Effect of basal forebrain stimulation on extracellular acetylcholine release and blood flow in the olfactory bulb

Abstract

The olfactory bulb receives cholinergic basal forebrain input, as does the neocortex; however, the in vivo physiological functions regarding the release of extracellular acetylcholine and regulation of regional blood flow in the olfactory bulb are unclear. We used in vivo microdialysis to measure the extracellular acetylcholine levels in the olfactory bulb of urethane-anesthetized rats. Focal chemical stimulation by microinjection of l-glutamate into the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, which is the main source of cholinergic input to the olfactory bulb, increased extracellular acetylcholine release in the ipsilateral olfactory bulb. When the regional cerebral blood flow was measured using laser speckle contrast imaging, the focal chemical stimulation of the HDB did not significantly alter the blood flow in the olfactory bulb, while increases were observed in the neocortex. Our results suggest a functional difference between the olfactory bulb and neocortex regarding cerebral blood flow regulation through the release of acetylcholine by cholinergic basal forebrain input.

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JNA Journal Club.

No abstract available

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Effect of Albumin in Combination With Mannitol on Whole-blood Coagulation In Vitro Assessed by Thromboelastometry.

Background: Albumin and mannitol may interfere with hemostasis, but their coinfluence is unclear. We aimed to determine the effects of albumin alone and in combination with mannitol or Ringer acetate (RAC) on hemostasis in crossover in vitro study. Materials and Methods: From citrated fresh whole blood withdrawn from 10 volunteers, we prepared 2.5, 5, 10, 15, and 20 vol% dilutions of 4% albumin (Alb group). Each sample was thereafter diluted by 15% mannitol (Alb/Man group) or RAC (Alb/RAC group) at a ratio of 9:1. Using thromboelastometry, FibTEM (fibrinogen ROTEM) and ExTEM (extrinsic ROTEM) tests were performed. Results: A 20 vol%, but not 2.5 to 15 vol% dilution of albumin caused a prolonged clot formation time, [alpha]-angle decrease, and maximum clot firmness (MCF) weakening compared with undiluted sample (P

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The ASA Committee for Neuroanesthesia and Anesthesia Quality Institute: Report for Demographic Patterns for Neurosurgical Anesthesia Practice in the United States.

No abstract available

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Epidural Injection of Platelet Rich Plasma for Postlumbar Puncture Headaches.

No abstract available

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Pregnant Women of African Descent Have Lower TSH Concentrations and a Lower Risk of TPO-Antibody Positivity

Clinical Thyroidology May 2017, Vol. 29, No. 5: 192-194.


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How Often Does a Thyroid Cancer Patient Need to Undergo Surveillance with Cervical Ultrasound?

Clinical Thyroidology May 2017, Vol. 29, No. 5: 173-175.


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LETTER: Women with Gestational Thyroid Dysfunction May Be at Higher Risk for Thyroid Disease Developing Postpartum

Clinical Thyroidology May 2017, Vol. 29, No. 5: 204-205.


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Meta-Analysis Confirms the Deleterious Effects of Combined BRAFV600E and Telomerase Reverse Transcriptase Promoter Mutations on the Course and Mortality of Papillary Thyroid Carcinoma

Clinical Thyroidology May 2017, Vol. 29, No. 5: 176-179.


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MYH9, a Nonmuscle Myosin, Regulates FOXE1 and PTCSC2, Two Genes Involved in Thyroid Development, Function, and Risk of Papillary Thyroid Cancer

Clinical Thyroidology May 2017, Vol. 29, No. 5: 198-199.


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First -Degree Family Members of Patients with Hypothyroidism Due to Hashimoto's Thyroiditis Are at a Ninefold Increased Risk for the Same

Clinical Thyroidology May 2017, Vol. 29, No. 5: 180-182.


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Surgery for Neck Recurrence of Thyroid Cancer Can Achieve Complete Remission in a Majority of Patients

Clinical Thyroidology May 2017, Vol. 29, No. 5: 169-172.


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Many Patients Who Become Hypothyroid After Lobectomy Will Recover Normal Thyroid Function Without Supplementation

Clinical Thyroidology May 2017, Vol. 29, No. 5: 183-185.


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124I PET–CT May Be Useful in Identifying Radioiodine-Avid Lesions in Differentiated Thyroid Cancer

Clinical Thyroidology May 2017, Vol. 29, No. 5: 195-197.


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A New Assessment of the Prevalence and Risk Factors of Liver Abnormalities in Hyperthyroidism

Clinical Thyroidology May 2017, Vol. 29, No. 5: 186-188.


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Case Report: The Utility of PTH Needle Washout in Distinguishing Recurrent Thyroid Bed Lesions in Thyroid Cancer Patients at Risk for Hyperparathyroidism

Clinical Thyroidology May 2017, Vol. 29, No. 5: 200-203.


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Higher Preconception TSH Values Are Associated With Adverse Obstetric Outcomes

Clinical Thyroidology May 2017, Vol. 29, No. 5: 189-191.


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The Author Replies

Clinical Thyroidology May 2017, Vol. 29, No. 5: 206-207.


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Continuous Regional Anesthesia and Inpatient Rehabilitation for Pediatric Complex Regional Pain Syndrome.

Background: Evidence supports treatment of pediatric complex regional pain syndromes (CRPS) with physical and occupational therapy and cognitive-behavioral therapy. Some patients have persistent pain and/or limb dysfunction despite these treatments. We performed a retrospective study of pediatric patients with CRPS treated by continuous epidural or peripheral perineural local anesthetic infusions along with inpatient rehabilitation at Boston Children's Hospital. Methods: After approval from the institutional review board, electronic medical records were reviewed for patients treated between September 2003 and September 2014. Primary outcomes were pain and functional scores. Data were collected at the first encounter, at follow-up visits between 4 months before and after admission, and daily while inpatient. Changes over time were assessed using Wilcoxon tests with Dunn corrections. Clinical significance of benefit or harm was assessed by the method of Jacobson and Truax. Response predictors were analyzed using linear mixed models and exploratory logarithmic regression analyses. Results: Pain, function, and disability scores improved during hospitalization and in follow-up over a 4-month period. Seventy percent of patients achieved clinically significant benefit (56% for pain reduction and 40% increased functionality, respectively). Univariate and adjusted predictors of favorable outcome included preadmission resting Numeric Pain Rating Scale score of less than 6 (odds ratio, 5.0; P = 0.0164 and subsequent attendance at the Pediatric Pain Rehabilitation Center at Boston Children's Hospital (odds ratio, 5.0; P = 0.0206). Mean pain scores greater than 3 during the regional anesthesia infusion predicted less favorable outcome. Conclusions: Continuous regional anesthesia may be an option to facilitate intensive rehabilitation for selected pediatric patients with CRPS. Further research should help clarify the role of regional anesthesia in a comprehensive management program. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Continuous Intrathecal Infusion of Cannabinoid Receptor Agonists Attenuates Nerve Ligation-Induced Pain in Rats.

