Τετάρτη 31 Οκτωβρίου 2018

The Regulation of Cbf1 by PAS Kinase Is a Pivotal Control Point for Lipogenesis Versus Respiration in Saccharomyces cerevisiae

PAS kinase 1 (Psk1) is a key regulator of respiration in Saccharomyces cerevisiae. Herein the molecular mechanisms of this regulation are explored through the characterization of its substrate, Centromere binding factor 1 (Cbf1). CBF1-deficient yeast displayed a significant decrease in cellular respiration, while PAS kinase-deficient yeast, or yeast harboring a Cbf1 phosphosite mutant (T211A) displayed a significant increase. Transmission electron micrographs showed an increased number of mitochondria in PAS kinase-deficient yeast consistent with the increase in respiration. Although the CBF1-deficient yeast did not appear to have an altered number of mitochondria, a mitochondrial proteomics study revealed significant differences in the mitochondrial composition of CBF1-deficient yeast including altered Atp3 levels, a subunit of the mitochondrial F1-ATP synthase complex. Both beta-galactosidase reporter assays and western blot analysis confirmed direct transcriptional control of ATP3 by Cbf1. In addition, we confirmed the regulation of yeast lipid genes LAC1 and LAG1 by Cbf1. The human homolog of Cbf1, Upstream transcription factor 1 (USF1), is also known to be involved in lipid biogenesis. Herein, we provide the first evidence for a role of USF1 in respiration since it appeared to complement Cbf1 in vivo as determined by respiration phenotypes. In addition, we confirmed USF1 as a substrate of human PAS kinase (hPASK) in vitro. Combined, our data supports a model in which Cbf1/USF1 functions to partition glucose towards respiration and away from lipid biogenesis, while PAS kinase inhibits respiration in part through the inhibition of Cbf1/USF1.



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Broadening the operative field: the extent of surgery beyond the patient`s informed consent (the so-called therapeutic exception)

W artykule omówiono przesłanki tzw. wyjątku terapeutycznego, uregulowanego w art. 35 ustawy z dnia 5 grudnia 1996 r. o zawodach lekarza i lekarza dentysty. Konstrukcja ta pozwala lekarzowi, w trakcie operacji, na zmianę zakresu zabiegu ponad zgodę wyrażoną przez pacjenta. Ponadto poruszono kwestię tzw. zgody antycypacyjnej oraz warunki jej skuteczności oraz wyjaśniono, czy w wypadku realizacji przesłanek wyjątku terapeutycznego lekarz jedynie może dokonać odpowiedniej modyfikacji czynności operacyjnych, czy też jest to jego obowiązek. Wskazano również, że w omawianej sytuacji lekarz nie może powoływać się na tzw. stan wyższej konieczności. Prezentowane treści zostały wzbogacone o przedstawienie konkretnych spraw sądowych i ich rozstrzygnięć.

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Inter-arm differences in blood pressure among subjects with disseminated atherosclerosis scheduled for vascular surgery

Background: The measurement of blood pressure (BP) is routinely performed in perioperative care. The reliability of results is essential for the implementation of treatment ensuring haemodynamic stability. The aim of the present study was to assess the prevalence and basic determinants of inter-arm BP differences among patients with advanced peripheral atherosclerosis undergoing vascular surgical procedures of the lower limbs. Methods: The prospective study was carried out in patients scheduled for elective lower limb vascular surgery. One-time non-invasive BP measurements were performed sequentially on the brachial arteries of both upper extremities before the induction of anaesthesia, maintaining the shortest possible interval between measurements. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded. Results: The results of 173 patients (including 123 men aged 67 ± 8 years) were analysed. In 16 (9.3%) patients, an inter-arm difference in BP was already observed during the preoperative examination. SBP and DBP was higher in the right limb in 86 (49.7%) an 80 (46.3%) patients, respectively. Moreover, the medians of inter-arm differences in SBP, DBP and MAP were 9 (IQR 4–17), 5 (IQR 3–10) and 7 mm Hg (IQR 3–12), respectively. An evaluation of the determinants of BP differences related to the presence of additional diseases demonstrated that patients with arterial hypertension were characterised by higher SBP and MAP disproportions (P = 0.04 and P = 0.01). Conclusions: In the population of patients with disseminated atherosclerosis, the inter-arm differences in BP substantially exceed the measurement error limits and are likely to be associated with arterial hypertension. If in doubt about BP disproportions, intraoperative monitoring of BP should be recommended using an invasive method on the limb presenting higher non-invasively measured values.



