Motor Cortical Correlates of Paired Associative Stimulation Induced Plasticity: A TMS-EEG Study

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique that modulates synaptic plasticity in the human motor cortex (M1). Since previous studies have primarily used motor-evoked potentials (MEPs) as outcome measure, cortical correlates of PAS-induced plasticity remain unknown. Therefore, the aim of this observational study was to investigate cortical correlates of a standard PAS induced plasticity in the primary motor cortex by using a combined TMS-EEG approach in a cohort of eighteen healthy subjects. In addition to the expected long-lasting facilitatory modulation of MEPs amplitude, PAS intervention also induced a significant increase in transcranial magnetic stimulation-evoked potentials (TEPs) P30 and P60 amplitude. No significant correlation between the magnitude of PAS-induced changes in TEP components and MEP amplitude were observed. However, the linear regression analysis revealed that the combined changes in P30 and P60 component amplitudes significantly predicted the MEP facilitation after PAS. The findings of our study offer novel insight into the neurophysiological changes associated with PAS-induced plasticity at M1 cortical level and suggest a complex relationship between TEPs and MEPs changes following PAS

A novel de novo dominant mutation in ISCU associated with mitochondrial myopathy

BACKGROUND: Hereditary myopathy with lactic acidosis and myopathy with deficiency of succinate dehydrogenase and aconitase are variants of a recessive disorder characterised by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, metabolic acidosis and rhabdomyolysis may occur. So far, this disease has been molecularly defined only in Swedish patients, all homozygous for a deep intronic splicing affecting mutation in ISCU encoding a scaffold protein for the assembly of iron-sulfur (Fe-S) clusters. A single Scandinavian family was identified with a different mutation, a missense change in compound heterozygosity with the common intronic mutation. The aim of the study was to identify the genetic defect in our proband. METHODS: A next-generation sequencing (NGS) approach was carried out on an Italian male who presented in childhood with ptosis, severe muscle weakness and exercise intolerance. His disease was slowly progressive, with partial recovery between episodes. Patient's specimens and yeast models were investigated. RESULTS: Histochemical and biochemical analyses on muscle biopsy showed multiple defects affecting mitochondrial respiratory chain complexes. We identified a single heterozygous mutation p.Gly96Val in ISCU, which was absent in DNA from his parents indicating a possible de novo dominant effect in the patient. Patient fibroblasts showed normal levels of ISCU protein and a few variably affected Fe-S cluster-dependent enzymes. Yeast studies confirmed both pathogenicity and dominance of the identified missense mutation. CONCLUSION: We describe the first heterozygous dominant mutation in ISCU which results in a phenotype reminiscent of the recessive disease previously reported.This work was supported by the TelethonItaly [GrantGGP15041]; the Pierfranco and Luisa Mariani Foundation; the MRC7QQR [201572020] grant; the ERC advanced grant [FP77322424]; the NRJ Foundation7Institut de France; the E7Rare project GENOMIT. RL acknowledges generous financial support from Deutsche Forschungsgemeinschaft [SFB 987 and SPP 1927] and the LOEWE program of state Hessen

Transverse colon volvulus : a rare cause of surgical acute abdomen

O volvo do cólon é uma condição cirúrgica incomum que ocorre devido a uma torção do eixo mesentérico, situação que resulta em redução parcial ou completa do trânsito intestinal. O cólon sigmóide é o segmento mais envolvido. O presente estudo descreve caso raro de abdome agudo provocado por um volvo do cólon transverso, associado a obstrução intestinal. A tomografia de abdome evidenciou importante distensão e níveis hidroaéreos nos cólons ascendente e transverso, com interposição de alça entre a cúpula diafragmática direita e o dômus hepático (Sinal de Chilaiditi). Foi submetido a laparotomia exploradora com colectomia direita extendida e anastomose íleocólica látero-lateral. O paciente apresentou boa evolução pós operatória. O diagnóstico dessa patologia nem sempre é feito com facilidade, sendo na maior parte dos casos o diagnóstico definitivo realizado no intra-operatória.Colonic volvulus is an uncommon surgical condition that occurs due to a twisting around the mesenteric axis, which results in partial or complete reduction in intestinal transit. The sigmoid colon is the most commonly affected segment. We report a rare case of acute abdomen caused by transverse colon volvulus, associated with intestinal obstruction. Abdominal computed tomography showed significant distension and air-fluid levels in the ascending and transverse colons, with loop interposition between the liver and right hemidiaphragm (Chilaiditi’s sign). The patient underwent exploratory laparotomy with extended right colectomy and side-to-side ileocolic anastomosis. The postoperative period was uneventful. Diagnosis of this condition is not always easy, and in most cases a definitive diagnosis is made intraoperatively

Volvo do cólon transverso: Uma causa rara de abdome agudo cirúrgico

O volvo do cólon é uma condição cirúrgica incomum que ocorre devido a uma torção do eixo mesentérico, situação que resulta em redução parcial ou completa do trânsito intestinal. O cólon sigmóide é o segmento mais envolvido. O presente estudo descreve caso raro de abdome agudo provocado por um volvo do cólon transverso, associado a obstrução intestinal. A tomografia de abdome evidenciou importante distensão e níveis hidroaéreos nos cólons ascendente e transverso, com interposição de alça entre a cúpula diafragmática direita e o dômus hepático (Sinal de Chilaiditi). Foi submetido a laparotomia exploradora com colectomia direita extendida e anastomose íleocólica látero-lateral. O paciente apresentou boa evolução pós operatória. O diagnóstico dessa patologia nem sempre é feito com facilidade, sendo na maior parte dos casos o diagnóstico definitivo realizado no intra-operatória

