Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Publication date: Available online 8 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Mads Bengtsen, Linda Sørensen, Linn Aabel, Marit Ledsaak, Vilborg Matre, Odd Stokke Gabrielsen
LIM-domain proteins, containing multiple cysteine-rich zinc finger-like motifs, have been shown to play diverse roles in several cellular processes. A common theme is that they mediate important protein-protein interactions that are key to their function. Androgen receptor-associated protein 55 (ARA55) belongs to this family of bridging proteins containing four C-terminal LIM domains. It has a dual role with functions both at focal adhesions and in the nucleus, apparently shuttling between the two compartments. In the present work, we have expanded our understanding of its nuclear functions by showing that it interacts with three nuclear regulators not previously linked to ARA55. We first identified ARA55 as a novel interaction partner of the nuclear kinase HIPK1 and found that ARA55, like HIPK1, also interacts with the transcription factor c-Myb. In search of a function for these associations, we observed that the coactivator p300 not only binds to c-Myb, but to ARA55 as well. When combined, c-Myb, p300, HIPK1 and ARA55 caused strong synergistic activation of a chromatinized reporter gene. In parallel, all partners, including p300, were efficiently recruited to chromatin at the c-Myb-bound promoter. Consistent with this cooperation, we found that c-Myb and ARA55 share a common set of target genes in an osteosarcoma cellular context. We propose that ARA55 and HIPK1 assist c-Myb in recruiting the coactivator and acetyltransferase p300 to chromatin.
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<span class="paragraphSection"><div class="boxedTextSection">Key points<ul><li class="bullet">Acute respiratory distress syndrome (ARDS) is commonly encountered in the critical care population and is associated with a high mortality of between 27% and 45%.</li><li class="bullet">ARDS is diagnosed according to the Berlin definition and is characterized as mild, moderate, or severe depending on the <span style="font-style:italic;">P</span>a<span style="text-transform:lowercase;font-variant:small-caps;">O</span><sub>2</sub>/<span style="font-style:italic;">FI</span><span style="text-transform:lowercase;font-variant:small-caps;">O</span><sub>2</sub> ratio.</li><li class="bullet">Accepted management strategies include lung protective ventilation with tidal volumes limited to 6 ml kg<sup>−</sup><sup>1</sup>, positive end expiratory pressure increasing in line with oxygen requirement, and prone positioning in severe cases.</li><li class="bullet">Steroids, statins, inhaled nitric oxide, and high-frequency oscillation ventilation do not have a role in the routine management of adults with ARDS.</li><li class="bullet">Adverse functional and neuropsychological outcomes are increasingly recognized in long-term ARDS survivors.</li></ul></div></span>
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Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications.
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Alzheimer's disease (AD) is a progressive degenerative disease, affecting memory and other cognitive functions. The neural characteristics of AD are structural changes such as widespread atrophy and deposits of amyloid plaques and tau protein neurofibrillary tangles, particularly in the hippocampus, entorhinal cortex and post-central parietal areas (Lizio et al. 2011).
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Intraoperative neurophysiological monitoring (IONM) has made tremendous steps forward in providing reliable techniques to assist surgeons, and neurosurgeons in particular, during challenging surgical procedures, where neural structures are at risk of injury. Over the past two decades a number of valuable IONM techniques have been introduced, with continuous monitoring of muscle motor evoked potentials (mMEPs) under general anesthesia (Taniguchi et al. 1993) being likely the one with a major impact in clinical practice.
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Background/contextThe evidence for the treatment for non-specific chronic low back pain (ns CLBP) is very weak. Besides the complexity of the pain experience, a good biological marker or tool enabling identification of a pain generator is lacking. Hybrid imaging, combining Single Photon Emission Computerized Tomography (SPECT) with Computerized Tomography (CT)-scan, has been proposed as useful in the diagnostic workup of CLBP patients.PurposeTo evaluate the sensitivity of SPECT-CT in patients with ns CLBP (group I) as compared to patients without CLBP (Group II).
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Prevertebral soft tissue swelling (PSTS) after anterior cervical spine surgery (ACSS) has been regarded as one of the critical complications that cause airway obstruction. Still, however, no research has dealt with how PSTS returns to pre-surgery status after ACSS; most recommendations are being performed without information about its natural course, focusing on acute-phase swelling after surgery.
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The patient experience of care as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is currently used to determine hospital reimbursement. The current literature inconsistently demonstrates an association between patient satisfaction and surgical outcomes.
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Previous studies have suggested pulmonary complications are common among patients undergoing fixation for traumatic spine fractures. This leads to prolonged hospital stay, worse functional outcomes, and increased economic burden. However, only limited prognostic information exists regarding which patients are at greatest risk for pulmonary complications.
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Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications.
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Rapid irrigant delivery, coupled with user-selected quantifiable pressure, revolutionizes wound management for optimal healing outcomes WILLIAMSTON, Mich. — Centurion Medical Products, a leader in medical product innovation and global patient care, is making a major stride in emergency room acute wound management with the launch of its IRIG-8™Wound Irrigation System. IRIG-8's sterile ...
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An emerging class of long noncoding RNAs (lncRNAs) function as decoy molecules that bind and sequester proteins thereby inhibiting their normal functions. Titration of proteins by lncRNAs has wide-ranging effects affecting nearly all steps in gene expression. While decoy lncRNAs play a role in normal physiology, RNAs expressed from alleles containing nucleotide repeat expansions can be pathogenic due to protein sequestration resulting in disruption of normal functions. This review focuses on commonalities between decoy lncRNAs that regulate gene expression by competitive inhibition of protein function through sequestration and specific examples of nucleotide repeat expansion disorders mediated by toxic RNA that sequesters RNA-binding proteins and impedes their normal functions. Understanding how noncoding RNAs compete with various RNA and DNA molecules for binding of regulatory proteins will provide insight into how similar mechanisms contribute to disease pathogenesis.