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Risk factors for occurrence of failed interscalene brachial plexus blocks for shoulder arthroscopy using 20 mL 0.5% ropivacaine: a randomised trial

Background: The red blood cell distribution width index (RDW) is one of several parameters routinely analysed in peripheral blood counts. The aim of the study was to assess the usefulness of RDW in the prediction of in-hospital mortality in patients undergoing high-risk gastroenterological surgery. Methods: Prospective observation covered 229 patients who underwent surgery, for whom the risk of cardiovascular complications was high due to the type of procedure. The patient's individual risk was assessed using the criteria of the American Society of Anesthesiologists (ASA-PS). Peripheral blood for morphological examination was collected preoperatively. The following parameters of the red blood cell system were evaluated: red blood cell count (RBC), haemoglobin (Hgb), haematocrit (Hct), mean corpuscular volume (MCV), RDW expressed as a standard deviation (SD) and a coefficient of variation (CV). The occurrence of hospital death was the main endpoint. Results: Patients who died had had statistically significantly lower RBC, Hgb and Hct values, as well as higher RDW-SD and RDW-CV values. Both the preoperative RDW-SD and RDW-CV values predicted the outcome, respectively: AUCRDW-SD = 0.744 (95% CI: 0.683–0.799; P RDW-CV = 0.762 (95% CI: 0.702–0.816; P RDW-SD = 1.21; P RDW-CV = 1.62; P = 0.01), even after adjustment for individual risk and other erythrocyte parameters. Conclusion: RDW is a valuable screening predictor of in-hospital mortality in patients undergoing high-risk gastroenterological surgery, regardless of the estimated individual risk and the value of other erythrocyte parameters. Evaluation of the RDW may be helpful in the identification of patients requiring correction of haematological disorders in the pre-operative period, as well as, in particular, surveillance in the perioperative period.

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Use of noninvasive mechanical ventilation with pressure support guaranteed with average volume in de novo hypoxaemic respiratory failure. A pilot study

Background: This study was designed to determine the results associated with the use of noninvasive mechanical ventilation (NIV) using the BiPAP S/T-AVAPS ventilation strategy in subjects with mild to moderate de novo hypoxaemic respiratory failure. Methods: This is a prospective study that includes subjects with de novo hypoxaemic respiratory failure (not produced by acute exacerbations of COPD, chronic lung disease, or congestive heart failure) with mild to moderate PaO2/FiO2, who were admitted to the Intensive Care Unit (ICU) of Santa Maria Clinic in Guayaquil, Ecuador. Subjects were divided into two groups and compared according to their PaO2/FiO2: higher than 100 and up to 200 mm Hg (moderate ARDS) or between 200 and 300 mm Hg (mild ARDS) (both groups were ventilated with the BiPAP S/T-AVAPS strategy). A value of P Results: A total of 38 subjects were analysed in this study. The total rate of intubation was 34.2% while the mortality rate was 28.9%. Significant differences were observed when comparing success versus failure in exhaled tidal volumes (P = 0.04), peak inspired pressure (P 2 (P 2 (P 2/FiO2 (P P P = 0.029) measured at baseline and at 12-hour, 24-hour and 48-hour intervals. Conclusion: The BiPAP S/T-AVAPS ventilatory mode can be used in subjects with de novo hypoxaemic respiratory failure with special vigilance concerning exhaled tidal volumes and inspired pressure.

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Peri-anaesthetic cardiac arrest with administration of enalapril, spironolactone and β-blocker

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Postoperative pain after spinal surgery in the paediatric population

Introduction: Postoperative pain is a major aftereffect of surgery. Especially severe occurs after extensive operations within the spine. The goal of the study was to investigate the laboratory predictive factors of intensive postoperative pain in children undergoing extensive surgery Patients and methods: We recruited 41 children, age median 13 years (IQR:10-15 years) undergoing extensive spine surgery. The subjects were divided into two groups based on the intensity of postoperative pain measured using the 10-point numerical rating scale (NRS), visual analog scale (VAS) or faces pain scale-revised (FPS-R). Patients with a score of 5 or higher were included in the study group and those with NRS of less than 5 were included in the control group. We collected detailed clinical and laboratory data before, during and after surgery. Results: The highest intensity of pain was observed in the first 6 hours after surgery. The postoperative pain was associated with a higher drop in hemoglobin concentration and hematocrit level in peri-operative period (p=0.006 and p=0.019 respectively) as well as higher changes in mean arterial pressure during surgery. Additionally, we found that children with intensive pain had higher total protein concentration after surgery. Conclusions: We reported that the drop in hemoglobin and hematocrit level, fluctuation in mean arterial pressure as well as total protein concentration could be useful prognostic factors of early postoperative pain.

