Pancreatic adenocarcinoma in type 2 progressive familial intrahepatic cholestasis

<p>Abstract</p> <p>Background</p> <p>BSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP). BSEP disease is associated with an increased risk of hepatobiliary cancer.</p> <p>Case Presentation</p> <p>A 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 × 1.3 cm mass was detected in the pancreas on abdominal CT scan. A 2 cm mass lesion was found at the neck and proximal body of the pancreas. Pathology demonstrated a grade 2-3 adenocarcinoma with invasion into the peripancreatic fat.</p> <p>Conclusions</p> <p>Clinicians should be aware of the possibility of pancreatic adenocarcinoma in patients with BSEP disease.</p

Intervention to enhance skilled arm and hand movements after stroke: A feasibility study using a new virtual reality system

<p>Abstract</p> <p>Background</p> <p>Rehabilitation programs designed to develop skill in upper extremity (UE) function after stroke require progressive practice that engage and challenge the learner. Virtual realty (VR) provides a unique environment where the presentation of stimuli can be controlled systematically for optimal challenge by adapting task difficulty as performance improves. We describe four VR tasks that were developed and tested to improve arm and hand movement skills for individuals with hemiparesis.</p> <p>Methods</p> <p>Two participants with chronic post-stroke paresis and different levels of motor severity attended 12 training sessions lasting 1 to 2 hours each over a 3-week period. Behavior measures and questionnaires were administered pre-, mid-, and post-training.</p> <p>Results</p> <p>Both participants improved VR task performance across sessions. The less impaired participant averaged more time on task, practiced a greater number of blocks per session, and progressed at a faster rate over sessions than the more impaired participant. Impairment level did not change but both participants improved functional ability after training. The less impaired participant increased the number of blocks moved on the Box & Blocks test while the more impaired participant achieved 4 more items on the Functional Test of the Hemiparetic UE.</p> <p>Conclusion</p> <p>Two participants with differing motor severity were able to engage in VR based practice and improve performance over 12 training sessions. We were able to successfully provide individualized, progressive practice based on each participant's level of movement ability and rate of performance improvement.</p

IMPULSE: the impact of gender on the presentation and management of aortic stenosis across Europe.

AIMS: There is an increasing awareness of gender-related differences in patients with severe aortic stenosis and their outcomes after surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). METHODS: Data from the IMPULSE registry were analysed. Patients with severe aortic stenosis (AS) were enrolled between March 2015 and April 2017 and stratified by gender. A subgroup analysis was performed to assess the impact of age. RESULTS: Overall, 2171 patients were enrolled, and 48.0% were female. Women were characterised by a higher rate of renal impairment (31.7 vs 23.3%; p<0.001), were at higher surgical risk (EuroSCORE II: 4.5 vs 3.6%; p=0.001) and more often in a critical preoperative state (7.0vs 4.2%; p=0.003). Men had an increased rate of previous cardiac surgery (9.4 vs 4.7%; p<0.001) and a reduced left ventricular ejection fraction (4.9 vs 1.3%; p<0.001). Concomitant mitral and tricuspid valve disease was substantially more common among women. Symptoms were highly prevalent in both women and men (83.6 vs 77.3%; p<0.001). AVR was planned in 1379 cases. Women were more frequently scheduled to undergo TAVI (49.3 vs 41.0%; p<0.001) and less frequently for SAVR (20.3 vs 27.5%; p<0.001). CONCLUSIONS: The present data show that female patients with severe AS have a distinct patient profile and are managed in a different way to males. Gender-based differences in the management of patients with severe AS need to be taken into account more systematically to improve outcomes, especially for women

Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect

Background: Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1) - critical for lung, thyroid and central nervous system morphogenesis and function - causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant.Methods: The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled 2H2O and 13C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry 2H and 13C enrichment curves. Six intubated infants with no primary lung disease were used as controls.Results: Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and in five ABCA3 mutation carriers. Kinetic studies demonstrated a marked reduction of SP-B synthesis (43.2 vs. 76.5 \ub1 24.8%/day); conversely, DSPC synthesis was higher (12.4 vs. 6.3 \ub1 0.5%/day) compared to controls, although there was a marked reduction of DSPC content in tracheal aspirates (29.8 vs. 56.1 \ub1 12.4% of total phospholipid content).Conclusion: Defective TTF-1 signaling may result in profound surfactant homeostasis disruption and neonatal/pediatric diffuse lung disease. Heterozygous ABCA3 missense mutations may act as disease modifiers in other genetic surfactant defects

