Efficacy of axillary versus infraclavicular brachial plexus block in preventing tourniquet pain: A randomised trial

BACKGROUND Axillary and infraclavicular brachial plexus blocks are commonly used for upper limb surgery. Clinicians require information on the relative benefits of each to make a rational selection for specific patients and procedures. OBJECTIVES The main objective of the study was to compare axillary and infraclavicular brachial plexus block in terms of the incidence and severity of tourniquet pain. DESIGN Single blinded, randomised trial. SETTING University affiliated hospital, level-1 trauma centre. PATIENTS Age more than 18 years, ASAI-III patients undergoing orthopaedic surgery distal to the elbow, with an anticipated tourniquet duration of more than 45 min were recruited. INTERVENTIONS Patients underwent either ultrasound guided axillary brachial plexus block or infraclavicular block (ICB). MAIN OUTCOME MEASURES Incidence of tourniquet pain (onset, severity, associated haemodynamic changes) and block characteristics (block performance/onset times, distribution, incidence of adverse events, patient satisfaction) were recorded. RESULTS Eighty two patients (40 in the axillary block and 42 in the ICB group) were recruited. The incidence (5/36 and 3/35; P = 0.71), onset time mean (SD) were 73.0 (14.8) and 86.6 (5.7) min (P = 0.18) and severity (mild/moderate; 4/1 and 1/2; P = 0.51) of tourniquet pain were similar in the two groups. The incidence of paraesthesia during block performance, and block performance time were greater in the axillary block group (P = 0.0054 and 0.012, respectively). The volume of local anaesthetic administered was greater in the ICB group (P 

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Characterization of Resistance Genes and Polymerase Chain Reaction-Based Replicon Typing in Carbapenem-Resistant Klebsiella pneumoniae

Microbial Drug Resistance, Ahead of Print.


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Wolbachia Infection Associated with Increased Recombination in Drosophila

Wolbachia is a maternally-transmitted endosymbiotic bacteria that infects a large diversity of arthropod and nematode hosts. Some strains of Wolbachia are parasitic, manipulating host reproduction to benefit themselves, while other strains of Wolbachia exhibit obligate or facultative mutualisms with their host. The effects of Wolbachia on its host are many, though primarily relate to host immune and reproductive function. Here we test the hypothesis that Wolbachia infection alters the frequency of homologous recombination during meiosis. We use D. melanogaster as a model system, and survey recombination in eight wild-derived Wolbachia-infected (strain wMel) and Wolbachia-uninfected strains, controlling for genotype. We measure recombination in two intervals of the genome. Our results indicate that Wolbachia infection is associated with increased recombination in one genomic interval and not the other. The effect of Wolbachia infection on recombination is thus heterogenous across the genome. Our data also indicate a reproductive benefit of Wolbachia infection; infected females show higher fecundity than their uninfected genotypic controls. Given the prevalence of Wolbachia infection in natural populations, our findings suggest that Wolbachia infection is likely to contribute to recombination rate and fecundity variation among individuals in nature.

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Genetic Basis of Variation in Heat and Ethanol Tolerance in Saccharomyces cerevisiae

Saccharomyces cerevisiae has the capability of fermenting sugar to produce concentrations of ethanol that are toxic to most organisms. Other Saccharomyces species also have a strong fermentative capacity, but some are specialized to low temperatures, whereas S. cerevisiae is the most thermotolerant. Although S. cerevisiae has been extensively used to study the genetic basis of ethanol tolerance, much less is known about temperature dependent ethanol tolerance. In this study, we examined the genetic basis of ethanol tolerance at high temperature among strains of S. cerevisiae. We identified two amino acid polymorphisms in SEC24 that cause strong sensitivity to ethanol at high temperature and more limited sensitivity to temperature in the absence of ethanol. We also identified a single amino acid polymorphism in PSD1 that causes sensitivity to high temperature in a strain dependent fashion. The genes we identified provide further insight into genetic variation in ethanol and temperature tolerance and the interdependent nature of these two traits in S. cerevisiae.