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A case report of inadvertent intranasal submucosal injection of concentrated epinephrine with no long-term sequelae



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Clinical and Molecular Characterization of Panton–Valentine Leukocidin-Positive Invasive Staphylococcus aureus Infections in Korea

Microbial Drug Resistance, Ahead of Print.


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First Detection of New Delhi Metallo-β-Lactamase-5-Producing Escherichia coli from Companion Animals in Korea

Microbial Drug Resistance, Ahead of Print.


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Genetic Analysis of p17S-208 Plasmid Encoding the Colistin Resistance mcr-3 Gene in Escherichia coli Isolated from Swine in South Korea

Microbial Drug Resistance, Ahead of Print.


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EMS Specialist Projects Supervisor - GAAA

Make A Difference in your community by being a leader of our Emergency Medical Service Team! Galveston County Health District is seeking a new EMS Special Projects Supervisor! The right candidate will be responsible for successfully managing daily operational aspects of non-emergency medical transport and emergency medical services provided by the Galveston County Health District's Galveston Area Ambulance ...

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FT/PT Paramedic - Med-Star Paramedic Ambulance, Inc.

MED-Star Paramedic Ambulance, Inc. located in Brandon, South Dakota is currently hiring full and part time Paramedics. We are a family owned and operated company. We respond to 911 calls in the southeast area of Minnehaha county and provide interfacility transports from area hospitals. We offer flexible scheduling with 12 and 24 hour shifts available and minimal call time. Pay starting at $36,500-$42,000/year ...

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Wash. responders, civilians honored for saving life of retired fire chief

Retired Chehalis Fire Department Chief Bill Nacht went into cardiac arrest while waiting for a friend so they could go on a motorcycle trip

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Deletion of IP 3 R1 by Pdgfrb-Cre in mice results in intestinal pseudo-obstruction and lethality

Abstract

Background

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are a family of intracellular Ca2+ release channels located on the membrane of endoplasmic reticulum, which have been shown to play critical roles in various cellular and physiological functions. However, their function in regulating gastrointestinal (GI) tract motility in vivo remains unknown. Here, we investigated the physiological function of IP3R1 in the GI tract using genetically engineered mouse models.

Methods

Pdgfrb-Cre mice were bred with homozygous Itpr1 floxed (Itpr1f/f) mice to generate conditional IP3R1 knockout (pcR1KO) mice. Cell lineage tracing was used to determine where Pdgfrb-Cre-mediated gene deletion occurred in the GI tract. Isometric tension recording was used to measure the effects of IP3R1 deletion on muscle contraction.

Results

In the mouse GI tract, Itpr1 gene deletion by Pdgfrb-Cre occurred in smooth muscle cells, enteric neurons, and interstitial cells of Cajal. pcR1KO mice developed impaired GI motility, with prolonged whole-gut transit time and abdominal distention. pcR1KO mice also exhibited lethality as early as 8 weeks of age and 50% of pcR1KO mice were dead by 40 weeks after birth. The frequency of spontaneous contractions in colonic circular muscles was dramatically decreased and the amplitude of spontaneous contractions was increased in pcR1KO mice. Deletion of IP3R1 in the GI tract also reduced the contractile response to the muscarinic agonist, carbachol, as well as to electrical field stimulation. However, KCl-induced contraction and expression of smooth muscle-specific contractile genes were not significantly altered in pcR1KO mice.

Conclusions

Here, we provided a novel mouse model for impaired GI motility and demonstrated that IP3R1 plays a critical role in regulating physiological function of GI tract in vivo.



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Halloween: Is it the most dangerous day for kids?

Analysis of the 56 million ePCR records in the NEMSIS national dataset shows days with the most traumatic pediatric cardiac arrests in 2013 and 2014

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CoTCCC Chair Dr. Frank Butler Receives NAEMT’s Most Prestigious 2018 Rocco V. Morando Lifetime Achievement Award

CLINTON, Miss. — Captain Frank K. Butler, Jr., (USN ret), MD was presented with the 2018 Rocco V. Morando Lifetime Achievement Award, recognizing a lifetime of commitment, contributions and leadership to Emergency Medical Services (EMS). The award is NAEMT's most prestigious and is generously sponsored by the National Registry of Emergency Medical Technicians (NREMT). The presentation...

