Παρασκευή, 22 Σεπτεμβρίου 2017

Are we practicing anesthesia in a 'current' manner?.

No abstract available

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Safety and efficacy of epidural analgesia.

Purpose of review: Epidural analgesia remains a widely used analgesic technique. This article aims to assess the safety of epidural analgesia by balancing efficacy and complications, of epidural analgesia for acute, labor and chronic pain. Recent findings: Main indications for epidural analgesia include major open abdominal surgery, thoracotomy and labor analgesia. Past and current literature show that epidural analgesia leads to statistically significant, but possibly clinically less meaningful, reductions in pain scores compared with intravenous analgesia. The debate continues whether epidural analgesia leads to decreased complications and improved outcome. Noninferiority of alternative regional analgesic approaches, that is continuous-wound-infiltration, peripheral nerve blocks or surgical site infiltration, appears to be present and is promising for the future. Serious adverse events after epidural analgesia seem to occur more often than was previously thought and clinicians must realize that incidence rates differ in specific perioperative patient populations. Summary: Epidural analgesia for obstetric analgesic purposes is considered to be well tolerated in young, healthy women, since efficacy has been proven and complications leading to permanent neurological damage seldomly occur. Safety of epidural analgesia for perioperative and chronic pain treatment is more difficult to balance; careful selection of appropriate patients cannot be over-emphasized. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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New advancements in spinal cord stimulation for chronic pain management.

Purpose of review: To update the recent development of spinal cord stimulation (SCS) technology in the management of chronic pain. Recent Findings: Efficacy of SCS therapy has been significantly improved by the recent development of high frequency (HF-10 kHz) stimulation, burst stimulation, and dorsal root ganglion (DRG) stimulation. A few latest SCS modalities are in clinical trial. New approaches to guide lead placement and advances in surgical lead are introduced. Summary: HF-10 SCS is free of paresthesia and associated with significantly better coverage of axial lower back pain. Burst stimulation invokes minimal paresthesia and provides better coverage of low back pain. DRG stimulation results in better outcomes in patients with complex regional pain syndrome. It requires less energy and delivers consistent stimulation regardless of postural variations. Clinical trials with new SCS modalities, such as Stimwaves, are under way to make SCS wireless. Intraoperative neuromonitoring and paresthesia atlas may be used to guide lead placement. Multicolumn surgical paddle leads enable a combination of independent current control with up to 32 contacts for better programming and better coverage. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Nonoperating room anesthesia for endoscopic procedures.

Purpose of review: The purpose of this review is to take a look on some practical aspects of anesthetic care in the endoscopy suite, concerning the general approach, safety, and monitoring issues. Recent findings: Concerning propofol popularity for sedation during endoscopic procedures new studies create doubt in the safety of higher doses of propofol used for sedation. Careful titration of propofol, addition of synergistic supplements like ketamine and dexmedetomidine, and monitoring of anesthetic depth may limit the dose of propofol given to the patients. Capnography has the potential to detect airway compromise earlier than pulse-oximetry and by this enhancing patient safety. Summary: Sedation or anesthesia in the endoscopy suite is not without risk. For complex and longer lasting procedures and in patients with significant comorbidities and risk factors, good clinical judgment, built on experience, is essential and to foster this, it seems prudent to build up a group of anesthesiologists dedicated to a special sedation service. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Enhancing the quality and safety of the perioperative patient.

Purpose of review: Many possible hazards bedevil the perioperative patient. This review focuses on a number of aspects of perioperative management where the patient's quality and safety can be enhanced. Recent findings: Our understanding of the relationship between preoperative preparation and postoperative outcomes has improved. There have also been recent developments in our understanding of how to construct useful cognitive aids and make the best use of checklists by understanding the cultural environment supporting their use. Postoperatively, the concept of 'failure to rescue' in the surgical patients has been explored. Summary: A clear vision of what postoperative recovery should mean for practitioner and patients; careful risk stratification and prophylactic measures to avoid postoperative complications; the judicious use of checklists and other cognitive aids to complement clinical expertise in promoting safety within each local context; and the prompt recognition and rescue of postoperative problems when they occur are all important aspects of a safe perioperative care. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Optimizing education in difficult airway management: meeting the challenge.

Purpose of review: The last 2 decades have seen a vast change in the science and technology of airway management. As a result, there is an increasing need to equip anesthesiologists with the new knowledge and skills for the safe management of a difficult airway. Recent findings: In addition to knowledge and expertise, human factors and nontechnical skills (NTS), including situational awareness, communication and team work, play an important role during difficult airway management and contribute to the outcome. Didactic sessions are useful to impart knowledge. Self-learning, interactive discussions, simulation and debriefing are important tools for teaching and training in difficult airway management. Manikin training and simulation enable development of technical as well as NTS without subjecting patients to risk and allow multiple training sessions of relatively uncommon scenarios. Guidelines are useful teaching tools, whereas cognitive tools such as the Vortex approach may be useful during a difficult airway. Summary: There is need for research on difficult airway management and optimized training methods. Research is also required to determine the barriers to adoption of guidelines and strategies to ensure widespread dissemination and implementation of guidelines and best practices for difficult airway management. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Are we fully utilizing the functionalities of modern operating room ventilators?.

