Τρίτη 24 Οκτωβρίου 2017

Spinal decision making for respiratory muscle recruitment?

Abstract

How does the central nervous system determine the recruitment order of the motor units which are involved in breathing?

This article is protected by copyright. All rights reserved



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Dexamethasone: The wonder drug in perioperative medicine

Anesthesiologist have a greater understanding of the role of the stress response and the development of inflammation following surgery on clinical outcomes [1,2]. Exacerbation of inflammation after surgery has been shown to be associated with multiple negative postsurgical outcomes (e.g., pain, cardiovascular events) [3]. The reduction of inflammation is, therefore, a common target used by anesthesiologists to minimize postoperative complications [4–7].

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Repression of Middle Sporulation Genes in Saccharomyces cerevisiae by the Sum1-Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation

The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for mono-, di- and tri-methylation and is linked to active transcription due to the euchromatic distribution of these methyl marks and the recruitment of Set1 during transcription. However, loss of Set1 results in increased expression of multiple classes of genes, including genes adjacent to telomeres and middle sporulation genes, which are repressed under normal growth conditions because they function in meiotic progression and spore formation. The mechanisms underlying Set1-mediated gene repression are varied and still unclear in some cases, although repression has been linked to both direct and indirect action of Set1, associated with noncoding transcription and often dependent on the H3K4me2 mark. We show that Set1, and particularly the H3K4me2 mark, are implicated in repression of a subset of middle sporulation genes during vegetative growth. In the absence of Set1, there is loss of the DNA-binding transcriptional regulator Sum1 and the associated histone deacetylase Hst1 from chromatin in a locus-specific manner. This is linked to increased H4K5ac at these loci and aberrant middle gene expression. These data indicate that, in addition to DNA sequence, histone modification status also contributes to proper localization of Sum1. In addition, our results show that the role for Set1 in middle gene expression control diverges as cells receive signals to undergo meiosis. Overall, this work dissects an unexplored role for Set1 in gene-specific repression and provides important insights into a new mechanism associated with the control of gene expression linked to meiotic differentiation.



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Mapping Second Chromosome Mutations to Defined Genomic Regions in Drosophila melanogaster

Hundreds of Drosophila melanogaster stocks are currently maintained at the Bloomington Drosophila Stock Center with mutations that have not been associated with sequence-defined genes. They have been preserved because they have interesting loss-of-function phenotypes. The experimental value of these mutations would be increased by tying them to specific genomic intervals so that geneticists can more easily associate them with annotated genes. Here we report the mapping of 86 second chromosome complementation groups in the Bloomington collection to specific, small clusters of contiguous genes or individual genes in the sequenced genome. This information should prove valuable to Drosophila geneticists interested in processes associated with particular phenotypes and those searching for mutations affecting specific sequence-defined genes.



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The Influence of Collaboration: Ralph Waters' Friendship With John Lundy and the Spread of Regional Anesthesia.

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Ralph Waters, the founder of the anesthesiology department and residency program at the University of Wisconsin-Madison, and John Lundy, the chair at the Mayo Clinic beginning in 1924, collaborated to expand regional anesthetic techniques and knowledge not only at their institutions, but also at institutions around the country through correspondence, meetings, and hosting of other anesthesiologists. The Ralph Waters Collection at the University of Wisconsin Archives was searched for information on Waters' and Lundy's involvement in regional anesthesia. This included publications by Waters and other anesthesiology department faculty, as well as personal correspondence with other leaders in anesthesia at that time. Correspondence between Waters and Lundy from this collection was reviewed in detail. This article underscores the importance of exchange of ideas by physicians through didactics, organizations, and research through the story of Ralph Waters and John Lundy's mutual exchange of ideas and even friendship beginning in the 1920s. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

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ESPGHAN Distinguished Service Award 2017 to Professor Olivier Goulet

imageNo abstract available

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Functional Neuroimaging in Irritable Bowel Syndrome: A Brain Twister

No abstract available

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Intestinal Rehabilitation Programs in the Management of Pediatric Intestinal Failure and Short Bowel Syndrome

imageABSTRACT: Intestinal failure is a rare, debilitating condition that presents both acute and chronic medical management challenges. The condition is incompatible with life in the absence of the safe application of specialized and individualized medical therapy that includes surgery, medical equipment, nutritional products, and standard nursing care. Intestinal rehabilitation programs are best suited to provide such complex care with the goal of achieving enteral autonomy and oral feeding with or without intestinal transplantation. These programs almost all include pediatric surgeons, pediatric gastroenterologists, specialized nurses, and dietitians; many also include a variety of other medical and allied medical specialists. Intestinal rehabilitation programs provide integrated interdisciplinary care, more discussion of patient management by involved specialists, continuity of care through various treatment interventions, close follow-up of outpatients, improved patient and family education, earlier treatment of complications, and learning from the accumulated patient databases. Quality assurance and research collaboration among centers are also goals of many of these programs. The combined and coordinated talents and skills of multiple types of health care practitioners have the potential to ameliorate the impact of intestinal failure and improve health outcomes and quality of life.

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Starved Guts: Morphologic and Functional Intestinal Changes in Malnutrition

imageABSTRACT: Malnutrition contributes significantly to death and illness worldwide and especially to the deaths of children younger than 5 years. The relation between intestinal changes in malnutrition and morbidity and mortality has not been well characterized; however, recent research indicates that the functional and morphologic changes of the intestine secondary to malnutrition itself contribute significantly to these negative clinical outcomes and may be potent targets of intervention. The aim of this review was to summarize current knowledge of experimental and clinically observed changes in the intestine from malnutrition preclinical models and human studies. Limited clinical studies have shown villous blunting, intestinal inflammation, and changes in the intestinal microbiome of malnourished children. In addition to these findings, experimental data using various animal models of malnutrition have found evidence of increased intestinal permeability, upregulated intestinal inflammation, and loss of goblet cells. More mechanistic studies are urgently needed to improve our understanding of malnutrition-related intestinal dysfunction and to identify potential novel targets for intervention.

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Associations Between Dietary Intake Before 6 Months of Age and Rapid Weight Gain Among HIV-exposed Uninfected Infants

imageIntroduction: HIV-exposed, uninfected (HEU) infants are potentially at risk for cardiovascular disease due to in utero exposures. Feeding practices of the infant could compound this risk. Few studies have, however, evaluated dietary intake of HEU infants. We determined dietary factors associated with rapid weight gain (RWG) among HEU infants from birth to 6 months followed at the University of Miami HIV Screening Program. Methods: In this cross-sectional analysis, logistic regression was used to determine dietary factors associated with RWG defined as a >0.67 SD change in weight-for-age z score from birth to assessment (0.3–6 months). Other covariates included demographics, birth, maternal and gestational characteristics, and antiretroviral exposures. Results: A total of 86 full-term HEU infants with a mean age of 3.4 months (SD 1.8 months) were included in this analysis. Fifty-five percent of mothers were obese. Overall, 39.5% of infants exhibited RWG. A significant association between consumption of infant cereal and RWG (odds ratio, 3.52; 95% confidence interval, 1.02–12.10) was found after adjusting for birth weight, current age, and energy intake. Those infants who consumed the highest tertile of protein were less likely to gain weight rapidly after adjusting for the same covariates (odds ratio, 0.15; 95% confidence interval, 0.02–0.94). Conclusions: Overall differences in weight gain during early infancy are at least partly explained by means of infant feeding in young HEU infants in the United States. Dietary counseling for families of HEU should reinforce current feeding practice recommendations of the American Academy of Pediatrics.

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Safe Energy Source in Battery-operated Toys for Children

imageObjectives: Serious and even fatal consequences of disk batteries ingestion in children are well known. Among other applications, disk batteries are used to power small toys, from which they can be unexpectedly extracted and swallowed. Methods: We tested a new cell intended for little toys (green cell [GC]), after 6 and 12 hours of in vitro close contact with esophageal swine mucosa. The GC was compared with lithium and silver button batteries under the same experimental conditions. Results: Tissues in contact with the GC did not show pH variations nor histological alterations after 6 and 12 hours. In such conditions, statistically significant differences were found between the GC and the lithium and silver batteries. Conclusions: So far, multidisciplinary medical effort has been driven to both emergency approach and subsequent operative strategies in children with ingested batteries. Our trial demonstrates the possibility to primarily prevent battery-induced damages by designing new-generation safe cells with no tissue toxicity to power little toys intended for children.

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Please Do Not Forget Muscle Disease When Evaluating Elevated Transaminases

No abstract available

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Effectiveness of Double-balloon Enteroscopy-facilitated Polypectomy in Pediatric Patients With Peutz-Jeghers Syndrome

imageABSTRACT: Sizable small-bowel (SB) polyps in Peutz-Jeghers syndrome (PJS) pose a high risk for intussusception, often necessitating laparotomy and intraoperative enteroscopy. This series examines the effectiveness of double-balloon enteroscopy (DBE) facilitated polypectomy for pediatric patients with PJS. Prospective analysis of collected data (6 years) on all patients with PJS referred for DBE-facilitated SB polypectomy at a pediatric tertiary-referral center. A total of 16 pediatric patients with PJS were referred for DBE-facilitated SB polypectomy. Twenty-two DBEs were performed. Large polyps (≥1 cm) were confirmed in 14 patients. Successful clearance of large SB polyps by DBE or laparoscopically assisted DBE (Lap-DBE) was achieved in all patients. One patient experienced post-Lap-DBE pelvic abscess. All other patients remained asymptomatic and intervention free throughout follow-up (median 26 months). This series demonstrates that DBE-facilitated polypectomy is an effective therapeutic option in pediatric patients with PJS. It should be considered at an early age where possible.

