Παρασκευή, 31 Αυγούστου 2018

Rhomboid Intercostal and Subserratus Plane Block: A Cadaveric and Clinical Evaluation

Background and Objectives Fascial plane blocks are rapidly emerging to provide safe, feasible alternatives to epidural analgesia for thoracic and abdominal pain. We define a new option for chest wall and upper abdominal analgesia, termed the rhomboid intercostal and subserratus plane (RISS) block. The RISS tissue plane extends deep to the erector spinae muscle medially and deep to the serratus anterior muscle laterally. We describe a 2-part proof-of-concept study to validate the RISS block, including a cadaveric study to evaluate injectate spread and a retrospective case series to assess dermatomal coverage and analgesic efficacy. Methods For the cadaveric portion of the study, bilateral ultrasound-guided RISS blocks were performed on 6 fresh cadavers with 30 mL of 0.5% methylcellulose with india ink. For the retrospective case series, we present 15 patients who underwent RISS block or RISS catheter insertion for heterogeneous indications including abdominal surgery, rib fractures, chest tube–associated pain, or postoperative incisional chest wall pain. Results In the cadaveric specimens, we identified staining of the lateral branches of the intercostal nerves from T3 to T9 reaching the posterior primary rami deep to the erector spinae muscle medially. In the clinical case series, dermatomal coverage was observed in the anterior hemithorax with visual analog pain scores less than 5 in patients who underwent both single-shot and continuous catheter infusions. Conclusions Our preliminary cadaveric and clinical data suggest that RISS block anesthetizes the lateral cutaneous branches of the thoracic intercostal nerves and can be used in multiple clinical settings for chest wall and upper abdominal analgesia. Accepted for publication March 10, 2018. Address correspondence to: Hesham Elsharkawy, MD, MBA, MSc, Department of General Anesthesia and Outcomes Research, Anesthesiology Institute, Cleveland Clinic, 9500 Euclid Ave, Mail Code E31, Cleveland, OH 44195 (e-mail: elsharh@ccf.org). H.E. has received unrestricted educational funding from PAJUNK (Norcross, GA) and consultant fees from Pacira Pharmaceuticals, Inc. Those companies had no input into any aspect of the present project design or manuscript preparation. The authors declare no conflict of interest. All images are created and used with permission of Cleveland Clinic Center for Medical Art and Photography. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.rapm.org). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Behavioural responses to environmental hypercapnia in two eusocial species of African mole rats

Abstract

Damaraland and naked mole rat are eusocial mammals that live in crowded burrows in which CO2 is elevated. These species are thought to be highly tolerant of CO2 but their behavioural responses to hypercapnia are poorly understood. We hypothesized that Damaraland and naked mole rats would exhibit blunted behavioural responses to hypercapnia and predicted that their activity levels would be unaffected at low to moderate (2–5%) CO2 but increased at > 7% CO2. To test this, we exposed Damaraland and naked mole rats to stepwise increases in environmental CO2 (0–10%) and measured activity, exploratory behaviour, and body temperature. Surprisingly, we found that both species exhibited no differences in movement velocity, distance travelled, zone transitions (exploration), or body temperature at any level of environmental hypercapnia. Conversely, when carbonic anhydrase was inhibited with acetazolamide (50 mg kg−1 intraperitonially, to increase whole-animal acidosis), exploration was significantly elevated relative to hypercapnic controls in both species at all levels of inhaled CO2, and naked mole rat body temperature decreased in > 7% CO2. We conclude that both species are largely non-responsive to environmental CO2, and that this tolerance may be dependent on bicarbonate buffering at the level of the kidney or within the blood.



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What Should We Do About Habitual Caffeine Use in Athletes?

Abstract

Caffeine is a well-established ergogenic aid, demonstrated to enhance performance across a wide range of capacities through a variety of mechanisms. As such, it is frequently used by both athletes and non-athletes alike. As a result, caffeine ingestion is ubiquitous in modern society, with athletes typically being exposed to regular non-supplemental caffeine through a variety of sources. Previously, it has been suggested that regular caffeine use may lead to habituation and subsequently a reduction in the expected ergogenic effects, thereby blunting caffeine's performance-enhancing impact during critical training and performance events. In order to mitigate this expected performance loss, some practitioners recommended a pre-competition withdrawal period to restore the optimal performance benefits of caffeine supplementation. However, at present the evidence base exploring both caffeine habituation and withdrawal strategies in athletes is surprisingly small. Accordingly, despite the prevalence of caffeine use within athletic populations, formulating evidence-led guidelines is difficult. Here, we review the available research regarding habitual caffeine use in athletes and seek to derive rational interpretations of what is currently known—and what else we need to know—regarding habitual caffeine use in athletes, and how athletes and performance staff may pragmatically approach these important, complex, and yet under-explored phenomena.



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Juvenile Idiopathic Arthritis: A Focus on Pharmacologic Management

Juvenile idiopathic arthritis is a chronic condition that affects many pediatric patients. It is a prevalent disease and has become the most common rheumatologic disease of childhood. The condition encompasses multiple different forms of chronic arthritides classified based on the location and number of joints affected as well as the presence or lack of a number of different inflammatory markers. The exact etiology is unknown but is thought to be multifactorial with genetic, humoral, and environmental factors playing a key role.

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A Case Study of a Child With Mitochondrial Disease

A 4-year-old girl recently diagnosed with epilepsy presented to her pediatric advanced practice registered nurse (APRN) in a primary care clinic with 2 weeks of increased seizure activity after a medication change from carbamazepine to valproic acid. Symptoms also included a sudden increase in lethargy, ataxia, and drowsiness. She is co-managed by a pediatric neurologist for seizure control who was currently away from the office. Associated test results included a normal valproic acid level, elevated ammonia and liver function (Table 1), and an abnormal electroencephalogram reading; indicating a generalized process with ongoing focal-like features.

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The ACEs Connection

While we do not routinely publish book reviews in this Journal, there is one book that I would like to draw to your attention: The Deepest Well: Healing the Long-term Effects of Childhood Adversity by Dr. Nadine Burke Harris (Harris, 2018).

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Skin Deep: Simplifying Practice Guidelines for Children With Atopic Dermatitis

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder in children. Often called eczema, AD is a papulosquamous eruption often characterized by pruritus and then the typical distribution and morphology of the rash (Saavedra et al., 2013). Thus, an idiom often used by health care professionals to describe AD is "the itch that rashes." Two leading organizations jointly authored an update on AD in 2012 (Schneider et al., 2013), and a third published several guidelines for the management of AD (Eichenfield et al., 2013, 2014, 2015; Sidbury et al., 2014).

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Table of Contents



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Information for Readers



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Editorial Board Page



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Juvenile Idiopathic Arthritis: A Focus on Pharmacologic Management



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Society Page



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Fostering Resiliency in Children, Families and our Profession

I grew up in Miami during a quiet, sleepy time. We rode bicycles, climbed trees, and played Olympic-level hide and go seek in lush neighborhood gardens. We skinned our knees and scraped our elbows. I was more ragamuffin than photoshoot-ready most days. It is easy to romanticize childhood as being carefree, but trauma and stress occur universally. For some, it is the loss of a loved one or beloved pet, others experience natural disasters, and some experience or witness violence, abuse, and/or neglect.

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Reciprocal F1 Hybrids of Two Inbred Mouse Strains Reveal Parent-of-Origin and Perinatal Diet Effects on Behavior and Expression

Parent-of-origin effects (POE) in mammals typically arise from maternal effects or imprinting. In some instances, such POE have been associated with psychiatric disorders, as well as with changes in a handful of animal behaviors. However, POE on complex traits such as behavior remain largely uncharacterized. Moreover, although both behavior and epigenetic effects are known to be modified by perinatal environmental exposures such as nutrient deficiency, the architecture of such environment-by-POE is mostly unexplored. To study POE and environment-by-POE, we employ a relatively neglected but especially powerful experimental system for POE-detection: reciprocal F1 hybrids (RF1s). We exposed female NOD/ShiLtJxC57Bl/6J and C57Bl/6JxNOD/ShiLtJ mice, perinatally, to one of four different diets, then after weaning recorded a set of behaviors that model psychiatric disease. Whole-brain microarray expression data revealed an imprinting-enriched set of 15 genes subject to POE. The most-significant expression POE, on the non-imprinted gene Carmil1 (a.k.a. Lrrc16a), was validated using qPCR in the same and in a new set of mice. Several behaviors, especially locomotor behaviors, also showed POE. Bayesian mediation analysis suggested Carmil1 expression suppresses behavioral POE, and that the imprinted gene Airn suppresses POE on Carmil1 expression. A suggestive diet-by-POE was observed on percent center time in the open field test, and a significant diet-by-POE was observed on one imprinted gene,Mir341, and on 16 non-imprinted genes. The relatively small, tractable set of POE and diet-by-POE detected on behavior and expression here motivates further studies examining such effects across RF1s on multiple genetic backgrounds.



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Nerve ultrasound findings differentiate Charcot-Marie-Tooth disease (CMT) 1A from other demyelinating CMTs

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disorder and encompasses a heterogeneous group of motor-sensory length-dependent polyneuropathies. Clinical phenotypes, modes of inheritance and nerve conduction study (NCS) still guide genetic testing (Rossor et al., 2016). CMT type 1 (CMT1) represents nearly 80% of all genetically confirmed cases (Fridman et al., 2015) and includes autosomal dominant or X-dominant neuropathies defined as "demyelinating" according to ulnar/median motor nerve conduction velocity (MNCV) ≤38 m/s with preserved compound motor action potentials (CMAP) (Rossor et al., 2016).