An EMS student and the patient on board were hurt in the crash
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Jeff Rehman shows a choking technique on how to save more lives.
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Jeff Rehman shows a choking technique on how to save more lives.
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Jeff Rehman shows a choking technique on how to save more lives.
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Jeff Rehman shows a choking technique on how to save more lives.
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Review the three indications that a patient needs their airway managed in this episode of Progressive Paramedicine, an EMS1 original video series.
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Review the three indications that a patient needs their airway managed in this episode of Progressive Paramedicine, an EMS1 original video series.
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Review the three indications that a patient needs their airway managed in this episode of Progressive Paramedicine, an EMS1 original video series.
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National Association of State EMS Officials FALLS CHURCH, Va. — The National Association of State EMS Officials is pleased to announce the release of a new report: Organization, Staffing, and Functions of State EMS Offices. Organization, Staffing, and Functions of State EMS Offices summarizes the findings from a 2016-2017 survey of state EMS offices on how EMS offices are organizationally situated; ...
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Progressive fire department offering exciting opportunities for a career in firefighting and emergency medical services! We are accepting applications beginning May 19 to establish a list of qualified candidates to fill anticipated vacancies due to retirement. Minimum qualifications are: full time career fire academy graduate with Virginia certifications or Virginia or National Registry Intermediate ...
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Anaesthesia can induce cognitive deficiency in young rodents and monkeys. Mitochondrial dysfunction contributes to the anaesthesia-induced neurotoxicity and neurobehavioural deficits. We therefore assessed the effects of the mitochondrial energy enhancer coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>) on anaesthesia-induced cognitive deficiency in young mice to investigate the role of mitochondrial dysfunction.<strong>Methods.</strong> Young mice (<span style="font-style:italic;">n</span>=134) were randomly assigned into the following four groups: control plus corn oil vehicle (60% oxygen); 3% sevoflurane [2 h daily on postnatal day (P) 6, 7, and 8] plus vehicle; CoQ<sub>10</sub> (50 mg kg<sup>−1</sup>) plus vehicle; or 3% sevoflurane plus CoQ<sub>10</sub> plus vehicle. We determined cognitive function using the Morris water maze at P31-P37. We quantified brain postsynaptic density protein-95, the presynaptic marker synaptophysin, adenosine triphosphate, reactive oxygen species, and mitochondrial membrane potential at P8 and P37.<strong>Results.</strong> Coenzyme Q<sub>10</sub> reduced sevoflurane-induced cognitive deficiency in young mice (<span style="font-style:italic;">F</span>=0.90, <span style="font-style:italic;">P</span>=0.49, <span style="font-style:italic;">n</span>=10–16) and attenuated sevoflurane-induced reductions in postsynaptic density protein-95 (<span style="font-style:italic;">F</span>=10.56, <span style="font-style:italic;">P</span><0.01, <span style="font-style:italic;">n</span>=6), synaptophysin (<span style="font-style:italic;">F</span>=8.44, <span style="font-style:italic;">P</span>=0.01, <span style="font-style:italic;">n</span>=6), adenosine triphosphate (<span style="font-style:italic;">F</span>=4.34, <span style="font-style:italic;">P</span>=0.05, <span style="font-style:italic;">n</span>=9), and mitochondrial membrane potential (<span style="font-style:italic;">F</span>=11.43, <span style="font-style:italic;">P</span><0.01, <span style="font-style:italic;">n</span>=6), but not sevoflurane-induced increases in reactive oxygen species (<span style="font-style:italic;">F</span>=1.17, <span style="font-style:italic;">P</span>=0.20, <span style="font-style:italic;">n</span>=6), in brain.<strong>Conclusions.</strong> These data suggest that CoQ<sub>10</sub> reduces sevoflurane-induced cognitive deficiency by mitigating sevoflurane-induced mitochondrial dysfunction, the reduction in adenosine triphosphate, and synaptic dysfunction. Coenzyme Q<sub>10</sub> could provide an approach to reduce the neurotoxicity of anaesthesia in the developing brain.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Perioperative anaemia is common. Physicians believe that patients at increased cardiac risk do not tolerate anaemia and, consequently, these patients receive transfusions earlier and more often. This practice runs counter to a growing body of evidence that perioperative red blood cell (RBC) transfusion is harmful<strong>.</strong> The aims of this study were as follows: (i) to assess the effects of transfusion at moderate to severely low ranges of postoperative haemoglobin concentrations; and (ii) to assess whether transfusion was beneficial in patients at high cardiac risk within these haemoglobin ranges.<strong>Methods.</strong> A single-centre retrospective cohort study enrolled 75 719 consecutive major, non-cardiac surgery patients. Multivariable logistic regressions with 98.4% confidence intervals looking at specific nadir postoperative haemoglobin groups were compared to examine the effects of anaemia, RBC transfusion, and cardiac risk on postoperative 30 day in-hospital mortality.<strong>Results.</strong> Patients at moderate to high cardiac risk had a two-fold greater prevalence of preoperative anaemia. In unadjusted analysis, RBC transfusion was associated with increased mortality at all transfusion thresholds in all patients. After adjustment, RBC transfusion in patients with high cardiac risk was associated with decreased mortality when the postoperative haemoglobin concentration was <80 g litre<sup>−1</sup> [odds ratio 0.37 (98.4% confidence interval 0.17–0.77)].<strong>Conclusions.</strong> High cardiac risk was associated with increased incidence of anaemia, transfusion, and mortality. Red blood cell transfusion is associated with reduced mortality only in high cardiac risk patients with nadir postoperative haemoglobin concentration <80 g litre<sup>−1</sup>. Transfusion, the main treatment for postoperative anaemia, does not appear to be associated with reduced postoperative mortality at higher nadir haemoglobin ranges.