Purpose of review: The modern operating room ventilators have become very sophisticated and many of their features are comparable with those of an ICU ventilator. To fully utilize the functionality of modern operating room ventilators, it is important for clinicians to understand in depth the working principle of these ventilators and their functionalities. Recent findings: Piston ventilators have the advantages of delivering accurate tidal volume and certain flow compensation functions. Turbine ventilators have great ability of flow compensation. Ventilation modes are mainly volume-based or pressure-based. Pressure-based ventilation modes provide better leak compensation than volume-based. The integration of advanced flow generation systems and ventilation modes of the modern operating room ventilators enables clinicians to provide both invasive and noninvasive ventilation in perioperative settings. Ventilator waveforms can be used for intraoperative neuromonitoring during cervical spine surgery. Summary: The increase in number of new features of modern operating room ventilators clearly creates the opportunity for clinicians to optimize ventilatory care. However, improving the quality of ventilator care relies on a complete understanding and correct use of these new features. Video abstract: http://ift.tt/2hpXORl. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Anesthesia information management: clinical decision support.

Purpose of review: Perioperative informatics tools continue to be developed at a rapid pace and offer clinicians the potential to greatly enhance clinical decision making. The goal of this review is to bring the reader updates on perioperative information management and discuss future research directions in the field. Recent findings: Clinical decision support tools become more timely, accurate, and, in some instances, have been shown to improve patient outcomes. When correctly implemented, they are critical tools for optimization of perioperative care. Summary: Perioperative informaticians continue to test new and innovative ways to enhance the delivery of anesthesia care, improving the safety and efficacy of perioperative management. Future work will continue to refine tools to ensure that perioperative informatics provides clinicians timely and accurate feedback, with demonstrable evidence that a decision support system improves patient outcomes. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Clinical prediction rules: the importance of the validation phase

Commentary On: Hicks K.E., Zhao Y., Fallah N, Rivers C, Noonan V, Plashkes T, Wai EK, Roffey DM, Tsai E, Paquet J, Attabib N, Marion T, Ahn H, Phan P. A simplified clinical prediction rule for prognosticating independent walking after spinal cord injury: a prospective study from a Canadian multicenter spinal cord injury registry. The Spine Journal. Article in press.

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Editorial Board



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Advice to give advice

COMMENTARY ON: Matthew L. Stevens, Chung-Wei C. Lin, Flavia A. de Carvalho, Kevin Phan, Bart Koes, Chris G. Maher. Advice for acute low back pain: A comparison of what research supports and what guidelines recommend. The Spine Journal, In Press.

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Table of Contents



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Table of Contents



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Meetings Calendar



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Table of Contents



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Table of Contents



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Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs.

Objectives: Dyslipidemia represents a major health issue in psychiatry. We determined whether weighted polygenic risk scores (wPRSs) combining multiple single-nucleotide polymorphisms (SNPs) associated with lipid levels in the general population are associated with lipid levels [high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides] and/or dyslipidemia in patients receiving weight gain-inducing psychotropic drugs. We also determined whether genetics improve the predictive power of dyslipidemia. Patients and methods: The influence of wPRS on lipid levels was firstly assessed in a discovery psychiatric sample (n=332) and was then tested for replication in an independent psychiatric sample (n=140). The contribution of genetic markers to predict dyslipidemia was evaluated in the combined psychiatric sample. Results: wPRSs were significantly associated with the four lipid traits in the discovery (P

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Short progressive muscle relaxation or motor coordination training does not increase performance in a brain-computer interface based on sensorimotor rhythms (SMR)

Publication date: November 2017
Source:International Journal of Psychophysiology, Volume 121
Author(s): L. Botrel, L. Acqualagna, B. Blankertz, A. Kübler
Brain computer interfaces (BCIs) allow for controlling devices through modulation of sensorimotor rhythms (SMR), yet a profound number of users is unable to achieve sufficient accuracy. Here, we investigated if visuo-motor coordination (VMC) training or Jacobsen's progressive muscle relaxation (PMR) prior to BCI use would increase later performance compared to a control group who performed a reading task (CG). Running the study in two different BCI-labs, we achieved a joint sample size of N=154 naïve participants. No significant effect of either intervention (VMC, PMR, control) was found on resulting BCI performance. Relaxation level and visuo-motor performance were associated with later BCI performance in one BCI-lab but not in the other. These mixed results do not indicate a strong potential of VMC or PMR for boosting performance. Yet further research with different training parameters or experimental designs is needed to complete the picture.