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Towards closed-loop deep brain stimulation for freezing of gait in Parkinson’s disease

Freezing of gait (FOG) is a highly debilitating symptom of advanced Parkinson's disease (PD) during which patients experience a sudden inability to take a step while walking, turning or when attempting to initiate gait, often resulting in falls (Nutt et al. 2011). FOG has a complex and heterogeneous pathophysiology whereby the impaired habitual control of gait in PD becomes vulnerable to interference from consecutive processing across motor, cognitive and limbic cortico-striatal circuits in the absence of striatal dopamine, whilst the ability to apply executive control over gait diminishes as a result of progressing extra-nigral neuropathology (Bohnen and Jahn 2013; Lewis and Shine 2016).

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Evidence for a differential visual M300 brain response in gamblers

In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013), the section including substance-related addictions was modified to incorporate behavioral addictions, namely addictions that do not include ingestion of a psychoactive substance (Grant et al. 2010). This amendment was a result of accumulating evidence that behavioral and substance-related addictions have many commonalities in phenomenology, epidemiology, neurobiological mechanisms, and response to treatment (Potenza 2008; Grant et al.

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Effect of Epileptiform Abnormality Burden on Neurologic Outcome and Antiepileptic Drug Management After Subarachnoid Hemorrhage

Epileptiform abnormalities (EAs) including seizures, periodic and rhythmic patterns, and sporadic discharges are seen in electroencephalogram (EEG) recordings in up to 20% percent of patients with aneurysmal subarachnoid hemorrhage (aSAH) (Claassen et al., 2006). The presence of periodic discharges and seizures has been linked to worse functional and cognitive outcomes (Claassen et al., 2006; De Marchis et al., 2016). Nevertheless, there is limited and conflicting data on how the burden and subtype of EAs influence outcome in patients with aSAH (Crepeau et al., 2013).

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The Median to Ulnar Cross-Sectional Surface Area Ratio in Carpal Tunnel Syndrome

Carpal tunnel syndrome (CTS) is the most common focal neuropathy worldwide and is among the most common reasons for electrodiagnostic consultation(Hobson-Webb and Padua, 2016). The current reference standard for CTS diagnosis includes history and physical examination as well as electrodiagnostic studies. However, it is well recognized that electrodiagnostic testing has certain limitations; while it can identify the site of compression, it may be painful and does not provide anatomic information (Cartwright et al.

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Sudomotor dysfunction is frequent and correlates with disability in Friedreich ataxia

Friedreich ataxia (FRDA) is considered the most prevalent autosomal recessive ataxia worldwide with estimated prevalence of 3/100,000. The disease is common in Caucasian populations, but practically absent in sub-saharan regions and in the Far East. In 95% of the cases, the underlying cause is a homozygous expansion of a (GAA) repeat in intron 1 of FXN at 9q21.1 (Koeppen, 2011; Durr et al, 1996; Campuzano et al, 1996; Fogel and Perlman, 2007). This leads to a transcriptional abnormality that results in the lack of frataxin, a mitochondrial protein related to iron homeostasis (Campuzano et al, 1997).

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New Evidence for Structural Integration across the Cartilage-Vertebral Endplate Junction and its Relation to Herniation

Both cartilaginous and bony material present in herniated tissue suggests that failure can involve both cartilaginous and vertebral-endplates. How structural integration is achieved across the junction between these two distinct tissue regions via its fibril and mineral components is clearly relevant to the modes of endplate failure that occur.

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Nomogram prediction of individual prognosis of patients with acute-on-chronic hepatitis B liver failure

The current definitions and etiologies of acute-on-chronic liver failure (ACLF) are clearly very different between East and West.

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Nomogram prediction of individual prognosis of patients with acute-on-chronic hepatitis B liver failure

The current definitions and etiologies of acute-on-chronic liver failure (ACLF) are clearly very different between East and West.

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Exploratory Factor Analysis of the Mishel Uncertainty in Illness Scale Among Adolescents and Young Adults With Chronic Medical Conditions

To identify a developmentally relevant factor structure of the Mishel Uncertainty in Illness Scale–Community form (MUIS-C) among adolescents and young adults with chronic medical conditions.

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NAEMSP president part of Fentanyl Safety Panel Discussion in Washington D.C.

WASHINGTON — Today Deputy Attorney General Rod J. Rosenstein delivered remarks at the Office of Justice Programs in Washington D.C. regarding the rollout of Fentanyl: The Real Deal, a training video created by a Federal Interagency Working Group and coordinated by the National Security Council. The Bureau of Justice Assistance presented the video and hosted a panel comprised of first...

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3 benefits of a community paramedicine program

A treatment-based approach can help your agency provide more appropriate care, reduce costly transports and benefit your staff as well as the patients you serve

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Editorial Board

Experimental Physiology, Volume 103, Issue 9, Page 1287-1289, 1 September 2018.


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Simultaneous resections of left lung cancer and esophageal schwannoma using video‐assisted thoracoscopic surgery: A case report

Asian Journal of Endoscopic Surgery, EarlyView.


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Recent advancements of robotic surgery for kidney cancer

Asian Journal of Endoscopic Surgery, EarlyView.


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Non–exposed endoscopic wall‐inversion surgery for pediatric gastrointestinal stromal tumor: A case report

Asian Journal of Endoscopic Surgery, EarlyView.


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Astrocyte‐mediated PAD: A new twist to a complicated tale?

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Issue Information

The Journal of Physiology, Volume 596, Issue 17, Page 3813-3814, 1 September 2018.


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“Compliance” to exercise: How much is really needed for a healthy heart (and mind)?

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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After-action report: Tactical EMS lessons from terror attack

Training rescue task force medics and SWAT medics for responding to mass casualty incidents

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Mastering the Art of Collaboration: Supporting Family Caregivers of Mental Health Patients by Service Providers in Iran

Abstract

Responsive support systems, designed and promoted by policy makers, are critical in supporting family caregivers. The purpose of this study was to explore viewpoints of service providers in supporting family caregivers of mental health patients in Iran. In this qualitative study, a purposive sample of 29 service providers and policy makers consented to participate in semi-structured interviews. Data were analyzed through qualitative content analysis and three main categories and seven sub-categories were identified. The main categories were: interpersonal collaboration, intra-organization collaboration and inter-sectorial collaboration. A common theme in this study was that service providers play a key role in coordinating responsive support services for Iranian family caregivers of mental health patients across all levels. The increasing complexity of the health care system and resource limitations have created complex problems, which require the use of participatory approaches by the various specialties, disciplines and departments to provide complementary services and mutual support. This approach is the best way of ensuring that service users receive the most relevant services from the right service providers in the right place as and when needed.



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Locating QTLs controlling overwintering seedling rate in perennial glutinous rice 89-1 ( Oryza sativa L.)

Abstract

A new cold tolerant germplasm resource named glutinous rice 89-1 (Gr89-1, Oryza sativa L.) can overwinter using axillary buds, with these buds being ratooned the following year. The overwintering seedling rate (OSR) is an important factor for evaluating cold tolerance. Many quantitative trait loci (QTLs) controlling cold tolerance at different growth stages in rice have been identified, with some of these QTLs being successfully cloned. However, no QTLs conferring to the OSR trait have been located in the perennial O. sativa L. To identify QTLs associated with OSR and to evaluate cold tolerance. 286 F12 recombinant inbred lines (RILs) derived from a cross between the cold tolerant variety Gr89-1 and cold sensitive variety Shuhui527 (SH527) were used. A total of 198 polymorphic simple sequence repeat (SSR) markers that were distributed uniformly on 12 chromosomes were used to construct the linkage map. The gene ontology (GO) annotation of the major QTL was performed through the rice genome annotation project system. Three main-effect QTLs (qOSR2, qOSR3, and qOSR8) were detected and mapped on chromosomes 2, 3, and 8, respectively. These QTLs were located in the interval of RM14208 (35,160,202 base pairs (bp))–RM208 (35,520,147 bp), RM218 (8,375,236 bp)–RM232 (9,755,778 bp), and RM5891 (24,626,930 bp)–RM23608 (25,355,519 bp), and explained 19.6%, 9.3%, and 11.8% of the phenotypic variations, respectively. The qOSR2 QTL displayed the largest effect, with a logarithm of odds score (LOD) of 5.5. A total of 47 candidate genes on the qOSR2 locus were associated with 219 GO terms. Among these candidate genes, 11 were related to cell membrane, 7 were associated with cold stress, and 3 were involved in response to stress and biotic stimulus. OsPIP1;3 was the only one candidate gene related to stress, biotic stimulus, cold stress, and encoding a cell membrane protein. After QTL mapping, a total of three main-effect QTLs—qOSR2, qOSR3, and qOSR8—were detected on chromosomes 2, 3, and 8, respectively. Among these, qOSR2 explained the highest phenotypic variance. All the QTLs elite traits come from the cold resistance parent Gr89-1. OsPIP1;3 might be a candidate gene of qOSR2.



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Natural radioactivity studies in a paleontology site and paleoclimate interpretation of the last 8 Mya

Publication date: October 2018

Source: Journal of Environmental Radioactivity, Volumes 193–194

Author(s): Ιoanna Maria Zougrou, Stilianos Stoulos, Nikolaos Kantiranis, Lambrini Papadopoulou, Ioakeim Ioakeimidis, Maria Katsikini, Eleni Paloura, Evangelia Tsoukala

Abstract

Fossil bones and sediments from different horizons of the Upper Miocene paleontological site of Platania, Drama-Greece were studied using 238U, 235U, 232Th series and 40K measurements obtained by γ-spectroscopy. Additionally, SEM and XRF analysis was applied to bone and sediment samples while a lithological analysis of the sediments was also carried out. The 226Ra/238U ratios in the fossilization layers are attributed to the 238U depletion from the sediment and its incorporation into the fossils. The 226Ra/231Pa ratio indicates that the absorption of the isotopes started long before 4.2 Ma ago. The 232Th/40K profile demonstrate two distinct geological substrates, the lower corresponding to the Upper Miocene whereas the upper to the Upper Pleistocene–Holocene. Among them mediates a Mn-rich layer associated with the "Zanclean flood" during Pliocene. One layer above the "Glacial maximum event" during the Early Pleistocene was recorded. The natural radioactive sedimentary profile obtained reproduces the paleo-climatic conditions in Southeast Europe, which could be useful for the future.



