A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia

Abstract

NDUFB11, a component of mitochondrial complex I, is a relatively small integral membrane protein, belonging to the 'supernumerary' group of subunits, but proved to be absolutely essential for the assembly of an active complex I. Mutations in in the X-linked nuclear encoded NDUFB11 gene have recently been discovered in association with two distinct phenotypes, i.e. microphthalmia with linear skin defects and histiocytoid cardiomyopathy. We report on a male with complex I deficiency, caused by a de novo mutation in NDUFB11 and displaying early onset sideroblastic anemia as the unique feature. This is the third report that describes a mutation in NDUFB11 but all are associated to a different phenotype. Our results further expand the molecular spectrum and associated clinical phenotype of NDUFB11 defects.

Inactivation of CI due to a de-novo mutation in NDUFBLL gene encoding for a smalland hydrophobic subunit of CI, producesa peculiar phenotype in our patient characterized by lactic acidosis and sideroblastic anemia.

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Firefighter/Medic - Jasper County Fire-Rescue

please see the job announcement at http://ift.tt/1NTtYet"pageID=92

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Combing neuroprotective agents: effect of riluzole and magnesium in a rat model of thoracic spinal cord injury

Damage to the spinal cord can result in irreversible impairments or complete loss of motor, sensory and autonomic functions. Riluzole and magnesium have been widely investigated as neuroprotective agents in animal models of spinal cord injury. As these drugs protect the injured spinal cord through different mechanisms we aimed to investigate if their neuroprotective efficacy could be cumulative.

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Pre- and post-procedural quality indicators for colonoscopy: A nationwide survey

The provision of high-quality colonoscopy can be assessed by evaluating technical aspects of the procedure and, at individual center level, by comparing structural indicators and institutional policies for managing peri-procedural issues with guideline recommendations.

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Pre- and post-procedural quality indicators for colonoscopy: A nationwide survey

The provision of high-quality colonoscopy can be assessed by evaluating technical aspects of the procedure and, at individual center level, by comparing structural indicators and institutional policies for managing peri-procedural issues with guideline recommendations.

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Accuracy of clinical and electrophysiological criteria for diagnosing amyotrophic lateral sclerosis

Except for the genetic forms, amyotrophic lateral sclerosis (ALS) is not a single disease but a syndrome. ALS is clinically characterised by the presence of progressive upper motor neuron (UMN) signs and lower motor neurone (LMN) signs in bulbar, upper limb, axial, and lower limb muscles [Riva et al. 2016]. Depending on the affected region at onset, bulbar-onset and limb-onset ALS is delineated [Morris, 2015]. At onset, affection of the limbs may be asymmetric. No specific test is available for diagnosing ALS and the golden standard is the neuropathological demonstration of the UMN and LMN lesion.

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Determining the role of skewed X-chromosome inactivation in developing muscle symptoms in carriers of Duchenne muscular dystrophy

Abstract

Duchenne and Becker dystrophinopathies (DMD and BMD) are X-linked recessive disorders caused by mutations in the dystrophin gene that lead to absent or reduced expression of dystrophin in both skeletal and heart muscles. DMD/BMD female carriers are usually asymptomatic, although about 8 % may exhibit muscle or cardiac symptoms. Several mechanisms leading to a reduced dystrophin have been hypothesized to explain the clinical manifestations and, in particular, the role of the skewed XCI is questioned. In this review, the mechanism of XCI and its involvement in the phenotype of BMD/DMD carriers with both a normal karyotype or with X;autosome translocations with breakpoints at Xp21 (locus of the DMD gene) will be analyzed. We have previously observed that DMD carriers with moderate/severe muscle involvement, exhibit a moderate or extremely skewed XCI, in particular if presenting with an early onset of symptoms, while DMD carriers with mild muscle involvement present a random XCI. Moreover, we found that among 87.1 % of the carriers with X;autosome translocations involving the locus Xp21 who developed signs and symptoms of dystrophinopathy such as proximal muscle weakness, difficulty to run, jump and climb stairs, 95.2 % had a skewed XCI pattern in lymphocytes. These data support the hypothesis that skewed XCI is involved in the onset of phenotype in DMD carriers, the X chromosome carrying the normal DMD gene being preferentially inactivated and leading to a moderate–severe muscle involvement.

