c-Jun N-Terminal Kinases and Their Pharmacological Modulation in Ischemic and Reperfusion Brain Injury

We present here a review of the literature on the role of c-Jun N-terminal kinases (JNK) and their inhibitors in ischemic and reperfusion brain injuries. The functions of JNK in the signal mechanisms involved in brain damage in ischemia and reperfusion are discussed. Effects linked with inhibition of JNK with synthetic and natural compounds in experimental models of ischemia and reperfusion brain injury are described. Results from experimental studies show that JNK provide potential therapeutic targets for protecting the brain from ischemic stroke. However, the fact that JNK have numerous physiological functions prevents systematic use of nonspecific inhibitors of these kinases for therapeutic purposes. The authors conclude that this task requires a further search for selective JNK3 inhibitors.

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Immune Reconstitution Inflammatory Syndrome and Rebound Syndrome on Withdrawal of Immunomodulatory Drugs for Multiple Sclerosis: Current Understanding and a Case Report

Recent years have seen significant increases in the numbers of patients with multiple sclerosis (MS) receiving treatment with new immunomodulatory drugs. The number of cases in which these drugs are withdrawn because of side effects, intolerance, inadequate efficacy or planned pregnancy also increases. We present here a review of the problem of severe complications associated with the termination of treatment with natalizumab and fingolimod, in the form of immune reconstitution inflammatory syndrome (IRIS) and ricochet syndrome (withdrawal syndrome or rebound syndrome). The history of the term IRIS is considered, along with the diagnostic criteria for this syndrome in patients infected with human immunodeficiency virus. Variants of IRIS in patients interrupting natalizumab treatment are described. The clinical and radiological signs are assessed, as are the possible mechanisms of development of rebound syndrome on withdrawal of natalizumab and fingolimod treatment. The need for developing diagnostic criteria and studying risk factors for the development of IRIS and rebound syndrome in MS patients terminating therapy with new immunomodulatory drugs is emphasized.

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Postnatal Morphogenesis of Purkinje Cells in the Rat Cerebellum

Electron microscopic and histochemical methods were used to obtain a quantitative assessment of the development of organelles in Purkinje cells in the cerebellum of mongrel rats (n = 36) during the postnatal period of ontogeny (days 2, 7, 15, and 45). The nucleus:cytoplasm ratio decreased, while nucleolar area increased, the size and length of mitochondria increased, the quantity of membrane-bound ribosomes and the length of endoplasmic reticular channels increased, the number and sizes of lysosomes increased, and the relative area occupied by lysosomes on sections of the cytoplasm also increased.

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The Functional State of Children Aged 6–8 Years on Testing by Exposure to Different Types of Tension-Inducing Loads

Factor analysis of various measures of functional status identified the key regulatory processes determining psychophysiological reactivity in children aged 6–8 years (n = 102) on performance of mental, sensorimotor, and physical tasks. The characteristics of children's reactivity to additional loads, apparent from the psychophysiological parameters combined to produce different factors, in most cases persisted in all test tasks. Stable patterns of physiological responses were demonstrated in conditions of tension-inducing mental, sensorimotor, and physical loads. The study results indicate that stress responses can be regarded as a psychophysiological process preparing the child's body for tension-inducing activity.

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The Role of Assay of Free Immunoglobulin Light Chains in the Diagnosis of the Onset of Multiple Sclerosis

Objective. To assess the diagnostic value of assaying immunoglobulin (IgG) light chains at the onset of multiple sclerosis (MS). Materials and methods. A total of 226 patients took part in the study; group 1 (n = 111) were patients with clinically isolated syndrome (CIS) with development to MS within the first two years; group 2 (n = 49) were patients with CIS who did not progress to MS in the first two years; group 3 (n = 20) consisted of patients with inflammatory diseases of the central nervous system. The reference group (group 4, n = 46) consisted of patients with noninflammatory CNS diseases. The following immunological indicators were assessed in the patients: the clonal nature of cerebrospinal fluid (CSF) IgG and the concentrations of free ϰ and λ light chains in the CSF and their ratio. Results. Synthesis of free light chains was significantly greater in group 1 than groups 2 and 4. Free light chain synthesis in group 3 was significantly greater than that in groups 2 and 4 but was not significantly different from that in group 1. Free light chain production was significantly greater in patients with oligoclonal IgG synthesis than in patients without oligoclonal synthesis. The level of production of free light chains in patients of group 1 was significantly greater than that in group 2, regardless of whether or not oligoclonal IgG was produced. The most valuable diagnostic markers were the concentration and the coefficient of CSF:serum concentrations of κ light chains. Use of these parameters along with assessment of the clonality of IgG synthesis produced a 50% reduction in number of false negative results. Independently of other factors, increases in κ chain levels led to a 9.718-fold increase in the probability of a diagnosis of MS. Conclusions. Assay of free light chains as a lab marker increases the accuracy of diagnoses of MS and provides an indirect evaluation of the risk that CIS will progress to complete MS in the next two years.

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Molecular Mechanism of Memory Modification

The present review of our own and published data proposes a hypothesis for the molecular mechanisms regulating synaptic efficiency which may underlie long-term changes in behavior and modification of memory on the reactivation. The hypotheses is based on data on role of the atypical protein kinase molecule Mζ in long-term changes in synaptic efficiency by controlling the delivery of AMPA receptors, and on data on the possible nitrosylation of these molecules by nitric oxide, which is produced in synapses when nerve cells are activated.