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> The learning environment describes the context and culture in which trainees learn. In order to establish the feasibility and reliability of measuring the anaesthetic learning environment in individual departments we implemented a previously developed instrument in hospitals across New South Wales.<strong>Methods.</strong> We distributed the instrument to trainees from 25 anaesthesia departments and supplied summarized results to individual departments. Exploratory and confirmatory factor analyses were performed to assess internal structure validity and generalizability theory was used to calculate reliability. The number of trainees required for acceptable precision in results was determined using the standard error of measurement.<strong>Results.</strong> We received 172 responses (59% response rate). Suitable internal structure validity was confirmed. Measured reliability was acceptable (G-coefficient 0.69) with nine trainees per department. Eight trainees were required for a 95% confidence interval of plus or minus 0.25 in the mean total score. Eight trainees as assessors also allow a 95% confidence interval of approximately plus or minus 0.3 in the subscale mean scores. Results for individual departments varied, with scores below the expected level recorded on individual subscales, particularly the 'teaching' subscale.<strong>Conclusions.</strong> Our results confirm that, using this instrument, individual departments can obtain acceptable precision in results with achievable trainee numbers. Additionally, with the exception of departments with few trainees, implementation proved feasible across a training region. Repeated use would allow departments or accrediting bodies to monitor their individual learning environment and the impact of changes such as the introduction of new curricular elements, or local initiatives to improve trainee experience.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Mask ventilation and tracheal intubation are basic techniques for airway management and mutually inclusive rescue measures to restore ventilation. The aim of this study was to compare the effectiveness of mask ventilation between two commonly used techniques of two-handed mask ventilation in obese unconscious apnoeic adults.<strong>Methods.</strong> Eighty-one obese adults received mask ventilation after induction using C-E clamp and modified V-E clamp techniques in a randomized crossover manner. Mechanical ventilation was provided using a pressure-control mode, at a rate of 10 bpm, with an inspiratory-to-expiratory time ratio of 1:2 and a pre-set plateau airway pressure of 20 cm H<sub>2</sub>O. The primary outcome was expired tidal volume.<strong>Results.</strong> The BMI for the subjects was 37 (<span style="text-transform:lowercase;font-variant:small-caps;">sd</span> 4.9) kg m<sup>−2</sup>. The failure rates for mask ventilation (tidal volume≤anatomical dead space) were 44% for the C-E technique and 0% for the V-E technique (<span style="font-style:italic;">P</span><0.001). Tidal volume was significantly lower for the C-E than the V-E technique [371 (<span style="text-transform:lowercase;font-variant:small-caps;">sd</span> 345) <span style="font-style:italic;">vs</span> 720 (244) ml, <span style="font-style:italic;">P</span><0.001]. The peak airway pressures were 21 (<span style="text-transform:lowercase;font-variant:small-caps;">sd</span> 1.5) cm H<sub>2</sub>O for the C-E technique and 21 (1.3) cm H<sub>2</sub>O for the V-E technique.<strong>Conclusions.</strong> Mask ventilation using the modified V-E technique is more effective than with the C-E technique in unconscious obese apnoeic adults. Subjects who fail ventilation with the C-E technique can be ventilated effectively with the V-E technique.<strong>Clinical trial registration.</strong> NCT02580526.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Compromised tissue oxygenation is one of the root causes of dysfunction of various organs and postoperative complications. Oxygenation of different tissue beds may follow different patterns of change during physiological derangement.<strong>Methods.</strong> Patients undergoing elective major posterior spine surgery participated in this prospective observational study. Cerebral tissue oxygen saturation (SctO<sub>2</sub>) was monitored on the upper forehead and muscular tissue oxygen saturation (SmtO<sub>2</sub>) on the lower leg. The associations of various oxygenation indices with postoperative composite complications and length of hospital stay (LOH) were investigated.<strong>Results.</strong> The number of composite complications per patient was 3 (2) while the LOH was 6 (3) days (n = 102). Multiple SmtO<sub>2</sub> indices (maximum, minimum, mean, median, and area under curve (AUC)) were associated with composite complications (univariate analysis, <span style="font-style:italic;">P</span> < 0.05). No SctO<sub>2</sub> indices were associated with complications. Multiple SmtO<sub>2</sub> indices (maximum, mean, median, and AUC) showed differences (<span style="font-style:italic;">P</span> < 0.05) between patients with composite complications ≤3 and >3, respectively. SmtO<sub>2</sub> standard deviation, AUC, and AUC weighted, and SctO<sub>2</sub> standard deviation, were associated with LOH (univariate analysis, <span style="font-style:italic;">P</span> < 0.05). Two SmtO<sub>2</sub> indices (AUC and AUC weighted), showed differences (<span style="font-style:italic;">P</span> < 0.05) between the patients with an LOH ≤6 and >6 days, respectively. SmtO<sub>2</sub>, but not SctO<sub>2</sub>, indices improved the adjusted R<sup>2</sup> for composite complications (+54.0%, <span style="font-style:italic;">P</span> = 0.0001) and LOH (+19.0%, <span style="font-style:italic;">P</span> = 0.02) based on multiple linear models.<strong>Conclusions.</strong> Muscular tissue oxygenation has a stronger association with postoperative complications and length of hospital stay than cerebral tissue oxygenation after major spine surgery.</span>
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<span class="paragraphSection">'…give us the tools and we will finish the job.'<span style="font-style:italic;">Winston Churchill (1874–1965)</span></span>
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<span class="paragraphSection">Editor–A 71-year-old female presented with polymicrobial sepsis and mediastinitis following a dental procedure. After resuscitation with fluids and antibiotics, she required increasing doses of norepinephrine (up to 0.3 µg kg<sup>−</sup><sup>1</sup> min<sup>−</sup><sup>1</sup>) prior to operative exploration. Point-of-care ultrasound revealed elevated cardiac filling pressures (dilated inferior vena cava without respiratory variation) and hyperdynamic cardiac function (ejection fraction >65%). Central venous pressure was 14 mmHg and central venous saturation was 70%. These findings, in addition to the requirement for high-dose intravenous vasopressors, confirmed a diagnosis of vasoplegia.<a href="#aex066-B1" class="reflinks"><sup>1</sup></a> An intraoperative infusion pump failure of norepinephrine resulted in profound hypotension [blood pressure (BP) 30/20 mm Hg] as measured by an indwelling arterial line. Intravenous vasopressor boluses and 100 mg of methylene blue increased systolic arterial BP to >100 mm Hg for 15 min. Because methylene blue was effective, but only for a short duration, we administered intravenous hydroxocobalamin (1 g/h) to treat her vasoplegia.<a href="#aex066-B2" class="reflinks"><sup>2</sup></a> Her acute oliguria (<10 ml h<sup>−</sup><sup>1</sup>) was reversed and urine output increased to >500 ml h<sup>−</sup><sup>1</sup> during the final hours of surgery.</span>