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Using Maize Chromosome Segment Substitution Line Populations for the Identification of Loci Associated with Multiple Disease Resistance

Southern Leaf Blight (SLB), Northern Leaf Blight (NLB), and Gray Leaf Spot (GLS) caused by Cochliobolus heterostrophus, Setosphaeria turcica, and Cercospora zeae-maydis respectively, are among the most important diseases of corn worldwide. Previously, moderately high and significantly positive genetic correlations between resistance levels to each of these diseases were identified in a panel of 253 diverse maize inbred lines. The goal of this study was to identify loci underlying disease resistance in some of the most multiple disease resistant (MDR) lines by the creation of chromosome segment substitution line (CSSL) populations in multiple disease susceptible (MDS) backgrounds. Four MDR lines (NC304, NC344, Ki3, NC262) were used as donor parents and two MDS lines (Oh7B, H100) were used as recurrent parents to produce eight BC₃F_4:5 CSSL populations comprising 1,611 lines in total. Each population was genotyped and assessed for each disease in replicated trials in two environments. Moderate to high heritabilities on an entry mean basis were observed (0.32 to 0.83). Several lines in each population were significantly more resistant than the MDS parental lines for each disease. Multiple quantitative trait loci (QTL) for disease resistance were detected for each disease in most of the populations. Seventeen QTLs were associated with variation in resistance to more than one disease (SLB/NLB: 2; SLB/GLS: 7; NLB/GLS: 2 and 6 to all three diseases). For most populations and most disease combinations, significant correlations were observed between disease scores and also between marker effects for each disease. The number of lines that were resistant to more than one disease was significantly higher than would be expected by chance. Using the results from individual QTL analyses, a composite statistic based on Mahalanobis distance (Md) was used to identify joint marker associations with multiple diseases. Across all populations and diseases, 246 markers had significant Md values. However further analysis revealed that most of these associations were due to strong QTL effects on a single disease. Together, these findings reinforce our previous conclusions that loci associated with resistance to different diseases are clustered in the genome more often than would be expected by chance. Nevertheless true MDR loci which have significant effects on more than one disease are still much rarer than loci with single disease effects.

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Towards Identifying Subnetworks from FBF Binding Landscapes in Caenorhabditis Spermatogenic or Oogenic Germlines

Metazoan PUF (Pumilio and FBF) RNA-binding proteins regulate various biological processes, but a common theme across phylogeny is stem cell regulation. In Caenorhabditis elegans, FBF (fem-3 Binding Factor) maintains germline stem cells regardless of which gamete is made, but FBF also functions in the process of spermatogenesis. We have begun to "disentangle" these biological roles by asking which FBF targets are gamete-independent, as expected for stem cells, and which are gamete-specific. Specifically, we compared FBF iCLIP binding profiles in adults making sperm to those making oocytes. Normally, XX adults make oocytes. To generate XX adults making sperm, we used a fem-3(gf) mutant requiring growth at 25°; for comparison, wild-type oogenic hermaphrodites were also raised at 25°. Our FBF iCLIP data revealed FBF binding sites in 1522 RNAs from oogenic adults and 1704 RNAs from spermatogenic adults. More than half of these FBF targets were independent of germline gender. We next clustered RNAs by FBF-RNA complex frequencies and found four distinct blocks. Block I RNAs were enriched in spermatogenic germlines, and included validated target fog-3, while Block II and III RNAs were common to both genders, and Block IV RNAs were enriched in oogenic germlines. Block II (510 RNAs) included almost all validated FBF targets and was enriched for cell cycle regulators. Block III (21 RNAs) was enriched for RNA-binding proteins, including previously validated FBF targets gld-1 and htp-1. We suggest that Block I RNAs belong to the FBF network for spermatogenesis, and that Blocks II and III are associated with stem cell functions.

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SACS variants are a relevant cause of autosomal recessive hereditary motor and sensory neuropathy

Abstract

Mutations in the SACS gene have been initially reported in a rare autosomal recessive cerebellar ataxia syndrome featuring prominent cerebellar atrophy, spasticity and peripheral neuropathy as well as retinal abnormalities in some cases (autosomal recessive spastic ataxia of Charlevoix–Saguenay, ARSACS). In the past few years, the phenotypic spectrum has broadened, mainly owing to the availability and application of high-throughput genetic testing methods. We identified nine patients (three sib pairs, three singleton cases) with isolated, non-syndromic hereditary motor and sensory neuropathy (HMSN) who carried pathogenic SACS mutations, either in the homozygous or compound heterozygous state. None of the patients displayed spasticity or pyramidal signs. Ataxia, which was noted in only three patients, was consistent with a sensory ataxia. Nerve conduction and nerve biopsy studies showed mixed demyelinating and axonal neuropathy. Brain MRI scans were either normal or revealed isolated upper vermis atrophy of the cerebellum. Our findings confirm the broad clinical spectrum associated with SACS mutations, including pure polyneuropathy without characteristic clinical and brain imaging manifestations of ARSACS.

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Points that need attention in auditory N100 gating research in schizophrenia

With great interest, we read the article by Dr. Rosburg, reporting a meta-analysis of the auditory N100 gating studies in schizophrenia patients (Rosburg, 2018). Nevertheless, regarding the conclusion that "Findings are difficult to reconcile with the concept of a N100 gating deficit", we would like to highlight three points, which complement his comments on potential moderators and study limitations.