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P 20 fMRI-associations with performance increase by mental imagery training of finger sequence

Motor imagery (MI) is the mental simulation of action frequently used by professionals in different fields. The knowledge about changes in functional representation of motor patterns trained with mental imagery is sparse. In addition, we do not know how changes in functional representation during imagery training are associated with preciseness of imagined performance. We therefore intended to investigate changes in functional representation going along with performance changes (error, velocity) during a highly controlled (for intensity and temporal accuracy) mental imagery training (finger sequence performance) in 51 healthy young volunteers.

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P 22 Defining the role of imaging methods in diagnostics symptomatic epilepsy in children

Defining the role of MRI and CT in the comprehensive assessment of the state of the central nervous system in children with symptomatic epilepsy.

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P 21 Specific indicators of diffusion weighted magnetic resonance imaging in child cerebral palsy with symptomatic epilepsy

was to determine the characteristics of diffusion weighted Magnetic Resonance imaging indicators in children with symptomatic epilepsy with cerebral palsy.

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P 19 Left posterior inferior frontal gyrus is causally involved in complex sentence comprehension

Storage and reordering of words are two core processes required for successful sentence comprehension. Storage is necessary whenever the verb and its arguments (i.e., subject and object) are separated over a long distance, while reordering is necessary whenever the argument order is atypical (e.g., object-first order in German, where subject-first order is typical). Previous neuroimaging work (Meyer et al., 2012) has associated storage with the left planum temporale (PT), and reordering with the left posterior inferior frontal gyrus (pIFG).

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Detection of copy number variations in epilepsy using exome data

Epilepsies are common neurological disorders and genetic factors contribute to their pathogenesis. Copy number variations (CNVs) are increasingly recognized as an important etiology of many human diseases including epilepsy. Whole exome sequencing (WES) is becoming a standard tool for detecting pathogenic mutations and has recently been applied to detecting CNVs. Here, we analyzed 294 families with epilepsy using WES, and focused on 168 families with no causative single nucleotide variants (SNVs) in known epilepsy-associated genes to further validate CNVs using two different CNV detection tools using WES data. We confirmed 18 pathogenic CNVs, and two deletions and two duplications at chr15q11.2 of clinically unknown significance. Of note, we were able to identify small CNVs less than 10 kb in size, which might be difficult to detect by conventional microarray. We revealed two cases with pathogenic CNVs that one of the two CNV detection tools failed to find, suggesting that using different CNV tools is recommended to increase diagnostic yield. Considering a relatively high discovery rate of CNVs (18 out of 168 families, 10.7%) and successful detection of CNV with <10 kb in size, CNV detection by WES may be able to surrogate, or at least complement, conventional microarray analysis.

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WES was performed in a total of 294 families with epilepsy. Then, WES-based CNV detection in 168 families were conducted after excluding 126 families with causative SNVs, and 18 families with pathogenic CNVs were identified. CNVs were detected in two ways: 1) two-step detection: XHMM and subsequent Nord's method (left in a dotted box), and 2) Nord's method targeting 303 epilepsy genes (right in a dotted box). Seventeen and one pathogenic CNVs were detected by methods 1) and 2), respectively. [WES: whole exome sequencing, CNV: copy number variation, SNV: single nucleotide variant, XHMM: eXome Hidden Markov Model]



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INPP5K variant causes autosomal recessive congenital cataract in a Pakistani family

Congenital cataract (CC) is clinically and genetically highly heterogeneous. Here, we enrolled a consanguineous kindred (LUCC15) from Pakistan, with three affected individuals suffering with CC. Exome sequencing revealed a transition mutation [c.149T>C; p.(Ile50Thr)] in INPP5K. Inositol polyphosphate-5-phosphatase K, encoded by INPP5K, is involved in dephosphorylation of phosphatidylinositol (PtdIns) 4,5-bisphosphate, and PtdIns 3,4,5-trisphosphate. Recently, pathogenic variants in INPP5K have been reported in families with congenital muscular dystrophies, intellectual disability, and cataract. In our family LUCC15, mild to moderate intellectual disability along with speech impairment was observed in two affected individuals. Magnetic resonance imaging of brain and muscles tissues did not reveal any cerebellar or muscular atrophy. However, electromyography of both upper and lower limbs revealed irritable myopathy. Comparison of clinical phenotype of all the known affected individuals, including LUCC15 family, homozygous for INPP5K alleles revealed reduced penetrance of muscular dystrophy and intellectual disability. Similarly, skeletal muscle abnormalities were highly variable among inpp5ka zebrafish mutants analyzed in this study. These phenotypic variabilities may be due to epigenetic factors and/or genetic modifiers.