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Dynamics of Changes in the Expression of the GLUR2 Subunit of the Ionotropic Glutamate Receptor in the Ventrolateral Part of the Solitary Tract Nucleus during the Early Postnatal Period in Health and Prenatal Serotonin Deficiency

Experiments on Wistar rats (n = 18) were performed to study changes in the expression of ionotropic glutamate receptor subunits (GluR2) in the respiratory subnuclei (ventral and lateral) of the solitary tract nucleus (STN). Observations were made during the early postnatal period (days 5, 10, and 20, 5–6 animals per group) in normal conditions and with prenatal decreases in serotonin levels due to inhibition of tryptophan hydroxylase with parachlorophenylalanine. Immunocytochemical detection of GluR2 revealed significant increases in GluR2 expression in the respiratory subnuclei of the STN in the early postnatal period (a 2-fold increase in the lateral subnucleus, 2.6-fold in the ventral). Prenatal serotonin deficiency altered GluR2 expression in the respiratory subnuclei of the STN. There was a significant delay in GluR2 expression in the early period, which increased to control levels by two weeks after birth, though GluR2 expression by juvenile age was lower (twofold) than in controls. Impairments to the glutamatergic receptor networks in the respiratory nuclei may be the basis of respiratory dysfunction.

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New Approaches to Cognitive Neurobiology: Methods for Two-Photon in Vivo Imaging of Cognitively Active Neurons

This review addresses the potential of current methods of in vivo two-photon imaging of the activity of neurons involved in episodes of cognitive activity in animals. The principles of fluorescent two-photon microscopy are described and methods for in vivo imaging of neuron activity using calcium indicators of two types – calcium stains and genetically encoded calcium indictors (GECI) – are discussed. A new approach is also considered, using in vivo imaging of genomic activation of cerebral neurons in transgenic animals with fluorescent probes for the expression of the immediate early genes c-fos, Arc, and Egr-1. The main advantages and disadvantages of these approaches are compared and the potentials for the development of in vivo two-photon imaging of neuron activity for studies of the cellular basis of higher brain functions are addressed.

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Oscillatory Activity and Cross-Frequency Interactions in the Hippocampus and Connected Brain Structures during Sensory Information Processing

It has been suggested that oscillations, or rhythms, are required for the execution of many cognitive functions, as they support rapid and flexible interactions between neurons in different brain structures [Livanov, 1977; Fries, 2005; Womelsdorf et al., 2007]. Until recently, little attention was focused on the question of how different types of oscillations are synchronized during the processing of information arriving in the brain. We report here an analysis of the extent and correlations of rhythmic activity in the θ, α, and γ ranges in animals in two behavioral states: during calm consciousness and during the perception of sensory signals. Local field potentials (LFP) were recorded in eight brain structures (cortical and subcortical). Many areas showed increases in oscillatory activity in different frequency bands on delivery of sensory stimuli. The main result of this study was a sharp increase in the cross-frequency interactions of all rhythms in both cortical and subcortical structures during sensory information processing. We suggest that the increase in interfrequency interactions between different rhythms in different parts of the brain is required for detailed assessment of environmental signals and their registration in the memory system.

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Comparison of the Chronic Anticonvulsant Activity and Safety of IEM-2062, Sodium Valproate, and Memantine in a Corasol Kindling Model in Rats

Chronic oral administration of IEM-2062 [1-(6-aminohexylamino)-1-phenylcyclohexyl dihydrochloride], which produces combined blockade of NMDA and AMPA receptors, at a dose of 3 mg/kg was found to induce a maximal anticonvulsant effect in rats with corasol kindling, producing a 100% decrease in the number of rats demonstrating corasol kindling and a 3.3-fold reduction in the mean severity of clonic-tonic kindled seizures. IEM-2062 induced significant anticonvulsant effects over a wide range of doses (1–48 mg/kg), which was 22–24 times greater than that of memantine (12–20 mg/kg) and sodium valproate (100–200 mg/kg). Sodium valproate and memantine induced significant impairment to movement activity in an open field at the doses having maximal anticonvulsant effects in rats with corasol kindling. At the same time, IEM-2062 induced impairments to movement activity only at a very high dose, 92 mg/kg, which was 30.7 times greater than the dose producing the maximal anticonvulsant effect in rats with corasol kindling. Thus, IEM-2062 decreases the severity of kindled seizures 1.7–1.9 times more effectively than sodium valproate and memantine, and has a range of therapeutic doses 22–24 times wider, as well as a 30.7 times greater level of safety than sodium valproate and memantine.

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Cellular and Molecular Bases of Changes to Neuroimmune Interactions in Stress

This article presents current views on the cellular and molecular bases of the central mechanisms of neuroimmune interactions, along with data on the effects of destabilizing factors (painful electrical stimulation, cold, psychoemotional stress) on the functions of neurons and immunocompetent cells. It is important to emphasize that stress is associated with changes in ligand-receptor interactions on the membranes of lymphoid cells which respond to the interleukin-1 regulatory signal; these changes consist either of enhanced responses to this regulatory signal (in mild stress situations) or sharp decreases in responses (on exposure to strongly stressful factors). Special attention is paid to the role of the orexinergic system in the mechanisms mediating the brain's responses to administration of antigens and exposure to stressors. We consider possible means of correcting the imbalance in the functional interaction between the nervous and immune systems occurring as a result of various destabilizing factors.