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

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

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How to Predict Oral Rehydration Failure in Children With Gastroenteritis

imageObjectives: Oral rehydration is the standard in most current guidelines for young children with acute gastroenteritis (AGE). Failure of oral rehydration can complicate the disease course, leading to morbidity due to severe dehydration. We aimed to identify prognostic factors of oral rehydration failure in children with AGE. Methods: A prospective, observational study was performed at the Emergency department, Erasmus Medical Centre, Rotterdam, The Netherlands, 2010–2012, including 802 previously healthy children, ages 1 month to 5 years with AGE. Failure of oral rehydration was defined by secondary rehydration by a nasogastric tube, or hospitalization or revisit for dehydration within 72 hours after initial emergency department visit. Results: We observed 167 (21%) failures of oral rehydration in a population of 802 children with AGE (median 1.03 years old, interquartile range 0.4–2.1; 60% boys). In multivariate logistic regression analysis, independent predictors for failure of oral rehydration were a higher Manchester Triage System urgency level, abnormal capillary refill time, and a higher clinical dehydration scale score. Conclusions: Early recognition of young children with AGE at risk of failure of oral rehydration therapy is important, as emphasized by the 21% therapy failure in our population. Associated with oral rehydration failure are higher Manchester Triage System urgency level, abnormal capillary refill time, and a higher clinical dehydration scale score.

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Severe Sarcopenia and Increased Fat Stores in Pediatric Patients With Liver, Kidney, or Intestine Failure

imageObjectives: Malnutrition and wasting predict clinical outcomes in children with severe chronic illness. Objectively calculated malnutrition in children with end-stage organ failure has not been well studied. This analysis compares children with kidney, liver or intestine failure to healthy controls to quantitate the disparity in muscle and fat stores. Methods: Children younger than 19 years with end-stage liver, kidney, or intestine failure and with pretransplant computed tomography (CT) imaging were selected from the transplant database. Age- and sex-matched healthy controls were selected from the trauma database. Measures of nutrition status included a scaled scoring of core muscle mass, and visceral and subcutaneous fat stores. Analysis was conducted using the pooled and individually matched subject-control differences. Results: There were 81 subjects included in the final analysis (liver [n = 35], kidney [n = 20], and intestine [n = 26]). Children with end-stage liver disease had a 23% reduction in muscle mass, a 69% increase in visceral fat, and a 29% increase in subcutaneous fat. End-stage renal disease patients had a 19% reduction in muscle mass and a 258% increase in subcutaneous fat. Intestine failure patients had a 24% reduction in muscle mass, a 30% increase in visceral fat, and a 46% increase in subcutaneous fat. Conclusions: These results demonstrate significant sarcopenia and increased fat stores in end-stage organ failure patients, which supports the idea of an active physiologic mechanism to store fat while losing muscle mass. Sarcopenia may be related to total protein loss from a catabolic state, or from decreased synthesis (liver), wasting (kidney), or malabsorption (intestine).

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Association of Maternal Gestational Weight Gain With the Infant Fecal Microbiota

imageObjectives: Pregnancy characteristics may influence the infant fecal microbiota during early life. We aimed to examine associations of maternal gestational weight gain with infant fecal microbiota composition, bacterial community richness, and Shannon diversity index. Methods: We analyzed data from a prospective cohort study of healthy infants. We collected prenatal data, including report of mother's gestational weight gain, and infant fecal samples from 84 infant-mother dyads. By applying 16S rRNA gene sequencing and an unbiased clustering by partitioning around medoids using Bray-Curtis distances, we identified 4 fecal microbiota profiles, and examined the associations of maternal gestational weight gain with the 4 fecal microbiota profiles, bacterial community richness, and Shannon diversity index. Results: Overall, the median age of infants was 4.0 months and 43% were girls. The mothers of the 84 infants gained a mean of 14.2 kg (standard deviation, 5.4 kg) during pregnancy. We identified 4 distinct microbiota profiles: Bifidobacterium-dominant (42%), Enterobacter/Veillonella-dominant (23%), Bacteroides-dominant (19%), and Escherichia-dominant (17%). Infants whose mothers had higher gestational weight gain were less likely to have a Bacteroides-dominant profile, corresponding to a relative risk ratio of 0.83 (95% confidence interval, 0.71–0.96; P = 0.01) per 1 kg increase in weight. In addition, higher gestational weight gain was also associated with lower bacterial community richness and Shannon diversity index (P 

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Cholangioscopic Management of Mirizzi Syndrome in a Pediatric Patient

imageNo abstract available

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Anxiety Associated With High-resolution Anorectal Manometry in Pediatric Patients and Parents

ABSTRACT: High-resolution anorectal manometry is an increasingly common procedure performed in pediatric patients to rule out Hirschsprung and assess anorectal function and sensation. The purpose of the present study was to evaluate anxiety of patients and their parents associated with high-resolution anorectal manometry. Preprocedural anxiety was assessed by standardized questionnaire in all parents and children older than 8 years and observed behavioral distress was recorded by the attending pediatric gastroenterologist. Thirty-five children (mean age = 7.2 years, ±2.8) and their parents completed the study. Patient anxiety was found to be markedly elevated. Observed behavioral distress was elevated compared to more invasive procedures. Self-reported parental anxiety was comparable to adults undergoing endoscopic procedures themselves. Despite the low risk of this procedure, healthcare providers should be aware of the high levels of anxiety and distress that occur in patients and their parents associated with anorectal manometry.

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Screening for NAFLD in Children: Do We Know the Optimal ALT Cut-off?

No abstract available

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Reduced Functional Connectivity Between the Hypothalamus and High-order Cortical Regions in Adolescent Patients With Irritable Bowel Syndrome

imageABSTRACT: The hypothalamus plays a critical role in maintaining visceral homeostasis. Altered hypothalamus activation has been implicated in functional gastrointestinal disorders, including irritable bowel syndrome (IBS). One important aspect of homeostatic regulation is the cortical modulation of limbic and paralimbic subsystems, including the hypothalamus, which in turn affects the descending regulatory processes mediating visceral homeostasis. Using neuroimaging, we evaluated hypothalamus functional connectivity in adolescent patients with IBS and age-matched healthy controls who received rectal distension stimulations. More extensive hypothalamus connectivity was observed in liminal than subliminal condition in controls, but not in patients with IBS. Compared with controls, patients with IBS showed significantly reduced hypothalamus connectivity in the bilateral prefrontal cortices, supplementary motor and premotor areas, bilateral sensorimotor cortex, and limbic subareas, which are specifically involved in homeostatic regulation. The findings support the generalized homeostatic regulation model that reduced cortical and limbic modulations of hypothalamus functioning underlies disrupted visceral homeostasis in patients with IBS.

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Early Onset of Wilson Disease: Diagnostic Challenges

imageObjectives: The aim of the study was to analyze the clinical presentations, diagnosis, and treatment of patients ages ≤5 years with early onset Wilson disease (WD). Methods: Data from 143 pediatric patients with WD treated at our center between January 1996 and November 2015 were retrospectively analyzed. Results: A review of the 143 pediatric patients with WD identified 21 (10 girls, 11 boys) with first symptoms or abnormal liver function test results at age ≤5 years. The diagnosis of WD was confirmed in 8 patients younger than 5 years. At baseline the mean serum alanine aminotransferase level was 222 U/L and the mean serum aspartate aminotransferase level was 130 U/L. The mean serum ceruloplasmin concentration in 16 tested patients was 100 μg/day. Liver copper quantification was >250 μg/g dry weight in 16 patients. The most common mutation was p.H1069Q, with compound heterozygosity in 5 patients and homozygosity in 9. Sixteen patients were treated with zinc salts and 5 with D-penicillamine. Both treatments were effective, with no serious side effects observed after 3 to 24 months. Conclusions: WD can present as early as 2 years of age. Because biochemical tests may be less sensitive in very young children, diagnoses may require a combination of tests. If molecular tests are inconclusive, liver copper content should be measured.

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Using Serum IgE Antibodies to Predict Esophageal Eosinophilia in Children

imageObjectives: Symptoms of eosinophilic esophagitis are variable and can be nonspecific. Food-specific serum immunoglobulin E (IgE) antibodies are frequently found in patients with eosinophilic esophagitis and are obtained using a widely available blood test. Our objective was to evaluate the ability of food-specific IgE antibodies to predict the presence of esophageal eosinophilia. Methods: We reviewed 144 medical records for pediatric patients having esophageal biopsy and serum analysis for IgE antibodies to food (exploratory group). We performed logistic regression using sex and number of positive food-specific IgE tests to develop a model that predicts ≥15 eosinophils/high-power field (hpf) in the esophagus. We tested the model using 142 additional patients (validation group). Results: The probability of having ≥15 eosinophils/hpf in the esophagus was higher in boys and increased with the number of positive food-specific IgE tests from 12% (95% confidence interval 4.8–26) in girls with 0 foods positive to 86% (95% confidence interval 71–94) for boys with 4 or 5 foods positive. The statistical model using sex and number of positive IgE tests to predict patients having ≥15 eosinophils/hpf showed acceptable discriminative ability (area under the receiver operating characteristic curve 0.80). The performance metrics for the model to predict ≥15 eosinophils/hpf in the validation group were similar (area under the receiver operating characteristic curve 0.75). Conclusions: Requiring only a blood test and a simple algorithm, analysis for IgE antibodies to food may expedite an esophagogastroduodenoscopy and decrease delays in the diagnosis and treatment of patients with nonspecific gastrointestinal symptoms who have increased eosinophils in the esophagus.