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“Gardner and Sutherland’s chromosome abnormalities and genetic counseling” by R.J. McKinlay Gardner, David J. Amor. Oxford University Press



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Halloween: Is it the most dangerous day for kids?

Analysis of the 56 million ePCR records in the NEMSIS national dataset shows days with the most traumatic pediatric cardiac arrests in 2013 and 2014

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EMS World Expo Quick Take: Assessing, treating and transporting patients with special needs

Be aware patients with special needs may have comorbidities, and their conditions fall on a spectrum

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A Systematic Review of Traditional, Complementary and Alternative Medicine Use Amongst Ethnic Minority Populations: A Focus Upon Prevalence, Drivers, Integrative Use, Health Outcomes, Referrals and Use of Information Sources

Abstract

Ethnic minority populations have been identified as high users of traditional, complementary and alternative medicine (TCAM). This paper reports the systematic review of TCAM use amongst ethnic minorities. A comprehensive literature search was conducted in Ovid, PubMed and CINAHL. Included studies were original, peer-reviewed, English language articles with the primary focus on TCAM use amongst ethnic minority populations. A total of 17 articles met the inclusion criteria and were included in the systematic review. A considerable level of TCAM use was observed amongst ethnic minority populations usually attributed to its perceived safe and natural properties. Ethnic minority populations predominantly used TCAM concurrently with conventional medicine and primary TCAM referral sources were family and friends. A substantial level of TCAM integration with conventional medicine is common practice amongst these populations and the lack of disclosure about TCAM use raises an important area for further research inquiry.



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EMS World Expo Quick Take: Active assailant preparation, response for EMS

20-60-90 minute rule underscores the importance of rapidly accessing trauma patients and transporting patients to definitive surgical care

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Paramedic Inpatient, (NICU/PICU - Flex) FT; 36 hours per week 5p-5a with weekend rotation - Children's Hospital & Medical Center

The inpaitent paramedic serves a clinical resource on inpateint units (critical care or med surg). Working to the full scope of their license, the paramedic will complete assessments, perform procedures, administer meds, and respond to emergencies in the assigned unit or division. The paramedic will interact with patients and famillies and be part of the pediatric and neonatal care team.

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Functional validation of miRNAs targeting genes of DNA double-strand break repair to radiosensitize non-small lung cancer cells

Publication date: Available online 30 October 2018

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

Author(s): Celeste Piotto, Alberto Biscontin, Caterina Millino, Maddalena Mognato

Abstract

DNA-Double strand breaks (DSBs) generated by radiation therapy represent the most efficient lesions to kill tumor cells, however, the inherent DSB repair efficiency of tumor cells can cause cellular radioresistance and impact on therapeutic outcome. Genes of DSB repair represent a target for cancer therapy since their down-regulation can impair the repair process making the cells more sensitive to radiation. In this study, we analyzed the combination of ionizing radiation (IR) along with microRNA-mediated targeting of genes involved in DSB repair to sensitize human non-small cell lung cancer (NSCLC) cells. MicroRNAs are natural occurring modulators of gene expression and therefore represent an attractive strategy to affect the expression of DSB repair genes. As possible IR-sensitizing targets genes we selected genes of homologous recombination (HR) and non-homologous end joining (NHEJ) pathway (i.e. RAD51, BRCA2, PRKDC, XRCC5, LIG1). We examined these genes to determine whether they may be real targets of selected miRNAs by functional and biological validation. The in vivo effectiveness of miRNA treatments has been examined in cells over-expressing miRNAs and treated with IR. Taken together, our results show that hsa-miR-96-5p and hsa-miR-874-3p can directly regulate the expression of target genes. When these miRNAs are combined with IR can decrease the survival of NSCLC cells to a higher extent than that exerted by radiation alone, and similarly to radiation combined with specific chemical inhibitors of HR and NHEJ repair pathway.