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Auditory gamma oscillations predict global symptomatic outcome in the early stages of psychosis: a longitudinal investigation

Publication date: Available online 30 August 2018

Source: Clinical Neurophysiology

Author(s): Daisuke Koshiyama, Kenji Kirihara, Mariko Tada, Tatsuya Nagai, Mao Fujioka, Eriko Ichikawa, Kazusa Ohta, Motoko Tani, Maiko Tsuchiya, Akiko Kanehara, Kentaro Morita, Kingo Sawada, Jun Matsuoka, Yoshihiro Satomura, Shinsuke Koike, Motomu Suga, Tsuyoshi Araki, Kiyoto Kasai

Abstract
Objectives

The gamma-band auditory steady-state response (ASSR) is thought to reflect the function of parvalbumin-positive γ-aminobutyric acid (GABA)-ergic interneurons and may be a candidate biomarker in early psychosis. Although previous cross-sectional studies have shown that gamma-band ASSR is reduced in early psychosis, whether reduced gamma-band ASSR could be a predictor of the long-term prognosis remains unknown.

Methods

In this longitudinal study, we investigated the association between gamma-band ASSR reduction and future global symptomatic or functional outcome in early psychosis. We measured 40-Hz ASSR in 34 patients with recent-onset schizophrenia (ROSZ), 28 ultra-high risk (UHR) individuals, and 30 healthy controls (HCs) at baseline. After 1 to 2 years, we evaluated the global assessment of functioning (GAF) in the ROSZ (N = 20) and UHR (N = 20) groups.

Results

The 40-Hz ASSR was significantly reduced in the ROSZ and UHR groups. The attenuated 40-Hz ASSR was correlated with the future global symptomatic outcome in the ROSZ, but not in the UHR groups.

Conclusions

A reduction in the gamma-band ASSR after the onset of psychosis may predict symptomatic outcomes in early psychosis.

Significance

Gamma-band ASSR may be a potentially useful biomarker of the long-term prognosis in patients with recent-onset schizophrenia.



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Electrodiagnosis and nerve ultrasound: “Castor and Pollux” in the management of neuropathies

Publication date: Available online 31 August 2018

Source: Clinical Neurophysiology

Author(s): Luca Padua, Costanza Pazzaglia, Daniele Coraci



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The effects of aging on early stages of the auditory deviance detection system

Publication date: Available online 31 August 2018

Source: Clinical Neurophysiology

Author(s): Maryam Aghamolaei, Zahra Jafari, Sabine Grimm, Katarzyna Zarnowiec, Mojtaba Najafi-Koopaie, Carles Escera

Abstract
Objective

The aging effects on auditory change detection have been studied using the Mismatch Negativity (MMN) potential. However, recent studies have found earlier correlates of deviance detection at the level of the middle-latency response (MLR) and the effects of aging on this deviant-related response have not yet been clarified. The purpose of this study was to examine the effects of aging on both levels of the auditory deviance detection system.

Methods

MMN and MLR responses were recorded in 33 young and 29 older adults from 32 scalp electrodes during frequency oddball and swapped-oddball conditions.

Results

In the young group, modulation of MLR and a clear MMN response were observed, whereas in the aged group, no evidence of deviance detection was found at the level of MLR and the MMN amplitude was significantly diminished.

Conclusions

Based on the obtained results, aging affects both levels of the auditory deviance detection system which seems to be a result of deficit in regularity encoding along the auditory hierarchy.

Significance

The current findings suggest that age-related physiological changes result in deficits in regularity encoding, starting from early stages of processing. This might eventually affect stream segregation and induce difficulties in understanding speech in complex environments.



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Harvesting responses to single pulse electrical stimulation for presurgical evaluation in epilepsy

Publication date: Available online 31 August 2018

Source: Clinical Neurophysiology

Author(s): Geertjan Huiskamp, Dorien van Blooijs, Michelle van der Stoel



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Effect of subthalamic nucleus deep brain stimulation on visual scanning

Publication date: Available online 30 August 2018

Source: Clinical Neurophysiology

Author(s): Shin-ichi Tokushige, Shunichi Matsuda, Genko Oyama, Yasushi Shimo, Atsushi Umemura, Takuya Sasaki, Satomi Inomata-Terada, Akihiro Yugeta, Masashi Hamada, Yoshikazu Ugawa, Shoji Tsuji, Nobutaka Hattori, Yasuo Terao

Abstract
Objective

Deep brain stimulation (DBS) can provide insights into the workings of the basal ganglia (BG) by interfering with their function. In patients with Parkinson's disease (PD) treated with DBS of the subthalamic nucleus, we studied the effect of DBS on scanning eye movements.

Methods

In the visual memory task, subjects viewed images of various complexities for later recall. In visual search tasks, subjects looked for and fixated one odd target ring, embedded among 48 Landolt rings, which either stood out or not from the distractors. We compared the parameters of scanning saccades when DBS was on and off.

Results

In the visual memory task, DBS increased the amplitude of saccades scanning simple but not complex drawings. In the visual search tasks, DBS showed no effect on saccade amplitude or frequency.

Conclusions

Saccades when viewing simple images were affected by DBS since they are internally guided saccades, for which the involvement of BG is large. In contrast, saccades when viewing complex images or during visual search, made with the help of visual cues in the images (externally guided saccades) and less dependent on BG, were resistant to the effect of DBS.

Significance

DBS affects saccades differentially depending on the task.



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Effects of Noise and Age on the Infant Brainstem Response to Speech

Publication date: Available online 30 August 2018

Source: Clinical Neurophysiology

Author(s): Gabriella Musacchia, Silvia Ortiz-Mantilla, Cynthia P. Roesler, Sree Rajendran, Julie Morgan-Byrne, April A. Benasich

Abstract
Objective

Background noise makes hearing speech difficult for people of all ages. This difficulty can be exacerbated by co-occurring developmental deficits that often emerge in childhood. Sentence-type speech-in-noise (SIN) tests are available clinically but cannot be administered to very young individuals. Our objective was to examine the use of an electrophysiological test of SIN, suitable for infants, to track developmental trajectories.

Methods

Speech-evoked brainstem potentials were recorded from 30 typically-developing infants in quiet and +10 dB SNR background noise. Infants were divided into two age groups (7-12 and 18-24 months) and examined across development. Spectral power of the frequency following response (FFR) was computed using a fast Fourier Transform. Cross-correlations between quiet and noise responses were computed to measure encoding resistance to noise.

Results

Older infants had more robust FFR encoding in noise and had higher quiet-noise correlations than their younger counterparts. No group differences were observed in the quiet condition.

Conclusions

By two years of age, infants show less vulnerability to the disruptive effects of background noise, compared to infants under 12 months.

Significance

Speech-in-noise electrophysiology can be easily recorded across infancy and provides unique insights into developmental differences that tests conducted in quiet may miss.



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The impairing effect of dyspnea on response inhibition

Publication date: Available online 31 August 2018

Source: International Journal of Psychophysiology

Author(s): Josef Sucec, Michaela Herzog, Ilse Van Diest, Omer Van den Bergh, Andreas von Leupoldt

Abstract

Dyspnea (=breathlessness) is an aversive and threatening symptom in various prevalent diseases. Established treatment procedures aim for behavioral changes in dyspneic patients in order to treat dyspnea successfully. To achieve these behavioral changes, response inhibition as one key executive function for goal-directed behavior is an important prerequisite. However, the impact of dyspnea on response inhibition is widely unknown. Therefore, the present study aimed at testing whether experimentally induced dyspnea would impair response inhibition. Thirty-six healthy participants performed the color-word Stroop task during an unloaded baseline and a resistive load-induced dyspnea condition. Response inhibition was investigated using behavioral measures (reaction time, accuracy) and, based on literature, the late positive complex (LPC) in the electroencephalogram. Furthermore, the N400 was investigated in an exploratory analysis. The results showed significantly reduced accuracy for incongruent compared to congruent color-words in the Stroop task during the dyspnea condition (p < .001) which was paralleled by a smaller LPC and a more negative centro-parietal N400 for incongruent color-words during the dyspnea compared to the baseline condition (p < .05). Possibly, during dyspnea more neural resources are allocated towards the semantic processing of incongruent color-words indexed as the N400 which are then not available for the partly overlapping LPC as an index for response inhibition. These findings demonstrate that resistive load-induced dyspnea has an impairing effect on response inhibition in healthy participants, both in terms of behavioral performance and respective neural processing. This might impair treatment efforts aimed at behavioral changes in patients suffering from dyspnea.



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Ontogeny and phylogeny of the cercopithecine cranium: A geometric morphometric approach to comparing shape change trajectories

Publication date: Available online 31 August 2018

Source: Journal of Human Evolution

Author(s): Evan A. Simons, Stephen R. Frost, Michelle Singleton

Abstract

While the analysis of ontogenetic trajectories is common in geometric morphometrics (GM), the simultaneous comparison of several trajectories can be unwieldy and is, in some cases, unable to make use of one of the main advantages of GM, visualization. Furthermore, due to the paucity of the paleontological record, analyses of trajectories are often limited to extant taxa. We address these issues by presenting a method for visualizing the similarities and differences of cranial ontogenetic trajectories among taxa and a method for reconstructing ancestral ontogenetic trajectories, so that these differences can be investigated in a phylogenetic context. We also tested for the presence of phylogenetic signal in the ontogenetic trajectories themselves. Using an ontogenetic series of 522 crania, representing 17 cercopithecine species from 8 genera, we first calculated ontogenetic trajectories of cranial shape change for each species, and then entered these trajectories into a principal components analysis to produce a developmental shape-change trajectory PCA (δPCA). Then, through an augmentation of the phylomorphospace approach, we projected a molecular phylogeny onto the major axes of trajectory shape variation from the δPCA to produce an 'ontophylomorphospace,' using squared-change parsimony to reconstruct interior nodes. Through these procedures, we were able to determine that the δPCAs illustrate patterns of variation in these developmental trajectories in a visually intuitive manner that allows for easier comparisons among taxa. Through examination of the ontophylomorphospace, we found that African papionins exhibit extensive homoplasy in the evolution of cranial ontogenetic trajectories, and that Asian species of Macaca show highly derived ontogenetic trajectories relative to other cercopithecines. Additionally, we found no support for the presence of a phylogenetic signal in cranial ontogenetic trajectories. The δPCA and the ontophylomorphospace are ways in which to visualize and compare complex, multivariate shape transformations, both among extant taxa and over evolutionary time, respectively.