Impact of movement training on upper limb motor strategies in persons with shoulder impingement syndrome

<p>Abstract</p> <p>Background</p> <p>Movement deficits, such as changes in the magnitude of scapulohumeral and scapulathoracic muscle activations or perturbations in the kinematics of the glenohumeral, sternoclavicular and scapulothoracic joints, have been observed in people with shoulder impingement syndrome. Movement training has been suggested as a mean to contribute to the improvement of the motor performance in persons with musculoskeletal impairments. However, the impact of movement training on the movement deficits of persons with shoulder impingement syndrome is still unknown. The aim of this study was to evaluate the short-term effects of supervised movement training with feedback on the motor strategies of persons with shoulder impingement syndrome.</p> <p>Methods</p> <p>Thirty-three subjects with shoulder impingement were recruited. They were involved in two visits, one day apart. During the first visit, supervised movement training with feedback was performed. The upper limb motor strategies were evaluated before, during, immediately after and 24 hours after movement training. They were characterized during reaching movements in the frontal plane by EMG activity of seven shoulder muscles and total excursion and final position of the wrist, elbow, shoulder, clavicle and trunk. Movement training consisted of reaching movements performed under the supervision of a physiotherapist who gave feedback aimed at restoring shoulder movements. One-way repeated measures ANOVAs were run to analyze the effect of movement training.</p> <p>Results</p> <p>During, immediately after and 24 hours after movement training with feedback, the EMG activity was significantly decreased compared to the baseline level. For the kinematics, total joint excursion of the trunk and final joint position of the trunk, shoulder and clavicle were significantly improved during and immediately after training compared to baseline. Twenty-four hours after supervised movement training, the kinematics of trunk, shoulder and clavicle were back to the baseline level.</p> <p>Conclusion</p> <p>Movement training with feedback brought changes in motor strategies and improved temporarily some aspects of the kinematics. However, one training session was not enough to bring permanent improvement in the kinematic patterns. These results demonstrate the potential of movement training in the rehabilitation of movement deficits associated with shoulder impingement syndrome.</p

Metabolic syndrome and risk factors for cardiovascular disease: are nonagenarians protected?

This study assessed cardiovascular disease risk factors in three groups of human subjects aged 20–34 [young, 20 male (M)/33 female (F)], 60–74 (aged, 29M/29F), and > 90 years (nonagenarian, 47M/50F). Components of the metabolic syndrome, cardiovascular disease, and markers of inflammation and oxidative stress were assessed. Nonagenarians weighed less than the two other groups (P < 0.001); however, there was no difference in percent fat among the three groups. Aged individuals had the highest prevalence of the metabolic syndrome (P < 0.001) according to the Adult Treatment Panel III classification. Both fibrinogen and homocysteine concentrations were significantly higher in the nonagenarians compared to younger groups. However, there were no significant differences between groups in fasting insulin, high sensitive C-reactive protein, and plasminogen activator inhibitor 1 concentrations. There were also no relationships between inflammation/ oxidative stress and the metabolic syndrome or cardiovascular disease although nonagenarians appear to be protected from oxidative damage to DNA

Syntactic learning by mere exposure - An ERP study in adult learners

<p>Abstract</p> <p>Background</p> <p>Artificial language studies have revealed the remarkable ability of humans to extract syntactic structures from a continuous sound stream by mere exposure. However, it remains unclear whether the processes acquired in such tasks are comparable to those applied during normal language processing. The present study compares the ERPs to auditory processing of simple Italian sentences in native and non-native speakers after brief exposure to Italian sentences of a similar structure. The sentences contained a non-adjacent dependency between an auxiliary and the morphologically marked suffix of the verb. Participants were presented four alternating learning and testing phases. During learning phases only correct sentences were presented while during testing phases 50 percent of the sentences contained a grammatical violation.</p> <p>Results</p> <p>The non-native speakers successfully learned the dependency and displayed an N400-like negativity and a subsequent anteriorily distributed positivity in response to rule violations. The native Italian group showed an N400 followed by a P600 effect.</p> <p>Conclusion</p> <p>The presence of the P600 suggests that native speakers applied a grammatical rule. In contrast, non-native speakers appeared to use a lexical form-based processing strategy. Thus, the processing mechanisms acquired in the language learning task were only partly comparable to those applied by competent native speakers.</p