and cardiovascular disease. We aimed to assess the presence of non-alcoholic fatty liver disease (NAFLD) in childhood ALL and if it is associated with early cardiovascular dysfunction. Methods: In total, 53 childhood ALL survivors and 34 controls underwent auxological evaluation, biochemical assay, liver, heart and vascular ultrasound study. Results: NAFLD was more frequent in ALL patients than in controls (39.6% vs 11.7%, P < 0.01). Patients with NAFLD were more obese and insulin resistant than patients without NAFLD. Flow-mediated dilatation and interventricular septum were lower in the ALL group than those in the control group (P < 0.001 for both). The patients with NAFLD showed lower left ventricular ejection fraction than those without NAFLD (P = 0.011). In ALL survivors, BMI-SDS and subcutaneous fat were the strongest predictors of NAFLD, whereas preperitoneal adipose tissue and C-reactive protein were the strongest predictors of left ventricular ejection fraction. Conclusions: Childhood ALL survivors had higher prevalence of NAFLD than healthy controls, which is associated with early left ventricular impairment. In the case of fatty liver, a comprehensive heart evaluation is mandatory. We strongly recommend to prevent visceral adiposity in ALL survivors, to search for metabolic syndrome or its components and to reinforce the need of intervention on diet and lifestyle during the follow-up of these patients

BRCA1 genetic testing in 106 breast and ovarian cancer families from southern Italy (Sicily): a mutation analyses.

PURPOSE: To evaluate the contribution of germline BRCA1 mutations in the incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer (OC) in patients from Southern Italy (in the region of Sicily) and to identify a possible association between the higher frequency of BRCA1 mutations and a specific familial profile. EXPERIMENTAL DESIGN: A consecutive series of 650 patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from the Southern Italian region of Sicily, after interview at the "Regional Reference Centre for the Characterization and Genetic Screening of Hereditary Tumors" at the University of Palermo. Genetic counselling allowed us to recruit a total of 106 unrelated families affected with breast and/or ovarian cancer screened for mutations occurring in the whole BRCA1 gene by automatic direct sequencing. RESULTS: Germline BRCA1 mutations were found in 17 of 106 (16%) Sicilian families. The HBOC profile had a major frequency (66%) of mutations (P < 0.01). A total of 28 sequence variants was identified. Seven of these were pathogenic, 5 unknown biological variant (UV) and 16 polymorphisms. We also identified a pathological mutation (4843delC) as a possible Sicilian founder mutation. CONCLUSIONS: The present study is the first BRCA1 disease-associated mutations analysis in Southern Italian families. The early age of onset of such tumors and the association with the HBOC familial profile could be two valid screening factors for the identification of BRCA1 mutation carriers. Finally, we identified a BRCA1 mutation with a possible founder effec

Day and night closed-loop control in adults with type 1 diabetes: a comparison of two closed-loop algorithms driving continuous subcutaneous insulin infusion versus patient self-management.

OBJECTIVE: To compare two validated closed-loop (CL) algorithms versus patient self-control with CSII in terms of glycemic control. RESEARCH DESIGN AND METHODS: This study was a multicenter, randomized, three-way crossover, open-label trial in 48 patients with type 1 diabetes mellitus for at least 6 months, treated with continuous subcutaneous insulin infusion. Blood glucose was controlled for 23 h by the algorithm of the Universities of Pavia and Padova with a Safety Supervision Module developed at the Universities of Virginia and California at Santa Barbara (international artificial pancreas [iAP]), by the algorithm of University of Cambridge (CAM), or by patients themselves in open loop (OL) during three hospital admissions including meals and exercise. The main analysis was on an intention-to-treat basis. Main outcome measures included time spent in target (glucose levels between 3.9 and 8.0 mmol/L or between 3.9 and 10.0 mmol/L after meals). RESULTS: Time spent in the target range was similar in CL and OL: 62.6% for OL, 59.2% for iAP, and 58.3% for CAM. While mean glucose level was significantly lower in OL (7.19, 8.15, and 8.26 mmol/L, respectively) (overall P = 0.001), percentage of time spent in hypoglycemia (<3.9 mmol/L) was almost threefold reduced during CL (6.4%, 2.1%, and 2.0%) (overall P = 0.001) with less time ≤2.8 mmol/L (overall P = 0.038). There were no significant differences in outcomes between algorithms. CONCLUSIONS: Both CAM and iAP algorithms provide safe glycemic control

When Ears Drive Hands: The Influence of Contact Sound on Reaching to Grasp

Background Most research on the roles of auditory information and its interaction with vision has focused on perceptual performance. Little is known on the effects of sound cues on visually-guided hand movements. Methodology/Principal Findings We recorded the sound produced by the fingers upon contact as participants grasped stimulus objects which were covered with different materials. Then, in a further session the pre-recorded contact sounds were delivered to participants via headphones before or following the initiation of reach-to-grasp movements towards the stimulus objects. Reach-to-grasp movement kinematics were measured under the following conditions: (i) congruent, in which the presented contact sound and the contact sound elicited by the to-be-grasped stimulus corresponded; (ii) incongruent, in which the presented contact sound was different to that generated by the stimulus upon contact; (iii) control, in which a synthetic sound, not associated with a real event, was presented. Facilitation effects were found for congruent trials; interference effects were found for incongruent trials. In a second experiment, the upper and the lower parts of the stimulus were covered with different materials. The presented sound was always congruent with the material covering either the upper or the lower half of the stimulus. Participants consistently placed their fingers on the half of the stimulus that corresponded to the presented contact sound. Conclusions/Significance Altogether these findings offer a substantial contribution to the current debate about the type of object representations elicited by auditory stimuli and on the multisensory nature of the sensorimotor transformations underlying action

DNA damage contributes to neurotoxic inflammation in Aicardi-Goutières Syndrome astrocytes

Aberrant induction of type I IFN is a hallmark of the inherited encephalopathy Aicardi-Goutières syndrome (AGS), but the mechanisms triggering disease in the human central nervous system (CNS) remain elusive. Here, we generated human models of AGS using genetically modified and patient-derived pluripotent stem cells harboring TREX1 or RNASEH2B loss-of-function alleles. Genome-wide transcriptomic analysis reveals that spontaneous proinflammatory activation in AGS astrocytes initiates signaling cascades impacting multiple CNS cell subsets analyzed at the single-cell level. We identify accumulating DNA damage, with elevated R-loop and micronuclei formation, as a driver of STING- and NLRP3-related inflammatory responses leading to the secretion of neurotoxic mediators. Importantly, pharmacological inhibition of proapoptotic or inflammatory cascades in AGS astrocytes prevents neurotoxicity without apparent impact on their increased type I IFN responses. Together, our work identifies DNA damage as a major driver of neurotoxic inflammation in AGS astrocytes, suggests a role for AGS gene products in R-loop homeostasis, and identifies common denominators of disease that can be targeted to prevent astrocyte-mediated neurotoxicity in AGS