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The spatio-temporal distribution of archaeological and faunal finds at Liang Bua (Flores, Indonesia) in light of the revised chronology for Homo floresiensis

Publication date: Available online 31 August 2018

Source: Journal of Human Evolution

Author(s): Thomas Sutikna, Matthew W. Tocheri, J. Tyler Faith, Jatmiko, Rokus Due Awe, Hanneke J.M. Meijer, E. Wahyu Saptomo, Richard G. Roberts

Abstract

Liang Bua, the type site of Homo floresiensis, is a limestone cave on the Indonesian island of Flores with sedimentary deposits currently known to range in age from about 190 thousand years (ka) ago to the present. Recent revision of the stratigraphy and chronology of this depositional sequence suggests that skeletal remains of H. floresiensis are between ∼100 and 60 ka old, while cultural evidence of this taxon occurs until ∼50 ka ago. Here we examine the compositions of the faunal communities and stone artifacts, by broad taxonomic groups and raw materials, throughout the ∼190 ka time interval preserved in the sequence. Major shifts are observed in both the faunal and stone artifact assemblages that reflect marked changes in paleoecology and hominin behavior, respectively. Our results suggest that H. floresiensis and Stegodon florensis insularis, along with giant marabou stork (Leptoptilos robustus) and vulture (Trigonoceps sp.), were likely extinct by ∼50 ka ago. Moreover, an abrupt and statistically significant shift in raw material preference due to an increased use of chert occurs ∼46 thousand calibrated radiocarbon (14C) years before present (ka cal. BP), a pattern that continues through the subsequent stratigraphic sequence. If an increased preference for chert does, in fact, characterize Homo sapiens assemblages at Liang Bua, as previous studies have suggested (e.g., Moore et al., 2009), then the shift observed here suggests that modern humans arrived on Flores by ∼46 ka cal. BP, which would be the earliest cultural evidence of modern humans in Indonesia.



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Early dates for ‘Neanderthal cave art’ may be wrong

Publication date: Available online 30 August 2018

Source: Journal of Human Evolution

Author(s): Maxime Aubert, Adam Brumm, Jillian Huntley



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Commencing out of bed rehabilitation in critical care – what influences clinical decision-making?

Publication date: Available online 30 August 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Sue C. Berney, Joleen W. Rose, Linda Denehy, Catherine L. Granger, George Ntoumenopoulos, Elise Crothers, Bronwyn Steel, Sandy Clarke, Elizabeth H. Skinner

Objectives

To develop a decision tree that objectively identifies the most discriminative variables in the decision to provide out-of-bed rehabilitation, measure the impact of this decision and to identify the factors that intensive care unit (ICU) practitioners think most influential in that clinical decision.

Design

A prospective three-part study: i) consensus identification of influential factors in mobilization via survey, ii) development of an early rehabilitation decision tree and iii) measurement of practitioner mobilisation decision-making. Treating practitioners of patients expected to stay > 96h were asked if they would provide out-of-bed rehabilitation and rank factors that influenced this decision from an a priori defined list developed from a literature review and expert consultation.

Setting

Four tertiary metropolitan ICUs

Participants

Practitioners (ICU medical, nursing and physiotherapy staff)

Interventions

Not applicable

Main Outcomes

A decision tree was constructed using binary recursive partitioning to determine the factor that best classified patients suitable for out-of-bed rehabilitation. Descriptive statistics were used to describe practitioner and patient samples as well as patient adverse events associated with out-of-bed rehabilitation and the factors prioritised by ICU practitioners.

Results

There were 1520 practitioner decisions representing 472 individual patient decisions. Practitioners classified patients suitable for out-of-bed rehabilitation on 149 occasions and not suitable on 323 occasions. Decision tree analysis showed the presence of an endotracheal tube (ETT) and sedation state were the only discriminative variables that predicted patient suitability for rehabilitation. In contrast, medical staff and nurses reported that ventilator status was the most influential factor in their decision not to provide rehabilitation whilst physiotherapists ranked sedation most highly. The presence of muscle weakness did not inform the decision to provide rehabilitation.

Conclusion

These results confirm previous observational reports that the presence of an ETT remains a major obstacle to the provision of rehabilitation for critically ill patients. Despite rehabilitation being effective for improving muscle strength, the presence of muscle weakness did not influence the decision to provide rehabilitation.



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Improving Outcomes for Critically Ill Cardiovascular Patients through Increased Physical Therapy Staffing

Publication date: Available online 30 August 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Joshua K. Johnson, Bryan Lohse, Haley A. Bento, Christopher S. Noren, Robin L. Marcus, Joseph E. Tonna

ABSTRACT
Objective

To examine the effect of increasing physical therapy staff in a cardiovascular ICU (CVICU) on temporal measures of physical therapy interventions and on outcomes important to patients and hospitals.

Design

Retrospective pre/post subgroup analysis from a quality improvement initiative.

Setting

Academic medical center.

Participants

Cardiovascular patients in either a baseline (N=52) or quality improvement period (N=62) with a CVICU length of stay (LOS) ≥ 7 days and use of any one of the following: mechanical ventilation, continuous renal replacement therapy, or mechanical circulatory support.

Interventions

The six-month quality improvement initiative increased CVICU-dedicated physical therapy staff from two to four.

Main Outcome Measures

Changes in physical therapy delivery were examined using the frequency and daily duration of physical therapy intervention. Post-CVICU LOS was the primary outcome. CVICU LOS, mobility change, and discharge level of care were secondary outcomes. A secondary analysis of hospital survivors was also conducted.

Results

Compared to those in the baseline period, cardiovascular patients in the quality improvement period participated in physical therapy for an additional 9.6 minutes (95% confidence interval [CI]: 1.9, 17.2) per day for all patients and 15.1 minutes (95% CI: 7.6, 22.6) for survivors. Post-CVICU LOS decreased 2.2 (95% CI: -6.0, 1.0) days for all patients and 2.6 days (95% CI: -5.3, 0.0) for survivors. CVICU LOS decreased 3.6 days (95% CI: -6.4, -0.8) for all patients and 3.1 days (95% CI: -6.4, -0.9) for survivors. Differences in mobility change and discharge level of care were not significant.

Conclusions

Additional CVICU-dedicated physical therapy staff was associated with increased physical therapy treatment and reductions in CVICU and post-CVICU LOS. The effects of each were greatest for hospital survivors.



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Comprehensive Neuropsychological Assessment of Cognitive Functioning of Adults with Lower Limb Amputation in Rehabilitation

Publication date: Available online 30 August 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Richard Lombard-Vance, Fiadhnait O'Keeffe, Deirdre Desmond, Robert Coen, Nicola Ryall, Pamela Gallagher

Objective

To establish a comprehensive profile of cognitive functioning in people engaged in lower limb amputation (LLA) rehabilitation.

Design

Cross-sectional study as part of a longitudinal prospective cohort.

Setting

A national, tertiary, rehabilitation hospital.

Participants

Adult volunteer participants (N=87) referred for comprehensive rehabilitation for major LLA were sampled from 207 consecutive admissions. Participants with both vascular (n=69) and non-vascular (n=18) LLA aetiologies were included.

Interventions

Not applicable

Main Outcome Measure(s)

Demographic and health information, and a battery of standardised neuropsychological assessments

Results

Compared to normative data, impairment was evident in overall cognitive functioning (p≤.003). Impairment was also evident in particular areas, including reasoning, psychomotor function, information processing, attention, memory, language/naming, visuospatial functions, and executive functions (all p≤.003 Holm-corrected). There were also higher frequencies of impaired functions across most aspects of functioning in this group, compared to expected frequencies in normative data (p≤.003 Holm-corrected). There were no significant differences in cognitive functioning between participants of vascular and non-vascular LLA aetiology.

Conclusions

Findings support the need for cognitive screening at rehabilitation admission regardless of aetiology. Administration of comprehensive neuropsychological assessment with a battery sensitive to vascular cognitive impairment is recommended in some cases, to generate an accurate and precise understanding of relative strengths and weaknesses in cognitive functioning. Cognitive functioning is a potential intervention point for improvement of rehabilitation outcomes for those with LLA and further research is warranted in this area.