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Expanding the genetic heterogeneity of intellectual disability

Abstract

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease–gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.



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Ultrasound-guided versus landmark-guided local corticosteroid injection for carpal tunnel syndrome: A systematic review and meta-analysis of randomized controlled clinical trials

Publication date: Available online 21 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Arash Babaei-Ghazani, Peyman Roomizadeh, Bijan Forogh, Seyed-Mohammad Moeini-Taba, Amin Abedini, Mona Kadkhodaie, Fateme Jahanjoo, Bina Eftekharsadat
ObjectiveTo review the literature and assess the comparative effectiveness of ultrasound-guided versus landmark-guided local corticosteroid injections in patients with carpal tunnel syndrome (CTS).Data SourcesCochrane Central Register of Controlled Trials, MEDLINE (PubMed), EMBASE (Ovid), and Web of Science (from inception to 1 February 2017).Study SelectionRandomized controlled trials (RCTs) comparing ultrasound-guided injection to landmark-guided injection in patients with CTS were included.Data ExtractionTwo authors independently screened abstracts and full texts. The Outcomes of interest were symptom severity scale (SSS) and functional status scale (FSS) scores of Boston Carpal Tunnel Questionnaire as well as four electro-diagnostic parameters including compound muscle action potential (CMAP), sensory nerve action potential (SNAP), distal motor latency (DML), and distal sensory latency (DSL).Data SynthesisOverall, 569 abstracts were retrieved and checked for eligibility and finally 3 RCTs were included (181 injected hands). Pooled analysis showed that ultrasound-guided injection was more effective in SSS improvement (mean difference [MD] = -0.46, 95% confidence interval (CI) = -0.59 to -0.32, P<0.00001); whereas, no significant difference was observed between the two methods in terms of FSS (MD= -0.25, 95%CI= -0.56 to 0.05, P=0.10). There were also no statistically significant differences in improvements of CMAP (MD=1.54, 95%CI=0.01 to 3.07, P=0.05), SNAP (MD= -0.02, 95%CI= -6.27 to 6.23, P=1.00), DML (MD=0.05, 95% CI= -0.30 to 0.39, P=0.80) or DSL (MD=0.00, 95%CI= -0.65 to 0.65, P=1.00).ConclusionsThis review suggested that ultrasound-guided injection was more effective than landmark-guided injection in symptom severity improvement in patients with CTS; however, no significant differences were observed in functional status or electro-diagnostic improvements between the two methods.



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Home Health Agency Characteristics and Quality Outcomes for Medicare Beneficiaries with Rehabilitation-Sensitive Conditions

Publication date: Available online 21 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Tracy M. Mroz, Ann Meadow, Elizabeth Colantuoni, Bruce Leff, Jennifer L. Wolff
ObjectiveTo examine associations between organizational characteristics of home health agencies (e.g., profit status, rehabilitation therapy staffing model, size, and rurality) and quality outcomes among Medicare beneficiaries with rehabilitation-sensitive conditions, conditions for which occupational, physical, and/or speech therapy have the potential to improve functioning, prevent or slow substantial decline in functioning, or increase ability to remain at home safely.Design, Setting, and ParticipantsRetrospective analysis of Medicare administrative data for 1,006,562 fee-for-service beneficiaries admitted to 9,250 Medicare-certified home health agencies in 2009.InterventionsNot applicable.Main Outcome MeasuresInstitutional admission during home health, community discharge, and institutional admission within 30 days of discharge.ResultsNonprofit (versus for-profit) home health agencies were more likely to discharge beneficiaries to the community (OR 1.23, 95%CI: 1.13-1.33) and less likely to have beneficiaries incur institutional admissions within 30 days of discharge (OR 0.93, 95%CI: 0.88-0.97). Agencies in rural (versus urban) counties were less likely to discharge patients to the community (OR 0.83 95%CI: 0.77-0.90) and more likely to have beneficiaries incur institutional admissions during home health (OR 1.24 95%CI: 1.18-1.30) and within 30 days of discharge (OR 1.15 95%CI: 1.10-1.22). Agencies with contract (versus in-house) therapy staff were less likely to discharge beneficiaries to the community (OR 0.79, 95%CI: 0.70-0.91) and more likely to have beneficiaries incur institutional admissions during home health (OR 1.09 95%CI: 1.03-1.15) and within 30 days of discharge (OR 1.17, 95%CI: 1.07-1.28).ConclusionsAs payers continue to test and implement reimbursement mechanisms that seek to reward value over volume of services, greater attention should be paid to organizational factors that facilitate better coordinated, higher quality home health care for beneficiaries who may benefit from rehabilitation.