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Induction infliximab levels among patients with acute severe ulcerative colitis compared with patients with moderately severe ulcerative colitis

Alimentary Pharmacology and Therapeutics

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Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: a systematic review and meta-analysis

Liver International

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Improvement of constipation in leukemia patients undergoing chemotherapy using sweet potato

Cancer Nursing

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Libertas: a phase II placebo-controlled study of NRL001 in patients with faecal incontinence showed an unexpected and sustained placebo response

International Journal of Colorectal Disease

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Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate

International Journal of Cancer

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Hepatitis C virus coinfection as a risk factor for osteoporosis and fracture

Current Opinion in HIV and AIDS

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Clinical outcomes efficacy and adverse events in patients undergoing esophageal stent placement for benign indications: a large multicenter study

Journal of Clinical Gastroenterology

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Alcohol consumption and colon cancer prognosis among participants in North Central Cancer Treatment Group phase III trial N0147

International Journal of Cancer

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Differences in motor recovery between upper and lower limbs: does stroke subtype make the difference?.

Previous studies comparing the patterns of recovery for upper (UL) and lower limbs (LL) reported similar patterns of motor recovery of extremities. However, the influence of clinical stroke subtypes on the difference between recovery of extremities has never been investigated. The aim of this study is to compare the time course of the UL and LL in a sample of patients who have had distinct subtypes of ischemic stroke. A total of 443 consecutive patients following ischemic stroke were assessed at admission, discharge, and 1 month after discharge with the arm and leg motor parts of the Fugl-Meyer scale. Separate analyses were carried out for the entire sample and for samples of each stroke subtype classified according to the Oxfordshire Community Stroke Project. All groups showed significant improvements in motor function (P

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Translational Neurocardiology: preclinical models and cardioneural integrative aspects

Abstract

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to assure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. Figure 1 presents the contextual framework for these interactions. This white paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics.

This article is protected by copyright. All rights reserved

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The predictive ability of six pharmacokinetic models of rocuronium developed using a single bolus: evaluation with bolus and continuous infusion regimen

Abstract

Purpose

Rocuronium concentration prediction using pharmacokinetic (PK) models would be useful for controlling rocuronium effects because neuromuscular monitoring throughout anesthesia can be difficult. This study assessed whether six different compartmental PK models developed from data obtained after bolus administration only could predict the measured plasma concentration (Cp) values of rocuronium delivered by bolus followed by continuous infusion.

Methods

Rocuronium Cp values from 19 healthy subjects who received a bolus dose followed by continuous infusion in a phase III multicenter trial in Japan were used retrospectively as evaluation datasets. Six different compartmental PK models of rocuronium were used to simulate rocuronium Cp time course values, which were compared with measured Cp values. Prediction error (PE) derivatives of median absolute PE (MDAPE), median PE (MDPE), wobble, divergence absolute PE, and divergence PE were used to assess inaccuracy, bias, intra-individual variability, and time-related trends in APE and PE values.

Results

MDAPE and MDPE values were acceptable only for the Magorian and Kleijn models. The divergence PE value for the Kleijn model was lower than −10 %/h, indicating unstable prediction over time. The Szenohradszky model had the lowest divergence PE (−2.7 %/h) and wobble (5.4 %) values with negative bias (MDPE = −25.9 %). These three models were developed using the mixed-effects modeling approach. The Magorian model showed the best PE derivatives among the models assessed.

Conclusions

A PK model developed from data obtained after single-bolus dosing can predict Cp values during bolus and continuous infusion. Thus, a mixed-effects modeling approach may be preferable in extrapolating such data.