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Health Status and Anthropometric Changes in Resettled Refugee Children

imageBackground: Recently the United States has experienced an increase in refugees. Pediatric refugees are at risk for health and nutrition problems. Literature on longitudinal change in nutritional status of resettled pediatric refugees is scant. Objective: The present study reports the health and nutritional status of pediatric refugees and tracks changes in nutritional status. Methods: Data were extracted retrospectively from the records of a community health center in Buffalo, NY. Two cohorts of refugees (0–18 years) were selected. Cohort A was followed during 5 years and consisted of 225 subjects whose initial visit occurred between January 1, 2007 and December 31, 2009. The 199 subjects in cohort B had an initial visit between January 1, 2013 and December 31, 2013 and were followed for 1 year. Cohort B was chosen because vitamin levels were available only for this group. Descriptive and anthropometric data, infectious disease status, and initial vitamin and hemoglobin levels were recorded. Height-for-age (HFA) z scores and body mass index (BMI) z scores were computed. Longitudinal changes were analyzed. Results: The cohorts A and B differed in country of origin and infectious disease burden. On arrival, both cohorts exhibited HFA z scores reflecting short stature. BMI z scores were normal. HFA and BMI z scores increased during 5 years and 1 year for cohorts A and B, respectively. Anemia, vitamin D deficiency, and lead toxicity were identified. Conclusions: Resettled pediatric refugees were short. Some were stunted. Catch-up growth, however, occurred. There were increases in HFA and BMI z scores. Vitamin D deficiency, anemia, and lead toxicity were documented.

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Reduced Bone Mineral Density in Children With Screening-detected Celiac Disease

imageObjectives: The aim of the study was to assess whether bone mass and metabolism are impaired in genetically at-risk children with screening-detected celiac disease. Methods: Included were 71 children with screening-detected celiac disease diagnosed at 10.0 ± 0.7 (mean ± standard deviation) years and 142 matched controls and 30 children with screening-detected celiac disease diagnosed at 3.3 ± 0.4 years of age presently on a gluten-free diet for 6.9 ± 1.1 years and 60 matched controls. All participants were assessed for bone mineral density (BMD) of total body and spine by dual x-ray absorptiometry, serum 25(OH) vitamin D3, parathyroid hormone (PTH), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, interferon gamma, and tumor necrosis factor alpha. Results: At diagnosis, screening-detected celiac disease children as compared to controls had a mean −0.03 g/cm2 reduced BMD of both total body and spine (P = 0.009 and P = 0.005, respectively), a mean −11.4 nmol/L lower level of 25(OH) vitamin D3 (P 

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Genetic engineering: On the road to efficient gene drives

Genetic engineering: On the road to efficient gene drives

Nature Reviews Genetics, Published online: 24 October 2017; doi:10.1038/nrg.2017.91



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Transcription: Intragenic enhancers dampen gene expression

Transcription: Intragenic enhancers dampen gene expression

Nature Reviews Genetics, Published online: 24 October 2017; doi:10.1038/nrg.2017.90



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Population genetics of sexual conflict in the genomic era

Population genetics of sexual conflict in the genomic era

Nature Reviews Genetics, Published online: 24 October 2017; doi:10.1038/nrg.2017.83

Sexual conflict is thought to increase population genetic diversity though balancing selection, which has important evolutionary implications. This Review discusses how population genomic approaches are contributing to a deeper understanding of sexual conflict and how it is resolved.



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The DNA methyltransferase family: a versatile toolkit for epigenetic regulation

The DNA methyltransferase family: a versatile toolkit for epigenetic regulation

Nature Reviews Genetics, Published online: 16 October 2017; doi:10.1038/nrg.2017.80

The DNA methyltransferase (DNMT) family comprises a conserved set of DNA-modifying enzymes. Recent studies have increased our understanding of how DNMT activity is regulated and revealed that, in addition to establishing and maintaining DNA methylation patterns, DNMT enzymes function in transcriptional silencing, transcriptional activation and post-transcriptional regulation.



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Genetic variation: Birds of a feather — genetic mapping of yellow pigmentation

Genetic variation: Birds of a feather — genetic mapping of yellow pigmentation

Nature Reviews Genetics, Published online: 16 October 2017; doi:10.1038/nrg.2017.87



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Emerging and evolving concepts in gene essentiality

Emerging and evolving concepts in gene essentiality

Nature Reviews Genetics, Published online: 16 October 2017; doi:10.1038/nrg.2017.74

Identifying which genes in a genome are essential for survival has been a long-standing goal of geneticists. This Review discusses our evolving understanding of cellular gene essentiality across diverse organisms. It describes how essentiality is often non-absolute but is instead dependent on the environment or genetic background and how this knowledge can be exploited therapeutically.



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Gene regulation: Closing the loop on noisy gene expression

Gene regulation: Closing the loop on noisy gene expression

Nature Reviews Genetics, Published online: 16 October 2017; doi:10.1038/nrg.2017.85



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Genome organization: Compartmentalizing chromatin without cohesin

Genome organization: Compartmentalizing chromatin without cohesin

Nature Reviews Genetics, Published online: 9 October 2017; doi:10.1038/nrg.2017.84



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Feasibility of real-time intestinal bloodstream evaluation using probe-based confocal laser endomicroscopy in a porcine intestinal ischemia model

Abstract

Background

Intestinal ischemia can lead to fatal complications if left unrecognized during surgery. The current techniques of intraoperative microvascular assessment remain subjective. Probe-based confocal laser endomicroscopy (pCLE) has the potential to objectively evaluate microvascular blood flow in real-time setting. The present study evaluated the technical feasibility of real-time intestinal bloodstream evaluation using pCLE in a porcine intestinal ischemia model.

Methods

Seven pigs were used. The intestinal ischemia model was prepared by sequentially dividing the mesenteric blood vessels. The intestinal bloodstream was evaluated on its serosal surface using pCLE (Cellvizio 488 probe, Ultra Mini O) at every 1-cm segment from a vessel-preservation border (i.e., the cut end of the vessel). Images of the blood vessels and flow of red blood cells (RBCs) in each visualized vessel were semi-qualitatively assessed using a 3-scale scoring system. In addition, 25 surgeons blindly assessed the 10 movies recorded at 0, 1, 2, 3, and 5 cm from a vessel-preservation border using a 4-scale scoring system to confirm the consistency of the evaluation of the pCLE system.

Results

Images of the blood vessels were successfully obtained from the cut end of the vessel to the segment 4 cm away. Good unidirectional flow of RBCs was observed from the cut end to the 2-cm segment, whereas the flow became bidirectional between 2 and 3 cm segments. Beyond 4 cm, no flow images were obtained. The specimen obtained from the segment beyond 4 cm showed remarkable mucosal color change, which was confirmed as a necrotic change histologically. The evaluations from the cut end of the vessel to the segment 1 cm away by surgeons were excellent or good and it was almost consistent.

Conclusions

Real-time bloodstream evaluation using pCLE is feasible and potentially effective for predicting intestinal ischemia during surgery.



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Impact of surgical approach on perioperative and long-term outcomes following esophagectomy for esophageal cancer

Abstract

Background

Surgical resection remains a critical component of esophageal cancer treatment with curative-intent. The aim of this study was to compare open (OE) to minimally invasive Ivor Lewis esophagectomy (MIE) with respect to perioperative and oncologic outcomes.

Methods

Retrospective single-institution review of MIE and OE patients operated between 2001 and 2015 was conducted. Univariable and multivariable models were created using Cox regression. The Kaplan–Meier method was used to compare oncologic outcomes. Propensity score matching was used to compare oncological outcomes in MIE and OE patients.

Results

Of 210 esophageal resection patients, 47% had OE (137/291) and 25% had MIE (73/291). The MIE and OE groups were comparable with respect to patient factors and operative details. Fewer OE patients received neoadjuvant chemoradiation. MIE was associated with improved lymph node yield, (MIE = 30 [IQR:22–39]; OE = 14 [IQR:7–19], p < 0.001), less intraoperative blood loss (MIE = 312 mL [100–400]; OE = 657 mL [350–700], p < 0.001), and shorter median length of stay (MIE = 10 days [IQR = 8–14]; OE = 14 days [IQR = 11–22] p < 0.01). The OE group had significantly more adverse events resulting in reoperation or intensive care unit admission (MIE = 21%; OE = 34%; p < 0.01). On multivariable analysis, age and positive resection margins were associated with decreased odds of survival. The number of lymph nodes retrieved, positive resection margins, and pathologic stage were significant predictors of disease-free survival. Analysis of 69 matched pairs showed equivalent median overall survival (MIE = 49 months [18–67]; OE = 29 months [17–69]; p = 0.26) and disease-free survival (MIE = 9 [6–22]; OE = 13 [6–22]; p = 0.45) between the two groups.

Conclusions

Although long-term oncologic outcomes appear to be similar, MIE is associated with significantly less intraoperative blood loss, improved lymph node yield, less risk of severe postoperative adverse events, and shorter length of stay.



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Growth in robotic-assisted procedures is from conversion of laparoscopic procedures and not from open surgeons’ conversion: a study of trends and costs

Abstract

Background

Utilization of laparoscopy (LAP) has been increasing in general surgery for years, and there is currently a rapid increase in the utilization of robotic-assisted surgeries (RAS). This study evaluates trends in the surgical approach utilized in some commonly performed surgeries, the proportion of each approach within the procedures, and the cost of these surgeries based on the surgical approach.