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<span class="paragraphSection">Quality Improvement has been around in healthcare for decades. However, the phrase "improvement science" is somewhat newer. In their Lancet Editorial in 2013, Marshall, Pronovost and Dixon-Woods proposed that Improvement Science was in Kuhn's <a href="#aew469-B1" class="reflinks"><sup>1</sup></a> previously described "pre-paradigm phase of the emergence of a new discipline, one of the characteristics of which is the absence of an agreed definition."<a href="#aew469-B2" class="reflinks"><sup>2</sup></a> Four yr on, the phrase "Improvement Science" is sometimes used interchangeably with quality improvement (QI). Are they the same thing? What is the point of drawing a distinction?</span>
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<span class="paragraphSection">Editor—Preoperative anaemia is independently associated with increased risk of morbidity and mortality.<a href="#aex024-B1" class="reflinks"><sup>1</sup></a> Although haemoglobin (Hb) levels are always measured before major surgery, preoperative anaemia management is not implemented in most hospitals worldwide. Here we report the first steps and pilot clinical effects of implementing a preoperative anaemia clinic to diagnose and treat iron deficiency anaemia (IDA), which continues to be the top ranking cause worldwide,<a href="#aex024-B2" class="reflinks"><sup>2</sup></a> to optimise preoperative anaemia and to reduce unnecessary red blood cell (RBC) utilization. This study is embedded in a previously published observational trial demonstrating the beneficial effects of implementing a patient blood management program.<a href="#aex024-B3" class="reflinks"><sup>3</sup></a> A defined preoperative patient pathway including screening process, diagnostic algorithms and treatment protocol was developed.<a href="#aex024-B4" class="reflinks"><sup>4</sup></a> The study protocol was approved by the ethics committee at the University Hospital Frankfurt. Primary endpoints were Hb increase and RBC transfusion rate. For the analysis of the dynamics of Hb levels over time, a complex non-parametric mixed effects model was used considering patients as random effects.<a href="#aex024-B5" class="reflinks"><sup>5</sup></a> Data are provided as mean (<span style="text-transform:lowercase;font-variant:small-caps;">sem</span>) and median [interquartile range (IQR)]. <span style="font-style:italic;">P</span>-values <0.005 were considered statistically significant.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> The incidence of hemidiaphragmatic paresis with continuous interscalene brachial plexus block (CISB) can approach 100%. We tested the hypothesis that extrafascial placement of the catheter tip reduces the rate of hemidiaphragmatic paresis compared with intrafascial tip placement for CISB while providing effective analgesia.<strong>Methods.</strong> Seventy patients undergoing elective major shoulder surgery under general anaesthesia were randomized to receive an ultrasound-guided CISB plexus block for analgesia with the catheter tip placed either within (intrafascial group) or immediately outside (extrafascial group) the brachial plexus sheath midway between the levels of C5 and C6. Catheters were bolus dosed with ropivacaine 0.5% 20 ml before surgery, followed by an infusion of ropivacaine 0.2% at 4 ml h<sup>−1</sup> for the first 2 days after surgery. The primary outcome was hemidiaphragmatic paresis measured by M-mode ultrasonography on postoperative day (POD) 1. Secondary outcomes included forced vital capacity, forced expiratory volume in 1 s, and rest pain scores.<strong>Results.</strong> The incidence of hemidiaphragmatic paresis on POD 1 was significantly reduced in the extrafascial group {intrafascial, 41% [95% confidence interval (CI) 25–59%]; extrafascial, 15% (95% CI 5–32%); <span style="font-style:italic;">P</span>=0.01}. We were unable to detect a difference between groups in any of the functional respiratory outcomes or in rest pain scores [numerical rating scale (1–10): intrafascial, 3 (95% CI 2–3); extrafascial, 3 (95% CI: 2–4); <span style="font-style:italic;">P</span>=0.93] on POD 1.<strong>Conclusions.</strong> Placement of the catheter tip immediately outside of the brachial plexus sheath reduced the incidence of hemidiaphragmatic paresis on POD 1 associated with ultrasound-guided CISB while providing effective analgesia after major shoulder surgery. Our results do not support the routine placement of the catheter tip within the brachial plexus sheath for CISB.<strong>Clinical trial registration.</strong> NCT02433561.</span>
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<span class="paragraphSection">Evolution of tissue oxygenation monitoring by near-infrared spectroscopy (NIRS) is one of the most interesting recent developments in clinical monitoring.<a href="#aex032-B1" class="reflinks"><sup>1</sup></a> Given the importance of organ tissue perfusion for outcomes from surgery and critical illness, the fact that this technology can be used to interrogate almost any body region of interest (that can be placed within the device's photon beam) has stimulated a tremendous amount of scientific work on the potential diagnostic utility of NIRS.</span>
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<span class="paragraphSection"><span style="font-style:italic;">Mayo Clinic Critical Care Case Review</span>, KashyapR., O'HoroJ. C., FarmerJ. C.. Published by Oxford University Press. Pp. 288. ISBN-978-0-19-046481-3.</span>