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Vestibular Prosthetics: Concepts, Approaches, Results

In contrast to hearing prosthetization, where the technology has been in development for more than 30 years, the challenge of vestibular prosthetization has been researched for no more than 15 years. However, the involvement of the vestibular system in supporting the normal functioning of the visual, motor, and other body systems defines its decisive contribution to spatial orientation in humans and animals. Damage to the vestibular apparatus (labyrinth) leads to serious impairment to posture control, gaze stabilization, spatial orientation, and psychological status, i.e., a person's overall quality of life is sharply degraded. Animal studies have developed techniques for the prosthetization of the semicircular canals, which perceive angular acceleration and control eye movements in dynamic situations. New approaches based on replacement of the lost natural afferent spike activity in the vestibular nerve by electrical stimulation via a multichannel vestibular prosthesis have been successfully introduced into clinical practice.

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Atypical Multiple Sclerosis – Baló’s Concentric Sclerosis: Two Case Reports and a Review

We present two case reports of patients with diagnoses of Baló's concentric sclerosis. The characteristics of the pathogenesis of this disease are considered in relation to the differential diagnosis against other types of multiple sclerosis and potential therapeutic tactics are discussed.

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Dendritic Cells in Multiple Sclerosis

This review presents data on the main functions of dendritic cells (DC) and their structure and stages of development. The role of DC in maintaining immunological tolerance is discussed, as it their role in the development of autoimmune diseases. The involvement of DC in the immunopathogenesis of multiple sclerosis (MS) is considered, along with their therapeutic potential in these cases.

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Statistical Characteristics of the Spike Activity of Neurons in the Midbrain Auditory Center in Frogs on Exposure to Tones Modulated by Low-Frequency Noise

The time parameters of the spike activity of single neurons in the brainstem part of the auditory system carry basic information on the properties of perceived signals. To characterize these parameters, the activity of single neurons in the midbrain center (semicircular torus) of the common frog (Rana temporaria) was studied on exposure to prolonged tones amplitude-modulated with repeating bursts of low-frequency noise. Time-shuffled autocorrelation functions were calculated, these corresponding to the sum of the correlation functions between responses to all bursts presented with the exception of responses evoked by one of the bursts. This approach excludes the effects of the refractory properties of the neuron being studied, allowing the responses of a single neuron to be used to evaluate the nature of the spike activity in the local population of cells with presumptively identical properties but which are statistically independent of each other. Significant variation in the statistical characteristics of output spike activity in different cells in the semicircular toroid was found, such that signals could be characterized in terms of different time properties. Neurons with highly specific reactions to the time characteristics of the envelope were observed.

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Current Perspectives in the MRI Diagnosis of Multiple Sclerosis: The 2016 Revised MRI Criteria

MRI scanning is the main widely used diagnostic method for multiple sclerosis (MS). This article discusses the current state of the question of the effectiveness of using brain and spinal cord MRI scans in the diagnosis of patients with suspected MS. Particular attention is paid to the McDonald MRI and MAGNIMS criteria as revised in 2010 and 2016 for both remitting MS and primary progressive MS. The data presented here allow radiologists and neurologists to optimize the use of MRI scans in clinical practice for the diagnosis of MS.

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Polymorphic Variants of Immune Response Genes as a Risk Factor for the Development of Primary Progressive Multiple Sclerosis

Objectives. To analyze the involvement of immune response genes in the pathogenesis of primary progressive multiple sclerosis (PPMS). Materials and methods. A representative cohort of 111 ethnically Russian patients with PPMS took part in a multicenter study. The involvement of immune system genes in the pathogenesis of PPMS was analyzed by investigating the associations of variants of cytokines genes and genes involved in antigen processing and presentation by antigen-presenting cells with the disease. Results and conclusions. Carriership of the IL4 genotype (rs2243250)*C/C and CLEC16A (rs6498169)*G/G was found to have a positive association with the development of PPMS in Russian patients. The association described in studies of other populations, HLA-DRB1*15 with a high risk of developing this form of MS, was confirmed.

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New insight into GABAergic neurons in the hypothalamic feeding regulation

Abstract

Several lines of study have suggested that GABA in the hypothalamic feeding center plays a role in promoting food intake. Recent studies revealed that not only NPY/AgRP neurons in the hypothalamic arcuate nucleus (ARC) that co-express GABA but also other GABAergic neurons act as an orexigenic. Here, we review the progress of studies on hypothalamic GABAergic neurons distributed in ARC, dorsomedial hypothalamus (DMH), and lateral hypothalamus (LH). Three advanced technologies have been applied and greatly contributed to the recent progress. Optogenetic (and chemogenetic) approaches map input and output pathways of particular subpopulations of GABAergic neurons. In vivo Ca²⁺ imaging using GRIN lens and GCaMP can correlate the activity of GABAergic neuron subpopulations with feeding behavior. Single-cell RNA-seq approach clarifies precise transcriptional profiles of GABAergic neuron subpopulations. These approaches have shown diversity of GABAergic neurons and the subpopulation-dependent role in feeding regulation.