Methods

This is a retrospective study using the Vizient database. The database was queried using ICD-9 codes for colectomy, cholecystectomy, inguinal and ventral hernia repairs, and bariatric surgeries, either open, LAP, or robotically performed. Utilization trends were evaluated between quarters, over a 7-year period, and direct cost was compared between approaches. IBM SPSS v.23.0.0 was used for data analysis, with α = 0.05.

Results

857,468 patients underwent colectomy, cholecystectomy, inguinal and ventral hernia repairs, and bariatric procedures. A significant decrease in open-approach utilization was seen in colectomy (71.8–61.9%), cholecystectomy (35.7–27.1%), and bariatric surgeries (20.1–10.1%), whereas both LAP and RAS utilization increased (p < 0.001). Significant RAS increase was seen in all five procedures: colectomy (0.4–8.0%), cholecystectomy (0.2–1.8%), IHR (19.9–29.4%), VHR (0.2–2.9%), and bariatric (0.6–5.4%), compared to a decrease in LAP (p < 0.001). Surgery cost was significantly higher for open ($14,364), followed by RAS ($11,376) and LAP ($7945), p < 0.001.

Conclusions

Robotic technology is commonly viewed as enabling open procedures to be converted to minimally invasive, a trend not observed in our study. Our trends analysis revealed significant RAS utilization increase from LAP procedures and not from open procedure conversion, although specific surgeon data were not available. RAS were costlier than LAP for all five procedures. The benefits of rapid robot adoption and the forces that are driving these must be examined against a backdrop of burdening an already expensive healthcare system.



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InSiCal – A tool for calculating calibration factors and activity concentrations in in situ gamma spectrometry

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Publication date: Available online 23 October 2017
Source:Journal of Environmental Radioactivity
Author(s): Alexander Mauring, Tim Vidmar, Torbjörn Gäfvert, Jon Drefvelin, Aldo Fazio
In situ gamma spectrometry is a widely applied analysis technique for the determination of radioactivity levels in soil. Compared to traditional laboratory analysis of soil samples, in situ techniques offer a quick and low-cost way of obtaining accurate results from on-site measurements. However, although the technique is well-known, the dependence of in situ gamma spectrometry on complex and time-consuming calibration procedures as well as in-depth knowledge of the geometric distribution of the source in the ground deters many potential users from employing it in their routine work. Aiming to alleviate this issue, a software tool named InSiCal (In Situ gamma spectrometry Calculator) has been developed to make in situ gamma spectrometry more accessible to both experts and non-experts in the field. This is done by simplifying and streamlining both calibration and activity calculation through a simple and intuitive graphical user interface. Testing in real field conditions show that InSiCal is capable of yielding results which are in very good agreement with soil sample analyses, and that the results may be obtained using different detector types (HPGe, NaI, LaBr and CZT). Overall, InSiCal, provides results which are comparable in accuracy to laboratory measurements, indicating that it fulfills its purpose successfully.



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Transanal versus abdominal low rectal dissection for rectal cancer: long-term results of the Bordeaux’ randomized trial

Abstract

Aim

The aim of the current study is to report long-term outcomes after transanal low rectal dissection compared with the conventional laparoscopic approach within the context of the Bordeaux' randomized trial. Results from this randomized trial have indicated that transanal approach was more effective than laparoscopic dissection regarding the rate of negative circumferential resection margin (CRM). Despite a high number of publications regarding the transanal approach for TME, there were no long-term data on survival and local recurrence which are now required.

Methods

One hundred patients with low rectal cancer suitable for laparoscopic TME with handsewn coloanal anastomosis were randomized in transanal versus laparoscopic low rectal dissection from 2008 to 2012. The randomization ratio was 1:1. All patients included in the trial were considered for long-term assessment. Local recurrence, overall- and disease-free survival were assessed by Kaplan–Meier and compared with Log-rank test.

Results

The follow up was 60.2 months, similar in both group (p = 0.321). Overall, there were no differences of long-term outcomes. There was a significant association between CRM involvement and local recurrence (p = 0.011), however, the 5-year local recurrence rate was 4%, without any significant difference between transanal and laparoscopic dissection: 3% vs. 5%; p = 0.300. The 5-year disease-free survival was 73%: 72% vs. 74; p = 0.351.

Conclusion

Lower positivity of the circumferential resection margin was reported after transanal low rectal dissection, but it did not translate into a decreased incidence of local recurrence. Further investigations are necessary to demonstrate advantages of this new procedure.



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Serial intermediate-term quality of life comparison after endoscopic submucosal dissection versus surgery in early gastric cancer patients

Abstract

Background

Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is expected to provide better long-term health-related quality of life (HRQOL) by preserving the entire stomach. We aimed to compare serial changes in HRQOL characteristics between patients who underwent ESD versus surgery for EGC.

Methods

A gastric cancer patient cohort was prospectively enrolled from 2004 to 2007. HRQOL of 161 EGC patients was prospectively assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) and the stomach cancer-specific module EORTC-QLQ-STO22 at baseline (i.e., diagnosis) and at 1, 6, 12, 18, and 24 months of post-treatment.

Results

Of 161 patients, 48 (29.8%) underwent ESD and 113 (70.2%) underwent surgery. HRQOL parameters of ESD patients were similar to or better than baseline values. At 1-month post-treatment, the surgery group had significantly poorer scores than the ESD group (P < 0.05) for factors except emotional and cognitive functioning, financial problems, anxiety, and hair loss. However, most of the HRQOL parameters in the surgery group improved during the first post-treatment year, with between-group differences becoming insignificant. Only five parameters (physical functioning, eating restriction, dysphagia, diarrhea, and body image) remained significantly better in the ESD group than the surgery group for > 1-year post-treatment (P < 0.05). The surgery group had significantly higher treatment-associated complications than the ESD group (15.0 vs. 2.1%; P = 0.017). The overall survival was not different between the both groups (5-year overall survival rates, 97.7% in the ESD group vs. 99.1% in the surgery group; P = 0.106 by the log-rank test).

Conclusion

Compared with surgery, ESD can provide better HRQOL benefits for EGC patients, especially during the early post-treatment period. However, surgical treatment should not be rejected only due to the concern about HRQOL impairments because most of them improved during follow-up periods.



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Comparison of laparoscopic to open pancreaticoduodenectomy in elderly patients with pancreatic adenocarcinoma

Abstract

Introduction

The purpose of the study is to compare perioperative and survival outcomes in elderly patients undergoing laparoscopic pancreaticoduodenectomy (LPD) to those undergoing open pancreaticoduodenectomy (OPD).

Methods

Patients aged ≥ 75 years with pancreatic adenocarcinoma undergoing LPD or OPD were identified from the NCDB (2010–2013). Baseline characteristics and perioperative outcomes were compared using a χ 2 and Student's t test. The Kaplan–Meier method was used to generate survival curves, and differences were tested using a log-rank test. A multivariate cox proportional hazard model was applied to estimate the hazard ratio (HR) of LPD on overall survival (OS).

Results

We identified 1768 patients aged ≥ 75 years who underwent LPD (n = 248, 14.0%) or OPD (n = 1520, 86.0%). The majority of patients in the LPD group had their surgery at facilities performing less than 5 LPDs per year (n = 165, 66.5%). 90-day mortality was significantly lower in the LPD compared to the OPD (7.2 vs. 12.2%, p = 0.049). The laparoscopic conversion rate was 30% (n = 74) and was associated with higher readmission rates (13.5 vs. 8.1%), 30-day mortality (8.0 vs. 3.8%), and 90-day mortality (10.4 vs. 6.0%), but these did not reach statistical significance. Median OS was significantly longer in the LPD group (19.8 vs. 15.6 months, p = 0.022). After adjusting for patient and tumor-related characteristics, there was a trend towards improved survival in the LPD group (HR 0.85, 95% CI 0.69–1.03).

Conclusion

The vast majority of the NCDB participating facilities perform less than 5 LPD cases per year, which was associated with an increased risk of perioperative mortality. Overall 90-day mortality was significantly lower in the LPD group and there was a trend towards improved OS in the LPD group compared to the OPD group after adjusting for patient and tumor-related characteristics. Studies with increased sample size and longer follow-up are needed before definitive conclusions can be made.



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Trends in the Fundamentals of Laparoscopic Surgery® (FLS) certification exam over the past 9 years

Abstract

Background

The Fundamentals of Laparoscopic Surgery® (FLS) certification exam assesses both cognitive and manual skills, and has been administered for over a decade. The purpose of this study is to report results over the past 9 years of testing in order to identify trends over time and evaluate the need to update scoring practices. This is a quality initiative of the SAGES FLS committee.

Methods

A representative sample of FLS exam data from 2008 to 2016 was analyzed. The de-identified data included demographics and scores for the cognitive and manual tests. Standard descriptive statistics were used to compare trends over the years, training levels, and to assess the pass/fail rate.

Results

A total of 7232 FLS tests were analyzed [64% male, 6.4% junior (postgraduate year—PGY1–2), 84% senior (PGY3–5), 2.8% fellows (PGY6), and 6.7% attending surgeons (PGY7)]. Specialties included 93% general surgery (GS), 6.2% gynecology, and 0.9% urology. The Pearson correlation between cognitive and manual scores was 0.09. For the cognitive exam, there was an increase in scores over the years, and the most junior residents scored the lowest. For the manual skills, there were marginal differences in scores over the years, and junior residents scored the highest. The odds ratio of PGY3+ passing was 1.8 (CI 1.2–2.8) times higher than that of a PGY1–2. The internal consistency between tasks on the manual skills exam was 0.73. If any one of the tasks was removed, the Cronbach's alpha dropped to between 0.65 and 0.71, depending on the task being removed.