Background and Objectives: Cannabinoid receptors (CB1R/CB2R) are known to play important roles in pain transmission. In this study, we investigated the effects of continuous intrathecal infusion of CB1/2R agonists in the L5/6 spinal nerve ligation pain model. Methods: Under isoflurane anesthesia, rats received nerve ligation and intrathecal catheter connected to an infusion pump. After surgery, saline (1 [mu]L/h), CB1/2R agonist WIN55,212-2, CB1R agonist ACEA, or CB2R agonist AM1241 (1 [mu]mol/h) was given intrathecally for 7 days. The mechanical and thermal sensitivities of rat hindpaw were determined by von Frey hair and radiant heat tests. The expression of CB1/2R and protein levels of CB1/2R, Iba1, glial fibrillary acidic protein, and tumor necrosis factor [alpha] were examined by immunofluorescence study and Western blotting. Results: On postligation day 7, rats that received WIN55,212-2, ACEA or AM1241 had significantly higher mean withdrawal thresholds (6.8, 8.4, and 10.2 g) and latencies (6.3, 7.3, and 9.1 seconds) than did saline-treated rats (1.7 g, 2.2 seconds). Cannabinoid receptors were expressed not only in IB4+ (isolectin B4) and CGRP+ (calcitonin gene-related peptide) dorsal root ganglion neurons, their central terminals, and peripheral axons, but also in neurons, microglia, and astrocytes in spinal cord. Cannabinoid receptor agonists enhanced nerve ligation-induced up-regulation of cannabinoid receptor in spinal cord and dorsal root ganglion. Treatment with WIN55,212-2 or AM1241, but not ACEA, markedly reduced nerve ligation-induced up-regulation of Iba1, glial fibrillary acidic protein, and tumor necrosis factor [alpha] in spinal cord. Conclusions: Continuous intrathecal infusion of CB1/2R agonists elicits antinociception in the pain model. The mechanisms might involve their actions on neurons and glial cells. CB2R, but not CB1R, seems to play an important role in the regulation of nerve injury-induced neuroinflammation. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Advancing Safety in Intrathecal Analgesia: A Novel Web-Based Pharmacologic Requisition Platform and Data Repository for Intrathecal Drug Delivery Devices.

No abstract available

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Retrobulbar Block in Pediatric Vitreoretinal Surgery Eliminates the Need for Intraoperative Fentanyl and Postoperative Analgesia: A Randomized Controlled Study.

Background and Objectives: Pediatric ophthalmologic surgery is traditionally accomplished by general anesthesia with opioids, but respiratory depression remains a major concern. Our study compared the efficacy of retrobulbar block with systemic fentanyl on pain, hemodynamic, and stress response in pediatric vitreoretinal surgery. Methods: A prospective double-blind, randomized controlled study was performed comparing retrobulbar block with intravenously administered fentanyl in 28 children aged 1 to 6 years undergoing vitreoretinal surgery. After general anesthesia was induced, retrobulbar block with 0.5% ropivacaine was accomplished in group RB (general anesthesia plus retrobulbar block) (n = 13), and normal saline was injected into retrobulbar space in group F (general anesthesia alone) (n = 15). Fentanyl 0.5 [mu]g/kg was administered when signs of inadequate anesthesia were observed. Results: Respiratory depression (defined as a persistent respiratory rate

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Diskitis, Osteomyelitis, Spinal Epidural Abscess, Meningitis, and Endocarditis Following Sacroiliac Joint Injection for the Treatment of Low-Back Pain in a Patient on Therapy for Hepatitis C Virus.

Objective: Sacroiliac joint injections are frequently performed procedures in the management of acute and chronic low-back pain, including patients with various immunocompromised states. Infectious complications following these procedures along with other spinal injections are rarely reported, but the true incidence is unknown. The purpose of this report is to highlight the devastating neurologic sequela that can occur, and to discuss potential future management strategies. Case Report: We present a patient who developed diskitis, osteomyelitis, spinal epidural abscess, meningitis, and endocarditis from Staphylococcus aureus, all of which developed shortly after a sacroiliac joint injection. The patient was on treatment for hepatitis C virus, and the resulting immunocompromised state likely contributed to the outcome. Conclusions: Immunocompromised patients should be identified prior to treatment, and the small possibility of devastating complications should be thoughtfully weighed against the potential benefit of the procedure. Conservative management should be maximized initially, and if a procedure is done, strict asepsis must be maintained. Prophylaxis for S. aureus should be considered for immunocompromised patients undergoing interventional spine procedures. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Residual Enoxaparin Activity, Anti-Xa Levels, and Concerns About the American Society of Regional Anesthesia and Pain Medicine Anticoagulation Guidelines.

Currently, the American Society of Regional Anesthesia and Pain Medicine (ASRA) anticoagulation guidelines recommend that before the performance of a neuraxial procedure a minimum of 24 hours should elapse following a treatment dose of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). The guidelines have since their inception also consistently recommended against the routine use of anti-Xa level monitoring for patients receiving enoxaparin. However, we noted in our clinical practice that anti-Xa levels were frequently still elevated despite patients meeting the time-based recommendation for treatment dose enoxaparin. To further investigate the possibility that residual anticoagulant activity may persist longer than 24 hours after a treatment dose of enoxaparin, we assessed anti-Xa level activity in patients presenting for elective surgery. Despite nearly universal compliance with ASRA's anticoagulation guidelines (1 sample was drawn at 23.25 hours), anti-Xa activity was found to be elevated in 11 of 19 patients. While 10 patients had an anti-Xa level within the peak prophylactic range (0.2-0.5 IU/mL), 1 patient's level was found to still be in the peak therapeutic range (0.5-1.0 IU/mL). These findings suggest that significant anticoagulant activity may persist longer than previously appreciated after the last treatment dose of enoxaparin and that the current time-based ASRA recommendation may not be conservative enough. Further research is needed to delineate the level of anti-Xa activity below which it is likely safe to proceed with a neuraxial procedure, but it may be time to reconsider the utility of anti-Xa level monitoring when it is available. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Evidence of Spontaneous Post-transplant HCV Eradication in Two Failed DAA Treatments Awaiting Liver Transplantation

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Sun Should Not Rise and Set on a Case of Acute Intestinal Obstruction

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Insights into the Pathogenesis of Pancreatic Cystic Neoplasms

Abstract

With the current epidemic of diagnosed pancreatic cystic neoplasms on the rise, a substantial amount of work has been done to unravel their biology, thus leading to implications on clinical decision making. Recent genetic profiling of resected human specimens has identified alterations in signaling pathways involving KRAS and GNAS signaling as early events in the pathogenesis of intraductal pancreatic mucinous neoplasms. Progressively, mutations in genes such as TP53, SMAD4, RNF43, and others are thought to characterize invasive and advanced lesions. The role of inflammation in fueling the growth and transformation of these cysts has also begun to be studied with greater interest. A number of promising clinical studies have attempted to integrate these genetic insights into classifying these cysts and treating patients. We have reviewed existing literature on similar lines besides commenting on some useful animal models that recapitulate molecular and phenotypic progression of these cysts.

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Prospective Analysis of Minor Adverse Events After Colon Polypectomy

Abstract

Background

The risks of minor adverse events (MAEs) such as abdominal pain and bloating after colon polypectomy (CP) are less clearly documented than major adverse events. However, these complications may cause significant discomfort during the performance of normal activities. We aimed to estimate the incidence of MAE, associated risk factors, and healthcare resource utilization after CP.

Methods

Patients who underwent CP were prospectively enrolled in this study. Trained nurses contacted patients by telephone at 7 and 30 days after the CP and administered a standardized questionnaire to obtain information regarding the development of complications. MAEs were defined as any discomfort the patient experienced after CP excluding major bleeding, perforation, and post-polypectomy coagulation syndrome.

Results

Among a total of 2716 patients, 2253 patients completed the interview at 7 and 30 days. MAEs occurred in 263 patients (11.7%) before day 7, among which the most common were abdominal pain (4.5%), rectal bleeding (2.8%), and bloating (2.6%). Cumulative incidence of MAEs was in 267 patients (11.9%) at 30 days. On multivariate analysis, female sex (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.58–3.18) and use of meperidine (OR 1.54, 95% CI 1.04–2.27) were risk factors for the occurrence of MAEs. Two patients (0.7%) required hospital admission, 117 patients (43.8%) were treated medically in the outpatient clinic, and the majority at 148 patients (55.4%) experienced resolution of symptoms after observation.

Conclusions

The post-CP MAE rate was as low as 11.8%. The MAEs occurred mainly in the first seven postoperative days and resulted in little use of healthcare resources.

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The effect of prophylactic vertebroplasty on the incidence of proximal junctional kyphosis and proximal junctional failure following posterior spinal fusion in adult spinal deformity: a 5 year follow up study

The incidence of proximal junctional kyphosis (PJK) ranges from 5-46% following adult spinal deformity (ASD) surgery. Approximately 66-76% of PJK occurs within 3 months of surgery. A subset of these patients, reportedly 26-47%, develop proximal junctional failure (PJF) within 6 months postoperatively. To date, there are no studies evaluating the impact of prophylactic vertebroplasty on PJK/PJF incidence at long term follow-up.