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Predictive factors of the treatment outcome in patients with advanced biliary tract cancer receiving gemcitabine plus cisplatin as first-line chemotherapy

Journal of Gastroenterology

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A multicenter observational study on the clinicopathological features of gastric cancer in young patients

Journal of Gastroenterology

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Oral metronidazole use and risk of acute pancreatitis: A population-based case-control study

Clinical Epidemiology

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Review of microbial resistance to chronic ionizing radiation exposure under environmental conditions

Publication date: January 2019

Source: Journal of Environmental Radioactivity, Volume 196

Author(s): Igor Shuryak

Abstract

Ionizing radiation (IR) produces multiple types of damage to nucleic acids, proteins and other crucial cellular components. Nevertheless, various microorganisms from phylogenetically distant taxa (bacteria, archaea, fungi) can resist IR levels many orders of magnitude above natural background. This intriguing phenomenon of radioresistance probably arose independently many times throughout evolution as a byproduct of selective pressures from other stresses (e.g. desiccation, UV radiation, chemical oxidants). Most of the literature on microbial radioresistance is based on acute γ-irradiation experiments performed in the laboratory, typically involving pure cultures grown under near-optimal conditions. There is much less information about the upper limits of radioresistance in the field, such as in radioactively-contaminated areas, where several radiation types (e.g. α and β, as well as γ) and other stressors (e.g. non-optimal temperature and nutrient levels, toxic chemicals, interspecific competition) act over multiple generations. Here we discuss several examples of radioresistant microbes isolated from extremely radioactive locations (e.g. Chernobyl and Mayak nuclear plant sites) and estimate the radiation dose rates they were able to tolerate. Some of these organisms (e.g. the fungus Cladosporium cladosporioides, the cyanobacterium Geitlerinema amphibium) are widely-distributed and colonize a variety of habitats. These examples suggest that resistance to chronic IR and chemical contamination is not limited to rare specialized strains from extreme environments, but can occur among common microbial taxa, perhaps due to overlap between mechanisms of resistance to IR and other stressors.



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Fibromyalgia: increased reactivity of the muscle membrane and a role of central regulation

Publication date: Available online 31 October 2018

Source: Clinical Neurophysiology

Author(s): E.G. Klaver-Krol, J.J. Rasker, M.M. Klaver, P.M. ten Klooster, M.J. Zwarts

Abstract
Objective

Fibromyalgia (FM) is characterized by widespread muscle pain and central neural deregulation. Previous studies showed increased muscle fiber conduction velocity (CV) in non-painful muscles of FM patients. This study investigates the relationship between central activation and the CV in FM.

Methods

Twenty-two females with primary FM and 21 controls underwent surface electromyography of the non-painful biceps brachii. Mean CVs were calculated from the motor unit potential velocities (CV-MUPs), and the CV-MUPs' statistical distributions were presented as histograms. The amount of muscle activity (average rectified voltage, ARV) was measured.

Results

The CV was higher in the FM-group than in the controls (P=0.021), with CV-MUPs generally shifted to higher values, indicative of increased muscle membrane propagation speeds. The largest increase in the CV of the FM-group occurred when adopting and maintaining a limb position at only 5% of maximum strength (P<0.001); the CV did not, as normal, increase with greater force. However, the ARV in both groups similarly increased with force.

Conclusions

In fibromyalgia patients, the muscle membrane propagation speed increases independently of the force load or amount of muscle activity produced. When adopting a limb position, the patients show an augmented muscle membrane reaction, suggesting deregulation from higher neural centers.

Significance

These findings contribute to understanding fibromyalgia.



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Electrophysiological evidence for changes in attentional orienting and selection in functional somatic symptoms

Publication date: Available online 30 October 2018

Source: Clinical Neurophysiology

Author(s): Maayan Karlinski, Alexander Jones, Bettina Forster

Abstract
Objective

We investigated changes in attention mechanisms in people who report a high number of somatic symptoms which cannot be associated with a physical cause.

Method

Based on scores on the Somatoform Disorder Questionnaire (SDQ-20; Nijenhuis et al., 1996) we compared two non-clinical groups, one with high symptoms on the SDQ-20 and a control group with low or no symptoms. We recorded EEG whilst participants performed an exogenous tactile attention task where they had to discriminate between tactile targets following a tactile cue to the same or opposite hand.

Results

The neural marker of attentional orienting to the body, the Late Somatosensory Negativity (LSN), was diminished in the high symptoms group and attentional modulation of touch processing was prolonged at mid and enhanced at later latency stages in this group.