Conclusion

The cognitive and manual components of FLS test different aspects of laparoscopy and demonstrate evidence for reliability and validity. More experienced trainees have a higher likelihood of passing the exam and tend to perform better on the cognitive skills. Each component of the manual skills contributes to the exam and should continue to be part of the test.



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Impact of hospital and surgeon case volume on morbidity in colorectal endometriosis management: a plea to define criteria for expert centers

Abstract

Summary of background data

National and international guidelines recommend referring patients with severe forms of endometriosis to expert centers. However, there is a lack of clear criteria to define an expert center. We examined the roles of surgeon and hospital procedure volumes as determinants of morbidity in deep infiltrating endometriosis of the rectum and sigmoid colon (DIERS).

Methods

We conducted a French retrospective multicenter study of hospital facilities performing colorectal surgery for DIERS in 2015. The primary end point was to analyze the relation between case volume and the incidence of complications. We estimated the optimal cut-off (OCO) determined by a minimal p-value approach.

Results

The study included 56 hospital facilities and collected data of 1135 cases of surgical management of colorectal endometriosis. The mean and median number of procedures per year and per surgeon were 9.17 and 5.58, respectively. The overall rate of grade III–V complication was 7.6% (82/1135). One grade V complication occurred. The rates of rectovaginal fistula, anastomotic leakage, pelvic abscess, and ureteral fistula were: 2.7% (31/1135), 0.79% (9/1135), 3.4% (39/1135), and 0.70% (8/1135), respectively. An OCO of 20 procedures per center and per year (p < 0.001) was defined. The OCO per surgeon and per year varied between seven (p = 0.007) and 13 procedures (p = 0.03). In a multivariate analysis, we found that only the volume of activity was independently correlated to complication outcomes (p = 0.0013).

Conclusion

Our results contribute to providing objective morbidity data to determine criteria for defining expert centers for colorectal surgery for endometriosis.



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A new fluorescence imaging technique for visualizing hepatobiliary structures using sodium fluorescein: result of a preclinical study in a rat model

Abstract

Background

Near-infrared fluorescence imaging has been recently applied in the field of hepatobiliary surgery. Our objective was to apply blue light fluorescence imaging to cholangiography and liver mapping during laparoscopic surgery. Therefore, we designed a preclinical study to evaluate the feasibility of using blue light fluorescence for cholangiography and liver mapping in a rat model.

Methods

Sodium fluorescein solution (1 mL to each individual) were administered intravenously to 20 male Sprague–Dawley rats (6 weeks old, 200–250 g), after laparotomy. Whole abdominal organs were observed under blue light (at a wavelength of 440–490 nm) emitted from a commercialized LED curing light.

Results

Immediately after the tracer solution was administered into the circulatory system of the rat, it was possible to visualize the location of the kidneys and the bile duct under blue light emitted from the light source. The liver was vaguely stained green by the tracer, while the ureters were not. After establishing biliary retention via duct clamping in the left lateral segment of the liver, the green color of the segment became distinct by the tracer, which showed vague coloration following release of the clamp.

Conclusion

We established the preclinical basis for using blue light fluorescence cholangiography and liver mapping in this study. The clinical feasibility of these techniques during laparoscopic cholecystectomy and hepatectomy remained to be demonstrated.



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Big Ass Light creates the world’s toughest portable work light

LEXINGTON, Ky. — Big Ass Light, a division of Big Ass Fans, announces the release of the world's toughest and brightest battery-powered LED work light: the Big Ass Light Bar. Big Ass Light Bar was built to uncompromising quality standards. Its durable design and ability to survive being doused and dropped make it ideal for use on the toughest jobs. Big Ass Light Bar's features include: ...

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Photo roundup: EMS World Expo 2017

Did you attend this year's conference? Add your photos in the comments

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Inguinal hernia repair: is there a benefit to using the robot?

Abstract

Background

The number of robotic surgical procedures performed yearly is constantly rising, due to improved dexterity and visualization capabilities compared with conventional methods. We hypothesized that outcomes after robotic-assisted inguinal hernia repair would not be significantly different from outcomes after laparoscopic or open repair.

Methods

All patients undergoing inguinal hernia repair between 2012 and 2016 were identified using institutional American College of Surgeons National Surgical Quality Improvement Program data. Demographics; preoperative, intraoperative, and postoperative characteristics; and outcomes were evaluated based on method of repair (Robot, Lap, or Open). Categorical variables were analyzed by Chi-square test and continuous variables using Mann–Whitney U.

Results

A total of 510 patients were identified who underwent unilateral inguinal hernia repair (Robot: 13.8% [n = 69], Lap: 48.1% [n = 241], Open: 38.1% [n = 191]). There were no demographic differences between groups other than age (Robot: 52 [39–62], Lap: 57 [45–67], and Open: 56 [48–67] years, p = 0.03). Operative duration was also different (Robot: 105 [76–146] vs. Lap: 81 [61–103] vs. Open: 71 [56–88] min, p < 0.001). There were no operative mortalities and all patients except one were discharged home the same day. Postoperative occurrences (adverse events, readmissions, and death) were similar between groups (Robot: 2.9% [2], Lap: 3.3% [8], Open: 5.2% [10], p = 0.53). Although rare, there was a significant difference in rate of postoperative skin and soft tissue infection (Robot: 2.9% [2] vs. Lap: 0% [0] vs. Open: 0.5% [1], p = 0.02). Cost was significantly different between groups (Robot: $7162 [$5942–8375] vs. Lap: $4527 [$2310–6003] vs. Open: $4264 [$3277–5143], p < 0.001).

Conclusions

Outcomes after robotic-assisted inguinal hernia repair were similar to outcomes after laparoscopic or open repair. Longer operative duration during robotic repair may contribute to higher rates of skin and soft tissue infection. Higher cost should be considered, along with surgeon comfort level and patient preference when deciding whether inguinal hernia repair is approached robotically.



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Predictive factors of weight regain following laparoscopic Roux-en-Y gastric bypass

Abstract

Background

Strategies to address weight recidivism following Roux-en-Y gastric bypass (RYGB) could be developed if patients at risk were identified in advance. This study aimed to determine factors that predict weight regain.

Methods

Retrospective review was performed of patients who underwent laparoscopic RYGB at a single institution over 10 years. Group-based modeling was used to estimate trajectories of weight regain after nadir and stratify patients based on percent weight change (%WC).

Results

Three trajectories were identified from 586 patients: 121 had ongoing weight loss, 343 were weight stable, and 122 regained weight. Male sex (p = 0.020) and white race (p < 0.001) were associated with stable weight or weight regain. Being from a neighborhood of socioeconomic advantage (p = 0.035) was associated with weight regain. Patients with weight regain experienced improved percent weight loss (%WL) at nadir (p < 0.001) and ΔBMI (p = 0.002), yet they had higher weight and BMI and lower %WL and ΔBMI than the other two groups during long-term follow-up. On multivariate analyses, those who regained weight were more likely from socioeconomically advantaged neighborhoods (OR 1.82, CI 1.18–2.79).

Conclusions

Several patient-related characteristics predicted an increased likelihood of weight regain. Further studies are needed to elucidate how these factors contribute to weight recidivism following bariatric surgery.



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MagneGrip exhaust removal systems firehouse installations have cleaner air for firefighters

MagneGrip Exhaust Removal Systems and AirHAWK Air Purification Systems remove vehicle exhaust emissions and other contaminants in firehouses to reduce firefighter risk for cancer, respiratory and cardiovascular diseases while keeping spaces clean and tidy. At Mount Pleasant Fire Department (Mount Pleasant, SC), a combination of MagneGrip Sliding Balancer Track (SBT), Straight Suction Rail (SSR) and ...

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Genetic engineering: On the road to efficient gene drives



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Transcription: Intragenic enhancers dampen gene expression



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Population genetics of sexual conflict in the genomic era



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FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs [Genetics]

Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 × 10−10) both identified a significant...

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UTX-guided neural crest function underlies craniofacial features of Kabuki syndrome [Genetics]

Kabuki syndrome, a congenital craniofacial disorder, manifests from mutations in an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A) or a H3 lysine 4 methylase (KMT2D). However, the cellular and molecular etiology of histone-modifying enzymes in craniofacial disorders is unknown. We now establish Kabuki syndrome as a neurocristopathy, whereby the majority...

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The Activity of Fosfomycin Against Extended-Spectrum Beta-Lactamase-Producing Isolates of Enterobacteriaceae Recovered from Urinary Tract Infections: A Single-Center Study Over a Period of 12 Years

Microbial Drug Resistance , Vol. 0, No. 0.


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Bone microvascular flow differs from skin microvascular flow in response to head-down tilt

Loss of hydrostatic pressures in microgravity may alter skin and bone microvascular flows in the lower extremities and potentially reduce wound healing and bone fracture repair. The purpose of this study was to determine the rate at which skin and bone microvascular flows respond to head-down tilt (HDT). We hypothesized that microvascular flows in tibial bone and overlying skin would increase at different rates during HDT. Tibial bone and skin microvascular flows were measured simultaneously using photoplethysmography (PPG) in a total of 17 subjects during sitting (control posture), supine, 6° HDT, 15° HDT, and 30° HDT postures in random order. With greater angles of HDT, bone microvascular flow increased significantly, but skin microvascular flow did not change. Tibial bone microvascular flow increased from the sitting control posture (0.77 ± 0.41 V) to supine (1.95 ± 1.01 V, P = 0.001) and from supine posture to 15° HDT (3.74 ± 2.43 V, P = 0.004) and 30° HDT (3.91 ± 2.68 V, P = 0.006). Skin microvascular flow increased from sitting (0.703 ± 0.75 V) to supine (2.19 ± 1.72 V, P = 0.02) but did not change from supine posture to HDT (P = 1.0). We show for the first time that microcirculatory flows in skin and bone of the leg respond to simulated microgravity at different rates. These altered levels of blood perfusion may affect rates of wound and bone fracture healing in spaceflight.