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The 22q11.2 deletion syndrome: Cancer predisposition, platelet abnormalities and cytopenias

The 22q11.2 deletion syndrome (DS) is associated with variable phenotypic expression as findings range from severely affected individuals with the classical triad of DiGeorge and velocardiofacial syndromes, including congenital heart disease, immunodeficiency, hypocalcemia, and palatal abnormalities, to subtly affected adults who only come to attention following the diagnosis of a more severely affected child. The multiple manifestations can affect all organ systems, including the hematologic system resulting in baseline lower platelet counts for individuals with 22q11.2DS and increased platelet size. In addition, there may be an associated increased risk of bleeding. Individuals with 22q11.2DS are also at increased risk of autoimmune cytopenias that can complicate the evaluation or management of other manifestations. Finally, there may be an increased risk of malignancy, although the mechanism for this risk is not fully understood. This review summarizes the currently available data on hematologic/oncologic manifestations of 22q11.2DS and reports on our findings within a large cohort of individuals with the deletion.



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Loss-of-function variants in NFIA provide further support that NFIA is a critical gene in 1p32-p31 deletion syndrome: A four patient series

The association between 1p32-p31 contiguous gene deletions and a distinct phenotype that includes anomalies of the corpus callosum, ventriculomegaly, developmental delay, seizures, and dysmorphic features has been long recognized and described. Recently, the observation of overlapping phenotypes in patients with chromosome translocations that disrupt NFIA (Nuclear factor I/A), a gene within this deleted region, and NFIA intragenic deletions has led to the hypothesis that NFIA is a critical gene within this region. The wide application and increasing accessibility of whole exome sequencing (WES) has helped identify new cases to support this hypothesis. Here, we describe four patients with loss-of-function variants in the NFIA gene identified through WES. The clinical presentation of these patients significantly overlaps with the phenotype described in previously reported cases of 1p32-p31 deletion syndrome, NFIA gene disruptions and intragenic NFIA deletions. Our cohort includes a mother and daughter as well as an unrelated individual who share the same nonsense variant (c.205C>T, p.Arg69Ter; NM_001145512.1). We also report a patient with a frameshift NFIA variant (c.159_160dupCC, p.Gln54ProfsTer49). We have compared published cases of 1p32-p31 microdeletion syndrome, translocations resulting in NFIA gene disruption, intragenic deletions, and loss-of-function mutations (including our four patients) to reveal that abnormalities of the corpus callosum, ventriculomegaly/hydrocephalus, macrocephaly, Chiari I malformation, dysmorphic features, developmental delay, hypotonia, and urinary tract defects are common findings. The consistent overlap in clinical presentation provides further evidence of the critical role of NFIA haploinsufficiency in the development of the 1p32-p31 microdeletion syndrome phenotype.



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Expected weight gain for children with microcephalic osteodysplastic primordial dwarfism type II



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Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth restricted fetal sheep

Abstract

Reduced skeletal muscle mass in the IUGR fetus persists into adulthood and may contribute to increased metabolic disease risk. To determine how placental insufficiency with reduced oxygen and nutrient supply to the fetus affects hindlimb blood flow, substrate uptake, and protein accretion rates in skeletal muscle, late gestation CON (n = 8) and IUGR (n = 13) fetal sheep were catheterized with aortic and femoral catheters and a flow transducer around the external iliac artery. Muscle protein kinetic rates were measured using isotopic tracers. Hindlimb weight, linear growth rate, muscle protein accretion rate, and fractional synthetic rate were lower in IUGR compared to CON (P < 0.05). Absolute hindlimb blood flow was reduced in IUGR (IUGR: 32.9 ± 5.6, CON: 60.9 ± 6.5 ml·min−1; P < 0.005), although flow normalized to hindlimb weight was similar between groups. Hindlimb oxygen consumption rate was lower in IUGR (IUGR: 10.4 ± 1.4, CON: 14.7 ± 1.3 μmol·min−1·100 g−1; P < 0.05). Hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was lower in IUGR (IUGR: 1.3 ± 0.5, CON: 2.9 ± 0.2 μmol·min−1·100 g−1; P < 0.05). Blood O2 saturation (R2 = 0.80, P < 0.0001) and plasma glucose (R2 = 0.68, P < 0.0001), insulin (R2 = 0.40, P < 0.005), and IGF-1 (R2 = 0.80, P < 0.0001) were positively associated and norepinephrine (R2 = 0.59, P < 0.0001) was negatively associated with hindlimb weight. Slower hindlimb linear growth and muscle protein synthesis rates match reduced hindlimb blood flow and oxygen consumption rates in the IUGR fetus. Metabolic adaptations to slow hindlimb growth are likely hormonally mediated by mechanisms that include increased fetal norepinephrine and reduced IGF-1 and insulin.