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Insight into the Recent Genome Duplication of the Halophilic Yeast Hortaea werneckii: Combining an Improved Genome with Gene Expression and Chromatin Structure

Extremophilic organisms demonstrate the flexibility and adaptability of basic biological processes by highlighting how cell physiology adapts to environmental extremes. Few eukaryotic extremophiles have been well studied and only a small number are amenable to laboratory cultivation and manipulation. A detailed characterisation of the genome architecture of such organisms is important to illuminate how they adapt to environmental stresses. One excellent example of a fungal extremophile is the halophile Hortaea werneckii (Pezizomycotina; Dothideomycetes, Capnodiales), a yeast-like fungus able to thrive at near-saturating concentrations of sodium chloride and which is also tolerant to both UV irradiation and desiccation. Given its unique lifestyle and its remarkably recent whole genome duplication, H. werneckii provides opportunities for testing the role of genome duplications and adaptability to extreme environments. We previously assembled the genome of H. werneckii using short-read sequencing technology and found a remarkable degree of gene duplication. Technology limitations, however, precluded high-confidence annotation of the entire genome. We therefore revisited the H. wernickii genome using long-read single molecule sequencing and provide an improved genome assembly, which combined with transcriptome and nucleosome analysis, provides a useful resource for fungal halophile genomics. Remarkably, the ~50 MB H. wernickii genome contains 15,974 genes of which 90% (7608) are duplicates formed by a recent WGD, with an average of 5% protein sequence divergence between them. We found that the WGD is extraordinarily recent, and compared to S. cerevisiae, the majority of the genome's ohnologs have not diverged at the level of gene expression of chromatin structure.

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Metabolic Adaptation to Nutrients Involves Co-regulation of Gene Expression by the RNA Helicase Dbp2 and the Cyc8 Co-repressor in Saccharomyces cerevisiae

Cells fine-tune their metabolic programs according to nutrient availability in order to maintain homeostasis. This is achieved largely through integrating signaling pathways and the gene expression program, allowing cells to adapt to nutritional change. Dbp2, a member of the DEAD-box RNA helicase family in Saccharomyces cerevisiae, has been proposed to integrate gene expression with cellular metabolism. Prior work from our laboratory has reported the necessity of DBP2 in proper gene expression, particularly for genes involved in glucose-dependent regulation. Here, by comparing differentially expressed genes in dbp2 to those of 700 other deletion strains from other studies, we find that CYC8 and TUP1, which form a complex and inhibit transcription of numerous genes, co-repress a common set of genes with DBP2. GO annotations reveal that these co-repressed genes are related to cellular metabolism, including respiration, gluconeogenesis, and alternative carbon source utilization genes. Consistent with a direct role in metabolic gene regulation, loss of either DBP2 or CYC8 results in increased cellular respiration rates. Furthermore, we find that co-repressed genes have a propensity to be associated with overlapping long non-coding RNAs and that up-regulation of these genes in the absence of DBP2 correlates with decreased binding of Cyc8 to these gene promoters. Taken together, this suggests that Dbp2 integrates nutrient availability with energy homeostasis by maintaining repression of glucose-repressed, Cyc8-targeted genes across the genome.

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A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia

Ascertaining the molecular and physiological basis of domestication and breeding is an active area of research. Due to the current wide distribution of its wild ancestor, the wild boar, the pig (Sus scrofa) is an excellent model to study these processes, which occurred independently in East Asia and Europe ca. 9,000 years ago. Analyzing genome variability patterns in terms of metabolic pathways is attractive since it considers the impact of interrelated functions of genes, in contrast to genome-wide scans that treat genes or genome-windows in isolation. To that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and Europe when metabolic pathway was the unit of analysis. We computed statistical significance for differentiation (Fst) and linkage disequilibrium (nSL) statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways significantly differentiated at a q-value < 0.05 in Asia and Europe, respectively; five were shared across continents. In Asia, we found six significant pathways related to behavior, which involved essential neurotransmitters like dopamine and serotonin. Several significant pathways were interrelated, and shared a variable percentage of genes. There were 12 genes present in more than 10 significant pathways (in terms of Fst), comprising genes involved in the transduction of a large number of signals, like phospholipase PCLB1, which is expressed in the brain, or ITPR3, which has an important role in taste transduction. In terms of nSL, significant pathways were mainly related to reproductive performance (ovarian steroidogenesis), an important target trait as well during domestication and modern animal breeding. Different levels of recombination cannot explain these results, since we found no correlation between Fst and recombination rate. However, we did find an increased ratio of deleterious mutations in domestic vs. wild populations, suggesting a relaxed functional constraint associated with the domestication and breeding processes. Purifying selection was, nevertheless, stronger in significantly differentiated pathways than in random pathways, mainly in Europe. We conclude that pathway analysis facilitates the biological interpretation of genome-wide studies. Notably in the case of pig, behavior played an important role, among other physiological and developmental processes.

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Exploring the Impact of Cleavage and Polyadenylation Factors on Pre-mRNA Splicing Across Eukaryotes

In human, mouse and Drosophila, the spliceosomal complex U1 snRNP (U1) protects transcripts from premature cleavage and polyadenylation at proximal intronic polyadenylation signals (PAS). These U1-mediated effects preserve transcription integrity and are known as telescripting. The watchtower role of U1 throughout transcription is clear. What is less clear is whether cleavage and polyadenylation factors (CPFs) are simply patrolled or if they may actively antagonize U1 recruitment. In addressing this question, we found that in the introns of human, mouse and Drosophila and of 14 other eukaryotes, including multi- and single-celled species, the conserved AATAAA PAS — a major target for CPFs — is selected against. This selective pressure, approximated using DNA strand asymmetry, is detected for peripheral and internal introns alike. It is surprisingly more pronounced within — rather than outside — the action range of telescripting and particularly intense in the vicinity of weak 5' splice sites. Our study uncovers a novel feature of eukaryotic genes: that the AATAAA PAS is universally counter-selected in spliceosomal introns. This pattern implies that CPFs may attempt to access introns at any time during transcription. However, natural selection operates to minimize this access. By corroborating and extending previous work, our study further indicates that CPF access to intronic PASs might perturb the recruitment of U1 to the adjacent 5' splice sites. These results open the possibility that CPFs may impact the splicing process across eukaryotes.

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Effects of the Ordering of Natural Selection and Population Regulation Mechanisms on Wright-Fisher Models

We explore the effect of different mechanisms of natural selection on the evolution of populations for one- and two-locus systems. We compare the effect of viability and fecundity selection in the context of the Wright-Fisher model with selection under the assumption of multiplicative fitness. We show that these two modes of natural selection correspond to different orderings of the processes of population regulation and natural selection in the Wright-Fisher model. We find that under the Wright-Fisher model these two different orderings can affect the distribution of trajectories of haplotype frequencies evolving with genetic recombination. However, the difference in the distribution of trajectories is only appreciable when the population is in significant linkage disequilibrium. We find that as linkage disequilibrium decays the trajectories for the two different models rapidly become indistinguishable. We discuss the significance of these findings in terms of biological examples of viability and fecundity selection, and speculate that the effect may be significant when factors such as gene migration maintain a degree of linkage disequilibrium.

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RNAi-Mediated Reverse Genetic Screen Identified Drosophila Chaperones Regulating Eye and Neuromuscular Junction Morphology

Accumulation of toxic proteins in neurons have been linked with the onset of neurodegenerative diseases, which in many cases, are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and resolubilization of unfolded proteins thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance largely remains unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes. Ubiquitous actin5C-Gal4 mediated RNAi knockdown revealed that about 50% of the chaperones are essential in Drosophila. Knocking down these genes in eyes revealed that about 30% of the essential chaperones are crucial for eye development. Using neuron-specific knockdown, immunocytochemistry and robust behavioural assays, we identified a new set of chaperones that play critical roles in the regulation of Drosophila NMJ structural organization. Together, our data presents the first classification and comprehensive analysis of Drosophila chaperones. Our screen identified new set of chaperones that regulate eye and NMJ morphogenesis. Outcome of the screen reported here provides a useful resource for further elucidating the role of individual chaperones in Drosophila eye morphogenesis and synaptic development.