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Overground walking with a robotic exoskeleton elicits trunk muscle activity in people with high-thoracic motor-complete spinal cord injury

The trunk muscles are critical for postural control. Recent neurophysiological studies have revealed sparing of trunk muscle function in individuals with spinal cord injury (SCI) classified with thoracic or ce...

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On the design of EEG-based movement decoders for completely paralyzed stroke patients

Brain machine interface (BMI) technology has demonstrated its efficacy for rehabilitation of paralyzed chronic stroke patients. The critical component in BMI-training consists of the associative connection (co...

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Regenerative peripheral nerve interfaces for real-time, proportional control of a Neuroprosthetic hand

Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models ha...

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Patterns of Fluoroquinolone Resistance in Enterobacteriaceae Isolated from the Assiut University Hospitals, Egypt: A Comparative Study

Microbial Drug Resistance, Ahead of Print.


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Changes in Fluorescence Recovery After Photobleaching (FRAP) as an indicator of SOX9 transcription factor activity

Publication date: Available online 20 November 2018

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

Author(s): Kannan Govindaraj, Jan Hendriks, Diane S. Lidke, Marcel Karperien, Janine N. Post

Abstract

Cells respond to their environment via an intricate cellular signaling network, directing cell fate. Changes in cell fate are characterized by changes in gene transcription, dictated by (master) transcription factor activity. SOX9 is the master transcription factor for chondrocyte development. Its impaired function is implicated in osteoarthritis and growth disorders, such as dwarfism. However, the factors regulating SOX9 transcriptional activity are not yet fully mapped. Current methods to study transcription factor activity are indirect and largely limited to quantification of SOX9 target gene and protein expression levels after several hours or days of stimulation, leading to poor temporal resolution. We used Fluorescence Recovery After Photobleaching (FRAP) to study the mobility of SOX9 and correlated the changes in mobility to changes in its transcriptional activity by cross-validating with chromatin immunoprecipitation and qPCR. We show that using FRAP, we can quantify the changes in SOX9 mobility on short time scales as an indication of transcriptional activity, which correlated to changes of SOX9 DNA-binding and long-term target gene expression.

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Deletion of an intronic HIF-2α binding site suppresses hypoxia-induced WT1 expression

Publication date: Available online 20 November 2018

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

Author(s): Katharina Krueger, Lorenzo Catanese, Lina K. Sciesielski, Karin M. Kirschner, Holger Scholz

Abstract

Hypoxia-inducible factors (HIFs) play a key role in the adaptation to low oxygen by interacting with hypoxia response elements (HREs) in the genome. Cellular levels of the HIF-2α transcription factor subunit influence the histopathology and clinical outcome of neuroblastoma, a malignant childhood tumor of the sympathetic ganglia. Expression of the Wilms tumor gene, WT1, marks a group of high-risk neuroblastoma. Here, we identify WT1 as a downstream target of HIF-2α in Kelly neuroblastoma cells. In chromatin immunoprecipitation assays, HIF-2α bound to a HRE in intron 3 of the WT1 gene, but not to another predicted HIF binding site (HBS) in the first intron. The identified element conferred oxygen sensitivity to otherwise hypoxia-resistant WT1 and SV40 promoter constructs. Deletion of the HBS in the intronic HRE by genome editing abolished WT1 expression in hypoxic neuroblastoma cells. Physical interaction between the HRE and the WT1 promoter in normoxic and hypoxic Kelly cells was shown by chromosome conformation capture assays. These findings demonstrate that binding of HIF-2α to an oxygen-sensitive enhancer in intron 3 stimulates transcription of the WT1 gene in neuroblastoma cells by hypoxia-independent chromatin looping. This novel regulatory mechanism may have implications for the biology and prognosis of neuroblastoma.

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Criticality in tumor evolution and clinical outcome [Genetics]

How mutation and selection determine the fitness landscape of tumors and hence clinical outcome is an open fundamental question in cancer biology, crucial for the assessment of therapeutic strategies and resistance to treatment. Here we explore the mutation-selection phase diagram of 6,721 tumors representing 23 cancer types by quantifying the...

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Human-like hyperplastic prostate with low ZIP1 induced solely by Zn deficiency in rats [Genetics]

Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a...