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miR-9 inhibits the metastatic ability of hepatocellular carcinoma via targeting beta galactoside alpha-2,6-sialyltransferase 1

Abstract

Glycosylation of cell surface proteins regulates critical cellular functions, including invasion and metastasis in cancer cells. Emerging evidence has shown that microRNAs (miRNAs) are involved in regulating both the glycosylation modifications on cell surface and the progression of cancer. In this study, we investigated the role of miR-9 in α-2,6-linked sialylation and the metastasis of mouse hepatocellular carcinoma (HCC). According to array-based miRNA expression profiling data of HCC cell lines Hepa1–6, Hca-P, and Hca-F with different lymphatic metastatic capacities, reverse correlation was found between miR-9 expression levels and the metastatic potential in these HCC cells. Additionally, β-galactoside α-2,6-sialyltransferase 1 (St6gal1) expression level is associated negatively with miR-9 and positively with metastatic potential. Bioinformatics analysis indicated that miR-9 could target St6gal1, which was verified by luciferase reporter assays. miR-9 overexpression reduced expression of St6gal1, which subsequently suppressed HCC cells metastatic potential. Moreover, upregulation of miR-9 could inhibit integrin-β1/FAK-mediated cell motility and migration signaling in mouse HCC cells. Together, our results suggest that miR-9 could act as a tumor suppressor and regulate mouse HCC cells migration and invasion by inhibiting the α-2,6-linked sialylation. This finding may provide insight into the relationship between abnormal miRNA expression and aberrant cell surface glycosylation during tumor lymphatic metastasis.

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Changes in the activity of some metabolic enzymes in the heart of SHR rat incurred by transgenic expression of CD36

Abstract

Hypertension, dyslipidemia, and insulin resistance in the spontaneously hypertensive rat (SHR) can be alleviated by rescuing CD36 fatty acid translocase. The present study investigated whether transgenic rescue of CD36 in SHR could affect mitochondrial function and activity of selected metabolic enzymes in the heart. These analyses were conducted on ventricular preparations derived from SHR and from transgenic strain SHR-Cd36 that expresses a functional wild-type CD36. Our respirometric measurements revealed that mitochondria isolated from the left ventricles exhibited two times higher respiratory activity than those isolated from the right ventricles. Whereas, we did not observe any significant changes in functioning of the mitochondrial respiratory system between both rat strains, enzyme activities of total hexokinase, and both mitochondrial and total malate dehydrogenase were markedly decreased in the left ventricles of transgenic rats, compared to SHR. We also detected downregulated expression of the succinate dehydrogenase subunit SdhB (complex II) and 70 kDa peroxisomal membrane protein in the left ventricles of SHR-Cd36. These data indicate that CD36 may affect in a unique fashion metabolic substrate flexibility of the left and right ventricles.

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The ABCs for Nutrition Poststroke: An Evidence-Based Practice Guide for Rehabilitation Professionals

Publication date: Available online 14 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Chetan P. Phadke, Jaclyn Schwartz, Hubert Vuagnat, Elena Philippou

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Linking spatial grids of the old and new excavations at Zhoukoudian Locality 1, China

Publication date: August 2018

Source: Journal of Human Evolution, Volume 121

Author(s): Feng Li, Fuyou Chen, Shuangquan Zhang, Xing Gao

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Editorial Board

Publication date: August 2018

Source: Journal of Human Evolution, Volume 121

Author(s):

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Comparison of High and Normal Birth Weight Infants on Eating, Feeding Practices, and Subsequent Weight

Abstract

Objectives High birth weight (HBW ≥ 4000 g) infants are at increased risk for obesity, but research has yet to identify the mechanism for this increased risk and whether certain subsets of HBW infants are at greater risk. Methods This exploratory study examined child eating behaviors and maternal feeding practices and beliefs across 21 HBW and 20 normal birth weight (NBW, 2500–3999 g) infants at 7–8 months of age using maternal-report measures (n = 41) and a bottle feeding task (n = 16). Results HBW infants were at increased risk for high weight-for-length at 7–8 months (F (2, 38) = 6.03, p = .02) compared to NBW infants, but no statistically significance differences on weight gained per day since birth, child eating behaviors, or most maternal feeding practices and beliefs were found between HBW and NBW infants. However, HBW infants who maintained a high weight-for-length (≥ 85th percentile) at 7–8 months had a higher birth weight, gained more weight per day, and had lower maternal-reported satiety responsiveness and maternal social interactions during feedings than their HBW counterparts who were currently below the 85th percentile. Conclusions for Practice HBW infants did not differ from NBW infants on eating behaviors and feeding practices, but children born at HBW who maintain excess weight during infancy do differ from those infants who fall below the 85th percentile for weight-for-length. Future research should identify risk factors that longitudinally differentiate HBW infants at greatest risk for maintaining excess weight and develop early screening and intervention efforts for this subset of at-risk infants.

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A genome scan for genes underlying adult body size differences between Central African hunter-gatherers and farmers

Abstract

The evolutionary and biological bases of the Central African "pygmy" phenotype, a characteristic of rainforest hunter-gatherers defined by reduced body size compared with neighboring farmers, remain largely unknown. Here, we perform a joint investigation in Central African hunter-gatherers and farmers of adult standing height, sitting height, leg length, and body mass index (BMI), considering 358 hunter-gatherers and 169 farmers with genotypes for 153,798 SNPs. In addition to reduced standing heights, hunter-gatherers have shorter sitting heights and leg lengths and higher sitting/standing height ratios than farmers and lower BMI for males. Standing height, sitting height, and leg length are strongly correlated with inferred levels of farmer genetic ancestry, whereas BMI is only weakly correlated, perhaps reflecting greater contributions of non-genetic factors to body weight than to height. Single- and multi-marker association tests identify one region and eight genes associated with hunter-gatherer/farmer status, and 24 genes associated with the height-related traits. Many of these genes have putative functions consistent with roles in determining their associated traits and the pygmy phenotype, and they include three associated with standing height in non-Africans (PRKG1, DSCAM, MAGI2). We find evidence that European height-associated SNPs or variants in linkage disequilibrium with them contribute to standing- and sitting-height determination in Central Africans, but not to the differential status of hunter-gatherers and farmers. These findings provide new insights into the biological basis of the pygmy phenotype, and they highlight the potential of cross-population studies for exploring the genetic basis of phenotypes that vary naturally across populations.