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A Systemic Analysis of Transcriptomic and Epigenomic Data To Reveal Regulation Patterns for Complex Disease

Integrating diverse genomics data can provide a global view of the complex biological processes related to the human complex diseases. Although substantial efforts have been made to integrate different omics data, there are at least three challenges for multi-omics integration methods: (i) How to simultaneously consider the effects of various genomic factors, since these factors jointly influence the phenotypes; (ii) How to effectively incorporate the information from publicly accessible databases and omics datasets to fully capture the interactions among (epi-)genomic factors from diverse omics data; and (iii) Until present, the combination of >2 omics datasets has been poorly explored. Current integration approaches are not sufficient to address all of these challenges together. We proposed a novel integrative analysis framework by incorporating sparse model, multivariate analysis, Gaussian graphical model and network analysis to address these three challenges simultaneously. Based on this strategy, we performed a systemic analysis for GBM (Glioblastoma multiforme) integrating genome-wide gene expression, DNA methylation, and miRNA expression data. We identified three regulatory modules of genomic factors associated with GBM survival time and revealed a global regulatory pattern for GBM by combining the three modules with respect to the common regulatory factors. Our method can not only identify disease-associated dysregulated genomic factors from different omics, but also more importantly, incorporate the information from publicly accessible databases and omics datasets to infer a comprehensive interaction map of all these dysregulated genomic factors. Our work represents an innovative approach to enhance our understanding of molecular genomic mechanisms underlying human complex diseases.

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Manipulating the Mitochondrial Genome To Enhance Cattle Embryo Development

The mixing of mitochondrial DNA (mtDNA) from the donor cell and the recipient oocyte in embryos and offspring derived from somatic cell nuclear transfer (SCNT) compromises genetic integrity and affects embryo development. We set out to generate SCNT embryos that inherited their mtDNA from the recipient oocyte only, as is the case following natural conception. Whilst SCNT blastocysts produced from Holstein (Bos Taurus) fibroblasts depleted of their mtDNA and oocytes derived from Angus (Bos Taurus) cattle possessed oocyte mtDNA only, the co-existence of donor cell and oocyte mtDNA resulted in blastocysts derived from non-depleted cells. Moreover, the use of the reprogramming agent, Trichostatin A (TSA), further improved the development of embryos derived from depleted cells. RNA-seq analysis highlighted 35 differentially expressed genes from the comparison between blastocysts generated from non-depleted cells and blastocysts from depleted cells, both in the presence of TSA. The only differences between these two sets of embryos were the presence of donor cell mtDNA and a significantly higher mtDNA copy number for embryos derived from non-depleted cells. Furthermore, the use of TSA on embryos derived from depleted cells positively modulated the expression of CLDN8, TMEM38A and FREM1, which affect embryonic development. In conclusion, SCNT embryos produced by mtDNA depleted donor cells have the same potential to develop to the blastocyst stage without the presumed damaging effect resulting from the mixture of donor and recipient mtDNA.

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Linkage Map of Lissotriton Newts Provides Insight into the Genetic Basis of Reproductive Isolation

Linkage maps are widely used to investigate structure, function and evolution of genomes. In speciation research, maps facilitate the study of the genetic architecture of reproductive isolation by allowing identification of genomic regions underlying reduced fitness of hybrids. Here we present a linkage map for European newts of the Lissotriton vulgaris species complex, constructed using two families of F2 L. montandoni x L. vulgaris hybrids. The map consists of 1146 protein coding genes on 12 linkage groups, equal to the haploid chromosome number, with a total length of 1484 cM (1.29 cM/marker). It is notably shorter than two other maps available for salamanders, but the differences in map length are consistent with cytogenetic estimates of the number of chiasmata per chromosomal arm. Thus large salamander genomes do not necessarily, as previously suggested, translate into long linkage maps. Consequently, salamanders are an excellent model to study evolutionary consequences of recombination rate variation in taxa with large genomes and similar number of chromosomes. A complex pattern of transmission ratio distortion (TRD) was detected: TRD occurred mostly in one family, in one breeding season and clustered in two genomic segments. This is consistent with environment-dependent mortality of individuals carrying L. montandoni alleles in these two segments and suggests a role of TRD blocks in reproductive isolation. The reported linkage map will empower studies on the genomic architecture of divergence and interactions between the genomes of hybridizing newts.

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Macrodactylia lipomatosa with fibrolipomatous hamartomas: macroscopic and ultrasound clues

Although representing congenital anomaly, fibrolipomatous hamartomas often present with uni- or multifocal peripheral nerve lesions in childhood, or at latest the third and fourth decade of adulthood owing to their slowly progressive growth and consecutive peripheral nerve compression (Silverman et al., 1985, Plaza et al., 2014). In this report, we present the clinical and ultrasound clues of an unusual presentation of a male patient with multifocal fibrolipomatous hamartomas of the left ulnar, median, musculocutaneous nerves and left brachial plexus together with macrodactylia lipomatosa.

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Seizure prediction in patients with focal hippocampal epilepsy

Epilepsy is a neurological disorder affecting 1% of the world's population. It causes seizures characterized by recurrent synchronous abnormal electrical discharges in the brain (Chaovalitwongse et al. 2006; Browne and Holmes 2008). Epileptic patients are often at high risk of serious injury or death (Cockerell et al. 1994). Moreover, accompanying psychological stress and helplessness can cause impaired everyday functioning (Buck et al. 1997; Baker et al. 1997). Thereby, reliable prediction of seizures can considerably improve the quality of life of epileptic patients by warning them of impeding seizures to avoid potentially dangerous situations like driving or swimming and enable administration of treatments (Cook et al., 2013; Ramgopal et al., 2014).

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Flexion Synergy Overshadows Flexor Spasticity During Reaching in Chronic Moderate to Severe Hemiparetic Stroke

Clinicians will be required to quantitatively measure and directly target the contributing underlying motor impairments in individuals with hemiparetic stroke to realize advances beyond conventional care in restoring upper extremity function (Krakauer et al., 2012). In the context of reaching function, impairment in joint individuation is the best predictor of recovery outcome over other common impairments observed in chronic stroke such as weakness and spasticity (Zackowski et al., 2004). The term "spasticity" is defined traditionally as a velocity-dependent hyperactive stretch reflex (Lance, 1980; Thilmann et al., 1991) measured under passive conditions.

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Route simulations, compass mechanisms and long-distance migration flights in birds

Abstract

Bird migration has fascinated humans for centuries and routes crossing the globe are now starting to be revealed by advanced tracking technology. A central question is what compass mechanism, celestial or geomagnetic, is activated during these long flights. Different approaches based on the geometry of flight routes across the globe and route simulations based on predictions from compass mechanisms with or without including the effect of winds have been used to try to answer this question with varying results. A major focus has been use of orthodromic (great circle) and loxodromic (rhumbline) routes using celestial information, while geomagnetic information has been proposed for both a magnetic loxodromic route and a magnetoclinic route. Here, we review previous results and evaluate if one or several alternative compass mechanisms can explain migration routes in birds. We found that most cases could be explained by magnetoclinic routes (up to 73% of the cases), while the sun compas s could explain only 50%. Both magnetic and geographic loxodromes could explain <25% of the routes. The magnetoclinic route functioned across latitudes (1°S–74°N), while the sun compass only worked in the high Arctic (61–69°N). We discuss the results with respect to orientation challenges and availability of orientation cues.