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Editorial Board

Publication date: September 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 9

Author(s):



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Sensory domain of the cell cycle kinase CckA regulates the differential DNA binding of the master regulator CtrA in Caulobacter crescentus

Publication date: Available online 31 August 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Sharath Narayanan, Lokesh Kumar, Sunish Kumar Radhakrishnan

Abstract

Sophisticated signaling mechanisms allow bacterial cells to cope with environmental and intracellular challenges. Activation of specific pathways ameliorates these challenges and thereby warrants integrity. Here, we demonstrate the pliability of the CckA-CtrA two component signaling system in the freshwater bacterium Caulobacter crescentus. Our forward genetic screen to analyze suppressor mutations that can negate the chromosome segregation block induced by the topoisomerase IV inhibitor, NstA, yielded various point mutations in the cell cycle histidine kinase, CckA. Notably, we identified a point mutation in the PAS-B domain of CckA, which resulted in increased levels of phosphorylated CtrA (CtrA~P), the master cell cycle regulator. Surprisingly, this increase in CtrA~P levels did not translate into a genome-wide increase in the DNA occupancy of CtrA, but specifically enriched its affinity for the chromosomal origin of replication, Cori, and for a very small sub-set of CtrA regulated promoters. We show that through this enhanced binding of CtrA to the Cori, cells are able to overcome the toxic defects rendered by stable NstA through a possible slow down in the chromosome replication cycle. Taken together, our work opens up an unexplored and intriguing aspect of the CckA-CtrA signal transduction pathway. The distinctive DNA binding nature of CtrA and its regulation by CckA might also be crucial for pathogenesis because of the highly conserved nature of the CckA-CtrA pathway in alphaproteobacteria.



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5 concepts for building a resilient community before an act of mass violence

These concepts will yield more prepared, capable and resilient communities

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Airway inflammation and injury in children with prevalent weakly acidic gastroesophageal refluxes

Respiratory Medicine

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Diabetes mellitus and hyperglycemia control on the risk of colorectal adenomatous polyps: A retrospective cohort study

BMC Family Practice

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Relationship between obstructive lung disease and non-alcoholic fatty liver disease in the Korean population: Korea National Health and Nutrition Examination Survey, 2007–2010

International Journal of COPD

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Impact of Immigration and Duration of Residence in US on Length of Gestation Among Black Women in Newark, New Jersey

Abstract

Little is known about pregnancy outcomes of black immigrant women to the US. We surveyed 447 black women post-partum in two hospitals in Newark, NJ. Length of gestation was obtained from medical records. Covariates and information on immigration were collected by in-person interview. Risks ratios for preterm birth (< 37 weeks) comparing immigrant to US-born women were calculated using log-binomial regression. Associations with gestational age at delivery were estimated using linear regression. Multivariable models adjusted for socioeconomic and social/behavioral variables. Immigrant women relative to US-born women had a 60% lower risk of preterm birth (adjusted risk ratio = 0.4; 95% confidence interval (CI) 0.2, 0.8) and longer gestation (adjusted difference = 1.4 weeks, 95%CI 0.6, 2.1). Gestation was 1.9 weeks longer for recent immigrants compared to US-born women (95%CI 0.2, 3.6), whereas for those who lived in the US for at least 10 years there was no difference. The healthy immigrant effect found among black immigrants may erode with time in the US.



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Endoscopic ultrasound-guided treatment of pancreatic fluid collections with lumen apposing metallic stents: lessons learned

Abstract

Pancreatic fluid collections are common pancreatitis complications that frequently require drainage. Endoscopic ultrasound-guided placement of expandable lumen apposing metallic stents has recently emerged as an effective and less invasive treatment option. It is associated with less morbidity, lower costs, and faster clinical recovery than other therapeutic modalities. Nevertheless, this procedure may result in severe complications such as bleeding, buried stent syndrome, and prosthesis dislodgement (with perforation and peritoneal leakage). We performed 108 EUS-guided drainages with lumen apposing metallic stents for the treatment of pancreatic fluid collections with 8 complications and only two cases that required urgent surgical procedures resulting in one fatality. We present this two severe complications submitted to surgical treatment and discuss potential signs of alarm that must be taken under consideration before choosing a treatment modality.



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Impacts of an Integrated Medicaid Managed Care Program for Adults with Behavioral Health Conditions: The Experience of Illinois

Abstract

This study assessed the impact of the Integrated Care Program (ICP), a new Medicaid managed care model in Illinois, on health services utilization and costs for adults with behavioral health conditions. Data sources included Medicaid claims, encounter records, and state payment data for 28,127 persons with a behavioral health diagnosis. Difference-in-differences models, in conjunction with propensity score weighting, were used to compare utilization and costs between ICP enrollees and a fee-for-service (FFS) comparison group. The model considered the impact of the SMART Act, which restricted access to care for the comparison group. Before the SMART Act, ICP was associated with 2.8 fewer all-cause primary care visits, 34.6 fewer behavioral health-specific outpatient visits, and 2.5 fewer all-cause inpatient admissions per 100 persons per month, and $228 lower total costs per member per month relative to the FFS group. After the SMART Act, ICP enrollees had increased outpatient and dental services utilization without significantly higher costs. The relative increase in utilization was due primarily to decreased utilization in the restricted FFS group after the SMART Act. By the end of the study period, the ICP group had 13.3 more all-cause primary care visits, 1.5 more emergency department visits, and 1.4 more dental visits per 100 persons per month relative to the FFS program. A fully-capitated, integrated managed care program has the potential to reduce overall Medicaid costs for people with behavioral health conditions without negative effects on service utilization.



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Successful treatment of an esophageal perforation that occurred during endoscopic submucosal dissection for esophageal cancer using polyglycolic acid sheets and fibrin glue

Abstract

A 74-year-old female, who was diagnosed with superficial esophageal cancer, underwent endoscopic submucosal dissection (ESD) at another hospital, but a perforation occurred during the procedure. The perforation was closed with endoscopic clips, and the ESD was halted. The patient was referred to our hospital, and ESD was retried. There was severe fibrosis around the lesion, and injections into the submucosal layer were difficult. In addition, it was not possible to identify the submucosal layer, and making an oral-side incision caused a large perforation along the incision line. As continuing the submucosal dissection with an endoknife was considered difficult, the lesion was finally resected with hybrid ESD using a snare. The perforation was closed using polyglycolic acid (PGA) sheets and fibrin glue. Endoscopy performed 6 days later showed that the defect had been closed, and no contrast leakage was detected. Follow-up endoscopy conducted 3 months after the ESD showed ulcer healing at the dissection site and scar formation, but no residual tumor or esophageal stricture was noted. Our experience suggests that the use of PGA sheets with fibrin glue is a feasible, safe, and effective way of treating large esophageal perforations during ESD.



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Πέμπτη, 30 Αυγούστου 2018

Oxidation of Ti-6Al-4V During Wire and Arc Additive Manufacture

3D Printing and Additive Manufacturing, Ahead of Print.


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Laparoscopic versus open repair for small paraumbilical hernia: A retrospective review

Asian Journal of Endoscopic Surgery, EarlyView.


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EMS Education Coordinator - Chesapeake Fire Department

This position is to provide Emergency Medical Service (EMS) education and training for quality improvement to the EMS personnel within the Fire Department. They will be responsible for assisting with the planning, development, implementation and training of education programs for EMS; evaluating EMS programs; establishing and maintaining EMS education schedules, recertification requirements and training ...

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Retraction

No abstract available

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WDR-23 and SKN-1/Nrf2 Coordinate with the BLI-3 Dual Oxidase in Response to Iodide-Triggered Oxidative Stress

Animals utilize conserved mechanisms to regulate oxidative stress. The Caenorhabditis elegans SKN-1 protein is homologous to the vertebrate Nrf (NF-E2-related factor) family of cap 'n' collar (CnC) transcription factors and functions as a core regulator of xenobiotic and oxidative stress responses. The WD40 repeat-containing protein WDR-23 is a key negative regulator of SKN-1 activity. We previously found that the oxidative stress induced by excess iodide can be relieved by loss of function in the BLI-3/TSP-15/DOXA-1 dual oxidase complex. To further understand the molecular mechanism of this process, we screened for new mutants that can survive in excess iodide and identified gain-of-function mutations in skn-1 and loss-of-function mutations in wdr-23. The SKN-1C isoform functions in the hypodermis to affect animal's response to excess iodide, while the SKN-1A isoform appears to play a minor role. wdr-23(lf) can interact with bli-3 mutations in a manner different from skn-1(gf). Transcriptome studies suggest that excess iodide causes developmental arrest largely independent of changes in gene expression, and wdr-23(lf) could affect the expression of a subset of genes by a mechanism different from SKN-1 activation. We propose that WDR-23 and SKN-1 coordinate with the BLI-3/TSP-15/DOXA-1 dual oxidase complex in response to iodide-triggered oxidative stress.



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Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events

The proper regulation of cell cycle transitions is paramount to the maintenance of cellular genome integrity. In Saccharomyces cerevisiae, the mitotic exit network (MEN) is a Ras-like signaling cascade that effects the transition from M phase to G1 during the cell division cycle in budding yeast. MEN activation is tightly regulated. It occurs during anaphase and is coupled to mitotic spindle position by the spindle position checkpoint (SPoC). Bfa1 is a key component of the SPoC and functions as part of a two-component GAP complex along with Bub2. The GAP activity of Bfa1-Bub2 keeps the MEN GTPase Tem1 inactive in cells with mispositioned spindles, thereby preventing inappropriate mitotic exit and preserving genome integrity. Interestingly, a GAP-independent role for Bfa1 in mitotic exit regulation has been previously identified. However the nature of this Bub2-independent role and its biological significance are not understood. Here we show that Bfa1 also activates the MEN by promoting the localization of Tem1 primarily to the daughter spindle pole body (dSPB). We demonstrate that the overexpression of BFA1 is lethal due to defects in Tem1 localization, which is required for its activity. In addition, our studies demonstrate a Tem1-independent role for Bfa1 in promoting proper cytokinesis. Cells lacking TEM1, in which the essential mitotic exit function is bypassed, exhibit cytokinesis defects. These defects are suppressed by the overexpression of BFA1. We conclude that Bfa1 functions to both inhibit and activate late mitotic events.



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Harvesting responses to single pulse electrical stimulation for presurgical evaluation in epilepsy

A Single Pulse Electrical Stimulation (SPES) protocol consists of pulses (repetition rate 0.1 – 1 Hz) of short lasting current stimuli (2-8 mA, pulse width <=1 ms) delivered to adjacent electrodes that are either part of intracranial grids (ECoG) or depth electrodes (SEEG) implanted in epilepsy patients for presurgical evaluation. Early studies using such a protocol aimed at confirming specific functional cortical connections in eloquent cortex by means of what was later called the cortico-cortical evoked potential (CCEP) (Wilson et al., 1990), or influencing cortical excitability in order to evoke (subclinical) habitual seizures (Kahane et al., 1993).