Conclusion

These results confirm that attentional processes are altered in people with somatic symptoms, even in a non-clinical group. Furthermore, the observed pattern fits explanations of changes in prior beliefs or expectations leading to diminished amplitudes of the marker of attentional orienting to the body (i.e. the LSN) and enhanced attentional gain of touch processing.

Significance

This study shows that high somatic symptoms are associated with neurocognitive attention changes.



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Predictive Value of Intraoperative Bulbocavernosus Reflex during Untethering Surgery for Post-operative Voiding Function

Publication date: Available online 30 October 2018

Source: Clinical Neurophysiology

Author(s): Seungwoo Cha, Kyu-Chang Wang, Kwanjin Park, Hyung-Ik Shin, Ji Yeoun Lee, Sangjoon Chong, Keewon Kim

Abstract
Objective

To evaluate the clinical significance of intraoperative bulbocavernosus reflex (BCR) during untethering surgery in predicting post-operative voiding function.

Methods

We conducted a retrospective review of pediatric patients who underwent untethering surgery with available intraoperative baseline BCR. BCR response during surgery was classified into loss or maintenance. Post-operative voiding function was determined as worsened or maintained based on history, postvoid residual urine measurement, and urodynamic study (UDS). Data regarding demographics, diagnosis, pre-operative voiding difficulty, re-untethering, syrinx, and abnormalities in electromyography were collected for analysis.

Results

We included 106 patients, with a mean age of 3.3 years, and 49 patients were male. BCR was lost in 15 patients during surgery and voiding function worsened in 14 patients after surgery. Lumbosacral lipoma was the most common diagnosis, and 16 patients were diagnosed with lipomyelomeningocele (LMMC). The sensitivity and specificity of intraoperative BCR for post-operative worsening of voiding function were 35.7%, and 88.5% at 6 months, respectively. The diagnosis of LMMC was statistically significant in a logistic regression analysis. The specificity of BCR at 6 months in patients with diagnosis other than LMMC was 93.4%, and intraoperative BCR was significant in a logistic regression analysis.

Conclusions

Intraoperative BCR during untethering could predict bladder function 6 months post-operatively with high specificity (88.5%), particularly in cases other than LMMC (93.4%), indicating that voiding function deterioration will not occur if intraoperative BCR is preserved.

Significance

Intraoperative BCR during untethering surgery is a useful tool to predict post-operative voiding outcome.



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Resting frontal EEG asymmetry in adolescents with major depression: impact of disease state and comorbid anxiety disorder

Publication date: Available online 30 October 2018

Source: Clinical Neurophysiology

Author(s): Lisa Feldmann, Charlotte E. Piechaczek, Barbara D. Grünewald, Verena Pehl, Jürgen Bartling, Michael Frey, Gerd Schulte-Körne, Ellen Greimel

Abstract
Objective

Greater relative right- than left-frontal cortical activity has been frequently found in adults with major depression (MD). As the few studies in adolescents with MD have been inconclusive, the aim of this study was to assess frontal alpha asymmetry (FAA) in an adolescent sample with MD whilst taking into account possible confounding variables such as disease state and comorbid anxiety disorder.

Methods

An 8-minute resting frontal EEG was assessed in 34 healthy controls (HCs), 16 adolescents with MD in remission without comorbid anxiety disorder (rMDa-), 22 adolescents with acute depression without comorbid anxiety disorder (MDa-), and 23 adolescents with acute depression and comorbid anxiety disorder (MDa+). Alpha power was analyzed over corresponding frontal Regions of Interests.

Results

Compared to HCs, MDa+ adolescents demonstrated more left- than right-sided EEG alpha power, indicating greater right-than left-frontal cortical activity. No other group differences emerged.

Conclusions

The results suggest that greater relative right-frontal cortical activity in adolescent MD is not a result of disease state but can be attributed to comorbid anxiety disorder.

Significance

Results suggest that FAA is not linked to adolescent depression per se and highlight the importance of considering comorbid disorders when examining asymmetry patterns in adolescent MD.



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Perceived Functional Social Support and Self-Rated Health: The Health Promoting Effects of Instrumental Support for the Irish Community in London

Abstract

Background

Despite an increasing volume of research on Irish migrants to the UK, limited scientific data exists on the main effects of social support on the health of this community.

Methods

A sample of Irish migrants in London was purposefully recruited (n = 790). Linear regression was used to predict social support. Logistic regression examined the independent association between functional social support and self-rated health (SRH) controlling for low risk covariates.