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<span class="paragraphSection">It is universally acknowledged that the public expect general anaesthesia to be an unconscious state.<a href="#aex040-B1" class="reflinks"><sup>1–4</sup></a> While apparently self-evident, knowing whether different conscious states under anaesthesia are acceptable is important for clarification of the research agenda in anaesthesia, that is appropriately focused on patient-centred outcomes. Furthermore understanding patient expectations may be a key way to improve patient satisfaction with anaesthesia. The great success of anaesthesia is validated through low rates of explicit recall of intraoperative events, however it remains unclear whether the public think amnesia of intraoperative events is a sufficient endpoint for anaesthesia. It is unclear whether dreaming ("disconnected consciousness from the environment") or connected consciousness ("consciousness of external stimuli") are acceptable outcomes under general anaesthesia. These questions are made more pertinent by our recent report that 4.6% of patients undergoing intubation under general anaesthesia respond on the isolated forearm technique, implying they have connected consciousness,<a href="#aex040-B5" class="reflinks"><sup>5</sup></a> with 1.9% reporting connected consciousness with pain. To provide some initial insight into public opinion on this, we conducted a survey posted on our website (<a href="http://ift.tt/2qhMQnw">http://ift.tt/2qSHFHI;), social media (Twitter, Reddit, and Facebook) and distributed electronically. We explored the public's views of states such as disconnected consciousness or dreaming during anaesthesia and intraoperative consciousness with and without amnesia.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background</strong>. Missense variants in the ryanodine receptor 1 gene (<span style="font-style:italic;">RYR1</span>) are associated with malignant hyperthermia but only a minority of these have met the criteria for use in predictive DNA diagnosis. We examined the utility of a simplified method of segregation analysis and a functional assay for determining the pathogenicity of recurrent <span style="font-style:italic;">RYR1</span> variants associated with malignant hyperthermia.<strong>Methods</strong>. We identified previously uncharacterised <span style="font-style:italic;">RYR1</span> variants found in four or more malignant hyperthermia families and conducted simplified segregation analyses. An efficient cloning and mutagenesis strategy was used to express ryanodine receptor protein containing one of six <span style="font-style:italic;">RYR1</span> variants in HEK293 cells. Caffeine-induced calcium release, measured using a fluorescent calcium indicator, was compared in cells expressing each variant to that in cells expressing wild type ryanodine receptor protein.<strong>Results.</strong> We identified 43 malignant hyperthermia families carrying one of the six <span style="font-style:italic;">RYR1</span> variants. There was segregation of genotype with the malignant hyperthermia susceptibility phenotype in families carrying the p.E3104K and p.D3986E variants, but the number of informative meioses limited the statistical significance of the associations. HEK293 functional assays demonstrated an increased sensitivity of RyR1 channels containing the p.R2336H, p.R2355W, p.E3104K, p.G3990V and p.V4849I compared with wild type, but cells expressing p.D3986E had a similar caffeine sensitivity to cells expressing wild type RyR1.<strong>Conclusions</strong>. Segregation analysis is of limited value in assessing pathogenicity of <span style="font-style:italic;">RYR1</span> variants in malignant hyperthermia. Functional analyses in HEK293 cells provided evidence to support the use of p.R2336H, p.R2355W, p.E3104K, p.G3990V and p.V4849I for diagnostic purposes but not p.D3986E.</span>
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<span class="paragraphSection">By the time you are reading this editorial, '<span style="font-style:italic;">La La Land</span>', an Academy Awards contender movie about love, passion, and professional challenges of two Hollywood dreamers, will have nearly swept the Oscars. In the dream world of general anaesthesia, the top la la land award should undoubtedly be bestowed on Gustafsson and colleagues<a href="#aex077-B1" class="reflinks"><sup>1</sup></a> for their publication in the April issue of <span style="font-style:italic;">British Journal of Anaesthesia</span>.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> The acute respiratory distress syndrome (ARDS) is a condition with a high mortality and morbidity. Mechanical ventilation prevents immediate mortality but may further damage patients' lungs. Low tidal volume lung-protective strategies have been shown to increase survival by reducing this iatrogenic damage. Current guidelines recommend tidal volumes of 6–8 ml kg<sup>−1</sup> of predicted body weight. We used data from three large randomized controlled trials of treatments for ARDS to determine compliance with these recommendations.<strong>Methods.</strong> We used the tidal volume recorded at randomization for all patients in the OSCAR, HARP-2, and BALTI-2 studies. In addition, we used the ventilation data for control arm patients in OSCAR and all patients in HARP-2 at days 1 and 7 after randomization.<strong>Results.</strong> The three trials enrolled 1660 patients, with tidal volume data available at least at one time point in 1412 patients. Compliance with the 6–8 ml kg<sup>−1</sup> recommendation for tidal volume ranged from 20 to 39% of patients across all time points in all three trials.<strong>Conclusion.</strong> Poor compliance with the guidelines for tidal volume in patients with ARDS has been demonstrated before in case series, but not in clinical trials where the patient population is specifically selected against standard ARDS diagnostic criteria and the investigators were encouraged to use low tidal volumes. This study may indicate a need to improve implementation and compliance with protective lung ventilation.</span>
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In the present study we investigated the role of hydrocortisone (HC) on UTP-stimulated ion transport in differentiated, pseudostratified epithelia derived from normal human bronchial basal cells. The presence of a UTP stimulated, paxilline-sensitive large conductance Ca2+-activated K+ (BK) current was demonstrated in control epithelia but was not stimulated in epithelia differentiated in the absence of HC (HC0). Addition of the BK opener NS11021 directly activated channels in control epithelia however under HC0 conditions, activation only occurred when UTP was added after NS11021. The PKC inhibitors GF109203x and Gö6983 blocked BK activation by UTP in control epithelia, suggesting that PKC-mediated phosphorylation plays a permissive role in purinoceptor-stimulated BK activation. Moreover HC0 epithelia expressed significantly more KCNMA1 containing the stress-regulated exon (STREX), a splice-variant of the α-subunit that displays altered channel regulation by phosphorylation, compared to control epithelia. Furthermore, BK channels as well as purinergic receptors were shown to localize in unique and overlapping domains at the apical membrane of ciliated surface cells. These results establish a previously unrecognized role for glucocorticoids in regulation of BK channels in airway epithelial cells.