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An exon three-way junction structure modulates splicing and degradation of the SUS1 yeast pre-mRNA

Publication date: August 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 8

Author(s): Ali AbuQattam, Joan Serrano-Quílez, Susana Rodríguez-Navarro, José Gallego

Abstract

The SUS1 gene of Saccharomyces cerevisiae is unusual as it contains two introns and undergoes alternative splicing, retaining one or both introns depending on growth conditions. The exon located between the two introns can be skipped during splicing and has been detected in circular form. This exon (E2) has also been found to influence the splicing of the flanking introns, an unusual situation in budding yeast where splicing mainly relies on intron recognition. Using SHAPE (selective 2′-hydroxyl acylation analyzed by primer extension), NMR spectroscopy, gel electrophoresis and UV thermal denaturation experiments combined with computational predictions, we show that E2 of SUS1 comprises a conserved double-helical stem topped by a three-way junction. One of the hairpins emerging from the junction exhibited significant thermal stability and was capped by a purine-rich loop structurally related to the substrate loop of the VS ribozyme. Cellular assays revealed that three mutants containing altered E2 structures had impaired SUS1 expression, and that a compensatory mutation restoring the conserved stem recovered expression to wild-type levels. Semi-quantitative RT-PCR measurements paralleled these results, and revealed that mutations in E2 altered splicing and transcript degradation processes. Thus, exon structure plays an important role in SUS1 RNA metabolism.

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Congrats to the recipients of the 2018 ZOLL EMT Scholarship!

BROOMFIELD, Colo.—We recently announced the 12 recipients of the 2018 ZOLL EMT Scholarship Program. Each year, we award medical education grants to qualifying caregivers who demonstrate a career commitment to the profession in order to support the education of EMTs working toward their paramedic certification. This Year's Winners "These individuals have demonstrated their...

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Firefighters Against Cancer and Exposures (FACEs) non-profit launches in Texas

IRVINE, Calif. — In an effort to help firefighters cover the high cost of cancer treatment as a result of the occupational risk of experiencing higher rates of certain types of cancer than the general U.S. population, Laboratory for Advanced Medicine (LAM) today announced the launch of Firefighters Against Cancer and Exposures (FACEs), a Texas-based non-profit that provides supplemental...

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Acuity Link, ZOLL integrate solutions to drive accuracy and efficiency in medical transport dispatch

YARMOUTH PORT, Mass. – Acuity Link, a provider of software solutions used to automate and optimize non-emergency medical transportation (NEMT) and ZOLL® Medical Corporation , an Asahi Kasei Group Company that manufactures medical devices and related software solutions, have integrated their dispatch solutions to simplify and streamline NEMT management. The integration delivers...

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Training day: Disaster response, transporting patients from the scene

From full-scale to tabletop exercises, preparing for a mass casualty incident should be part of disaster management training

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Iowa county police begin equipping vehicles with AEDs

The Story County Sheriff's Office has launched its Defibs Save Lives campaign, which aims to ensure that the county becomes a heart safe community

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The American Trauma Society welcomes new Executive Director Sue Prentiss

FALLS CHURCH — The American Trauma Society (ATS) Board of Directors and staff welcomed their new Executive Director, Sue Prentiss to the organization. Prentiss succeeds Interim Executive Director Clay Tyeryar. Prentiss will lead the ATS national office efforts in support of trauma system development, trauma education, injury prevention and the rebuilding of lives for victims of trauma and...

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Johnson and Johnson Innovation opens JLABS @ NYC in collaboration with New York state and the New York Genome Center

NEW YORK CITY — Johnson & Johnson Innovation LLC today announced the opening of JLABS @ NYC. The 30,000-square foot facility, located at the New York Genome Center in the heart of SoHo, is a collaboration between Johnson & Johnson Innovation, New York State and the New York Genome Center. JLABS @ NYC can accommodate up to 30 biotech, pharmaceutical, medical device, consumer and...