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Current Approach to the Diagnosis and Management of Portopulmonary Hypertension

Abstract

Portopulmonary hypertension (POPH) is a form of pulmonary arterial hypertension occurring in the setting of portal hypertension with or without hepatic cirrhosis. The presence of both portal and pulmonary vascular disease contributes to complicated hemodynamics and therapeutic challenges, though the severities do not appear to correlate directly. Diagnosis of POPH, and distinction from the commonly observed hyperdynamic state of end-stage liver disease, is typically accomplished with an initial screening transthoracic echocardiogram, followed by right heart catheterization for confirmation of hemodynamic parameters. Though few studies have directly evaluated use in POPH, pulmonary artery-directed therapy is the cornerstone of management, along with consideration of liver transplantation. Perioperative and long-term outcomes are variable, but uniformly worse in the setting of uncontrolled pulmonary pressures. Risk stratification and optimal patient selection for these interventions are areas of ongoing investigation.

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Exploring the Small Bowel: Update on Deep Enteroscopy

Abstract

Deep enteroscopy allows for the diagnosis and treatment of small bowel disorders that historically required operative intervention. There are a variety of endoscopic platforms using balloons and rotational overtubes to facilitate small bowel intubation and even allow for total enteroscopy. Obscure gastrointestinal bleeding is the most common indication for deep enteroscopy. By visualizing segments of the small bowel not possible through standard EGD or push enteroscopy, deep enteroscopy has an established high rate of identification and treatment of bleeding sources. In addition to obscure bleeding, other common indications include diagnosis and staging of Crohn's disease, evaluation of findings on capsule endoscopy and investigation of possible small bowel tumors. Large endoscopy databases have shown deep enteroscopy to be not only effective but safe. Recent research has focused on comparing the diagnostic rates, efficacy, and total enteroscopy rates of the different endoscopic platforms.

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What Can We Do to Optimize Colonoscopy and How Effective Can We Be?

Abstract

In the USA, colorectal cancer is the third most common cancer and third leading cause of cancer death among both men and women. Declining rates of colon cancer in the past decade have been attributed in part to screening and removal of precancerous polyps via colonoscopy. Recent emphasis has been placed on measures to increase the quality and effectiveness of colonoscopy. These have been divided into pre-procedure quality metrics (bowel preparation), procedural quality metrics (cecal intubation, withdrawal time, and adenoma detection rate), post-procedure metrics (surveillance interval), and other quality metrics (patient satisfaction and willingness to repeat the procedure). The purpose of this article is to review the data and controversies surrounding each of these and identify ways to optimize the performance of colonoscopy.

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Endoscopic Bariatric Therapies

Abstract

Obesity and its associated cardio-metabolic comorbidities have emerged as a global pandemic. The efficacy of various hypo-caloric diets and prescription drugs has been poor with respect to sustained weight loss. Recent advancements in endoscopic technology and techniques have opened a new field of minimally invasive endoscopic treatment options for combatting obesity both as a first line and adjunctive therapy. Presently, two endoscopic space-occupying devices in the form of intragastric balloons have received FDA approval for 6-month implantation in patients within a BMI range of 30–40 kg/m². Furthermore, full-thickness suturing has led to the development of primary endoscopic sleeve gastroplasty and Roux-en-Y gastric bypass revision as viable endoscopic alternatives to surgical approaches. These techniques have the potential to reduce adverse events, cost, and recovery times. Looking forward, a variety of promising and novel medical devices and endoscopic platforms that target obesity and diabetes are in various phases of development and investigation. The present review aims to discuss the current and forthcoming endoscopic bariatric therapies with emphasis on relevant procedural technique and review of available evidence.

