Increased amygdala and decreased frontolimbic r esting- s tate functional connectivity in children with aggressive behavior

Childhood maladaptive aggression is associated with disrupted functional connectivity within amygdala-prefrontal circuitry. In this study, neural correlates of childhood aggression were probed using the intrinsic connectivity distribution, a voxel-wise metric of global resting-state brain connectivity. This sample included 38 children with aggressive behavior (26 boys, 12 girls) ages 8–16 years and 21 healthy controls (14 boys, 6 girls) matched for age and IQ. Functional MRI data were acquired during resting state, and differential patterns of intrinsic functional connectivity were tested in a priori regions of interest implicated in the pathophysiology of aggressive behavior. Next, correlational analyses tested for associations between functional connectivity and severity of aggression measured by the Reactive-Proactive Aggression Questionnaire in children with aggression. Children with aggressive behavior showed increased global connectivity in the bilateral amygdala relative to controls. Greater severity of aggressive behavior was associated with decreasing global connectivity in the dorsal anterior cingulate and ventromedial prefrontal cortex. Follow-up seed analysis revealed that aggression was also positively correlated with left amygdala connectivity with the dorsal anterior cingulate, ventromedial and dorsolateral prefrontal cortical regions. These results highlight the potential role of connectivity of the amygdala and medial prefrontal and anterior cingulate cortices in modulating the severity of aggressive behavior in treatment-seeking children.     

Neurocognitive profiles in Duchenne muscular dystrophy and gene mutation site

The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing.     

Prevalence and Severity of Sleep Apnea in a Group of Morbidly Obese Patients

Background Obesity is the most important risk factor for obstructive sleep apnea. It is estimated that 70% of sleep apnea patients are obese. In the morbidly obese, the prevalence may reach 80% in men and 50% in women. The aim of this study was to determine the prevalence and severity of sleep apnea in a group of morbidly obese patients, leading to bariatric surgery. Methods In a cross-sectional study developed in Bahia, northeastern Brazil. 108 patients (78 women and 30 men) from the Obesity Treatment and Surgery Center - “Núcleo de Tratamento e Cirurgia da Obesidade” underwent standard polysomnography. Patients with an apnea-hypopnea index (AHI) ≥ 5 events/hour were considered apneic. Results Mean ± SD for age and BMI were 37.1 ± 10.2 years and 45.2 ± 5.4 kg/m2, respectively. The calculated AHI ranged widely from 2.5 to 128.9 events/hour. Sleep apnea was detected in 93.6% of the sample, wherein 35.2% had mild, 30.6% moderate and 27.8% severe apnea. Oxyhemoglobin desaturation was directly related to the AHI and was more severe in men. Conclusion There was a high frequency of sleep apnea in this group of morbidly obese patients, for whom it was very important to request polysomnography, thus enabling therapeutic management and prognostication.     

EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma

The treatment of patients with recurrent glioblastoma remains a major oncologic problem, with median survival after progression of 7–9 months. To determine the maximum tolerated dose and dose-limiting toxicity (DLT), the combination of dasatinib and cyclonexyl-chloroethyl-nitrosourea (CCNU) was investigated in this setting. The study was designed as multicenter, randomized phase II trial, preceded by a lead-in safety phase. The safety component reported here, which also investigated pharmacokinetics and preliminary clinical activity, required expansion and is therefore considered a phase I part to establish a recommended dosing regimen of the combination of CCNU (90–110 mg/m²) and dasatinib (100–200 mg daily). Overall, 28 patients were screened, and 26 patients were enrolled. Five dose levels were explored. DLTs, mainly myelosuppression, occurred in 10 patients. Grade 3 or 4 neutropenia was recorded in 7 patients (26.9%) and thrombocytopenia in 11 patients (42.3%). No significant effect of CCNU coadministration on dasatinib pharmacokinetics was found. Median progression-free survival (PFS) was 1.35 months (95% confidence interval: 1.2–1.4) and 6-month PFS was 7.7%. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents.     

Study of mycotoxin calibration approaches on the example of trichothecenes analysis from flour

The aim of this study was to evaluate the applicability of different calibration approaches in trichothecenes analysis from wheat flour. Concretely eight trichothecenes (five type B trichothecenes and three type A trichothecenes) were analyzed by matrix solid-phase dispersion (MSPD) and liquid chromatography–tandem mass spectrometry (LC–MS/MS). In the first set of experiments the presence of matrix effects was evaluated; values ranged between 59% and 79%. In the second set of experiments, solutions to compensate these signal suppressions were examined. Different calibration methods showed to tackle matrix effects obtaining values between 69% and 85% for external matrix matched calibration and values from 76% to 111% and from 78% to 108% by analog and deuterated internal standard calibrations, respectively. Trueness of the method was studied using quality control material and certificated reference material (DON 1062 ± 110 μg kg⁻¹). The values were compared by matrix-matched, analog internal standard (deepoxydeoxynivalenol (DOM-1)) and deuterated internal standard (DON-d₁).     