This article is protected by copyright. All rights reserved



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RNA methylation regulates hematopoietic stem and progenitor cell development

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Publication date: Available online 21 September 2017
Source:Journal of Genetics and Genomics
Author(s): Jason Ear, Shuo Lin




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A glycolysis-based ten-gene signature correlates with the clinical outcome, molecular subtype and IDH1 mutation in glioblastoma

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Publication date: Available online 21 September 2017
Source:Journal of Genetics and Genomics
Author(s): Cong Chen, Yu Shi, Yong Li, Zhi-Cheng He, Kai Zhou, Xiao-Ning Zhang, Kai-Di Yang, Jin-Rong Wu, Hsiang-Fu Kung, Yi-Fang Ping, Xiu-Wu Bian
Reprogrammed metabolism is a hallmark of cancer. Glioblastoma (GBM) tumor cells predominantly utilize aerobic glycolysis for the biogenesis of energy and intermediate nutrients. However, in GBM, the clinical significance of glycolysis and its underlying relations with the molecular features such as IDH1 mutation and subtype have not been elucidated yet. Herein, based on glioma datasets including TCGA (The Cancer Genome Atlas), REMBRANDT (Repository for Molecular Brain Neoplasia Data) and GSE16011, we established a glycolytic gene expression signature score (GGESS) by incorporating ten glycolytic genes. Then we performed survival analyses and investigated the correlations between GGESS and IDH1 mutation as well as the molecular subtypes in GBM. The results showed that GGESS independently predicted unfavorable prognosis and poor response to chemotherapy of GBM patients. Notably, GGESS was high in GBMs of mesenchymal subtype but low in IDH1-mutant GBMs. Furthermore, we found that the promoter regions of tumor-promoting glycolytic genes were hypermethylated in IDH1-mutant GBMs. Finally, we found that high GGESS also predicted poor prognosis and poor response to chemotherapy when investigating IDH1-wildtype GBM patients only. Collectively, glycolysis represented by GGESS predicts unfavorable clinical outcome of GBM patients and is closely associated with mesenchymal subtype and IDH1 mutation in GBM.



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Roles for the VCP co-factors Npl4 and Ufd1 in neuronal function in Drosophila melanogaster

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Publication date: Available online 21 September 2017
Source:Journal of Genetics and Genomics
Author(s): Dwayne J. Byrne, Mark J. Harmon, Jeremy C. Simpson, Craig Blackstone, Niamh C. O'Sullivan
The VCP-Ufd1-Npl4 complex regulates proteasomal processing within cells by delivering ubiquitinated proteins to the proteasome for degradation. Mutations in VCP are associated with two neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD), and extensive study has revealed crucial functions of VCP within neurons. By contrast, little is known about the functions of Npl4 or Ufd1 in vivo. Using neuronal-specific knockdown of Npl4 or Ufd1 in Drosophila melanogaster, we infer that Npl4 contributes to microtubule organization within developing motor neurons. Moreover, Npl4 RNAi flies present with neurodegenerative phenotypes including progressive locomotor deficits, reduced lifespan and increased accumulation of TAR DNA-binding protein-43 homolog (TBPH). Knockdown, but not overexpression, of TBPH also exacerbates Npl4 RNAi-associated adult-onset neurodegenerative phenotypes. In contrast, we find that neuronal knockdown of Ufd1 has little effect on NMJ organization, TBPH accumulation or adult behaviour. These findings suggest the differing neuronal functions of Npl4 and Ufd1 in vivo.



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Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures

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Publication date: Available online 21 September 2017
Source:Journal of Genetics and Genomics
Author(s): Daqing Jin, Diqi Zhu, Yabo Fang, Yiwei Chen, Gaihong Yu, Weijun Pan, Dong Liu, Fen Li, Tao P. Zhong
Vascular endothelial growth factor A (Vegfa) signaling regulates vascular development during embryogenesis and organ formation. However, the signaling mechanisms that govern the formation of various arteries/veins in various tissues are incompletely understood. We utilized transcription activator-like effector nuclease (TALEN) to generate zebrafish vegfaa mutants. vegfaa−/− embryos are embryonic lethal, and display a complete loss of the dorsal aorta (DA) and expansion of the cardinal vein. Activation of Vegfa signaling expands the arterial cell population at the expense of venous cells during vasculogenesis of the axial vessels in the trunk. Vegfa signaling regulates endothelial cell (EC) proliferation after arterial-venous specification. Vegfa deficiency and overexpression inhibit the formation of tip cell filopodia and interfere with the pathfinding of intersegmental vessels (ISVs). In the head vasculature, vegfaa‒/‒ causes loss of a pair of mesencephalic veins (MsVs) and central arteries (CtAs), both of which usually develop via sprouting angiogenesis. Our results indicate that Vegfa signaling induces the formation of the DA at the expense of the cardinal vein during the trunk vasculogenesis, and that Vegfa is required for the angiogenic formation of MsVs and CtAs in the brain. These findings suggest that Vegfa signaling governs the formation of diverse arteries/veins by distinct cellular mechanisms in vertebrate vasculatures.