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What's the meaning of this? A behavioral and neurophysiological investigation into the principles behind the classification of visual emotional stimuli

Abstract

Two experiments were performed to investigate the principles by which emotional stimuli are classified on the dimensions of valence and arousal. In Experiment 1, a large sample of healthy participants rated emotional stimuli according to both broad dimensions. Hierarchical cluster analyses performed on these ratings revealed that stimuli were clustered according to their semantic content at the beginning of the agglomerative process. Example semantic themes include food, violence, nudes, death, and objects. Importantly, this pattern occurred in a parallel fashion for ratings on both dimensions. In Experiment 2, we investigated if the same semantic clusters were differentiated at the neurophysiological level. Intracerebral EEG was recorded from 18 patients with intractable epilepsy who viewed the same set of stimuli. Not only did electrocortical responses differentiate between these data-defined semantic clusters, they converged with the behavioral measurements to highlight the importance of categories associated with survival and reproduction. These findings provide strong evidence that the semantic content of affective material influences their classification along the broad dimensions of valence and arousal, and this principle of categorization exerts an effect on the evoked emotional response. Future studies should consider data-driven techniques rather than normative ratings to identify more specific, semantically related emotional images.

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The Association Between Preoperative Frailty and Postoperative Delirium After Cardiac Surgery.

Delirium is common after cardiac surgery, and preoperative identification of high-risk patients could guide prevention strategies. We prospectively measured frailty in 55 patients before cardiac surgery and assessed postoperative delirium using a validated chart review. The prevalence of frailty was 30.9%. Frail patients had a higher incidence of delirium (47.1%) compared with nonfrail patients (2.6%; P =2.1-fold greater in frail compared with nonfrail patients (relative risk, 18.3; 95% confidence interval, 2.1-161.8; P = 0.009). Frailty may identify patients who would benefit from delirium-prevention strategies because of increased baseline risk for delirium. (C) 2016 International Anesthesia Research Society

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Reply to: importance of half-the-air pressure test in Shamrock lumbar plexus block.

No abstract available

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Altered development in GABA co-release shapes glycinergic synaptic currents in cultured spinal slices of the SOD1G93A mouse model of ALS

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset neurological disease characterized by progressive degeneration of motoneurons (MNs). In our previous study we developed organotypic spinal cultures from an ALS mouse model expressing a mutant form of human superoxide dismutase 1 (SOD1^G93A). We reported the presence of a significant synaptic rearrangement expressed by these embryonic cultured networks, which may lead to altered development of spinal synaptic signalling, potentially linked to the adult disease phenotype. Recent studies on the same ALS mouse model, reported a selective loss of glycinergic innervation in cultured MNs, suggestive of a contribution of synaptic inhibition to MNs dysfunction and degeneration. Here we further exploit organotypic cultures from wild type and SOD1^G93A mice to investigate the development of glycine-receptor mediated synaptic currents recorded from interneurons of the premotor ventral circuits. We perform single cell electrophysiology, immunocytochemistry and confocal microscopy and we suggest that GABA co-release may speed the decay of glycine responses altering, in SOD1^G93A developing networks, temporal precision and signal integration at the postsynaptic site. Our hypothesis is supported by the finding of an increased MN bursting activity in immature SOD1^G93A spinal cords and by immunofluorescence microscopy detection of longer persistence of GABA in SOD1^G93A glycinergic terminals in cultured and ex-vivo spinal slices.

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Preclinical and clinical evaluation of autonomic function in humans

This review focuses on how to assess autonomic function in humans including various ways to measure heart rate, catecholamines, and sympathetic neural activity. The need to assess autonomic function is paramount in many experimental paradigms because: 1) Autonomic dysfunction is present in common diseases like hypertension, diabetes, and heart failure and the magnitude of this dysfunction is broadly related to morbidity and mortality in these disorders. 2) The relationship between autonomic dysfunction and morbidity and mortality can be causal. 3) Interventions that modulate or reverse autonomic dysfunction can improve outcomes in the affected patients. The techniques discussed are also frequently used to understand the autonomic responses sympathoexcitatory maneuvers like exercise, the cold pressor test or mental stress. Because these maneuvers can engage a variety of sensory and efferent pathways under some circumstances the physiological responses measured by many of the techniques are directionally similar, in others they are divergent. Thus any investigator seeking to study the autonomic nervous system or its contribution to either normal physiology or pathophysiologic conditions must carefully balance a number of considerations to ensure that the right technique is used to address the question of interest.

This article is protected by copyright. All rights reserved

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