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Increased tongue thickness is likely to be associated with difficult airways. However, no methods to evaluate tongue thickness were available. Currently, tongue thickness can be measured by ultrasonography. The present study investigated the predictive value of tongue thickness to predict difficult tracheal intubation.<strong>Methods.</strong> Adult patients undergoing tracheal intubation and general anaesthesia were enrolled in the study. Tongue thickness was assessed using submental ultrasonography in the median sagittal plane before anaesthesia. Airway assessments were conducted. Ratios of tongue thickness to thyromental distance were calculated to investigate the potential predictive value of their combination. The primary outcome was difficult tracheal intubation. A multivariable logistic regression and receiver operating characteristic curve analysis were used.<strong>Results.</strong> In total, 2254 patients were analysed. One hundred and forty-two (6.3%) patients experienced difficult laryngoscopy, and 51 (2.3%) patients experienced difficult tracheal intubation. Increased tongue thickness (>6.1 cm) was an independent predictor for difficult tracheal intubation [sensitivity 0.75, 95% confidence interval (CI) 0.60–0.86; specificity 0.72, 95% CI 0.70–0.74]. An area under the curve of 0.78 (95% CI 0.77–0.80) for predicting difficult tracheal intubation was calculated. Increased ratios of tongue thickness to thyromental distance (>0.87) presented a considerable area under the curve (0.86, 95% CI 0.84–0.87), sensitivity (0.84, 95% CI 0.71–0.93), and specificity (0.79, 95% CI 0.77–0.81).<strong>Conclusions.</strong> Tongue thickness measured by ultrasonography and its ratio to thyromental distance present significant capacities to predict difficult tracheal intubation.<strong>Clinical trial registration.</strong> ChiCTR-RCS-14004539.</span>
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Previous studies indicate that low-load muscle contractions performed under local blood-flow restriction (BFR) may initially induce muscle damage and stress. However, whether these factors are evoked with longitudinal BFR training remains unexplored at the myocellular level.
Two distinct study protocols were conducted (3 wk/1 wk). Subjects performed BFR exercise (100 mmHg, 20%-1RM) to concentric failure (BFRE) (3 wk/1 wk), while controls performed work-matched (LLE)(3 wk) or high-load (HLE; 70%-1RM)(1 wk), free-flow exercise. Muscle biopsies (3 wk) were obtained at baseline (Pre), 8 days into the intervention (Mid8) and 3 and 10 days after training cessation (Post3,Post10) to examine macrophage (M1/M2) content as well as heat-shock protein (HSP27/70) and tenascin-C expression. Blood samples (1 wk) were collected before and after (0.1–24 h) the first and last training session to examine markers of muscle damage (CK), oxidative stress (TAC,GSH) and inflammation (MCP1,IL-6,TNFa).
M1-macrophage content increased 108–165% with BFRE and LLE at Post3 (P < 0.05), while M2-macrophages increased (163%) with BFRE only (P < 0.01). Membrane and intracellular HSP27 expression increased 60–132% at Mid8 with BFRE (P < 0.05–0.01). No or only minor changes were observed in circulating markers of muscle damage, oxidative stress and inflammation. The amplitude, timing and localization of the above changes indicate that only limited muscle damage was evoked with BFRE.
This study is the first to show that a period of high-frequency low-load BFR training does not appear to induce general myocellular damage. However, signs of tissue inflammation and focal myocellular membrane stress and/or reorganization were observed, that may be involved in the adaptation processes evoked by BFR muscle exercise.