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The Intersection Between Women’s Reproductive Desires and HIV Care Providers’ Reproductive Health Practices: A Mixed Methods Analysis

Abstract

Background HIV-positive women in the United States can have healthy pregnancies and avoid transmitting HIV to their children. Yet, little is known about the extent to which HIV care providers' reproductive health practices match women's pregnancy desires. Accordingly, we explored young HIV-positive women's pregnancy desires and reproductive health behaviors and examined reproductive health information offered by HIV care clinics. Methods A mixed-method analysis was conducted using data from a 14-site Adolescent Medicine Trials Network (ATN) study. We conducted descriptive statistics on data from 25 HIV-positive women (e.g., demographics, pregnancy desires, and sexual- and health-related behaviors). Qualitative interviews with 58 adolescent and adult clinic providers were analyzed using the constant comparative method. Results About half of the women reported using reproductive health care services (i.e., contraception and pregnancy tests) (n = 12) and wanted a future pregnancy (n = 13). Among women who did not desire a future pregnancy (n = 5), three used dual methods and two used condoms at last sexual encounter. Qualitative themes related to clinics' approaches to reproductive health (e.g., "the emphasis…is to encourage use of contraceptives") and the complexity of merging HIV and reproductive care (e.g., "We [adolescent clinic] transition pregnant moms from our care back and forth to adult care"). Discussion Despite regular HIV-related medical appointments, HIV-positive women may have unaddressed reproductive health needs (e.g., pregnancy desire with providers focused on contraceptive use). Findings from this study suggest that increased support for young HIV-positive women's reproductive health is needed, including supporting pregnancy desires (to choose when, how, and if, to have children).

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Compromise of α-Defensin Function in Liver Cirrhosis Facilitates the Toxic Relationship Between Gut Permeability and Endotoxemia

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Virtual Reality Analgesia in Labor: The VRAIL Pilot Study—A Preliminary Randomized Controlled Trial Suggesting Benefit of Immersive Virtual Reality Analgesia in Unmedicated Laboring Women

This pilot study investigated the use of virtual reality (VR) in laboring women. Twenty-seven women were observed for equivalent time during unmedicated contractions in the first stage of labor both with and without VR (order balanced and randomized). Numeric rating scale scores were collected after both study conditions. Significant decreases in sensory pain −1.5 (95% CI, −0.8 to −2.2), affective pain −2.5 (95% CI, −1.6 to −3.3), cognitive pain −3.1 (95% CI, −2.4 to −3.8), and anxiety −1.5 (95% CI, −0.8 to −2.3) were observed during VR. Results suggest that VR is a potentially effective technique for improving pain and anxiety during labor. Accepted for publication June 6, 2018. D. P. Frey is currently affiliated with the Oregon Anesthesiology Group, Obstetric Anesthesiology, Providence Portland Medical Center, Portland, Funding: Funding for this study was provided by the Department of Anesthesiology, University of Michigan as well as in part by the National Institutes of Health (AR054115 and GM042725). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Clinical trial: NCT02926469 at https://ift.tt/2zCUsXv. Reprints will not be available from the authors. Address correspondence to David P. Frey, DO, Oregon Anesthesiology Group, Obstetric Anesthesiology, Providence Portland Medical Center, 707 SW Washington St, Suite 700, Portland, OR 97205. Address e-mail to VRAILQuestions@gmail.com. © 2018 International Anesthesia Research Society

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In Response

No abstract available

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Frequency of Operative Anesthesia Care After Traumatic Injury

BACKGROUND: Virtually all anesthesiologists care for patients who sustain traumatic injuries; however, the frequency with which operative anesthesia care is provided to this specific patient population is unclear. We sought to better understand the degree to which anesthesia providers participate in operative trauma care and how this differs by trauma center designation (levels I–V), using data from a comprehensive, regional database—the Washington State Trauma Registry (WSTR). We also sought to specifically assess operative anesthesia care frequency vis a vis the American College of Surgeons guidelines for continuous anesthesiology coverage for Level II trauma center accreditation. METHODS: We conducted a retrospective analysis measuring the frequency of operative anesthesia care among patients enrolled in the WSTR. Univariate comparisons were made between trauma patients who had surgery during their admission and those who did not (medical management only). In addition, clinical factors associated with surgical intervention were measured. We also measured the average times from hospital admission to surgery and compared these times across trauma centers, grouped level I, II, and III–V. RESULTS: From 2004 to 2014, there were approximately 176,000 encounters meeting WSTR inclusion criteria. Approximately 60% of these trauma encounters included exposure to operative anesthesia during the admission. Among all surgical procedures during the trauma admission, approximately 33% occurred within a level I trauma center, 23% occurred within a level II trauma center, and 44% occurred in a trauma center with a III, IV, or V designation. The predominant procedure category during a trauma admission was orthopedic. The presence of hypotension on admission (P

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A Systematic Review Evaluating Neuraxial Morphine and Diamorphine-Associated Respiratory Depression After Cesarean Delivery

The prevalence of neuraxial opioid–induced clinically significant respiratory depression (CSRD) after cesarean delivery is unknown. We sought to review reported cases of author-reported respiratory depression (ARD) to calculate CSRD prevalence. A 6-database literature search was performed to identify ARD secondary to neuraxial morphine or diamorphine, in parturients undergoing cesarean delivery. "Highest" (definite and probable/possible) and "lowest" (definite) prevalences of CSRD were calculated. Secondary outcomes included: (1) prevalence of CSRD associated with contemporary doses of neuraxial opioid, (2) prevalence of ARD as defined by each study's own criteria, (3) case reports of ARD, and (4) reports of ARD reported by the Anesthesia Closed Claims Project database between 1990 and 2016. We identified 78 articles with 18,455 parturients receiving neuraxial morphine or diamorphine for cesarean delivery. The highest and lowest prevalences of CSRD with all doses of neuraxial opioids were 8.67 per 10,000 (95% CI, 4.20–15.16) and 5.96 per 10,000 (95% CI, 2.23–11.28), respectively. The highest and lowest prevalences of CSRD with the use of clinically relevant doses of neuraxial morphine ranged between 1.63 per 10,000 (95% CI, 0.62–8.77) and 1.08 per 10,000 (95% CI, 0.24–7.22), respectively. The prevalence of ARD as defined by each individual paper was 61 per 10,000 (95% CI, 51–74). One published case report of ARD met our inclusion criteria, and there were no cases of ARD from the Closed Claims database analysis. These results indicate that the prevalence of CSRD due to neuraxial morphine or diamorphine in the obstetric population is low. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Accepted for publication May 31, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Nadir Sharawi, MBBS, FRCA, MSc, Department of Anesthesiology, University of Arkansas for Medical Sciences, 4301 W Markham, Slot 515, Little Rock, AR 72205. Address e-mail to nelsharawi@uams.edu. © 2018 International Anesthesia Research Society