Una causa excepcional de hepatitis aguda en el adulto: parvovirus B19

There are multiple causes of hepatitis. The most frequent etiologies are viral, usually hepatitis A, B and C viruses. However, other, non-hepatotropic viruses can cause this disease, including parvovirus B19. We present a case of acute hepatitis due to parvovirus B19, as well as a review of the epidemiological, clinical, diagnostic and therapeutic features of this entity.     

Retinal involvement of Paracoccioidomycosis: A Case Report

Purpose: to describe the clinicopathologic features and treatment of a rare case of systemic paracoccidioidomycosis with choroidal and retinal involvement. Design: retrospective interventional case report. Participant: A 36-year-old young man with visual impairment in left eye with anterior uveitis and presence of whitish perimacular choroidal nodule, multiple underlying whitish spots and mid-periphery exudative retinal detachment. A primary extensive work-up for systemic infectious, autoimmune, neoplasic or inflammatory conditions was performed and high-resolution computer tomography scan demonstrated asymmetric parietal thickening of the trachea and bilateral diffuse multiple lobular opacities. Pulmonary bronchoscopy/biopsy of larynx, trachea and bronchial tube were also performed. Histopathological evaluation showed characteristic of Paracoccidioidomycosis. Intervention: Patient was treated with oral sulphadiazine (1.5 g/day). Main Outcome Measures: Anterior uveitis, retinal examination, histopathological evaluation and primary clinical outcome were observed during systemic treatment. Results: After 3 months of irregular treatment, choroidal lesions decreased in size forming atrophic scars and fibrotic spots; however visual acuity did not show any improvement. Conclusion: We report a rare case of systemic paracoccidioidomycosis with choroidal and retinal involvement treated with oral sulphadiazine.     

Long-lasting remission of type 1 diabetes following treatment with topiramate for generalized seizures

We report a case of unusually long-lasting remission of type 1 diabetes (T1D). The patient, a Caucasian man, at the age of 43 years developed a ketotic diabetes, classified as type 1 based on clinical presentation and positivity for islet autoantibodies. Shortly after diabetes onset, oral topiramate was added to preexisting valproic acid for generalized seizures and maintained thereafter. Initial intensive insulin treatment was rapidly reduced to low doses (3 Units/day) maintained for a long time and then discontinued at month 55; fasting glucose and glycosylated hemoglobin were basically normalized at 58 months. An oral glucose tolerance test performed at month 53 showed an impaired fasting glucose (6.0 mmol/l) and a value slightly above the threshold for the diagnosis of diabetes at 2 h (11.2 mmol/l). We hypothesize that this unusually prolonged preservation of β-cell function might be ascribed to the concomitant therapy with topiramate, an antiepileptic agent with demonstrated efficacy as antidiabetic in type 2 diabetes (T2D). Topiramate should be further investigated as candidate agent for the preservation of β-cell function also in T1D.     

Dietary restriction interferes with oxidative status and intrinsic intestinal innervation in aging rats

ObjectivesTo evaluate the effects of dietary restriction on oxidative status, the HuC/D–neuronal nitric oxide synthase (nNOS) myenteric neuron population, HuC/D-S100 glial cells, and the morphometry of the small intestine in rats at various ages.MethodsFifteen Wistar rats were divided into 7-and 12-mo-old control groups and a 12-mo-old experimental group subjected to dietary restrictions (50% of normal ration) for 5 mo. At 7 and 12 mo of age, the animals were anesthetized, and blood was collected to assess the biochemical components and oxidative status. Ileum samples were subjected to double-marker (HuC/D-nNOS and HuC/D-S100) immunostaining and histologic processing to morphometrically analyze intestinal wall elements and determine the metaphase index and rate of caliciform cells. The data were subjected to analysis of variance and the Tukey post hoc test with a 5% significance level.ResultsAge affected the oxidative status by increasing lipid peroxidation, with no effect on blood components, intrinsic innervation, and intestinal wall elements. The animals subjected to dietary restriction showed improved levels of total cholesterol, triacylglycerols, and oxidative status, with no changes in the nNOS neuron population. However, the dietary restriction dramatically decreased the glial and HuC/D myenteric populations, led to atrophy of the neuronal cell body, induced glial hypertrophy, and decreased the thickness of the intestinal wall.ConclusionThe high oxidative status of the aging animals was reversed by dietary restriction, which also lowered cholesterol and triacylglycerol levels. The present dietary restriction elicited morpho-quantitative changes in the myenteric plexus and histology of the ileum, with likely effects on intestinal functions.