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From Hospital to Home to Participation: A Position Paper on Transition Planning after Stroke

Publication date: Available online 19 November 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Kristine K. Miller, Susan H. Lin, Marsha Neville

Abstract

Based on a review of the evidence, members of the American Congress of Rehabilitation Medicine Stroke Group's Movement Interventions Task Force offer these five recommendations to help improve transitions of care for patients and their caregivers: (1) improving communication processes, (2) utilizing transition specialists, (3) implementing a patient-centered discharge checklist, (4) utilizing standardized outcome measures, and (5) establishing partnerships with community wellness programs.

Due to changes in healthcare policy, there are incentives to improve transitions during stroke rehabilitation. Although transition management programs often include multidisciplinary teams, medication management, caregiver education, and follow-up care management, there is a lack of a comprehensive and standardized approach to implement transition management protocols during post-stroke rehabilitation. This article uses the Transitions of Care (TOC) model to conceptualize how to facilitate a comprehensive patient-centered hand-off at discharge to maximize patient functioning and health. Specifically, this article reviews current guidelines and provides an evidence summary of several commonly cited approaches (early supported discharge, planned pre-discharge home visits, discharge checklists) to manage TOC, followed by a description of documented barriers to effective transitions. Patient-centered and standardized transition management may improve community integration, activities of daily living performance, and quality of life for stroke survivors while also decreasing hospital readmission rates during the transition from hospital to home to community.

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Seeking Help for Mental Health Problems in Hong Kong: The Role of Family

Abstract

Family members, rather than mental health professionals, are often the first responders for emotional or mental problems, particularly in Chinese societies where family is regarded as the primary care unit. Using data from the third wave of a representative sample of Chinese adults in the Hong Kong Panel Study of Social Dynamics, we investigate how family, and particularly family functioning, is associated with individual mental health help seeking and perceived barriers to professional service use, and how the associations vary across different generations of immigrants and between individuals with high versus low psychological distress. Our results demonstrate that family is still the primary source of help sought for mental health problems. Stronger family functioning is particularly significant for second-generation immigrants when they consider seeking help from immediate family members. Seeking professional help is uncommon, and stronger family functioning is associated with a lower probability of seeking help from general health professionals and alternative services. A well-functioning family is related to certain structural and cultural barriers to seeking professional help, yet trust in professional mental health services does not diminish along with stronger family functioning, even among the high psychological distress subgroup. The findings indicate that family can facilitate mental illness prevention and service integration. It is recommended that appropriate family support and services be incorporated into mental health treatment according to clients' differential family circumstances.

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A novel CRX variant (p.R98X) is identified in a Chinese family of Retinitis pigmentosa with atypical and mild manifestations

Abstract

Background

Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration that can cause inherited blindness. RP has extreme genetic and clinical heterogeneity, which brings a major obstacle to obtaining an accurate molecular diagnosis.

Objective

To analyze the genetic defect in a Chinese family of RP with a few atypical manifestations.

Methods

Whole-exome sequencing (WES) was applied to identify the disease-associated genes. Sanger sequencing was performed to validate the variants of candidate genes in the patient and his parents. In vitro expression analysis was further conducted to examine the potential biological function of the gene variant.

Results

A heterozygous nonsense variant c.292C > T (p.R98X) of CRX gene was identified to be present in the affected male. The c.292C > T variant of CRX was absent in all of the searched databases, including the 10,000 Chinese exome database. The nonsense variant was supposed to result in a truncated CRX protein with a destroyed homedomain (HD), which is essential for CRX translation. Interestingly, the following assay showed that the potential truncated protein was not detected, indicating that the variant may cause a loss-of-function mutation of CRX gene.

Conclusion

We identified a novel heterozygous null mutation in the CRX gene which was the first evidence of a nonsense mutation in the HD domain of CRX. Our finding suggested that the haploinsufficiency mutation of CRX gene contributed to the atypical and mild manifestations of the autosomal dominant RP in the Chinese family.

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The Biomechanics of Competitive Male Runners in Three Marathon Racing Shoes: A Randomized Crossover Study

Abstract

Background

We have shown that a prototype marathon racing shoe reduced the metabolic cost of running for all 18 participants in our sample by an average of 4%, compared to two well-established racing shoes. Gross measures of biomechanics showed minor differences and could not explain the metabolic savings.

Objective

To explain the metabolic savings by comparing the mechanics of the shoes, leg, and foot joints during the stance phase of running.

Methods

Ten male competitive runners, who habitually rearfoot strike ran three 5-min trials in prototype shoes (NP) and two established marathon shoes, the Nike Zoom Streak 6 (NS) and the adidas adizero Adios BOOST 2 (AB), at 16 km/h. We measured ground reaction forces and 3D kinematics of the lower limbs.

