Oxidation of Ti-6Al-4V During Wire and Arc Additive Manufacture

3D Printing and Additive Manufacturing, Ahead of Print.


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Laparoscopic versus open repair for small paraumbilical hernia: A retrospective review

Asian Journal of Endoscopic Surgery, EarlyView.


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EMS Education Coordinator - Chesapeake Fire Department

This position is to provide Emergency Medical Service (EMS) education and training for quality improvement to the EMS personnel within the Fire Department. They will be responsible for assisting with the planning, development, implementation and training of education programs for EMS; evaluating EMS programs; establishing and maintaining EMS education schedules, recertification requirements and training ...

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Retraction

No abstract available

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WDR-23 and SKN-1/Nrf2 Coordinate with the BLI-3 Dual Oxidase in Response to Iodide-Triggered Oxidative Stress

Animals utilize conserved mechanisms to regulate oxidative stress. The Caenorhabditis elegans SKN-1 protein is homologous to the vertebrate Nrf (NF-E2-related factor) family of cap 'n' collar (CnC) transcription factors and functions as a core regulator of xenobiotic and oxidative stress responses. The WD40 repeat-containing protein WDR-23 is a key negative regulator of SKN-1 activity. We previously found that the oxidative stress induced by excess iodide can be relieved by loss of function in the BLI-3/TSP-15/DOXA-1 dual oxidase complex. To further understand the molecular mechanism of this process, we screened for new mutants that can survive in excess iodide and identified gain-of-function mutations in skn-1 and loss-of-function mutations in wdr-23. The SKN-1C isoform functions in the hypodermis to affect animal's response to excess iodide, while the SKN-1A isoform appears to play a minor role. wdr-23(lf) can interact with bli-3 mutations in a manner different from skn-1(gf). Transcriptome studies suggest that excess iodide causes developmental arrest largely independent of changes in gene expression, and wdr-23(lf) could affect the expression of a subset of genes by a mechanism different from SKN-1 activation. We propose that WDR-23 and SKN-1 coordinate with the BLI-3/TSP-15/DOXA-1 dual oxidase complex in response to iodide-triggered oxidative stress.

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Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events

The proper regulation of cell cycle transitions is paramount to the maintenance of cellular genome integrity. In Saccharomyces cerevisiae, the mitotic exit network (MEN) is a Ras-like signaling cascade that effects the transition from M phase to G1 during the cell division cycle in budding yeast. MEN activation is tightly regulated. It occurs during anaphase and is coupled to mitotic spindle position by the spindle position checkpoint (SPoC). Bfa1 is a key component of the SPoC and functions as part of a two-component GAP complex along with Bub2. The GAP activity of Bfa1-Bub2 keeps the MEN GTPase Tem1 inactive in cells with mispositioned spindles, thereby preventing inappropriate mitotic exit and preserving genome integrity. Interestingly, a GAP-independent role for Bfa1 in mitotic exit regulation has been previously identified. However the nature of this Bub2-independent role and its biological significance are not understood. Here we show that Bfa1 also activates the MEN by promoting the localization of Tem1 primarily to the daughter spindle pole body (dSPB). We demonstrate that the overexpression of BFA1 is lethal due to defects in Tem1 localization, which is required for its activity. In addition, our studies demonstrate a Tem1-independent role for Bfa1 in promoting proper cytokinesis. Cells lacking TEM1, in which the essential mitotic exit function is bypassed, exhibit cytokinesis defects. These defects are suppressed by the overexpression of BFA1. We conclude that Bfa1 functions to both inhibit and activate late mitotic events.

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Harvesting responses to single pulse electrical stimulation for presurgical evaluation in epilepsy

A Single Pulse Electrical Stimulation (SPES) protocol consists of pulses (repetition rate 0.1 – 1 Hz) of short lasting current stimuli (2-8 mA, pulse width <=1 ms) delivered to adjacent electrodes that are either part of intracranial grids (ECoG) or depth electrodes (SEEG) implanted in epilepsy patients for presurgical evaluation. Early studies using such a protocol aimed at confirming specific functional cortical connections in eloquent cortex by means of what was later called the cortico-cortical evoked potential (CCEP) (Wilson et al., 1990), or influencing cortical excitability in order to evoke (subclinical) habitual seizures (Kahane et al., 1993).

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The effects of aging on early stages of the auditory deviance detection system

The ability of the auditory system in extracting acoustic regularities and signaling deviance detection is critical for survival as it enables fast processing of novel events and preparing the organism to react quickly to potentially significant stimuli. Moreover, these two functional properties underlie the formation and segregation of auditory objects, which are necessary for solving the cocktail party problem and understanding speech in complex and noisy environments.