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Ability of a New Smartphone Pulse Pressure Variation and Cardiac Output Application to Predict Fluid Responsiveness in Patients Undergoing Cardiac Surgery

BACKGROUND: Pulse pressure variation (PPV) can be used to predict fluid responsiveness in anesthetized patients receiving controlled mechanical ventilation but usually requires dedicated advanced monitoring. Capstesia (Galenic App, Vitoria-Gasteiz, Spain) is a novel smartphone application that calculates PPV and cardiac output (CO) from a picture of the invasive arterial pressure waveform obtained from any monitor screen. The primary objective was to compare the ability of PPV obtained using the Capstesia (PPVCAP) and PPV obtained using a pulse contour analysis monitor (PPVPC) to predict fluid responsiveness. A secondary objective was to assess the agreement and the trending of CO values obtained with the Capstesia (COCAP) against those obtained with the transpulmonary bolus thermodilution method (COTD). METHODS: We studied 57 mechanically ventilated patients (tidal volume 8 mL/kg, positive end-expiratory pressure 5 mm Hg, respiratory rate adjusted to keep end tidal carbon dioxide [32–36] mm Hg) undergoing elective coronary artery bypass grafting. COTD, COCAP, PPVCAP, and PPVPC were measured before and after infusion of 5 mL/kg of a colloid solution. Fluid responsiveness was defined as an increase in COTD of >10% from baseline. The ability of PPVCAP and PPVPC to predict fluid responsiveness was analyzed using the area under the receiver-operating characteristic curve (AUROC), the agreement between COCAP and COTD using a Bland-Altman analysis and the trending ability of COCAP compared to COTD after volume expansion using a 4-quadrant plot analysis. RESULTS: Twenty-eight patients were studied before surgical incision and 29 after sternal closure. There was no significant difference in the ability of PPVCAP and PPVPC to predict fluid responsiveness (AUROC 0.74 [95% CI, 0.60–0.84] vs 0.68 [0.54–0.80]; P = .30). A PPVCAP >8.6% predicted fluid responsiveness with a sensitivity of 73% (95% CI, 0.54–0.92) and a specificity of 74% (95% CI, 0.55–0.90), whereas a PPVPC >9.5% predicted fluid responsiveness with a sensitivity of 62% (95% CI, 0.42–0.88) and a specificity of 74% (95% CI, 0.48–0.90). When measured before surgery, PPV predicted fluid responsiveness (AUROC PPVCAP= 0.818 [P = .0001]; PPVPC= 0.794 [P = .0007]) but not when measured after surgery (AUROC PPVCAP= 0.645 [P = .19]; PPVPC= 0.552 [P = .63]). A Bland-Altman analysis of COCAP and COTD showed a mean bias of 0.3 L/min (limits of agreement: −2.8 to 3.3 L/min) and a percentage error of 60%. The concordance rate, corresponding to the proportion of CO values that changed in the same direction with the 2 methods, was poor (71%, 95% CI, 66–77). CONCLUSIONS: In patients undergoing cardiac surgery, PPVCAP and PPVPC both weakly predict fluid responsiveness. However, COCAP is not a good substitute for COTD and cannot be used to assess fluid responsiveness. Accepted for publication June 7, 2018. A. Joosten and C. Boudart contributed equally and share first authorship. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Registration: Clinicaltrials.gov (NCT02692222). Reprints will not be available from the authors. Address correspondence to Alexandre Joosten, MD, Department of Anesthesiology, Hopital Erasme, 808 Rt de Lennik, 1070 Bruxelles, Brussels, Belgium. Address e-mail to Alexandre.Joosten@erasme.ulb.ac.be. © 2018 International Anesthesia Research Society

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Attempt XYZ: airway management at the opposite end of the alphabet.

Related Articles

Attempt XYZ: airway management at the opposite end of the alphabet.

Anaesthesia. 2018 Jul 11;:

Authors: Chrimes N, Marshall SD

PMID: 29998563 [PubMed - as supplied by publisher]

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Did ultrasound fulfill the promise of safety in regional anesthesia?