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Drosophila Rhodopsin 7 can partially replace the structural role of Rhodopsin 1, but not its physiological function

Abstract

Rhodopsin 7 (Rh7), a new invertebrate Rhodopsin gene, was discovered in the genome of Drosophila melanogaster in 2000 and thought to encode for a functional Rhodopsin protein. Indeed, Rh7 exhibits most hallmarks of the known Rhodopsins, except for the G-protein-activating QAKK motif in the third cytoplasmic loop that is absent in Rh7. Here, we show that Rh7 can partially substitute Rh1 in the outer receptor cells (R1–6) for rhabdomere maintenance, but that it cannot activate the phototransduction cascade in these cells. This speaks against a role of Rh7 as photopigment in R1–6, but does not exclude that it works in the inner photoreceptor cells.

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Deep intronic mutations and human disease

Abstract

Next-generation sequencing has revolutionized clinical diagnostic testing. Yet, for a substantial proportion of patients, sequence information restricted to exons and exon–intron boundaries fails to identify the genetic cause of the disease. Here we review evidence from mRNA analysis and entire genomic sequencing indicating that pathogenic mutations can occur deep within the introns of over 75 disease-associated genes. Deleterious DNA variants located more than 100 base pairs away from exon–intron junctions most commonly lead to pseudo-exon inclusion due to activation of non-canonical splice sites or changes in splicing regulatory elements. Additionally, deep intronic mutations can disrupt transcription regulatory motifs and non-coding RNA genes. This review aims to highlight the importance of studying variation in deep intronic sequence as a cause of monogenic disorders as well as hereditary cancer syndromes.

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Global skin colour prediction from DNA

Abstract

Human skin colour is highly heritable and externally visible with relevance in medical, forensic, and anthropological genetics. Although eye and hair colour can already be predicted with high accuracies from small sets of carefully selected DNA markers, knowledge about the genetic predictability of skin colour is limited. Here, we investigate the skin colour predictive value of 77 single-nucleotide polymorphisms (SNPs) from 37 genetic loci previously associated with human pigmentation using 2025 individuals from 31 global populations. We identified a minimal set of 36 highly informative skin colour predictive SNPs and developed a statistical prediction model capable of skin colour prediction on a global scale. Average cross-validated prediction accuracies expressed as area under the receiver-operating characteristic curve (AUC) ± standard deviation were 0.97 ± 0.02 for Light, 0.83 ± 0.11 for Dark, and 0.96 ± 0.03 for Dark-Black. When using a 5-category, this resulted in 0.74 ± 0.05 for Very Pale, 0.72 ± 0.03 for Pale, 0.73 ± 0.03 for Intermediate, 0.87±0.1 for Dark, and 0.97 ± 0.03 for Dark-Black. A comparative analysis in 194 independent samples from 17 populations demonstrated that our model outperformed a previously proposed 10-SNP-classifier approach with AUCs rising from 0.79 to 0.82 for White, comparable at the intermediate level of 0.63 and 0.62, respectively, and a large increase from 0.64 to 0.92 for Black. Overall, this study demonstrates that the chosen DNA markers and prediction model, particularly the 5-category level; allow skin colour predictions within and between continental regions for the first time, which will serve as a valuable resource for future applications in forensic and anthropologic genetics.

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Paramedic - $5,000 Sign On Bonus - Champion EMS

Champion EMS, based in Longview, TX is a non-Profit, 501(c)3 organization and we are seeking highly skilled Paramedics. Champion EMS provides EMS through a coordinated system utilizing 28 stations and 38 on duty paramedic units positioned throughout east Texas. EMS is committed to providing high quality pre-hospital medicine in our urban/rural and super rural communities. Shifts include 12 hour and ...

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Narrow-band imaging can increase the visibility of fibrin caps after bleeding of esophageal varices: a case with extensive esophageal candidiasis

Abstract

A 58-year-old man with hepatitis B cirrhosis noticed black stools and underwent an endoscopy at a community hospital. The presence of esophageal varices (EVs) was confirmed, but the bleeding point was not found. He was referred to our institution and underwent a second endoscopy. Extensive white patches of esophageal candidiasis were visible on endoscopy by white-light imaging (WLI), but it was difficult to find the fibrin cap of the EVs. This was easier under narrow-band imaging (NBI), however, as the color turned red from absorption by hemoglobin adhered to it. We retrospectively measured the color differences (CD) between the fibrin cap and the surrounding mucosa 10 times using the CIE (L*a*b*) color space method. The median value of CD increased after NBI (13.9 → 43.0, p < 0.001), with increased visibility. However, the median CD between the white patch and surrounding mucosa decreased after NBI (44.8 → 30.3, p < 0.001). The fibrin cap was paler than the white patch of candidiasis, but the increased visibility of the fibrin cap by NBI enabled it to be found more easily. This is the first report of a case in which NBI was helpful in locating a fibrin cap of EVs.

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5 things to know about endotracheal intubation

If you've ever wondered why the little hole near the tip of an endotracheal tube is called the Murphy Eye, or who Macintosh was, or even who performed the first intubatio, this quick trip through the history of endotracheal tubes and laryngoscopy is for you. Here are five things to know about the invention, indications and use of an endotracheal tube. 1. Endotracheal tube history There is debate ...

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Selected Literature Watch

Journal of Caffeine Research , Vol. 0, No. 0.


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Real-time three-dimensional jaw tracking in temporomandibular disorders

Abstract

When a dysfunction occurs in any component of the stomatognathic system, temporomandibular disorders (TMD) may originates. The aim of this study was to compare the deviations, displacement, and the execution speed of mandibular movements among asymptomatic participants and those with TMD. Convenience sampling was used; forty participants diagnosed by clinical evaluation following the Research Diagnostic Criteria for Temporomandibular Disorders were divided into three groups: Arthropathy (GART, 10 participants, 40% men), Myopathy (GMYO, 10 participants, 30% men), and the Control Group (CG, 20 asymptomatic-participants, 25% men). Participants were asked to perform the movements of free maximal mouth opening and closing, right and left lateral excursions, and protrusion with sliding teeth contacts. The mandibular trajectory was recorded using opto-electronic devices tracking reflective markers placed in front of the "soft tissue pogonion point". The movements were analyzed on the following axis: x–medial-lateral, y – vertical, z – antero-posterior. Significative differences were found in CGxGART – OCY (unassisted maximal mouth opening and closing projection on y-axis), CGxGMYO – OCX (unassisted maximal mouth opening and closing projection on x-axis), and in the measures OLDX (Opening lateral deviation on x-axis), CLDX (Closing lateral deviation on x-axis) and in the measures of speed for both. In regards to GARTxGMYO a significative difference was found in PLDX (Protrusion lateral deviation on x-axis) "Conover-Iman Test of Multiple Comparisons Using Rank Sums" using Bonferroni correction (p<0.05). In conclusion, the total opening movements in individuals with TMD tended to have higher deviation than in those asymptomatic individuals and a reduction in the speed of movements.

This article is protected by copyright. All rights reserved.

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Critical Care Transport Paramedic – Vitalink - New Hanover Regional Medical Center

Critical Care Transport Paramedic – Vitalink Full-Time, Rotating Schedule New Hanover Regional Medical Center Wilmington, NC New Hanover Regional Medical Center's Emergency Transport Services (ETS) is a recognized leader at both state and national levels. Recent awards include: the 2016 American Heart Association Mission Lifeline Gold Award Recognition for EMS, AirLink, and VitaLink, the ...

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Staff Nurse – Vitalink - New Hanover Regional Medical Center

Staff Nurse – Vitalink Full-Time, Rotating Schedule New Hanover Regional Medical Center Wilmington, NC New Hanover Regional Medical Center's Emergency Transport Services (ETS) is a recognized leader at both state and national levels. Recent awards include: the 2016 American Heart Association Mission Lifeline Gold Award Recognition for EMS, AirLink, and VitaLink, the 2016 EMS National Association ...

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Selected Literature Watch

Journal of Caffeine Research , Vol. 0, No. 0.