Results

Hip and knee joint mechanics were similar between the shoes, but peak ankle extensor moment was smaller in NP versus AB shoes. Negative and positive work rates at the ankle were lower in NP shoes versus the other shoes. Dorsiflexion and negative work at the metatarsophalangeal (MTP) joint were reduced in the NP shoes versus the other shoes. Substantial mechanical energy was stored/returned in compressing the NP midsole foam, but not in bending the carbon-fiber plate.

Conclusion

The metabolic savings of the NP shoes appear to be due to: (1) superior energy storage in the midsole foam, (2) the clever lever effects of the carbon-fiber plate on the ankle joint mechanics, and (3) the stiffening effects of the plate on the MTP joint.

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Testing the generality of non-genetic inheritance

Testing the generality of non-genetic inheritance

Testing the generality of non-genetic inheritance, Published online: 20 November 2018; doi:10.1038/s41576-018-0079-x

A study in Cell examines the pervasiveness of a classic form of non-genetic inheritance involving transposable element DNA methylation in mice. It reports that non-genetic inheritance is likely to be the exception rather than the rule across other loci genome-wide.

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Frequency and risk factors for liver disease following pancreatitis: A population-based cohort study

Digestive and Liver Diseases

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“Normal” creatinine levels predict persistent kidney injury and waitlist mortality in outpatients with cirrhosis

Hepatology

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Effect of alcohol consumption on survival in nonalcoholic fatty liver disease: A national prospective cohort study

Hepatology

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Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort

Hepatology

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Salivary markers of hepato-metabolic comorbidities in pediatric obesity

Digestive and Liver Diseases

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Testing the generality of non-genetic inheritance

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Sequential processing in the classic oddball task: ERP components, probability, and behavior

Abstract

This study compared the ERP components and behavior associated with the auditory equiprobable and classic oddball tasks, to relate the cognitive processing stages in those paradigms and continue the development of the sequential processing schema. Target and nontarget ERP data were acquired from 66 healthy young adults (M _age = 20.1, SD = 2.4 years, 14 male) who completed both equiprobable (target p = 0.5) and oddball tasks (target p = 0.3). Separate temporal PCAs were used to decompose the ERP data in each task and condition, and the similarity of the components identified in each condition was examined between tasks. Probability effects on component amplitudes and behavior were also analyzed to identify task differences in cognitive demands. A highly similar series of components was identified in each task, closely matching the schema: targets elicited N1‐3, N1‐1, PN, N2c, P3b, SW1, SW2; whereas nontargets elicited N1‐3, N1‐1, PN, N2b, P3a, SW1, SW2. N1‐1 and PN amplitudes increased as stimulus probability decreased, irrespective of the condition. N2b, P3b, SW1, and SW2 amplitudes also varied between tasks, illustrating task‐specific demands on those processing stages. These findings complemented the behavioral outcomes, which demonstrated greater accuracy and control in the classic oddball task. Overall, this study demonstrated comparable processing in the auditory equiprobable and classic oddball tasks, extending the generalizability of the schema and enabling further integration of the ERP theory associated with these tasks. This study also clarifies stimulus probability effects on the schema, providing important insight into the functionality of common ERP components.

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Cerebral blood flow modulations during antisaccade preparation in chronic hypotension

Abstract

In addition to symptoms including fatigue, dizziness, reduced drive, or mood disturbance, individuals with chronic low blood pressure (hypotension) frequently report cognitive complaints. While attentional deficits have been empirically confirmed, it is still unknown whether the impairments also encompass executive functions. This study investigated cerebral blood flow modulations in hypotension during a precued antisaccade/prosaccade task requiring the executive function of proactive inhibition in addition to preparatory attention. Using functional transcranial Doppler sonography, bilateral blood flow velocities in the middle cerebral arteries (MCA) were recorded in 39 hypotensive and 40 normotensive participants. In the task, a stimulus appeared left or right of a fixation point 5 s after a cuing stimulus; subjects had to move their gaze to the mirror image position of the stimulus (antisaccade) or toward it (prosaccade control condition). Video‐based eye tracking was used for ocular recording. A right dominant MCA blood flow increase arose during task preparation, which was smaller in hypotensive than normotensive participants. In addition, hypotensive participants exhibited lower peak velocity of the saccadic response. The extent of the reductions in blood flow and task performance in hypotension did not differ between antisaccade and prosaccade conditions. The smaller MCA flow increase may reflect reduced activity in the dorsolateral prefrontal and inferior parietal cortices during proactive inhibition and preparatory attention in hypotension. Given that group differences in blood flow and performance arose independent of task complexity and executive function load, hypotension may be characterized by basic attentional impairments rather than particular executive function deficits.

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