Leber's Hereditary Optic Neuropathy: A Report on Novel mtDNA Pathogenic Variants

Leber's hereditary optic neuropathy (LHON) is due to missense point mutations affecting mitochondrial DNA (mtDNA); 90% of cases harbor the m.3460G>A, m.11778G>A, and m.14484T>C primary mutations. Here, we report and discuss five families with patients affected by symptomatic LHON, in which we found five novel mtDNA variants. Remarkably, these mtDNA variants are located in complex I genes, though without strong deleterious effect on respiration in cellular models: this finding is likely linked to the tissue specificity of LHON. This study observes that in the case of a strong clinical suspicion of LHON, it is recommended to analyze the whole mtDNA sequence, since new rare mtDNA pathogenic variants causing LHON are increasingly identified

The CHOLEGAS study: multicentric randomized, blinded, controlled trial of gastrectomy plus prophylactic cholecystectomy versus gastrectomy only, in adults submitted to Gastric cancer surgery with curative intent

<p>Abstract</p> <p>Background</p> <p>The incidence of gallstones and gallbladder sludge is known to be higher in patients after gastrectomy than in general population. This higher incidence is probably related to surgical dissection of the vagus nerve branches and the anatomical gastrointestinal reconstruction. Therefore, some surgeons perform routine concomitant cholecystectomy during standard surgery for gastric malignancies. However, not all the patients who are diagnosed to have cholelithiasis after gastric cancer surgery will develop symptoms or require additional surgical treatments and a standard laparoscopic cholecystectomy is feasible even in those patients who underwent previous gastric surgery. At the present, no randomized study has been published and the decision of gallbladder management is left to each surgeon preference.</p> <p>Design</p> <p>The study is a randomized controlled investigation. The study will be performed in the General and Oncologic Surgery, Department of Oncology – Azienda Ospedaliero-Universitaria Careggi – Florence – Italy, a large teaching institution, with the participation of all surgeons who accept to be involved in, together with other Italian Surgical Centers, on behalf of the GIRCG (Italian Research Group for Gastric Cancer).</p> <p>The patients will be randomized into two groups: in the first group the patient will be submitted to prophylactic cholecystectomy during standard surgery for curable gastric cancer (subtotal or total gastrectomy), while in the second group he/she will be submitted to standard gastric surgery only.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID. NCT00757640</p

Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer

Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer. Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m(2) day 1, LV 100 mg/m(2) as 2 h infusion and 5-FU 400 mg/m(2) as bolus, days 1 and 2 followed by 600 mg/m(2)/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm). From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85-1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82-1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively. A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy

Volvo do cólon transverso: Uma causa rara de abdome agudo cirúrgico

O volvo do cólon é uma condição cirúrgica incomum que ocorre devido a uma torção do eixo mesentérico, situação que resulta em redução parcial ou completa do trânsito intestinal. O cólon sigmóide é o segmento mais envolvido. O presente estudo descreve caso raro de abdome agudo provocado por um volvo do cólon transverso, associado a obstrução intestinal. A tomografia de abdome evidenciou importante distensão e níveis hidroaéreos nos cólons ascendente e transverso, com interposição de alça entre a cúpula diafragmática direita e o dômus hepático (Sinal de Chilaiditi). Foi submetido a laparotomia exploradora com colectomia direita extendida e anastomose íleocólica látero-lateral. O paciente apresentou boa evolução pós operatória. O diagnóstico dessa patologia nem sempre é feito com facilidade, sendo na maior parte dos casos o diagnóstico definitivo realizado no intra-operatória

Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects

Leber’s hereditary optic neuropathy (LHON) is a disease that affects the optical nerve, causing visual loss. The diagnosis of LHON is mostly defined by the identification of three pathogenic variants in the mitochondrial DNA. Idebenone is widely used to treat LHON patients, but only some of them are responders to treatment. In our study, we assessed the maximal respiration rate (MRR) and other respiratory parameters in eight fibroblast lines from subjects carrying LHON pathogenic variants. We measured also the effects of idebenone treatment on cell growth and mtDNA amounts. Results showed that LHON fibroblasts had significantly reduced respiratory parameters in untreated conditions, but no significant gain in MRR after idebenone supplementation. No major toxicity toward mitochondrial function and no relevant compensatory effect in terms of mtDNA quantity were found for the treatment at the tested conditions. Our findings confirmed that fibroblasts from subjects harboring LHON pathogenic variants displayed impaired respiration, regardless of the disease penetrance and severity. Testing responsiveness to idebenone treatment in cultured cells did not fully recapitulate in vivo data. The in-depth evaluation of cellular respiration in fibroblasts is a good approach to evaluating novel mtDNA variants associated with LHON but needs further evaluation as a potential biomarker for disease prognosis and treatment responsiveness