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Comparison of Periodized and Non-Periodized Resistance Training on Maximal Strength: A Meta-Analysis

Abstract

Background

Periodization is a logical method of organizing training into sequential phases and cyclical time periods in order to increase the potential for achieving specific performance goals while minimizing the potential for overtraining. Periodized resistance training plans are proposed to be superior to non-periodized training plans for enhancing maximal strength.

Objective

The primary aim of this study was to examine the previous literature comparing periodized resistance training plans to non-periodized resistance training plans and determine a quantitative estimate of effect on maximal strength.

Methods

All studies included in the meta-analysis met the following inclusion criteria: (1) peer-reviewed publication; (2) published in English; (3) comparison of a periodized resistance training group to a non-periodized resistance training group; (4) maximal strength measured by 1-repetition maximum (1RM) squat, bench press, or leg press. Data were extracted and independently coded by two authors. Random-effects models were used to aggregate a mean effect size (ES), 95% confidence intervals (CIs) and potential moderators.

Results

The cumulative results of 81 effects gathered from 18 studies published between 1988 and 2015 indicated that the magnitude of improvement in 1RM following periodized resistance training was greater than non-periodized resistance training (ES = 0.43, 95% CI 0.27–0.58; P < 0.001). Periodization model (β = 0.51; P = 0.0010), training status (β = −0.59; P = 0.0305), study length (β = 0.03; P = 0.0067), and training frequency (β = 0.46; P = 0.0123) were associated with a change in 1RM. These results indicate that undulating programs were more favorable for strength gains. Improvements in 1RM were greater among untrained participants. Additionally, higher training frequency and longer study length were associated with larger improvements in 1RM.

Conclusion

These results suggest that periodized resistance training plans have a moderate effect on 1RM compared to non-periodized training plans. Variation in training stimuli appears to be vital for increasing maximal strength, and longer periods of higher training frequency may be preferred.

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5 things to know about endotracheal intubation

From the 1500s until today, techniques for placing a tube into the trachea have continuously evolved and will continue to improve in the future

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The Influence of Drinking Fluid on Endurance Cycling Performance: A Meta-Analysis

Abstract

Background

Fluid replacement during cycling exercise evolves on a spectrum from simply drinking to thirst to planned structured intake, with both being appropriate recommendations. However, with mixed findings suggesting fluid intake may or may not improve endurance cycling performance (ECP) in a diverse range of trained individuals, there is a clear need for summarised evidence regarding the effect of fluid consumption on ECP.

Objectives

(1) Determine the magnitude of the effect of drinking fluid on performance during cycling exercise tasks of various durations, compared with no drinking; (2) examine the relationship between rates of fluid intake and ECP; and (3) establish fluid intake recommendations based on the observations between rates of fluid intake and ECP.

Study Design

Meta-analysis.

Methods

Studies were located via database searches and cross-referencing. Performance outcomes were converted to a similar metric to represent percentage change in power output. Fixed- and random-effects weighted mean effect summaries and meta-regression analyses were used to identify the impact of drinking fluid on ECP.

Results

A limited number of research manuscripts (n = 9) met the inclusion criteria, producing 15 effect estimates. Meta-regression analyses demonstrated that the impact of drinking on ECP under 20–33 °C ambient temperatures was duration-dependent. Fluid consumption of, on average, 0.29 mL/kg body mass/min impaired 1 h high-intensity (80% peak oxygen uptake [ \({\dot{\text{V}}}\) o_2peak]) ECP by −2.5 ± 0.8% (95% confidence interval [CI] −4.1 to −0.9%) compared with no fluid ingestion. In contrast, during >1 to ≤2 h and >2 h moderate-intensity (60–70% \({\dot{\text{V}}}\) o_2peak) cycling exercise, ECP improved by 2.1 ± 1.5% (95% CI 1.2–2.9%) and 3.2 ± 1.2% (95% CI 0.8–5.6%), respectively, with fluid ingestion compared with no fluid intake. The associated performance benefits were observed when the rates of fluid intake were in the range of 0.15–0.20 mL/kg body mass/min for >1 to ≤2 h cycling exercise and ad libitum or 0.14–0.27 mL/kg body mass/min for cycling exercise >2 h.

Conclusions

A rate of fluid consumption of between 0.15 and 0.34 mL/kg body mass/min during high-intensity 1 h cycling exercise is associated with reductions in ECP. When cycling at moderate intensity for >1 to ≤2 h, cyclists should expect a gain in performance of at least 2% if fluid is consumed at a rate of 0.15–0.20 mL/kg body mass/min. For cycling exercise >2 h conducted at moderate intensity, consuming fluid ad libitum or at a rate of 0.14–0.27 mL/kg body mass/min should improve performance by at least 3%. Until further research is conducted, these recommendations should be used as a guide to inform hydration practices.

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The Impact of Resistance Training on Swimming Performance: A Systematic Review

Abstract

Background

The majority of propulsive forces in swimming are produced from the upper body, with strong correlations between upper body strength and sprint performance. There are significant gaps in the literature relating to the impact of resistance training on swimming performance, specifically the transfer to swimming performance.

Objective

The aims of this systematic literature review are to (1) explore the transfer of resistance-training modalities to swimming performance, and (2) examine the effects of resistance training on technical aspects of swimming.

Methods

Four online databases were searched with the following inclusion criteria: (1) journal articles with outcome measures related to swimming performance, and (2) competitive swimmers participating in a structured resistance-training programme. Exclusion criteria were (1) participants with a mean age <16 years; (2) untrained, novice, masters and paraplegic swimmers; (3) triathletes and waterpolo players; (4) swimmers with injuries or illness; and (5) studies of starts and turns specifically. Data were extracted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the Physiotherapy Evidence Database (PEDro) scale was applied.

Results

For optimal transfer, specific, low-volume, high-velocity/force resistance-training programmes are optimal. Stroke length is best achieved through resistance training with low repetitions at a high velocity/force. Resisted swims are the most appropriate training modality for improving stroke rate.

Conclusion

Future research is needed with respect to the effects of long-term resistance-training interventions on both technical parameters of swimming and overall swimming performance. The results of such work will be highly informative for the scientific community, coaches and athletes.

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Exercise Interventions for the Prevention and Treatment of Groin Pain and Injury in Athletes: A Critical and Systematic Review

Abstract

Background

Groin injury is a common musculoskeletal complaint for athletes competing in a variety of sports. The extent to which exercise interventions incorporating external load are an appropriate option for the treatment and prevention of groin injury in athletes is not yet clear.

Objectives

The aim of this review was to describe and evaluate exercise therapy interventions and outcomes for the treatment and prevention of groin injury with specific attention to application of external load.

Data Sources

The databases Medline, PubMed, SPORTDiscus, Web of Science, and Cochrane were searched on 18 April 2016.

Study Eligibility Criteria

This review was registered as PROSPERO CRD42016037752 and a systematic search was conducted with the following inclusion criteria: any study design evaluating exercise interventions for the prevention or treatment of groin pain in athletes.

Data Analysis

Two independent authors screened search results, performed data extraction, assessed risk of bias using the modified Downs and Black appraisal tool and determined strength and level of evidence. Reporting standards for exercise interventions were assessed using the Consensus for Exercise Reporting Template (CERT).

Results

A total of 1320 titles were identified with 14 studies satisfying the inclusion criteria, four (29%) of which demonstrated low risk of bias. Ten (71%) studies utilised external load as a component of the exercise intervention. Reporting standards for exercise intervention scores ranged from 0 to 63%.

Conclusion

There is limited evidence from level 2 and 3 studies indicating exercise therapy may reduce the incidence and hazard risk of sustaining a groin injury in athletes. There is strong evidence from level 4 studies indicating exercise therapy is beneficial as a treatment for groin injury in athletes in terms of symptom remission, return to sport and recurrence outcomes. However, there are limited studies with low risk of bias, and exercise interventions for the treatment of groin injury are poorly described.