Results

Older age, economic factors and better SRH precited stronger social support. Irish migrants who reported being able to rely on at least three people in times of crisis and those who perceived stronger emotional support were more likely to report good SRH when adjusted for demography and socio-economic factors. As risks increased only perceived support in times of crisis predicted SRH.

Discussion

Interventions which build reliable and trusted social networks may have a direct effect on migrant health.



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TLL1 variant associated with development of hepatocellular carcinoma after eradication of hepatitis C virus by interferon-free therapy

Abstract

Background

The aim of this study is to ascertain whether the TLL1 variant at rs17047200 is associated with the development of HCC after achieving sustained virological response (SVR) by interferon (IFN)-free therapy for chronic hepatitis C (CHC).

Methods

A total of 1029 Japanese CHC patients with the following inclusion criteria were enrolled: (i) achieved SVR by IFN-free therapy, (ii) followed up at least 1 year from the end of treatment (EOT) (median 104 weeks), (iii) no history of hepatocellular carcinoma (HCC) by 1 year from the EOT.

Results

Nineteen patients developed HCC (HCC group) and 1010 did not (non-HCC group). The proportion of rs17047200 AT/TT was significantly higher in the HCC group than the non-HCC group (47.4% vs. 20.1%, P = 0.008). Multivariate analysis showed that higher levels of α-fetoprotein, FIB-4 and rs17047200 AT/TT were independent risk factors for developing HCC (HR = 3.22, P = 0.021 for α-fetoprotein > 4.6 ng/ml; HR = 3.89, P = 0.036 for FIB-4 > 2.67; HR = 2.80, P = 0.026 for rs17047200 AT/TT). Cumulative incidence of HCC was significantly higher in patients with rs17047200 AT/TT than in those with AA (P = 0.006). Comparing clinical characteristics according to the TLL1 genotypes, patients with rs17047200 AT/TT had significantly lower platelet counts and higher levels of FIB-4 than those with AA (P = 0.011 and 0.032, respectively).

Conclusions

The TLL1 variant was independently associated with HCC development after HCV eradication by IFN-free regimen. It might be involved in hepatic fibrogenesis and thereby carcinogenesis.



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Associations of Resistance Exercise with Cardiovascular Disease Morbidity and Mortality

Purpose Resistance exercise (RE) can improve many cardiovascular disease (CVD) risk factors, but specific data on the effects on CVD events and mortality are lacking. We investigated the associations of RE with CVD and all-cause mortality, and further examined the mediation effect of body mass index between RE and CVD outcomes. Methods We included 12,591 participants (mean age 47 years) who received at least two clinical examinations 1987-2006. RE was assessed by a self-reported medical history questionnaire. Results During a mean follow-up of 5.4 and 10.5 years, 205 total CVD events (morbidity and mortality combined) and 276 all-cause deaths occurred, respectively. Compared with no RE, weekly RE frequencies of one, two, three times or total amount of 1-59 minutes were associated with approximately 40-70% decreased risk of total CVD events, independent of aerobic exercise (AE) (all p-values

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Associations between Distance and Loading Symmetry during Return to Sport Hop Testing

Purpose Hop tests are widely used to quantify recovery from anterior cruciate ligament reconstruction (ACLR) surgery. However, there is evidence that simply measuring hop distance may not be indicative of the quality of movement or representative of potential limitations in hopping mechanics, particularly during landing. The first purpose of the present study was to compare hop distance and loading symmetry between ACLR athletes and healthy uninjured recreational athletes. The second was to determine the association between hop distance and loading symmetry. Methods Twenty-five ACLR patients and 30 healthy controls completed the single hop, triple hop, and crossover hop test on each limb while the loadsol®, a single-sensor force insole, collected impact forces (100 Hz). A limb symmetry index was calculated for hop distance, peak impact force, loading rate, and impulse from the final landing of each trial. LSIs were compared between groups using Mann-Whitney U-Tests and distance and loading LSIs were compared using Spearman rank correlations. Results ACLR patients had reduced symmetry in hop distance and loading relative to healthy controls for every hop test and outcome measure (p

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The Role of Aerobic Exercise in Reducing Persistent Sport-related Concussion Symptoms