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The effects of aging on early stages of the auditory deviance detection system

The ability of the auditory system in extracting acoustic regularities and signaling deviance detection is critical for survival as it enables fast processing of novel events and preparing the organism to react quickly to potentially significant stimuli. Moreover, these two functional properties underlie the formation and segregation of auditory objects, which are necessary for solving the cocktail party problem and understanding speech in complex and noisy environments.

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Effects of Noise and Age on the Infant Brainstem Response to Speech

Speech perception depends on healthy sound transduction and faithful encoding of speech sound acoustics. Background noise can distort frequency analysis in the inner ear and disrupt auditory processing more centrally, making speech sounds difficult to decode. Problems in the middle ear, inner ear or central nervous system can exacerbate difficulties in hearing speech in noise, including early conductive hearing impairment (Keogh et al., 2010), sensorineural hearing loss at low or high frequencies (Laukli et al., 1985, Horwitz et al., 2002), diminished linguistic content during development (Cooper et al., 1989, Lieu, 2004, Stelmachowicz et al., 2004, Eisenberg, 2007, Moeller et al., 2015), and attention (Soderlund et al., 2016) or memory problems (McCreery et al., 2017, Millman et al., 2017).

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Auditory gamma oscillations predict global symptomatic outcome in the early stages of psychosis: a longitudinal investigation

The gamma-band auditory steady-state response (ASSR) is hypothesized to be a useful biomarker for psychosis (Uhlhaas and Singer, 2010). Kwon et al. (1999) performed the first study of 40-Hz ASSR in patients with schizophrenia using electroencephalography (EEG) and demonstrated a reduced power and synchronization in response to 40-Hz stimulation, but not to the 20-Hz stimulation, in these patients. This initial finding has been replicated in many studies using EEG (Brenner et al., 2003; Hamm et al., 2015; Hirano et al., 2015; Kirihara et al., 2012; Light et al., 2006; Spencer et al., 2008; Tada et al., 2016) or magnetoencephalography (MEG; Edgar et al., 2014; Teale et al., 2008; Tsuchimoto et al., 2011; Vierling-Claassen et al., 2008; Wilson et al., 2008).

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Effect of subthalamic nucleus deep brain stimulation on visual scanning

Since saccades reflect the activity of the superior colliculus, which receives projections from the basal ganglia, studies on saccades provide insights into the function of basal ganglia in various neurological conditions, including Parkinson's disease (PD) (Terao et al., 2011; Gorges et al., 2014). In fact, many studies have studied the performance of saccades in PD (White et al., 1983; Crawford et al., 1989; Nakamura et al., 1994; Vermersch et al., 1994; Kimmig et al., 2002; Yugeta et al., 2010; Terao et al., 2011; Matsumoto et al., 2011, 2012; Gorges et al., 2014).

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Electrodiagnosis and nerve ultrasound: “Castor and Pollux” in the management of neuropathies

The image of Dioscuri is used to describe the efficient union of two elements contributing to achieve a goal. They were Castor and Pollux, two strong brothers of Greek mythology, defenders of the sailors, during the sea storms. Similarly, electrodiagnosis (EDx) and nerve ultrasound (US) together "defend" the complex and "stormy" management of patients with peripheral neuropathies. A large amount of papers has shown the efficacy of association of EDx and US in nerve evaluation. Now, as hoped years ago, the association between US and EDx is often part of neurophysiological activity (Padua et al., 2013).

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A Modified Translaryngeal Tracheostomy Technique in the Neurointensive Care Unit. Rationale and Single-center Experience on 199 Acute Brain-damaged Patients

Background: Brain-injured patients frequently require tracheostomy, but no technique has been shown to be the gold standard for these patients. We developed and introduced into standard clinical practice an innovative bedside translaryngeal tracheostomy (TLT) technique aided by suspension laryngoscopy (modified TLT). During this procedure, the endotracheal tube is left in place until the airway is secured with the new tracheostomy. This study assessed the clinical impact of this technique in brain-injured patients. Materials and Methods: This is a retrospective analysis of prospectively collected data from adult brain-injured patients who had undergone modified TLT during the period spanning from January 2010 to December 2016 at the Neurointensive care unit, San Gerardo Hospital (Monza, Italy). The incidence of intraprocedural complications, including episodes of intracranial hypertension (intracranial pressure [ICP] >20 mm Hg), was documented. Neurological, ventilatory, and hemodynamic parameters were retrieved before, during, and after the procedure. Risk factors for complications and intracranial hypertension were assessed by univariate logistic analysis. Data are presented as n (%) and median (interquartile range) for categorical and continuous variables, respectively. Results: A total of 199 consecutive brain-injured patients receiving modified TLT were included. An overall 52% male individuals who were 66 (54 to 74) years old and who had an admission Glasgow Coma Scale of 7 (6 to 10) were included in the cohort. Intracerebral hemorrhage (30%) was the most frequent diagnosis. Neurointensivists performed 130 (65%) of the procedures. Patients underwent tracheostomy 10 (7 to 13) days after intensive care unit admission. Short (ie, 20 mm Hg were observed in 11 cases. Overall, the procedure was associated with an increase in ICP from 7 (4 to 10) to 12 (7 to 18) mm Hg (P

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Opioid exposure safety, superglottic airways and other EMS news of the week

Our co-hosts discuss hot topics related to EMS personnel, from cardiac arrest survival to a DOJ video regarding opioid exposure while on the job

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Incidental Durotomy in Degenerative Lumbar Spine Surgery – A register study of 64,431 operations

Incidental durotomy (ID) is one of the most common intraoperative complications seen in spine surgery. Conflicting evidence has been presented regarding whether or not outcomes are affected by the presence of an ID.

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Information needs of patients in spine surgery: development of a question prompt list to guide informed consent consultations

Informed consent is mandatory before surgery and fundamental in physician–patient interaction. However, communication is sometimes suboptimal.

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Clinical effect of early bisphosphonate treatment for pyogenic vertebral osteomyelitis with osteoporosis: An analysis by the Cox proportional hazard model

Patients with pyogenic vertebral osteomyelitis (PVO) are expected to have an increased risk of bone loss. Therefore, early bisphosphonate therapy would be clinically effective for PVO patients with osteoporosis.

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MicroRNA-494-dependent WDHDI inhibition suppresses epithelial-mesenchymal transition, tumor growth and metastasis in cholangiocarcinoma

Cholangiocarcinoma (CCA) represents a devastating malignancy characterized by high mortality, and notoriously problematic to diagnose. Recently, microRNAs (miRs) have been intensively investigated due to their potential usefulness from a tumor treatment perspective.

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MicroRNA-494-dependent WDHDI inhibition suppresses epithelial-mesenchymal transition, tumor growth and metastasis in cholangiocarcinoma

Cholangiocarcinoma (CCA) represents a devastating malignancy characterized by high mortality, and notoriously problematic to diagnose. Recently, microRNAs (miRs) have been intensively investigated due to their potential usefulness from a tumor treatment perspective.

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Rac1: supports muscle glucose uptake independently of Akt

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Nutritional programming by maternal obesity: Insights into the development of NAFLD

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Recovery of respiratory function in mdx mice co‐treated with neutralizing interleukin‐6 receptor antibodies and Urocortin‐2

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Army Expeditionary Technology Search selects SimpleSense’s first responder technology for Army modernization competition

Playa Vista, Calif. - Otherwise known as xTechSearch, the Army Expeditionary Search is part of a transformation underway in all branches of the military to innovative rapidly to attack problems, like a startup. After reviewing 340 white papers submitted by small businesses and startups that showcased how novel research and technology ideas could benefit the Army's modernization priorities,...

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Genome-wide analysis of Hanwoo and Chikso populations using the BovineSNP50 genotyping array

Abstract

Hanwoo and Chikso are classified as Korean native cattle breeds that are currently registered with the Food and Agriculture Organization. However, there is still a lack of genomic studies to compare Hanwoo to Chikso populations. The objective of this study was to perform genome-wide analysis of Hanwoo and Chikso populations, investigating the genetic relationships between these two populations. We genotyped a total of 319 cattle including 214 Hanwoo and 105 Chikso sampled from Gangwon Province Livestock Technology Research Institute, using the Illumina Bovine SNP50K Beadchip. After performing quality control on the initially generated datasets, we assessed linkage disequilibrium patterns for all the possible SNP pairs within 1 Mb apart. Overall, average r2 values in Hanwoo (0.048) were lower than Chikso (0.074) population. The genetic relationship between the populations was further assured by the principal component analysis, exhibiting clear clusters in each of the Hanwoo and Chikso populations, respectively. Overall heterozygosity for Hanwoo (0.359) was slightly higher than Chikso (0.345) and inbreeding coefficient was also a bit higher in Hanwoo (− 0.015) than Chikso (− 0.035). The average FST value was 0.036 between Hanwoo and Chikso, indicating little genetic differentiation between those two breeds. Furthermore, we found potential selection signatures including LRP1B and NTRK2 genes that might be implicated with meat and reproductive traits in cattle. In this study, the results showed that both Hanwoo and Chikso populations were not under severe level of inbreeding. Although the principal component analysis exhibited clear clusters in each of the populations, we did not see any clear evidence that those two populations are highly differentiated each other.