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<span class="paragraphSection"><div class="boxTitle">Abstract</div>Neuropathic pain, a maladaptive and chronic condition that can develop after a lesion or disease affecting the somatosensory system, is characterized by allodynia, hyperalgesia and spontaneous pain, and comorbidities such as sleep deprivation, depression and anxiety. The activation of microglial cells in response to nerve injury has been implicated in the development of neuropathic pain. Mediators such as Neuregulin-1, matrix metalloproteinase (MMP)-2, MMP-9, <span style="font-style:italic;">The chemokine (C-C motif) ligand 2 (CCL2)</span> and fractalkine are released after nerve injury and are involved in the activation of microglial cells. These activated cells in turn release factors that increase the excitation and decrease the inhibition of interneurons. Microglial cells release factors such as interleukin (IL)-6, IL-1β and tumour necrosis factor-α (TNF-α) that cause the painful symptoms. It is becoming increasingly apparent that an intricate network of cytokines and cellular signalling mechanisms underpin the complex relationship between microglia and various cell types including neurones, astrocytes, oligodendrocytes, mast cells and T-cells. Although the precise mechanism of action of microglial cells in producing neuropathic pain has not been completely elucidated, research into these different activating factors and cytokines is providing further insight into the role of microglial cells in the development and maintenance of neuropathic pain. Further studies also are required to elucidate how "pain" mediators act on neurones and how the interactions between these mediators, or between neurones and glia in the presence of these mediators occur, in order to develop effective therapies for the management of neuropathic pain.</span>
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<span class="paragraphSection">Editor—Life-threatening events with an acute airway obstruction require immediate intervention. Nevertheless, most cases of foreign body aspiration (FBA) result in expectoration or dislodgment into a main-stem bronchus, with subsequent normalization of breathing and non-specific respiratory symptoms occurring days or even weeks after the FBA, often not recognized by health care providers<a href="#aex023-B1" class="reflinks"><sup>1</sup></a> or parents.<a href="#aex023-B2" class="reflinks"><sup>2</sup></a> Bronchoscopy is a potentially harmful procedure requiring specialist expertise in small children.<a href="#aex023-B3" class="reflinks"><sup>3</sup></a> Therefore, simple and reliable identifiers for the probability of actual FBA would be highly desirable.</span>
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<span class="paragraphSection">Editor—Typically, insulin is administered subcutaneously, intravenously, or intramuscularly. Alternate routes of insulin delivery, including oral, nasal, buccal, sublingual, ocular, rectal, and vaginal, have been described, but have resulted in unreliable effects.<a href="#aex065-B1" class="reflinks"><sup>1</sup></a></span>
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<span class="paragraphSection">Editor—Recently, Soffin and YaDeau<a href="#aex058-B1" class="reflinks"><sup>1</sup></a> published 'a review of the evidence' of enhanced recovery after surgery (ERAS) for total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although admittedly a narrative review, the review is not up to date, and at several points does not present 'the evidence'. For instance, a lot of space is used on fasting, carbohydrate loading, antimicrobial prophylaxis, and metabolic responses (all of which have no or limited effects on ERAS in these specific procedures). However, the review did not mention the more important recent research on the role of the inflammatory response for recovery<a href="#aex058-B2" class="reflinks"><sup>2</sup></a> and its modification by high-dose steroids.<a href="#aex058-B3" class="reflinks"><sup>3</sup></a><a href="#aex058-B4" class="reflinks"><sup>4</sup></a> Also, the statement that epidural analgesia is to be recommended is against the evidence for many years.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Non-invasive cardiac output monitoring (NICOM) using bioreactance (BRT) in pregnancy is gaining interest but lacks validation. We compared simultaneous cardiac output (CO) measurements obtained using the NICOM<sup>®</sup> (BRT-CO) and echocardiography (echo-CO), and assessed the relationship between maternal characteristics and myocardial performance.<strong>Methods.</strong> Paired stroke volume (SV) and CO readings were obtained using NICOM<sup>®</sup> and echocardiography, in a group of healthy nulliparous women throughout a 15 min period. Agreement between NICOM<sup>®</sup> and echocardiography was assessed using Bland–Altman analysis and the intraclass correlation coefficient (ICC). Left ventricular (LV) function was assessed using systolic strain and tissue Doppler velocities (S′, E′, and A′ waves).<strong>Results.</strong> Thirty-five women with a median [interquartile range] age, weight, and gestation of 29 [26–34] yr, 71 [64–79] kg, and 28 [21–29] weeks, respectively, were enrolled. There was good agreement between NICOM<sup>®</sup>-measured and echocardiographically measured SV [mean bias 6 ml (limits of agreement −18 to 29); ICC 0.8 (95% confidence interval 0.6–0.9), <span style="font-style:italic;">P</span><0.001] and CO [mean bias 0.2 litres (limits of agreement −1.3–1.7); ICC 0.8 (95% confidence interval 0.7–0.9), <span style="font-style:italic;">P</span><0.001; mean percentage error ±26%; coefficient of error (precision)=3.4%]. The mean (<span style="text-transform:lowercase;font-variant:small-caps;">sd</span>) LV S′ was 9.7 (2.3) cm s<sup>−1</sup>. The mean (<span style="text-transform:lowercase;font-variant:small-caps;">sd</span>) LV strain was −18.6 (2.6)%. There was a negative relationship between BMI and LV diastolic function measured using the E′:A′ ratio (<span style="font-style:italic;">r</span> = −0.51, <span style="font-style:italic;">P</span><0.01).<strong>Conclusions.</strong> Stroke volume and CO measurements obtained using NICOM<sup>®</sup> were comparable to those obtained using echocardiography, with acceptable limits of agreement. Increased maternal BMI negatively impacts LV diastolic function measured using tissue Doppler imaging.</span>
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Laura Metro didn't know CPR when her son almost died by drowning
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Fire Commissioner Eric Jones secured funding to outfit responders with the protective gear
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The ambulance was transporting a patient at the time of the crash
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An EMS student and the patient on board were hurt in the crash
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Review the three indications that a patient needs their airway managed in this episode of Progressive Paramedicine, an EMS1 original video series.
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The purpose of this study was to investigate the effects of a single bout of high-intensity interval training (HIIT) and continuous aerobic exercise (CAE) on inhibitory control. The P3 component of the stimulus-locked ERP was collected in 64 young adults during a modified flanker task following 20 min of seated rest, 20 min of CAE, and 9 min of HIIT on separate days in counterbalanced order. Participants exhibited shorter overall reaction time following CAE and HIIT compared to seated rest. Response accuracy improved following HIIT in the task condition requiring greater inhibitory control compared to seated rest and CAE. P3 amplitude was larger following CAE compared to seated rest and HIIT. Decreased P3 amplitude and latency were observed following HIIT compared to seated rest. The current results replicated previous findings indicating the beneficial effect of acute CAE on behavioral and neuroelectric indices of inhibitory control. With a smaller duration and volume of exercise, a single bout of HIIT resulted in additional improvements in inhibitory control, paralleled by a smaller and more efficient P3 component. In sum, the current study demonstrated that CAE and HIIT differentially facilitate inhibitory control and its underlying neuroelectric activation, and that HIIT may be a time-efficient approach for enhancing cognitive health.