Aerobic exercise has received increasing attention in the scientific literature as a component of management for individuals who sustain a concussion. Since exercise training has been reported to reduce symptoms and improve function for those experiencing persistent postconcussion symptoms, it represents a potentially useful and clinically pragmatic rehabilitation technique. However, the specific exercise parameters that best facilitate recovery from concussion remain poorly defined and unclear. This review will provide a brief summary of the current understanding of the role of sub-symptom exercise to improve outcomes after a concussion and will describe the exercise parameters that appear to be important. This latter will take into account the three pillars of exercise dose – frequency, duration, and intensity – to examine what is currently known. In addition, we identify important gaps in our knowledge of exercise as a treatment for those who develop persistent symptoms of concussion. Corresponding author: David R. Howell, Children's Hospital Colorado, Sports Medicine Center, 13123 East 16th Avenue, Box 060, Aurora, Colorado 80045, UNITED STATES, 720-777-4869. David.Howell@ucdenver.edu This work was funded by The Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (R03HD094560) and The National Institute of Neurological Disorders and Stroke of the National Institutes of Health (R03NS106444). The results of the present study do not constitute endorsement by ACSM. Our work is presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for publication October 2018. © 2018 American College of Sports Medicine

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Effect of Ice Slurry Ingestion on Cardiovascular Drift and V[Combining Dot Above]O2max during Heat Stress

External body cooling by fan airflow mitigates the decrease in maximal oxygen uptake (V[Combining Dot Above]O2max) associated with cardiovascular (CV) drift during cycling in hot conditions. It remains unknown whether internal body cooling via ice slurry ingestion elicits a similar response. Purpose To test the hypothesis that ice slurry ingestion attenuates the magnitude of CV drift and accompanying decrement in V[Combining Dot Above]O2max during heat stress. Methods Eight men completed a graded exercise test on a cycle ergometer in 22 °C to measure V[Combining Dot Above]O2max. Then on 3 separate occasions (in randomly assigned counterbalanced treatment orders), they cycled at 60%V[Combining Dot Above]O2max in hot conditions (35 °C, 40% RH) for either 15 min, 45 min with tepid (23 °C) fluid ingestion (45FL), or 45 min with ice (-1° C) slurry ingestion (45ICE), followed immediately by measurement of V[Combining Dot Above]O2max. The purpose of the separate 15- and 45-min trials was to measure CV drift and V[Combining Dot Above]O2max over the same time interval. Results The increase in HR between 15 and 45 min was twice as large in 45FL (8.6%) compared to 45ICE (4.6%; P=0.02). SV declined by 6.2% in 45FL but was maintained with 45ICE (P=0.02). V[Combining Dot Above]O2peak decreased from 15 to 45 min by 8.6% and 9.0% in 45FL and 45ICE, respectively, but was not different between conditions (P=0.79). Conclusion While ice slurry ingestion attenuated CV drift more than fluid ingestion, it did not mitigate the decline in V[Combining Dot Above]O2max. Contrary to previous findings, when ice slurry is ingested, changes in HR may not reflect changes in relative metabolic intensity during prolonged exercise in the heat. Corresponding Author: Jason Ng, Ph.D., CSCS, 5500 University Parkway, San Bernardino, CA 92407-2393, Phone: (909) 537-5412, Fax: (909) 537-7085. Email: jason.ng@csusb.edu CSUSB Faculty Center for Excellence for supporting the publication of this paper with funded writing time. The authors declare no conflict of interest. The results of the present study do not constitute endorsement by the American College of Sports Medicine. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 25 September 2018 © 2018 American College of Sports Medicine

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Physical Activity, Television Viewing Time, and DNA Methylation in Peripheral Blood

Introduction Physical activity may affect health via DNA methylation. The epigenetic influences of sedentary behaviours such as television viewing are unknown. We performed a genome-wide study of DNA methylation in peripheral blood in relation to physical activity and television viewing time. Methods DNA methylation was measured using the Illumina Infinium HumanMethylation450K BeadChip array in blood samples collected at baseline (N=5,513) and follow-up (N=1,249) from participants in the Melbourne Collaborative Cohort Study. At baseline, times/week of leisure-time physical activity was self-reported. At follow-up, the International Physical Activity Questionnaire was used to assess MET-hours/week of total and leisure-time physical activity, and hours/day of television viewing time. Linear mixed models were used to assess associations between the physical activity and television viewing measures and DNA methylation at individual CpG sites, adjusted for potential confounders and batch effects. Results At follow-up, total physical activity was associated with DNA methylation at cg10266336 (P=6.0x10-9), annotated to the SAA2 gene. Weaker evidence of associations (P

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