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Bilateral independent periodic discharges are associated with electrographic seizures and poor outcome: a case-control study

Publication date: Available online 29 August 2018

Source: Clinical Neurophysiology

Author(s): Gamaleldin Osman, Rahul Rahangdale, Jeffrey W. Britton, Emily J. Gilmore, Hiba Arif Haider, Stephen Hantus, Aline Herlopian, Sara E. Hocker, Jong Woo Lee, Benjamin Legros, Michael Mendoza, Vineet Punia, Nishi Rampal, Jerzy P. Szaflarski, Adam D. Wallace, M. Brandon Westover, Lawrence J. Hirsch, Nicolas Gaspard

Abstract
Objective

To determine the clinical correlates bilateral independent periodic discharges (BIPDs) and their association with electrographic seizures and outcome.

Methods

Retrospective case-control study of patients with BIPDs compared to patients without periodic discharges ("No PDs") and patients with lateralized periodic discharges ("LPDs"), matched for age, etiology and level of alertness.

Results

We included 85 cases and 85 controls in each group. The most frequent etiologies of BIPDs were stroke, CNS infections, and anoxic brain injury. Acute bilateral cerebral injury was more common in the BIPDs group than in the No PDs and LPDs groups (70% vs. 37% vs. 35%). Electrographic seizures were more common with BIPDs than in the absence of PDs (45% vs. 8%), but not than with LPDs (52%). Mortality was higher in the BIPDs group (36%) than in the No PDs group (18%), with fewer patients with BIPDs achieving good outcome (moderate disability or better; 18% vs. 36%), but not than in the LPDs group (24% mortality, 26% good outcome). In multivariate analyses, BIPDs remained associated with mortality (OR: 3.0 [1.4-6.4]) and poor outcome (OR: 2.9 [1.4-6.2]).

Conclusion

BIPDs are caused by bilateral acute brain injury and are associated with a high risk of electrographic seizures and of poor outcome.

Significance

BIPDs are uncommon but their identification in critically ill patients has potential important implications, both in terms of clinical management and prognostication.



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Neurophysiological Monitoring during Cervical Spine Surgeries: Longitudinal Costs and Outcomes

Publication date: Available online 29 August 2018

Source: Clinical Neurophysiology

Author(s): John P. Ney, Daniel P. Kessler

Abstract
Objectives

Well-designed longitudinal studies assessing effectiveness of intraoperative neurophysiologic monitoring (IONM) are lacking. We investigate IONM effects on cost and administrative markers for health outcomes in the year after cervical spine surgery.

Methods

We identified single-level cervical spine surgeries in commercial claims. We constructed linear regression models estimating the effect of IONM (controlling for patient demographics, pre-operative health, services during index admission) on total spending, neurological complications, readmissions, and outpatient opiate usage in the year following index surgery.

Results

IONM was associated with increased spending during index admission of $1,229 (p = 0.001), but decreased spending post-discharge of $1,615 (p = 0.010), for a net -$386 (p = 0.608) for the year after surgery. Shorter length of stay (0.116 days, p = 0.004) and fewer readmissions (20.5 per thousand, p = 0.036) accounted for some post-discharge savings. IONM was associated with decreased rates of nervous system complications (4/1000, p = 0.048) and post-discharge opiate use (17 prescriptions/1000, p = 0.050) in the year after index admission.

Conclusions

IONM was associated with administrative markers suggesting improved health outcomes after cervical spine surgery without greater costs for the year.

Significance

This study suggests IONM may have lasting health and cost benefits.



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Bowel wall healing assessed using magnetic resonance imaging predicts sustained clinical remission and decreased risk of surgery in Crohn’s disease

Abstract

Background

Endoscopic mucosal healing is considered as the best therapeutic target in Crohn's disease (CD) as it is associated with better long-term outcomes. We investigated whether bowel wall healing (BWH) assessed using magnetic resonance imaging (MRI) could predict favorable outcomes and could be a potential therapeutic target.

Methods

We performed a post hoc analysis from two prospective studies (n = 174 patients). All the patients with previous objective signs of bowel inflammation and assessed by MRI for therapeutic efficacy had a standardized and blinded evaluation, and underwent MRI. Complete BWH was defined as no segmental MaRIA > 7 or no segmental Clermont score > 8.4 and BWH as no segmental MaRIA > 11 or no segmental Clermont score > 12.5. Clinical corticosteroid-free remission (CFREM) was defined as no reappearance or worsening of clinical manifestation leading to therapeutic modification, hospitalization or CD-related surgery. Multivariate analyses were performed including all the relevant parameters.

Results

Overall, 63 patients with CD were included (mean follow-up = 4.8 ± 3.1 semesters). In multivariate analysis (n = 303 semesters), complete BWH or BWH was associated with sustained CFREM according to MaRIA [OR = 4.42 (2.29–26.54); p = 0.042 and OR = 3.43 (1.02–27.02); p = 0.047, respectively] or Clermont score [OR = 3.09 (1.01–12.91); p = 0.049 and OR = 3.88 (1.40–13.80); p = 0.036, respectively]. In multivariate analysis (n = 63 patients), complete BWH or BWH was associated with decreased risk of surgery using MaRIA [HR = 0.16 (0.043–0.63); p = 0.008 and HR = 0.24 (0.07–0.77); p = 0.017, respectively] or Clermont score [HR = 0.24 (0.07–0.78); p = 0.016 and HR = 0.23 (0.07–0.76); p = 0.016, respectively].

Conclusions

MRI endpoints are predictive of favorable outcomes after medical therapy and could be used as therapeutic target in daily practice and clinical trials.



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Remifentanil suppresses increase in interleukin-6 mRNA in the brain by inhibiting cyclic AMP synthesis

Abstract

Purpose

Neuronal inflammation is caused by systemic inflammation and induces cognitive dysfunction. IL-6 plays a crucial role in therapies for neuronal inflammation and cognitive dysfunction. Remifentanil, an ultra-short-acting opioid, controls inflammatory reactions in the periphery, but not in the brain. Therefore, the anti-inflammatory effects of remifentanil in neuronal tissue and the involvement of cAMP in these effects were investigated in the present study.

Methods

Mice were divided into 4 groups: control, remifentanil, LPS, and LPS + remifentanil. Brain levels of pro-inflammatory cytokine mRNA, and serum levels of corticosterone, catecholamine and IL-6 were measured in the 4 groups. The co-localization of IL-6 and astrocytes in the mouse brain after the LPS injection was validated by immunostaining. LPS and/or remifentanil-induced changes in intracellular cAMP levels in cultured glial cells were measured, and the effects of cAMP on LPS-induced IL-6 mRNA expression levels were evaluated.

Results

Remifentanil suppressed increase in IL-6 mRNA levels in the mouse brain, and also inhibited the responses of plasma IL-6, corticosterone, and noradrenaline in an inflammatory state. In the hypothalamus, IL-6 was localized in the median eminence, at which GFAP immunoreactivity was specifically detected. In cultured cells, remifentanil suppressed increase in IL-6 mRNA levels and intracellular cAMP levels after the administration of LPS, and this enhanced IL-6 mRNA expression in response to LPS.

Conclusion

Remifentanil suppressed increase in IL-6 mRNA levels in the brain in an inflammatory state, and this effect may be attributed to its direct action on neuronal cells through the inhibition of intracellular cAMP rather than corticosterone.



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Randomized comparative study between two different techniques of intercostobrachial nerve block together with brachial plexus block during superficialization of arteriovenous fistula

Abstract

Background

This study compared proximal and distal approaches of intercostobrachial nerve block (ICBNB) combined with infraclavicular brachial plexus block (ICBPB) during superficialization of arteriovenous fistula.

Methods

Seventy adult patients were randomized to receive ICBPB and 6 ml 0.25% bupivacaine at the level of the 3rd rib in the anterior axillary line between pectoralis minor and serratus anterior muscles (group P) or subcutaneously along the medial side of the upper arm (group D). The primary outcome was the achievement of complete sensory block. Secondary outcomes were onset of analgesia, volume of local anesthetic (LA) supplementation, fentanyl administration, success rate, and conversion to general anesthesia (GA).

Results

Complete sensory block in the medial side of the upper arm was achieved in 91% of patients in group P and 51% in group D. Failure rate of ICBNB was higher in group D (49%) than group P (14%). Conversion to GA was determined by the attending anesthesiologist in 26% of patients in group D and 0% in group P. LA supplementation was required in 5 patients in group P and 11 patients in group D, and the mean volume of LA was statistically higher in group D than group P (9.5 ± 1.5, 7.5 ± 2 ml, respectively). Onset of sensory block was faster in group P than group D (8.75 ± 1.67 and 10 ± 2.14 min, respectively). No differences were observed regarding fentanyl administration.

Conclusion

ICBNB proximal approach provides a high success rate with less amount of rescue analgesia compared to the distal approach.



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Identification of the Novel Nup188-brr7 Allele in a Screen for Cold-Sensitive mRNA Export Mutants in Saccharomyces cerevisiae

The maturation and export of mRNA from the nucleus through the nuclear pore complex is critical for maintaining an appropriate proteome in all eukaryotic cells. Here we summarize a previously unpublished screen in S. cerevisiae that utilized an established dT50 in situ hybridization assay to identify cold-sensitive mutants that accumulated bulk poly A RNA in the nucleus. The screen identified seven mutants in six complementation groups, including the brr6-1 strain that we described previously. In addition to brr6-1, we identified novel alleles of the key transport gene GLE1 and NUP188, a component of the Nic96 nucleoporin complex. Notably, we show that the nup188-brr7 allele causes defects in select protein import pathways as well as mRNA export. Given recent structural and functional evidence linking the Nic96 complex to transport components, this mutant may be particularly useful to the transport community.