The spatial location of objects is processed in egocentric and allocentric reference frames, the early temporal dynamics of which have remained relatively unexplored. Previous experiments focused on ERP components related only to egocentric navigation. Thus, we designed a virtual reality experiment to see whether allocentric reference frame-related ERP modulations can also be registered. Participants collected reward objects at the end of the west and east alleys of a cross maze, and their ERPs to the feedback objects were measured. Participants made turn choices from either the south or the north alley randomly in each trial. In this way, we were able to discern place and response coding of object location. Behavioral results indicated a strong preference for using the allocentric reference frame and a preference for choosing the rewarded place in the next trial, suggesting that participants developed probabilistic expectations between places and rewards. We also found that the amplitude of the P1 was sensitive to the allocentric place of the reward object, independent of its value. We did not find evidence for egocentric response learning. These results show that early ERPs are sensitive to the location of objects during navigation in an allocentric reference frame.
A series of studies investigated the effects of hedonic content, brightness, and contrast on pupil diameter during free viewing of natural scenes, assessing the amplitude of the initial light reflex and subsequent sustained pupil diameter change. Hedonic picture content varied from highly arousing scenes of erotica and violence to scenes depicting nature, babies, loss, contamination, food, and more. Despite equivalent overall picture brightness and contrast, pupil diameter still varied as a function of the local brightness of central vision at fixation. Statistical (Experiment 1) and methodological (Experiment 2, 3) solutions produced complementary data indicating that scenes of erotica and violence reliably attenuate the amplitude of the initial light reflex and prompt enhanced late diameter pupil changes, compared to other scene contents. A principal components analysis supported the hypothesis that a single sympathetically mediated process enhances pupil dilation during picture viewing, modulating both initial constriction and late diameter changes. Rather than being a subtle index of "liking," pupil diameter is primarily sensitive to events that reliably elicit measurable sympathetic nervous system activity.
Alexithymia is associated with deficiencies in recognizing and expressing emotions and impaired emotion regulation, though few studies have verified the latter assertion using objective measures. This study examined startle reflex modulation by fearful imagery and its associations with heart rate variability in alexithymia. Fifty-four adults (27 alexithymic) imagined previously normed fear scripts. Startle responses were assessed during baseline, first exposure, and reexposure. During first exposure, participants, in separate trials, engaged in either shallow or deep emotion processing, giving emphasis on descriptive or affective aspects of imagery, respectively. Resting heart rate variability was assessed during 2 min of rest prior to the experiment, with high alexithymic participants demonstrating significantly higher LF/HF (low frequency/high frequency) ratio than controls. Deep processing was associated with nonsignificantly larger and faster startle responses at first exposure for alexithymic participants. Lower LF/HF ratio, reflecting higher parasympathetic cardiac activity, predicted greater startle amplitude habituation for alexithymia but lower habituation for controls. Results suggest that, when exposed to prolonged threat, alexithymics may adjust poorly, showing a smaller initial defensive response but slower habituation. This pattern seems related to their low emotion regulation ability as indexed by heart rate variability.
Recent evidence indicates that patients with obsessive-compulsive disorder (OCD) as well as their unaffected first-degree relatives show deficits in the volitional control of saccades, suggesting that volitional saccade performance may constitute an endophenotype of OCD. Here, we aimed to replicate and extend these findings in a large, independent sample. One hundred and fifteen patients with OCD, 103 healthy comparison subjects without a family history of OCD, and 31 unaffected first-degree relatives of OCD patients were examined using structured clinical interviews and performed a volitional saccade task as well as a prosaccade task. In contrast to previous reports, neither patients nor relatives showed impairments in the performance of volitional saccades compared to healthy controls. Notably, medicated patients did not differ from nonmedicated patients, and there was no effect of depressive comorbidity. Additional analyses investigating correlations between saccade performance and OCD symptom dimensions yielded no significant associations. In conclusion, the present results do not support the notion that volitional saccade execution constitutes an endophenotype of OCD. Possible explanations for inconsistencies with previous studies are discussed.
The Monty Hall Dilemma (MHD) poses a counterintuitive probabilistic problem to the players of this game. In the MHD task, a participant chooses one of three options where only one contains a reward. After one of the unchosen options (always no reward) is disclosed, the participant is asked to make a final decision: either change to the remaining option or stick with their first choice. Although the probability of winning if they change is higher (2/3) compared to sticking with their first choice (1/3), most people stick with their original selection and often lose. In accordance with previous research, repetitive exposure to the MHD task increases the change behavior without any obvious understanding of the mathematical reasons why changing increases their chance of being rewarded. We recorded the stimulus-preceding negativity (SPN), an ERP that might reflect the informative value of the feedback. In the second half of the task, feedback was predicted to be less informative because learning had taken place. Indeed, the SPN amplitude became smaller over the frontal region. Also, the SPN amplitude was larger for change than for stick trials. These results suggest that learning in the MHD might be manifest in affective-motivational anticipation as indicated by the SPN.
Digestive Diseases
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AP
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Abdominal Imaging
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Reuters Health News
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European Journal of Clinical Microbiology & Infectious Diseases
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Alimentary Pharmacology and Therapeutics
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Journal of Gastroenterology and Hepatology
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Journal of Gastroenterology and Hepatology
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Clinical Nutrition
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Journal of Magnetic Resonance Imaging
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The Oncologist
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AP
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European Journal of Pain
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Obesity Surgery
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European Journal of Gastroenterology & Hepatology
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Nature Reviews Genetics. doi:10.1038/nrg.2017.39
Author: Katharine H. Wrighton
Nature Reviews Genetics. doi:10.1038/nrg.2017.37
Author: Carolina Perdigoto
Nature Reviews Genetics. doi:10.1038/nrg.2017.17
Authors: Teddy Jégu, Eric Aeby & Jeannie T. Lee
Nature Reviews Genetics. doi:10.1038/nrg.2017.21
Authors: Arnau Sebé-Pedrós, Bernard M. Degnan & Iñaki Ruiz-Trillo
Nature Reviews Genetics. doi:10.1038/nrg.2017.19
Authors: Alessandra Breschi, Thomas R. Gingeras & Roderic Guigó