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ACEP marks EMS Week with CPR challenge, 'Safe Citizen Day'

American College of Physicians WASHINGTON — The American College of Emergency Physicians is promoting two new consumer campaigns in this year's EMS Week: The World CPR Challenge and Safe Citizen Day. EMS Week's theme for 2017 is "Always in Service," and is intended to raise awareness of and celebrate the men and women of EMS, such as paramedics, EMTs and other first responders ...

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Autosomal dominant frontometaphyseal dysplasia: Delineation of the clinical phenotype

Frontometaphyseal dysplasia (FMD) is caused by gain-of-function mutations in the X-linked gene FLNA in approximately 50% of patients. Recently we characterized an autosomal dominant form of FMD (AD-FMD) caused by mutations in MAP3K7, which accounts for the condition in the majority of patients who lack a FLNA mutation. We previously also described a patient with a de novo variant in TAB2, which we hypothesized was causative of another form of AD-FMD. In this study, a cohort of 20 individuals with AD-FMD is clinically evaluated. This cohort consists of 15 individuals with the recently described, recurrent mutation (c.1454C>T) in MAP3K7, as well as three individuals with missense mutations that result in substitutions in the N-terminal kinase domain of TGFβ-activated kinase 1 (TAK1), encoded by MAP3K7. Additionally, two individuals have missense variants in the gene TAB2, which encodes a protein with a close functional relationship to TAK1, TAK1-associated binding protein 2 (TAB2). Although the X-linked and autosomal dominant forms of FMD are very similar, there are distinctions to be made between the two conditions. Individuals with AD-FMD have characteristic facial features, and are more likely to be deaf, have scoliosis and cervical fusions, and have a cleft palate. Furthermore, there are features only found in AD-FMD in our review of the literature including valgus deformity of the feet and predisposition to keloid scarring. Finally, intellectual disability is present in a small number of subjects with AD-FMD but has not been described in association with X-linked FMD.

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Adaptive and maladaptive functioning in Kleefstra syndrome compared to other rare genetic disorders with intellectual disabilities

Detailed neurobehavioural profiles are of major value for specific clinical management, but have remained underexposed in the population with intellectual disabilities (ID). This was traditionally classified based on IQ level only. Rapid advances in genetics enable etiology based stratification in the majority of patients, which reduces clinical heterogeneity. This paper illustrates that specific profiles can be obtained for rare syndromes with ID. Our main aim was to study (mal)adaptive functioning in Kleefstra Syndrome (KS) by comparing and contrasting our findings to three other subgroups: Koolen-de Vries Syndrome, GATAD2B-related syndrome, and a mixed control group of individuals with ID. In total, we studied 58 individuals (28 males, 30 females) with ID; 24 were diagnosed with KS, 13 with Koolen-de Vries Syndrome, 6 with the GATAD2B-related syndrome, and 15 individuals with undefined neurodevelopmental disorders. All individuals were examined with a Vineland Adaptive Behavior Scale, mini PAS-ADD interview, and an Autism Diagnostic Observation Schedule to obtain measures of adaptive and maladaptive functioning. Each of the three distinctive genetic disorders showed its own specific profile of adaptive and maladaptive functioning, while being contrasted mutually. However, when data of the subgroups altogether are contrasted to the data of KS, such differences could not be demonstrated. Based on our findings, specific management recommendations were discussed for each of the three syndromes. It is strongly suggested to consider the genetic origin in individuals with congenital neurodevelopmental disorders for individual based psychiatric and behavioral management.

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Recurrent ATP2A2 p.(Pro602Leu) mutation differentiates Acrokeratosis verruciformis of Hopf from the allelic condition Darier disease

Darier disease and Acrokeratosis Verruciformis of Hopf (AKV) are rare disorders of keratinization with autosomal dominant inheritance and very distinct clinical pictures. Both have been shown to be caused by mutations in ATP2A2 (ATPase, Ca⁺⁺ transporting, cardiac muscle, slow-twitch) a gene encoding one of the SERCA (sarcoplasmic/endoplasmic reticulum calcium ATPase2) intracellular pumps with a crucial role in cell-to-cell adhesion in both skin and heart. While hundreds of different missense and nonsense mutations cause Darier disease, only one missense mutation, p.(Pro602Leu), has been identified in families with AKV. We report a family with AKV due to the p.(Pro602Leu) mutation and discuss implications for this recurrent mutation on knowledge of ATP2A2 structure and function.

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Study: Apple Watch can detect abnormal heart rhythm

The study achieved 97 percent accuracy in the ability to find irregular heart activity

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EMS rehab sector: Treating heat illness treatment on the fireground

Here's a look at what some of the changes in the revised NFPA 1584 mean for fireground rehab procedures, especially for heat-related illnesses

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UK anaesthetists’ perspectives and experiences of severe perioperative anaphylaxis: NAP6 baseline survey †

Abstract

Background: There is limited information on UK anaesthetists' perspectives and experiences of perioperative anaphylaxis. This baseline survey of the Sixth National Audit Project (NAP6) aimed to identify relevant departmental preparedness and practices, and individual experiences, perceptions and drug-avoidance patterns.Methods: All anaesthetists in 356 UK NHS hospitals were invited to complete an electronic survey.Results: 11 104 anaesthetists (77% crude response rate) from 341 (96%) hospitals responded. Most had immediate access to guidelines for anaphylaxis treatment (87%) and established referral pathways for investigation (82%), but a minority reported access to designated treatment packs (37%) or an anaphylaxis lead (35%). Anaesthetists reported 1734 cases of suspected perioperative anaphylaxis in 2014–5 of which 81% were referred for specialist investigation and 14% reported to the Medicines and Healthcare Products Regulatory Agency (MHRA). In their career, 76% of respondents had seen a case of perioperative anaphylaxis (1:7.25 years of practice) and 4% reported a death (1:311 years of practice), equivalent to 2.3% of events being fatal. Agents most frequently perceived to cause anaphylaxis were antibiotics, particularly penicillins, and neuromuscular blocking agents, notably rocuronium. Suxamethonium and penicillins were avoided by a higher proportion of respondents than events attributed to these drugs whereas the converse was true for atracurium and teicoplanin.Conclusions: This is the largest ever survey of anaesthetists' practices and experiences relating to perioperative anaphylaxis. It identifies gaps in preparedness and referral for further investigation and to the UK MHRA. It provides important data about drugs implicated in such events and anaesthetists' attitudes to anaphylaxis.

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Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries

British Journal of Anaesthesia, 2016; 117(5): 601–9, DOI10.1093/bja/aew316

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Patient reported outcome of adult perioperative anaesthesia in the United Kingdom: a cross-sectional observational study

British Journal of Anaesthesia, 2016; 117(6): 758–66, DOI 10.1093/bja/aew381

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Assessment of standard laboratory tests and rotational thromboelastometry for the prediction of postoperative bleeding in liver transplantation

Abstract

Background. Perioperative bleeding remains a major challenge in liver transplantation. We aimed to compare standard laboratory tests with thromboelastometry (ROTEM^®) with regard to their ability to predict postoperative non-surgical bleeding.Methods. Data from 243 adult liver transplant recipients from January 2012 to May 2014 were evaluated retrospectively. Upon admission to the intensive care unit, coagulation status was assessed using standard laboratory tests [prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and platelet count] and ROTEM^® whole blood coagulation assays. Bleeding was defined as transfusion of ≥ 3 units of red blood cells or reoperation for non-surgical bleeding within 48 h after transplantation. Coagulation test results were analysed using receiver operating characteristics (ROC) in order to identify variables predictive of postoperative bleeding. Coagulation management was based on ROTEM^®-guided factor concentrate treatment.Results. The overall incidence of bleeding was 12.3% (n=30). Twenty-three (9.5%) patients underwent reoperation and seven (2.9%) received ≥3 units of red blood cells and non-operative management. Standard laboratory tests predictive of postoperative bleeding were aPTT and PT [area under the ROC curve (AUC) 0.688 and 0.623, respectively]. Tests predictive of bleeding with ROTEM^® were CT_EXTEM, CFT_INTEM, A10_FIBTEM, and MCF_FIBTEM, with AUCs of 0.682, 0.615, 0.615, and 0.611, respectively. Fibrinogen concentration, platelet count, and other ROTEM^® variables failed to demonstrate predictive value for postoperative bleeding (AUC <0.6). Dialysis-dependent kidney failure, 30 day mortality, and median model for endstage liver disease score were all significantly higher in bleeding patients.Conclusions. Although both postoperative standard laboratory tests and ROTEM^® assays could identify patients at risk for postoperative bleeding, ROTEM^® assays demonstrated a greater predictive value for impaired fibrinogen polymerization-related coagulopathy.