NEW & NOTEWORTHY Our data show that bone microvascular flow increases more than cutaneous blood flow with greater degrees of head-down tilt. A higher level of perfusion in bone may give insight into the bone mineral density loss in lower extremities of astronauts and why similar tissue degradation is not observed in the skin of the same areas.



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Comparing anesthesia with isoflurane and fentanyl/fluanisone/midazolam in a rat model of cardiac arrest

Only one in ten patients survives cardiac arrest (CA), underscoring the need to improve CA management. Isoflurane has shown cardio- and neuroprotective effects in animal models of ischemia-reperfusion injury. Therefore, the beneficial effect of isoflurane should be tested in an experimental CA model. We hypothesize that isoflurane anesthesia improves short-term outcome following resuscitation from CA compared with a subcutaneous fentanyl/fluanisone/midazolam anesthesia. Male Sprague-Dawley rats were randomized to anesthesia with isoflurane (n = 11) or fentanyl/fluanisone/midazolam (n = 11). After 10 min of asphyxial CA, animals were resuscitated by mechanical chest compressions, ventilations, and epinephrine and observed for 30 min. Hemodynamics, including coronary perfusion pressure, systemic O2 consumption, and arterial blood gases, were recorded throughout the study. Plasma samples for endothelin-1 and cathecolamines were drawn before and after CA. Compared with fentanyl/fluanisone/midazolam anesthesia, isoflurane resulted in a shorter time to return of spontaneous circulation (ROSC), less use of epinephrine, increased coronary perfusion pressure during cardiopulmonary resusitation, higher mean arterial pressure post-ROSC, increased plasma levels of endothelin-1, and decreased levels of epinephrine. The choice of anesthesia did not affect ROSC rate or systemic O2 consumption. Isoflurane reduces time to ROSC, increases coronary perfusion pressure, and improves hemodynamic function, all of which are important parameters in CA models.

NEW & NOTEWORTHY The preconditioning effect of volatile anesthetics in studies of ischemia-reperfusion injury has been demonstrated in several studies. This study shows the importance of anesthesia in experimental cardiac arrest studies as isoflurane raised coronary perfusion pressure during resuscitation, reduced time to return of spontaneous circulation, and increased arterial blood pressure in the post-cardiac arrest period. These effects on key outcome measures in cardiac arrest research are important in the interpretation of results from animal studies.



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Heat shock protein 90 contributes to cutaneous vasodilation through activating nitric oxide synthase in young male adults exercising in the heat

While the mechanisms underlying the control of cutaneous vasodilation have been extensively studied, there remains a lack of understanding of the different factors that may modulate cutaneous perfusion during an exercise-induced heat stress. We evaluated the hypothesis that heat shock protein 90 (HSP90) contributes to the heat loss response of cutaneous vasodilation via the activation of nitric oxide synthase (NOS) during exercise in the heat. In 11 young males (25 ± 5 yr), cutaneous vascular conductance (CVC) was measured at four forearm skin sites that were continuously treated with 1) lactated Ringer solution (control), 2) NOS inhibition with 10 mM NG-nitro-l-arginine methyl ester (l-NAME), 3) HSP90 inhibition with 178 μM geldanamycin, or 4) a combination of 10 mM l-NAME and 178 μM geldanamycin. Participants rested in a moderate heat stress (35°C) condition for 70 min. Thereafter, they performed a 50-min bout of moderate-intensity cycling (~52% Vo2peak) followed by a 30-min recovery period. We showed that NOS inhibition attenuated CVC (~40–50%) relative to the control site during pre- and postexercise rest in the heat (P ≤ 0.05); however, no effect of HSP90 inhibition was observed (P > 0.05). During exercise, we observed an attenuation of CVC with the separate inhibition of NOS (~40–50%) and HSP90 (~15–20%) compared with control (both P ≤ 0.05). However, the effect of HSP90 inhibition was absent in the presence of the coinhibition of NOS (P > 0.05). We show that HSP90 contributes to cutaneous vasodilation in young men exposed to the heat albeit during exercise only. We also show that the HSP90 contribution is due to NOS-dependent mechanisms.

NEW & NOTEWORTHY We show that heat shock protein 90 functionally contributes to the heat loss response of cutaneous vasodilation during exercise in the heat, and this response is mediated through the activation of nitric oxide synthase. Therefore, interventions that may activate heat shock protein 90 may facilitate an increase in heat dissipation through an augmentation of cutaneous perfusion. In turn, this may attenuate or reduce the increase in core temperature and therefore the level of heat strain.



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Associations between motor unit action potential parameters and surface EMG features

The surface interference EMG signal provides some information on the neural drive to muscles. However, the association between neural drive to muscle and muscle activation has long been debated with controversial indications due to the unavailability of motor unit population data. In this study, we clarify the potential and limitations of interference EMG analysis to infer motor unit recruitment strategies with an experimental investigation of several concurrently active motor units and of the associated features of the surface EMG. For this purpose, we recorded high-density surface EMG signals during linearly increasing force contractions of the tibialis anterior muscle, up to 70% of maximal force. The recruitment threshold (RT), conduction velocity (MUCV), median frequency (MDFMU), and amplitude (RMSMU) of action potentials of 587 motor units from 13 individuals were assessed and associated with features of the interference EMG. MUCV was positively associated with RT (R2 = 0.64 ± 0.14), whereas MDFMU and RMSMU showed a weaker relation with RT (R2 = 0.11 ± 0.11 and 0.39 ± 0.24, respectively). Moreover, the changes in average conduction velocity estimated from the interference EMG predicted well the changes in MUCV (R2 = 0.71), with a strong association to ankle dorsiflexion force (R2 = 0.81 ± 0.12). Conversely, both the average EMG MDF and RMS were poorly associated with motor unit recruitment. These results clarify the limitations of EMG spectral and amplitude analysis in inferring the neural strategies of muscle control and indicate that, conversely, the average conduction velocity could provide relevant information on these strategies.

NEW & NOTEWORTHY The surface EMG provides information on the neural drive to muscles. However, the associations between EMG features and neural drive have been long debated due to unavailability of motor unit population data. Here, by using novel highly accurate decomposition of the EMG, we related motor unit population behavior to a wide range of voluntary forces. The results fully clarify the potential and limitation of the surface EMG to provide estimates of the neural drive to muscles.



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Active sleep unmasks apnea and delayed arousal in infant rat pups lacking central serotonin

Sudden infant death syndrome (SIDS), occurring during sleep periods, is highly associated with abnormalities within serotonin (5-HT) neurons, including reduced 5-HT. There is evidence that future SIDS cases experience more apnea and have abnormal arousal from sleep. In rodents, a loss of 5-HT neurons is associated with apnea in early life and, in adulthood, delayed arousal. As the activity of 5-HT neurons changes with vigilance state, we hypothesized that the degree of apnea and delayed arousal displayed by rat pups specifically lacking central 5-HT varies with state. Two-week-old tryptophan hydroxylase 2-deficient (TPH2–/–) and wild-type (WT) rat pups were placed in plethysmographic chambers supplied with room air. At the onset of active (AS) or quiet (QS) sleep, separate groups of rats were exposed to hypercapnia (5% CO2) or mild hypoxia (~17% O2) or maintained in room air. Upon arousal, rats received room air. Apnea indexes and latencies to spontaneous arousal from AS and QS were determined for pups exposed only to room air. Arousal latencies were also calculated for TPH2–/– and WT pups exposed to hypoxia or hypercapnia. Compared with WT, TPH2–/– pups hypoventilated in all states but were profoundly more apneic solely in AS. TPH2–/– pups had delayed arousal in response to increasing CO2, and AS selectively delayed the arousal of TPH2–/– pups, irrespective of the gas they breathed. Thus infants who are deficient in CNS 5-HT may be at increased risk for SIDS in AS because of increased apnea and delayed arousal compared with QS.

NEW & NOTEWORTHY Sudden infant death syndrome (SIDS) occurs during sleep and is associated with central serotonin (5-HT) deficiency. We report that rat pups deficient in central 5-HT (TPH2–/–) are profoundly more apneic in active sleep (AS) but not quiet sleep (QS). Unlike control pups, the arousal of TPH2–/– pups in air, CO2, and hypoxia was delayed in AS compared with QS. Thus for infants deficient in central 5-HT, the risk of SIDS may be higher in AS than in QS.