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Key elements for designing and performing a CRISPR/Cas9-based genetic screen

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Publication date: Available online 22 September 2017
Source:Journal of Genetics and Genomics
Author(s): Wanjing Shang, Fei Wang, Gaofeng Fan, Haopeng Wang
Reverse genetic screens are invaluable for uncovering gene functions, but are traditionally hampered by some technical limitations. Over the past few years, since the advent of the revolutionary CRISPR/Cas9 technology, its power in genome editing has been harnessed to overcome the traditional limitations in reverse genetic screens, with successes in various biological contexts. Here, we outline these CRISPR/Cas9-based screens, provide guidance on the design of effective screens and discuss the potential future directions of development of this field.



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Setting the baseline for estimated background observations at IMS systems of four radioxenon isotopes in 2014

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Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Christophe Gueibe, Martin B. Kalinowski, Jonathan Baré, Abdelhakim Gheddou, Monika Krysta, Jolanta Kusmierczyk-Michulec




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Congenital Diarrhea from DGAT1 Mutation Leading to Electrolyte Derangements, Protein-Losing Enteropathy, and Rickets.

No abstract available

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Herpes Simplex Virus Esophagitis in Immunocompetent Children: A Harbinger of Eosinophilic Esophagitis?.

Herpes simplex virus (HSV) is a common cause of infectious esophagitis. The aim of this retrospective study is to identify comorbid and predisposing conditions and sequelae of HSV esophagitis in immunocompetent children. We reviewed sixteen cases of HSV esophagitis diagnosed from January, 1982 to March, 2016. Five patients were immunosuppressed, 11 were immunocompetent and included in the study. Three (27%) had no other significant medical history. Five patients (45%) had repeat biopsies following their HSV infection which showed eosinophilic infiltrate consistent with current diagnostic criteria of eosinophilic esophagitis (EoE), one of whom had known EoE. Environmental allergies and/or asthma were present in 4/5 of these patients. Among the immunocompetent patients, EoE was a co-morbidity in almost half, although biopsies at the time of HSV esophagitis did not show diagnostic features of EoE. Clinical follow-up is therefore warranted for immunocompetent children presenting with HSV esophagitis, particularly those with atopic conditions. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Body Composition Predicts Growth in Infants and Toddlers With Chronic Liver Disease.

This cross-sectional study was conducted on 15 infants and toddlers with chronic liver disease (CLD) to validate arm anthropometry as an accurate measure of body composition (BC) compared to dual-energy X-ray absorptiometry (DXA) and to predict growth from BC. The z-score means of the anthropometric indicators were

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Can Patients with Neonatal Digestive Diseases be Protected from Unnecessary Radiation?.

No abstract available

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Cholangiocarcinoma among Children and Adolescents: A Review of the Literature and SEER-Database Analysis.

Objectives: Cholangiocarcinoma (CCA) is a biliary malignancy found primarily in adults. The incidence of CCA in children is unknown. The aim of this study was to describe characteristics of CCA in children and adolescents. Methods: Using the Surveillance, Epidemiology, and End Results Program (SEER 18) database, we identified incident cases of CCA diagnosed at

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Severe Neonatal Cholestasis in Cerebrotendinous Xanthomatosis: Genetics, Immunostaining, Mass Spectrometry.

Objectives: Cerebrotendinous xanthomatosis (CTX) is caused by defects in sterol 27-hydroxylase (CYP27A1, encoded by CYP27A1), a key enzyme in the bile acid synthesis pathway. CTX usually presents as neurologic disease in adults or older children. The very rare reports of CTX manifest as neonatal cholestasis assess the cholestasis as transient, with patient survival. Our experience differs. Methods: Homozygous or compound heterozygous CYP27A1 mutations were detected in 8 neonatal cholestasis patients by whole exome sequencing, panel sequencing, or Sanger sequencing. Their clinical and biochemical data were retrospectively reviewed. Immunostaining for CYP27A1 was conducted in liver of 4 patients. Mass spectrometry was used to analyze patients' urine samples. Results: All 8 infants had severe cholestasis. Five died from, or were transplanted for, liver failure; 3 cleared their jaundice eventually. Marking for CYP27A1 was weak or absent in 3 of the 4 patient specimens. Mass spectrometry of urine revealed a predominance of sulfated and doubly conjugated (sulfated-glucuronidated) bile alcohols. No patient harbored a putatively pathogenic mutation in genes other than CYP27A1 that have been implicated in cholestatic liver disease. Conclusion: CTX manifest as neonatal cholestasis has a bile acid profile different from CTX manifest in later life, and thus may be overlooked. Immunostaining, mass spectrometry of urine, and genetic studies can support one another in making the diagnosis. A substantial proportion of CTX patients with severe neonatal cholestasis may die or need liver transplantation. CTX manifest in infancy as severe cholestasis warrants further investigation of biochemical diagnostic criteria and best management. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Effects of propofol on wound closure and barrier function of cultured endothelial cells: An in vitro experimental study.