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Tandem Duplicate Genes in Maize Are Abundant and Date to Two Distinct Periods of Time

Tandem duplicate genes are proximally duplicated and as such occur in similar genomic neighborhoods. Using the maize B73 and PH207 de novo genome assemblies, we identified thousands of tandem gene duplicates that account for ~10% of the annotated genes. These tandem duplicates have a bimodal distribution of ages, which coincide with ancient allopolyploidization and more recent domestication. Tandem duplicates are smaller on average and have a higher probability of containing LTR elements than other genes, suggesting origins in nonhomologous recombination. Within relatively recent tandem duplicate genes, ~26% appear to be undergoing degeneration or divergence in function from the ancestral copy. Our results show that tandem duplicates are abundant in maize, arose in bursts throughout maize evolutionary history under multiple potential mechanisms, and may provide a substrate for novel phenotypic variation.



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Whole Genome Sequence of the Parasitoid Wasp Microplitis demolitor That Harbors an Endogenous Virus Mutualist

Microplitis demolitor (Hymenoptera: Braconidae) is a parasitoid used as a biological control agent to control larval-stage Lepidoptera and serves as a model for studying the function and evolution of symbiotic viruses in the genus Bracovirus. Here we present the M. demolitor genome (assembly version 2.0), with a genome size of 241 Mb, and a N50 scaffold and contig size of 1.1 Mb and 14 Kb, respectively. Using RNA-Seq data and manual annotation of genes of viral origin, we produced a high-quality gene set that includes 18,586 eukaryotic and 171 virus-derived protein-coding genes. Bracoviruses are dsDNA viruses with unusual genome architecture, in which the viral genome is integrated into the wasp genome and is comprised of two distinct components: proviral segments that are amplified, circularized, and packaged into virions for export into the wasp's host via oviposition; and replication genes. This genome assembly revealed that at least two scaffolds contain both nudivirus-like genes and proviral segments, demonstrating that at least some of these components are near each other in the genome on a single chromosome. The updated assembly and annotation are available in several publicly accessible databases; including the National Center for Biotechnology Information and the Ag Data Commons. In addition, all raw sequence data available for M. demolitor have been consolidated and are available for visualization at the i5k Workspace. This whole genome assembly and annotation represents the only genome-scale, annotated assembly from the lineage of parasitoid wasps that has associations with bracoviruses (the 'microgastroid complex'), providing important baseline knowledge about the architecture of co-opted virus symbiont genomes.



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Targeted Gene Sequencing in Children with Crohns Disease and Their Parents: Implications for Missing Heritability

Crohn's disease is a complex genetic trait characterized by chronic relapsing intestinal inflammation. Genome wide association studies (GWAS) have identified more than 170 loci associated with the disease, accounting for ~14% of the disease variance. We hypothesized that rare genetic variation in GWAS positional candidates also contribute to disease pathogenesis. We performed targeted, massively-parallel sequencing of 101 genes in 205 children with Crohn's disease, including 179 parent-child trios and 200 controls, both of European ancestry. We used the gene burden test implemented in VAAST and estimated effect sizes using logistic regression and meta-analyses. We identified three genes with nominally significant p-values: NOD2, RTKN2, and MGAT3. Only NOD2 was significant after correcting for multiple comparisons. We identified eight novel rare variants in NOD2 that are likely disease-associated. Incorporation of rare variation and compound heterozygosity nominally increased the proportion of variance explained from 0.074 to 0.089. We estimated the population attributable risk and total heritability of variation in NOD2 to be 32.9% and 3.4%, respectively, with 3.7% and 0.25% accounted for by rare putatively functional variants. Sequencing probands (as opposed to genotyping) to identify rare variants and incorporating phase by sequencing parents can recover a portion of the missing heritability of Crohn's disease.



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Transcriptome Analysis of Four Arabidopsis thaliana Mediator Tail Mutants Reveals Overlapping and Unique Functions in Gene Regulation

The Mediator complex is a central component of transcriptional regulation in Eukaryotes. The complex is structurally divided into four modules known as the head, middle, tail and kinase modules, and in Arabidopsis thaliana, comprises 28-34 subunits. Here, we explore the functions of four Arabidopsis Mediator tail subunits, MED2, MED5a/b, MED16, and MED23, by comparing the impact of mutations in each on the Arabidopsis transcriptome. We find that these subunits affect both unique and overlapping sets of genes, providing insight into the functional and structural relationships between them. The mutants primarily exhibit changes in the expression of genes related to biotic and abiotic stress. We find evidence for a tissue specific role for MED23, as well as in the production of alternative transcripts. Together, our data help disentangle the individual contributions of these MED subunits to global gene expression and suggest new avenues for future research into their functions.



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Optimising Genomic Selection in Wheat: Effect of Marker Density, Population Size and Population Structure on Prediction Accuracy

Genomic selection applied to plant breeding enables earlier estimates of a line's performance and significant reductions in generation interval. Several factors affecting prediction accuracy should be well understood if breeders are to harness genomic selection to its full potential. We used a panel of 10,375 bread wheat (Triticum aestivum) lines genotyped with 18,101 SNP markers to investigate the effect and interaction of training set size, population structure and marker density on genomic prediction accuracy. Through assessing the effect of training set size we showed the rate at which prediction accuracy increases is slower beyond approximately 2,000 lines. The structure of the panel was assessed via principal component analysis and K-means clustering, and its effect on prediction accuracy was examined through a novel cross-validation analysis according to the K-means clusters and breeding cohorts. Here we showed that accuracy can be improved by increasing the diversity within the training set, particularly when relatedness between training and validation sets is low. The breeding cohort analysis revealed that traits with higher selection pressure (lower allelic diversity) can be more accurately predicted by including several previous cohorts in the training set. The effect of marker density and its interaction with population structure was assessed for marker subsets containing between 100 and 17,181 markers. This analysis showed that response to increased marker density is largest when using a diverse training set to predict between poorly related material. These findings represent a significant resource for plant breeders and contribute to the collective knowledge on the optimal structure of calibration panels for genomic prediction.



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A Bayesian Decision Theory Approach for Genomic Selection

Plant and animal breeders are interested in selecting the best individuals from a candidate set for the next breeding cycle. In this paper, we propose a formal method under the Bayesian decision theory framework to tackle the selection problem based on genomic selection (GS) in single- and multi-trait settings. We proposed and tested three univariate loss functions (Kullback-Leibler, KL; Continuous Ranked Probability Score, CRPS; Linear-Linear loss, LinLin) and their corresponding multivariate generalizations (Kullback-Leibler, KL; Energy Score, EnergyS; and the Multivariate Asymmetric Loss Function, MALF). We derived and expressed all the loss functions in terms of heritability and tested them on a real wheat dataset for one cycle of selection and in a simulated selection program. The performance of each univariate loss function was compared with the standard method of selection (Std) that does not use loss functions. We compared the performance in terms of the selection response and the decrease in the population's genetic variance during recurrent breeding cycles. Results suggest that it is possible to obtain better performance in a long-term breeding program using the single-trait scheme by selecting 30% of the best individuals in each cycle but not by selecting 10% of the best individuals. For the multi-trait approach, results show that the population mean for all traits under consideration had positive gains, even though two of the traits were negatively correlated. The corresponding population variances were not statistically different from the different loss function during the 10th selection cycle. Using the loss function should be a useful criterion when selecting the candidates for selection for the next breeding cycle.



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Tripartite Chromatin Localization of Budding Yeast Shugoshin Involves Higher-Ordered Architecture of Mitotic Chromosomes

The spindle assembly checkpoint (SAC) is key to faithful segregation of chromosomes. One requirement that satisfies SAC is appropriate tension between sister chromatids at the metaphase-anaphase juncture. Proper tension generated by poleward pulling of mitotic spindles signals biorientation of the underlying chromosome. In the budding yeast, the tension status is monitored by the conserved Shugoshin protein, Sgo1p, and the tension sensing motif (TSM) of histone H3. ChIP-seq reveals a unique TSM-dependent, tripartite domain of Sgo1p in each mitotic chromosome. This domain consists of one centromeric and two flanking peaks 3 – 4 kb away, present exclusively in mitosis. Strikingly, this trident motif coincides with cohesin localization, but only at the centromere and the two immediate adjacent loci, despite that cohesin is enriched at numerous regions throughout mitotic chromosomes. Chromosome conformation capture assays reveal apparent looping at the centromeric and pericentric regions. The TSM-Sgo1p-cohesin triad is therefore at the center stage of higher-ordered chromatin architecture for error-free segregation.



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Physiological Starvation Promotes Caenorhabditis elegans Vulval Induction

Studying how molecular pathways respond to ecologically relevant environmental variation is fundamental to understand organismal development and its evolution. Here we characterize how starvation modulates Caenorhabditis elegans vulval cell fate patterning – an environmentally sensitive process, with a nevertheless robust output. Past research has shown many vulval mutants affecting EGF-Ras-MAPK, Delta-Notch and Wnt pathways to be suppressed by environmental factors, such as starvation. Here we aimed to resolve previous, seemingly contradictory, observations on how starvation modulates levels of vulval induction. Using the strong starvation suppression of the Vulvaless phenotype of lin-3/egf reduction-of-function mutations as an experimental paradigm, we first tested for a possible involvement of the sensory system in relaying starvation signals to affect vulval induction: mutation of various sensory inputs, DAF-2/Insulin or DAF-7/TGF-β signaling did not abolish lin-3(rf) starvation suppression. In contrast, nutrient deprivation induced by mutation of the intestinal peptide transporter gene pept-1 or the TOR pathway component rsks-1 (the ortholog of mammalian P70S6K) very strongly suppressed lin-3(rf) mutant phenotypes. Therefore, physiologically starved animals induced by these mutations tightly recapitulated the effects of external starvation on vulval induction. While both starvation and pept-1 RNAi were sufficient to increase Ras and Notch pathway activities in vulval cells, the highly penetrant Vulvaless phenotype of a tissue-specific null allele of lin-3 was not suppressed by either condition. This and additional results indicate that partial lin-3 expression is required for starvation to affect vulval induction. These results suggest a cross-talk between nutrient deprivation, TOR-S6K and EGF-Ras-MAPK signaling during C. elegans vulval induction.



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