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Different gene response to mechanical loading during early and late phases of rat Achilles tendon healing

Mechanical loading stimulates tendon healing both when applied in the inflammatory phase and in the early remodeling phase of the process, although not necessarily via the same mechanisms. We investigated the gene response to mechanical loading in these two phases of tendon healing. The right Achilles tendon in rats was transected, and the hindlimbs were unloaded by tail suspension. The rats were exposed to 5 min of treadmill running 3 or 14 days after tendon transection. Thereafter, they were resuspended for 15 min or 3 h until euthanasia. The controls were suspended continuously. Gene analysis was first performed by microarray analysis followed by quantitative RT-PCR on selected genes, focusing on inflammation. Fifteen minutes after loading, the most important genes seemed to be the transcription factors EGR1 and C-FOS, regardless of healing phase. These transcription factors might promote tendon cell proliferation and differentiation, stimulate collagen production, and regulate inflammation. Three hours after loading on day 3, inflammation was strongly affected. Seven inflammation-related genes were upregulated according to PCR: CCL20, CCL7, IL-6, NFIL3, PTX3, SOCS1, and TLR2. These genes can be connected to macrophages, T cells, and recruitment of leukocytes. According to Ingenuity Pathway Analysis, the recruitment of leukocytes was increased by loading on day 3, which also was confirmed by histology. This inflammation-related gene response was not seen on day 14. Our results suggest that the immediate gene response after mechanical loading is similar in the early and late phases of healing but the late gene response is different.

NEW & NOTEWORTHY This study investigates the direct effect of mechanical loading on gene expression during different healing phases in tendon healing. One isolated episode of mechanical loading was studied in otherwise unloaded healing tendons. This enabled us to study a time sequence, i.e., which genes were the first ones to be regulated after the loading episode.



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Effects of strict prolonged bed rest on cardiorespiratory fitness: systematic review and meta-analysis

The aim of this systematic review and meta-analysis [International Prospective Register of Systematic Reviews (PROSPERO) CRD42017055619] was to assess the effects of strict prolonged bed rest (without countermeasures) on maximal oxygen uptake (Vo2max) and to explore sources of variation therein. Since 1949, 80 studies with a total of 949 participants (>90% men) have been published with data on strict bed rest and Vo2max. The studies were conducted mainly in young participants [median age (interquartile range) 24.5 (22.4–34.0) yr]. The duration of bed rest ranged from 1 to 90 days. Vo2max declined linearly across bed rest duration. No statistical difference in the decline among studies reporting Vo2max as l/min (–0.3% per day) compared with studies reporting Vo2max normalized to body weight (ml·kg–1·min–1; –0.43% per day) was observed. Although both total body weight and lean body mass declined in response to bed rest, we did not see any associations with the decline in Vo2max. However, 15–26% of the variation in the decline in Vo2max was explained by the pre-bed-rest Vo2max levels, independent of the duration of bed rest (i.e., higher pre-bed-rest Vo2max levels were associated with larger declines in Vo2max). Furthermore, the systematic review revealed a gap in the knowledge about the cardiovascular response to extreme physical inactivity, particularly in older subjects and women of any age group. In addition to its relevance to spaceflight, this lack of data has significant translational implications because younger women sometimes undergo prolonged periods of bed rest associated with the complications of pregnancy and the incidence of hospitalization including prolonged periods of bed rest increases with age.

NEW & NOTEWORTHY Large interindividual responses of maximal oxygen uptake (Vo2max) to aerobic exercise training exist. However, less is known about the variability in the response of Vo2max to prolonged bed rest. This systematic review and meta-analysis showed that pre-bed-rest Vo2max values were inversely associated with the change in Vo2max independent of the duration of bed rest. Moreover, we identified a large knowledge gap about the causes of decline in Vo2max, particularly in postmenopausal women, which may have clinical implications.



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Heat acclimation has a protective effect on the central but not peripheral nervous system

This study aimed to clarify the pathway mediating hyperthermia-induced alterations in neural drive transmission and determine if heat acclimation protects voluntary muscle activation and cognitive function in hyperthermic humans. Electrically evoked potentials (H reflex and M wave), executive function (special planning and working memory), and maximal voluntary isometric contractions (120 s) were assessed in 14 participants in control conditions [CON, 24°C, 40% relative humidity (RH)] and in a hyperthermic state (HYP, 44–50°C, 50% RH) on consecutive days in a counterbalanced order. Thereafter, participants were passively heat acclimated for 11 days (1 h per day, 48–50°C, 50% RH) before repeating the initial assessments. Heat acclimation decreased rectal temperature in CON (–0.2°C, P < 0.05), but participants were maintained at ~39°C in HYP. Heat acclimation increased the time required to reach 39°C (+9 min), along with sweat rate (+0.7 l/h), and serum extracellular expression of heat shock protein 72 (eHSP72; +20%) in HYP (P < 0.05). M-wave and H-reflex amplitudes were lower in HYP than CON (P < 0.05) and were not protected by heat acclimation. Nerve conduction velocity was faster in HYP than CON (P < 0.05) without being influenced by heat acclimation. These results suggest that peripheral neural drive transmission in the hyperthermic state is primarily affected by axonal conduction velocity rather than synaptic failure. Executive function, voluntary activation, and the ability to sustain torque were impaired in HYP (P < 0.05). However, despite no perceptual changes (P > 0.05), heat acclimation restored executive function, while protecting the ability to sustain voluntary activation and torque production during a prolonged contraction in hyperthermia (P < 0.05). Ultimately, heat acclimation induces beneficial central but not peripheral neural adaptations.

NEW & NOTEWORTHY Heat acclimation restores planning accuracy and working memory in hyperthermic humans, together with the supraspinal capacity to sustain motor drive during a sustained maximal voluntary contraction. Electrically evoked potential data (M wave, H reflex) indicate that heat acclimation does not protect against hyperthermia-induced impairments in peripheral neural drive transmission. Heat acclimation induces beneficial central but not peripheral neural adaptations.



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A study of clinical and physiological relations of daily physical activity in precapillary pulmonary hypertension

Daily physical activity is reduced in precapillary pulmonary hypertension (PH), but the underlying mechanisms are inadequately explored. We sought to investigate clinical and physiological relations of daily physical activity and profile differences between less and more active patients with precapillary PH. A prospective, cross-sectional study of 20 patients with precapillary PH who undertook 1) a comprehensive clinical assessment, 2) a preliminary treadmill test, 3) 7-day monitoring of daily walking intensity with triaxial accelerometry, and 4) a personalized treadmill test corresponding to the individual patient mean daily walking intensity with real-time physiological measurements. Significant clinical correlations with individual patient mean walking intensity [1.71 ± 0.27 (SD) m/s2] were observed for log-transformed N-terminal probrain natriuretic peptide (log NT-proBNP; r = –0.75, P = <.001), age (r = –0.70, P = 0.001), transfer factor for carbon monoxide %predicted (r = 0.51, P = 0.022), and 6-min walk distance (r = 0.50, P = 0.026). Significant physiological correlations were obtained for heart rate reserve (r = 0.68, P = 0.001), quadriceps tissue oxygenation index (Q-StO2; r = 0.58, P = 0.008), change in Q-StO2 from rest (r = 0.60, P = 0.006), and ventilatory equivalent for oxygen uptake (r = –0.56, P = 0.013). Stepwise multiple regression analyses retained log NT-proBNP (R2 = 0.55), heart rate reserve (R2 = 0.44), and Q-StO2 (R2 = 0.13) accounting for a significant variance in individual walking intensity. Less active patients had greater physical activity-induced cardiopulmonary impairment, worse quadriceps oxygenation profile, and compromised health-related quality of life compared with more active patients. These preliminary findings suggest a significant relation between right ventricular and peripheral muscle oxygenation status and reduced daily physical activity in precapillary PH. Further research is warranted to unravel the physiological determinants, establish clinical predictors, and identify beneficial interventions.

NEW & NOTEWORTHY Daily physical activity holds promise to be a meaningful, patient-related outcome measure in pulmonary hypertension. In this study, novel findings in a representative sample of patients with precapillary pulmonary hypertension link reduced daily walking activity, as measured by triaxial accelerometry, with compromised right ventricular and pulmonary vascular status, peripheral muscle oxygenation, and health-related quality of life, providing a preliminary insight into the physiological mechanisms and clinical predictors of daily physical activity in precapillary pulmonary hypertension.



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School district partners with ambulance service in career program

By Teresa Stepzinski The Florida Times-Union GREEN COVE SPRINGS, Fla. — Clay County career academy students soon will have an opportunity for hands-on training and clinical hours necessary to complete industry certifications through a partnership between the school district and Liberty Ambulance Service Inc. Students in the Emergency Medical Response (EMR) program in the Academy of Health Science ...

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Standards for use of drones by public safety agencies released

The new standards will provide guidance on the tactical, legal and ethical use of unmanned aircraft systems

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A novel finding of Rapunzel syndrome

Abstract

Rapunzel syndrome is a rare form of gastric trichobezoar (hair ball) involving extension of a tail of the hair into the small bowel. A 13-year-old girl was admitted with a 4-day history of epigastric pain and nausea which worsened after meals. Abdominal ultrasound showed duodenal wall thickening and lymphadenopathy. Esophagogastroduodenoscopy identified a gastric trichobezoar with a tail extending into the duodenum. In addition, multiple longitudinal duodenal and jejunal ulcers were noted. The ulcers appeared to be a result of direct pressure by the tail itself against the intestinal mucosa. The trichobezoar was successfully retrieved endoscopically under general anesthesia. Her symptoms resolved completely after retrieval. Psychiatric follow-up was carried out to help reduce the risk of recurrence. Here, we describe a novel complication of Rapunzel syndrome, i.e., multiple longitudinal ulcers of the small intestine. This novel finding suggests that the mucosal damage caused by the trichobezoar of Rapunzel syndrome can occur in an earlier stage than previously thought. In addition, we also strongly recommend using general anesthesia with intubation when removing a gastric trichobezoar to ensure protection of the airway.