Purpose of review Ultrasound guidance has become the accepted standard of practice for peripheral regional anesthesia. Despite evidence supporting the efficacy of ultrasound-guided regional anesthesia, its impact on patient safety has been less clear. Recent findings Evidence has been consistent that ultrasound guidance reduces the incidence of vascular injury, local anesthetic systemic toxicity, pneumothorax and phrenic nerve block. Within the limited global scope of the epidemiology and etiologic complexity of perioperative (including block-related) peripheral nerve injury, there has not been consistent evidence that ultrasound guidance is associated with a reduced incidence of nerve injury. However, a recently published retrospective cohort study has demonstrated that the incidence of short-term nerve injury was decreased with ultrasound guidance compared with nerve stimulation. Ultrasound has led to development of novel blocks, approaches and refinement of existing ones, which may contribute to patient safety. Summary Ultrasound has revolutionized the way we approach regional anesthesia and contributed to patient safety. It is important to note that patient safety does not hinge on one single technology. Patient safety in regional anesthesia relies on a well trained practitioner to pay meticulous attention to indication, block and patient selection, anatomy, pharmacology, equipment and technique. Correspondence to Michael J. Barrington, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC 3010, Australia. Tel: +61 3 9288 2211; e-mail: Michael.BARRINGTON@svha.org.au Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Traumatic brain injured patients: primum non nocere

Purpose of review Traumatic brain injury (TBI) remains an unfortunately common disease with potentially devastating consequences for patients and their families. However, it is important to remember that it is a spectrum of disease and thus, a one 'treatment fits all' approach is not appropriate to achieve optimal outcomes. This review aims to inform readers about recent updates in prehospital and neurocritical care management of patients with TBI. Recent findings Prehospital care teams which include a physician may reduce mortality. The commonly held value of SBP more than 90 in TBI is now being challenged. There is increasing evidence that patients do better if managed in specialized neurocritical care or trauma ICU. Repeating computed tomography brain 12 h after initial scan may be of benefit. Elderly patients with TBI appear not to want an operation if it might leave them cognitively impaired. Summary Prehospital and neuro ICU management of TBI patients can significantly improve patient outcome. However, it is important to also consider whether these patients would actually want to be treated particularly in the elderly population. Correspondence to Dr Dhuleep S. Wijayatilake, Department of Anaesthesia and Intensive Care Medicine, Queens Hospital, Rom Valley Way, Romford RM7 0AG, UK. Tel: +44 1708503727; e-mail: sanjay.wijayatilake@nhs.net Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Stratification of neuropathic pain patients: the road to mechanism-based therapy?

Purpose of review It has been demonstrated that within one pain entity, patients may report highly heterogenic sensory signs and symptoms. Although mechanism might differ fundamentally between those patients, yet the treatment recommendations are uniform throughout all phenotypes. Therefore, the introduction of new stratification tools could pave the way to an individualized pain treatment. Recent findings In the past, retrospective stratifications of patients successfully identified responders to certain pharmacological treatments. This indicated predictive validity and reliability of this classification tool in those patient subgroups. Further on, these observations have been confirmed in prospective studies. Summary This review focusses on recent achievements in neuropathic pain and suggests a promising implementation of an individualized pharmacological therapy in the future. Correspondence to Dr Ralf Baron, MD, Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. Tel: +49 431 500 23911; fax: +49 431 500 23914; e-mail: r.baron@neurologie.uni-kiel.de Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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New blocks for the same old joints

Purpose of review New block techniques are being constantly developed or old techniques modified to improve outcomes after surgery. This review discusses the reasons why new block techniques need to be developed to match the needs of contemporary anesthetic practice. Recent findings New block techniques have been developed for joint surgeries of both upper and lower extremities. New upper extremity blocks focus on decreasing the risk of complications like diaphragmatic paresis and improving the quality of blocks. Techniques for lower extremity surgeries are being performed distally, closer to the joints, to minimize weakness of the extremity. A review of the available evidence for these techniques is undertaken to get an understanding of the indications and limitations of these techniques. Summary Future studies need to be undertaken to further refine these techniques and produce evidence of support for analgesic efficacy, safety, and reliability. Correspondence to Sanjay K. Sinha, MBBS, Department of Anesthesiology, St. Francis Hospital and Medical Center, 114 Woodland Street, Hartford, CT 06105, USA. E-mail: sanjaysinha@comcast.net Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Regional anesthesia by nonanesthesiologists

Purpose of review As the evidence supporting the notion that regional anesthesia improves patient outcomes grows, utilization of regional anesthesia techniques has similarly increased. Best care should not be restricted by the background of care providers, however, the evidence replicating benefits of regional anesthesia when it is delivered by nonanesthesiologists is unclear. In this review, the provision of regional anesthesia by nonanesthesiologists is discussed so that readers can come to their own conclusions. Recent findings Regional anesthesia procedures are performed by nonanesthesiology physicians such as emergency physicians, critical care specialists, and surgeons. Patients benefit from the provision of regional anesthesia by these groups, but inconsistencies exist in training, service provision, and collaboration between these specialties and anesthesiologists. Nonphysician anesthesia providers also provide regional anesthesia. There are limited data on outcomes or benefits of this nonphysician-provided service, but consideration of team-based care and alternative models of care based upon geographical need is worthwhile. Summary The provision of regional anesthesia requires the accumulation of a suitable knowledge, skills, and behaviors that can be taught. Whilst it may not be appropriate for all techniques to be performed by all individuals, the possession of these competencies with the appropriate training and quality assurance means that more patients may ultimately benefit from the provision of regional anesthesia services. Correspondence to Amit Pawa, BSc(Hons), MBBS(Hons), FRCA, EDRA, Department of Anaesthesia, Guy's & St Thomas' NHS Foundation Trust, Great Maze Pond, SE1 9RT London, UK. Tel: +44 207 188 0644; fax: +44 207 188 0642; e-mail: amit.pawa@gstt.nhs.uk. Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Neuroanesthesiology: building the path to superior clinical care through research and education

No abstract available

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