BACKGROUND: Propofol is widely used in routine clinical practice for the induction and maintenance of anaesthesia. Although propofol is regarded as a well tolerated anaesthetic, its effect on intact or damaged endothelial cells has not yet been elucidated. OBJECTIVE: The aim of this study was to investigate the effects of different concentrations of propofol on cell damage, metabolic activity, barrier function and wound healing capacity of human endothelial cells. DESIGN: An in vitro investigation. SETTING: Research Laboratory of the Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Kiel, Germany. MATERIALS: In vitro cultures of primary human umbilical vein endothelial cells (HUVECs). INTERVENTIONS: Intact HUVEC or wounded HUVEC monolayers were incubated with or without different concentrations of propofol (10, 30 and 100 [mu]mol l-1). MAIN OUTCOME MEASURES: Cell damage, metabolic activity, monolayer permeability, wound healing capacity, protein phosphorylation. RESULTS: Propofol did not alter the morphology, induce cell damage or influence metabolic activity of intact HUVEC cells. Permeability of a HUVEC monolayer was increased by propofol 100 [mu]mol l-1 (P

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Effects of magnesium chloride on rocuronium-induced neuromuscular blockade and sugammadex reversal in an isolated rat phrenic nerve-hemidiaphragm preparation: An in-vitro study.

BACKGROUND: Magnesium potentiates the effects of nondepolarising muscle relaxants. However, few studies have used magnesium chloride (MgCl2). Sugammadex reverses neuromuscular block by steroidal nondepolarising muscle relaxants. OBJECTIVES: To assess the effects of MgCl2 on rocuronium-induced neuromuscular blockade and its reversal by sugammadex. DESIGN: In-vitro experimental study. SETTING: Animal laboratory, Asan Medical Center, Seoul, South Korea, from 20 March 2016 to 3 April 2016. ANIMALS: Forty male Sprague Dawley rats. INTERVENTION: Left phrenic nerve-hemidiaphragms from 40 Sprague Dawley rats were allocated randomly to four groups (1, 2, 3 and 4 mmol l-1 MgCl2 group, n = 10 each). Rocuronium was administered cumulatively until the first twitch of train-of-four (TOF) disappeared completely. Then, equimolar sugammadex was administered. MAIN OUTCOME MEASURES: The effective concentration (EC) of rocuronium was obtained in each group. After administering sugammadex, recovery of the first twitch height and the TOF ratio were measured for 30 min. RESULTS: EC50, EC90 and EC95 significantly decreased as the concentration of MgCl2 increased (all P

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Median effective dose of intranasal dexmedetomidine sedation for transthoracic echocardiography examination in postcardiac surgery and normal children: An up-and-down sequential allocation trial.

BACKGROUND: Dexmedetomidine (DEX) has been used for sedation in young infants and children undergoing transthoracic echocardiography (TTE). The median effective dose of intranasal DEX has not been described for postcardiac surgery children. Postcardiac surgery children could require more DEX to achieve satisfactory sedation for TTE examination than children suspected of congenital heart disease. OBJECTIVES: To study whether postcardiac surgery children need a larger dose of DEX for TTE than normal children. DESIGN: A double-blind sequential allocation trial with doses determined by the Dixon and Massey up-and-down method. SETTING: A tertiary care teaching hospital from 25 October to 30 November 2016. PATIENTS: Children under the age of 3 years requiring intranasal DEX for TTE. INTERVENTIONS: Children were allocated to a postcardiac surgery group (n = 20) or a normal group (n = 19). The first patient in both groups received intranasal DEX (2 [mu]g kg-1): using the up-and-down method of Dixon and Massey, the next dose was dependent on the previous patient's response. MAIN OUTCOME MEASURES: Median effective dose was estimated from the up-and-down method of Dixon and Massey and probit regression. A second objective was to study haemodynamic stability and adverse events with these doses. RESULTS: The median effective dose (95% confidence interval) of intranasal DEX was higher in postcardiac surgery children than in normal children, 3.3 (2.72 to 3.78) [mu]g kg-1 versus 1.8 (1.71 to 2.04) ([mu]g kg-1), respectively (P

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Oh Excellent Air Bag - Under the influence of Nitrous Oxide, 1799-1920.

No abstract available

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