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Which way do the ions go? A graph-drawing exercise for understanding electrochemical gradients

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Evaluation of performance and perceptions of electronic vs. paper multiple-choice exams

In the veterinary professional curriculum, methods of examination in many courses are transitioning from the traditional paper-based exams to electronic-based exams. Therefore, a controlled trial to evaluate the impact of testing methodology on examination performance in a veterinary physiology course was designed and implemented. Formalized surveys and focus group discussions were also used to determine student attitudes toward the examination formats. In total, 134 first-year veterinary students and 11 PhD/MS students were administered a total of 4 exams throughout 1 semester (2 on paper and 2 electronically) using a split-halves design. The paper (P) and electronic (E) exams contained 25 identical multiple-choice questions. Students were randomly assigned to two groups and were given exams in one of two sequences (E-P-E-P or P-E-P-E). Participants consented to and completed two anonymous surveys vis à vis their experience. Out of a maximum raw score of 25, the mean score for electronic examinations (20.8; 95% confidence interval, 20.3–21.2) was significantly (P = 0.01) greater than that for paper examinations (20.3; 95% confidence interval, 20.0–20.7). However, students expressed numerous concerns with the electronic examination format, and, at the completion of the study, 87% preferred to take their examination on paper rather than the electronic format. These data show that student attitudes concerning the examination format are not primarily determined by examination results, and that the additional anxiety related to the electronic examination format plays a large role in student attitudes.



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Symposium report on "Dynamic Methods For Improving Undergraduate Physiology Education": IUPS 38th World Congress



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In appreciation: Charles M. Tipton and the history of physiology

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Reminiscing about Jan Evangelista Purkinje: a pioneer of modern experimental physiology

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This article reminisces about the life and key scientific achievements of Jan Evangelista Purkinje (1787–1869), a versatile 19th century Czech pioneer of modern experimental physiology. In 1804, after completing senior high school, Purkinje joined the Piarist monk order, but, after a 3-yr novitiate, he gave up the religious calling "to deal more freely with science." In 1818, he earned a Medical Doctor degree from Prague University by defending a dissertation on intraocular phenomena observed in oneself. In 1823, Purkinje became a Physiology and Pathology professor at the Prussian Medical University in Breslau, where he innovated the traditional teaching methods of physiology. Purkinje's contributions to physiology were manifold: accurate descriptions of various visual phenomena (e.g., Purkinje-Sanson images, Purkinje phenomenon), discovery of the terminal network of the cardiac conduction system (Purkinje fibers), identification of cerebellar neuronal bodies (Purkinje cells), formulation of the vertigo law (Purkinje's law), discovery of criteria to classify human fingerprints, etc. In 1850, Purkinje accepted and held until his death the Physiology chair at Prague Medical Faculty. During this period, he succeeded in introducing the Czech idiom (in addition to long-established German and Latin) as a Medical Faculty teaching language. Additionally, as a zealous Czech patriot, he actively contributed to the naissance and consolidation of a national Czech identity conscience. Purkinje was a trend-setting scientist who, throughout his career, worked to pave the way for the renovation of physiology from a speculative discipline, ancilla of anatomy, into a factual, autonomous science committed to the discovery of mechanisms governing in-life functions.



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The control of ventilation during exercise: a lesson in critical thinking

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Learning the basic competencies of critical thinking are very important in the education of any young scientist, and teachers must be prepared to help students develop a valuable set of analytic tools. In my experience, this is best achieved by encouraging students to study areas with little scientific consensus, such as the control mechanisms of the exercise ventilatory response, as it can allow greater objectivity when evaluating evidence, while also giving students the freedom to think independently and problem solve. In this article, I discuss teaching strategies by which physiology, biomedical science, and sport science students can simultaneously develop their understanding of respiratory control mechanisms and learn to critically analyze evidence thoroughly. This can be best achieved by utilizing both teacher-led and student-led learning environments, the latter of which encourages the development of learner autonomy and independent problem solving. In this article, I also aim to demonstrate a systematic approach of critical assessment that students can be taught, adapt, and apply independently. Among other things, this strategy involves: 1) defining the precise phenomenon in question; 2) understanding what investigations must demonstrate to explain the phenomenon and its underlying mechanisms; 3) evaluating the explanations/mechanisms of the phenomenon and the evidence for them; and 4) forming strategies to produce strong evidence, if none exists.



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Cooling muscles following exercise

Abstract

Cooling has a long history as an aid to muscle recovery after exercise.

This article is protected by copyright. All rights reserved



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Nurse-driven analgesia and sedation in pediatric patients with univentricular hearts requiring extracorporeal life support after first-stage palliation surgery: A pilot study

Summary

Background

Few data are available regarding requirements of sedation and analgesia in children during extracorporeal life support.

Aims

The aim of this study was to evaluate if children with functionally univentricular hearts on extracorporeal life support after first-stage palliation surgery have higher requirement of analgesics and sedatives compared with children without extracorporeal life support using a goal-directed nurse-driven analgesia and sedation protocol.

Methods

This prospective observational matched case-control pilot study was conducted at a cardiac pediatric intensive care unit of a tertiary referral center. Seventeen patients with functionally univentricular hearts including hypoplastic left heart syndrome who were on extracorporeal life support after first-stage palliation surgery were enrolled from July 2012 to January 2017. Seventeen matched patients served as controls. Doses of morphine, midazolam, clonidine, and muscle relaxants as well as sedation scores (COMFORT behavior scale and the nurse interpretation of sedation scale) were assessed according to a nurse-driven protocol every 8 hours up to 120 hours after first-stage palliation surgery.

Results

Sedation scores were equal in the extracorporeal life support group and in the control group at most points in time. There was no significant difference in cumulative doses of morphine and midazolam. However, children of the extracorporeal life support group received higher doses of midazolam and morphine at some points in time.

Conclusion

A nurse-driven protocol for analgesia and sedation of children with extracorporeal life support is feasible. Patients with extracorporeal life support do not need deeper sedation levels and have not higher cumulative sedation requirements than children without extracorporeal life support.



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A retrospective comparison of thoracic epidural infusion and multimodal analgesia protocol for pain management following the minimally invasive repair of pectus excavatum

Summary

Background

Pain management following minimally invasive repair of pectus excavatum is variable. We recently adopted a comprehensive multimodal analgesic protocol that standardizes perioperative analgesic management. We hypothesized that patients managed with this protocol would use more opioids postoperatively, have similar pain control, and shorter length of stay compared to patients managed with thoracic epidural infusion.

Aims

We retrospectively compared opioid consumption, pain scores, and length of stay between a cohort of patients managed with our multimodal analgesic protocol and a cohort managed with a thoracic epidural infusion.

Methods

This retrospective cohort comparison includes patients, 8 to 21 years of age, managed with either thoracic epidural infusion (n = 21) or multimodal analgesic protocol (n = 29) following minimally invasive repair of pectus excavatum from January 1, 2011 through September 15, 2015. The primary outcome, total daily opioid consumption in morphine equivalents, is presented as an average by postoperative day. Secondary outcomes included median daily pain score and length of stay.

Results

Patients were similar in age, weight, sex, and physical status. Patients managed with thoracic epidural infusion received less opioid (morphine equivalents—mg/kg) intraoperatively compared to multimodal analgesic protocol (difference of mean [95% confidence interval] 0.22 [0.16-0.28] P ≤ .01) but required more total opioid through postoperative day 3 (difference of mean [95% confidence interval] 1.2 [0.26-2.14] P = .01). We did not observe a difference in pain scores. Median length of stay was 1 day less in patients managed with multimodal analgesic protocol (difference of median [95% confidence interval] 1 [0.3-1.7] P = .003).

Conclusion

Implementation of a standardized comprehensive multimodal analgesic protocol following minimally invasive repair of pectus excavatum resulted in equivalent analgesia with a modest reduction in length of stay when compared to thoracic epidural. We did not observe an opioid sparing effect in our thoracic epidural which may reflect technique variability.



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A quality improvement initiative to increase the safety of pediatric emergency airway management

Summary

Background

Emergency airway management is commonly associated with life-threatening hypoxia and hypotension which may be preventable.

Aims

The aim of this quality improvement study was to reduce the frequency of intubation-related hypoxia and hypotension.

Methods

This prospective quality improvement study was conducted over 4 years in the Emergency Department of The Royal Children's Hospital, Melbourne, Australia. A preintervention cohort highlighted safety gaps and was used to design study interventions, including an emergency airway algorithm, standardized airway equipment, a preintubation checklist and equipment template, endtidal carbon dioxide monitoring, postintubation team debriefing, and multidisciplinary team training. Following implementation, a postintervention cohort was used to monitor the impact of study interventions on clinical process and patient outcome. Process measures were as follows: use of a preintubation checklist, verbalization of an airway plan, adequate resuscitation prior to intubation, induction agent dose titration, use of apneic oxygenation, and use of endtidal carbon dioxide to confirm endotracheal tube position. The primary outcome measure was first pass success rate without hypoxia or hypotension. Potential harms from study interventions were monitored.

Results

Forty-six intubations were included over one calendar year in the postintervention cohort (compared to 71 in the preintervention cohort). Overall clinical uptake of the 6 processes measures was 85%. First pass success rate without hypoxia or hypotension was 78% in the postintervention cohort compared with 49% in the preintervention cohort (absolute risk reduction: 29.0%; 95% confidence interval 12.3%-45.6%, number needed to treat: 3.5). No significant harms from study interventions were identified.

Conclusions

Quality improvement initiatives targeting emergency airway management may be successfully implemented in the emergency department and are associated with a reduction in adverse intubation-related events.



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