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Part-Time Paramedic Needed to Assist Anesthesiologist - Northeast Dental Anesthesia Associates

We are looking to hire another member to our team of paramedics. We are a dental anesthesia practice that provides anesthesia for pediatric dental patients. Our anesthesia assistants are Medics/Firefighters/Nurses looking to fill their schedules in a different environment. Responsibilities as a Paramedic/Anesthesia Assistant: *Assist during the induction phase of the case (managing airway during IV ...

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Utility and reliability of non-invasive muscle function tests in high-fat fed mice

Abstract

Non-invasive tests are commonly used for assessing muscle function in animal models. The value of these tests in obesity, a condition where muscle strength is reduced, is unclear. We investigated the utility of three non-invasive muscle function tests, namely grip strength (GS), hang wire (HW), and four-limb hanging (FLH) in C57BL/6 mice fed chow (n = 48) or high-fat diet (HFD, n = 48) for 20 weeks. Muscle function tests were performed at 5, 10, and 20 weeks. After 10 and 20 weeks, HFD mice had significantly reduced GS (10 weeks chow:1.89 ± 0.1, HFD:1.79 ± 0.1; 20 weeks chow:1.99 ± 0.1, HFD:1.75 ± 0.1N), FLH (10 weeks chow:2552 [1337–4964], HFD:1230 [749–1994]; 20 weeks chow:2048 [765–3864], HFD:1036 [717–1855] seconds*gram body weight) and HW reaches (10 weeks chow:4 [2–5], HFD:2 [1–3]; 20 weeks chow:3 [1–5], HFD:1 [0–2] (n)) and higher falls (10 weeks: chow:0 [0–2], HFD:3 [1–7]; 20 weeks chow:1 [0–4], HFD:8 [5–10] (n)). GS was reliable in both dietary groups (Intraclass Correlation Coefficient (ICC) = 0.5–0.8; P < 0.05) whereas FLH showed good reliability in chow (ICC = 0.7; P < 0.05) but not in HFD mice after 10 weeks (ICC < 0.5). Our data demonstrate that non-invasive muscle function tests are valuable and reliable tools for assessment of muscle strength and function in high-fat fed mice.

This article is protected by copyright. All rights reserved

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Safety and efficacy of sofosbuvir-based DAA regimens for hepatitis C virus genotypes 1 - 4 and 6 in Myanmar: Real-world experience

Journal of Viral Hepatitis

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Looking to cut back on salt? Study says don't start with the shaker

Reuters Health News

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The SAFE-T assessment tool: Derivation and validation of a web-based application for point-of-care evaluation of gastroenterology fellow performance in colonoscopy

Gastrointestinal Endoscopy

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REFILE-In Europe, US, modern AIDS drugs add extra 10 years of life expectancy

Reuters Health News

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Examining the role of patient values in decisions about long-term enteral feeding: A qualitative study

Clinical Nutrition

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As infliximab use for ulcerative colitis has increased, so has the rate of surgical resection

Journal of Gastrointestinal Surgery

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The impact of perioperative fluid therapy on short-term outcomes and 5-year survival among patients undergoing colorectal cancer surgery: A prospective cohort study within an ERAS protocol

European Journal of Surgical Oncology

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Efficacy and safety outcomes of sofosbuvir-based treatment regimens for hepatitis C virus-infected patients with or without cirrhosis from phase III clinical trials

Therapeutics and Clinical Risk Management

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18F-Fluorodeoxyglucose uptake on positron emission tomography/computed tomography is associated with metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma

Clinical and Experimental Metastasis

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Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease

World Journal of Gastroenterology

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Esophagogastric junction in systemic sclerosis: A study with the functional lumen imaging probe

Neurogastroenterology & Motility

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Concurrent infection with hepatitis C virus and Streptococcus pneumoniae

Emerging Infectious Diseases

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ACA exchanges grow thinner with Aetna leaving for 2018

AP

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Early hepatitis B viral DNA clearance predicts treatment response at week 96

World Journal of Gastroenterology

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Variability in outcomes after gastroschisis closure across U.S. childrens hospitals

Journal of Pediatric Surgery

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The ethnic distribution of sessile serrated polyps in the United States is inversely associated with H. pylori prevalence

Colorectal Disease

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Promoting notification and linkage of HBs antigen and anti-HCV antibody-positive patients through hospital alert system

BMC Infectious Diseases

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Additive effect of non-alcoholic fatty liver disease on the development of diabetes in individuals with metabolic syndrome

Diabetes Research and Clinical Practice

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Financial incentives for adherence to HCV clinical care and treatment: A randomized trial of two strategies

Open Forum Infectious Diseases

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In irritable bowel syndrome, postprandial abdominal distention is associated with a reduction of intestinal tone

Neurogastroenterology & Motility

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Acquiring research-grade ERPs on a shoestring budget: A comparison of a modified Emotiv and commercial SynAmps EEG system

Abstract

This study compared the performance of a low-cost wireless EEG system to a research-grade EEG system on an auditory oddball task designed to elicit N200 and P300 ERP components. Participants were 15 healthy adults (6 female) aged between 19 and 40 (M = 28.56; SD = 6.38). An auditory oddball task was presented comprising 1,200 presentations of a standard tone interspersed by 300 trials comprising a deviant tone. EEG was simultaneously recorded from a modified Emotiv EPOC and a NeuroScan SynAmps RT EEG system. The modifications made to the Emotiv system included attaching research grade electrodes to the Bluetooth transmitter. Additional modifications enabled the Emotiv system to connect to a portable impedance meter. The cost of these modifications and portable impedance meter approached the purchase value of the Emotiv system. Preliminary analyses revealed significantly more trials were rejected from data acquired by the modified Emotiv compared to the SynAmps system. However, the ERP waveforms captured by the Emotiv system were found to be highly similar to the corresponding waveform from the SynAmps system. The latency and peak amplitude of N200 and P300 components were also found to be similar between systems. Overall, the results indicate that, in the context of an oddball task, the ERP acquired by a low-cost wireless EEG system can be of comparable quality to research-grade EEG acquisition equipment.

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Inducing unconscious stress: Cardiovascular activity in response to subliminal presentation of threatening and neutral words

Abstract

Stress-related cognitive processes may occur outside of awareness, here referred to as unconscious stress, and affect one's physiological state. Evidence supporting this idea would provide necessary clarification of the relationship between psychological stress and cardiovascular (CV) health problems. We tested the hypothesis that increases in mean arterial pressure (MAP) and total peripheral resistance (TPR) and decreases in heart rate variability (HRV) would be larger when threatening stimuli are presented outside of awareness, or subliminally, compared with neutral stimuli. Additionally, it was expected that trait worry and resting HRV, as common risk factors for CV disease, would moderate the effect. We presented a subliminal semantic priming paradigm to college students that were randomly assigned to the threat (n = 56) or neutral condition (n = 60) and assessed changes from baseline of MAP, TPR, and HRV. Level of trait worry was assessed with the Penn State Worry Questionnaire. The findings indicate that CV activity changed according to the hypothesized pattern: A higher MAP and TPR and a lower HRV in the threat condition compared with the neutral condition were found with practically meaningful effect sizes. However, these findings were only statistically significant for TPR. Furthermore, changes in CV activity were not moderated by trait worry or resting HRV. This is the first study to explicitly address the role of subliminally presented threat words on health-relevant outcome measures and suggests that unconscious stress can influence peripheral vascular resistance.

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