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Effects of Noise and Age on the Infant Brainstem Response to Speech

Speech perception depends on healthy sound transduction and faithful encoding of speech sound acoustics. Background noise can distort frequency analysis in the inner ear and disrupt auditory processing more centrally, making speech sounds difficult to decode. Problems in the middle ear, inner ear or central nervous system can exacerbate difficulties in hearing speech in noise, including early conductive hearing impairment (Keogh et al., 2010), sensorineural hearing loss at low or high frequencies (Laukli et al., 1985, Horwitz et al., 2002), diminished linguistic content during development (Cooper et al., 1989, Lieu, 2004, Stelmachowicz et al., 2004, Eisenberg, 2007, Moeller et al., 2015), and attention (Soderlund et al., 2016) or memory problems (McCreery et al., 2017, Millman et al., 2017).

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Auditory gamma oscillations predict global symptomatic outcome in the early stages of psychosis: a longitudinal investigation

The gamma-band auditory steady-state response (ASSR) is hypothesized to be a useful biomarker for psychosis (Uhlhaas and Singer, 2010). Kwon et al. (1999) performed the first study of 40-Hz ASSR in patients with schizophrenia using electroencephalography (EEG) and demonstrated a reduced power and synchronization in response to 40-Hz stimulation, but not to the 20-Hz stimulation, in these patients. This initial finding has been replicated in many studies using EEG (Brenner et al., 2003; Hamm et al., 2015; Hirano et al., 2015; Kirihara et al., 2012; Light et al., 2006; Spencer et al., 2008; Tada et al., 2016) or magnetoencephalography (MEG; Edgar et al., 2014; Teale et al., 2008; Tsuchimoto et al., 2011; Vierling-Claassen et al., 2008; Wilson et al., 2008).

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Effect of subthalamic nucleus deep brain stimulation on visual scanning

Since saccades reflect the activity of the superior colliculus, which receives projections from the basal ganglia, studies on saccades provide insights into the function of basal ganglia in various neurological conditions, including Parkinson's disease (PD) (Terao et al., 2011; Gorges et al., 2014). In fact, many studies have studied the performance of saccades in PD (White et al., 1983; Crawford et al., 1989; Nakamura et al., 1994; Vermersch et al., 1994; Kimmig et al., 2002; Yugeta et al., 2010; Terao et al., 2011; Matsumoto et al., 2011, 2012; Gorges et al., 2014).

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Electrodiagnosis and nerve ultrasound: “Castor and Pollux” in the management of neuropathies

The image of Dioscuri is used to describe the efficient union of two elements contributing to achieve a goal. They were Castor and Pollux, two strong brothers of Greek mythology, defenders of the sailors, during the sea storms. Similarly, electrodiagnosis (EDx) and nerve ultrasound (US) together "defend" the complex and "stormy" management of patients with peripheral neuropathies. A large amount of papers has shown the efficacy of association of EDx and US in nerve evaluation. Now, as hoped years ago, the association between US and EDx is often part of neurophysiological activity (Padua et al., 2013).

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A Modified Translaryngeal Tracheostomy Technique in the Neurointensive Care Unit. Rationale and Single-center Experience on 199 Acute Brain-damaged Patients

Background: Brain-injured patients frequently require tracheostomy, but no technique has been shown to be the gold standard for these patients. We developed and introduced into standard clinical practice an innovative bedside translaryngeal tracheostomy (TLT) technique aided by suspension laryngoscopy (modified TLT). During this procedure, the endotracheal tube is left in place until the airway is secured with the new tracheostomy. This study assessed the clinical impact of this technique in brain-injured patients. Materials and Methods: This is a retrospective analysis of prospectively collected data from adult brain-injured patients who had undergone modified TLT during the period spanning from January 2010 to December 2016 at the Neurointensive care unit, San Gerardo Hospital (Monza, Italy). The incidence of intraprocedural complications, including episodes of intracranial hypertension (intracranial pressure [ICP] >20 mm Hg), was documented. Neurological, ventilatory, and hemodynamic parameters were retrieved before, during, and after the procedure. Risk factors for complications and intracranial hypertension were assessed by univariate logistic analysis. Data are presented as n (%) and median (interquartile range) for categorical and continuous variables, respectively. Results: A total of 199 consecutive brain-injured patients receiving modified TLT were included. An overall 52% male individuals who were 66 (54 to 74) years old and who had an admission Glasgow Coma Scale of 7 (6 to 10) were included in the cohort. Intracerebral hemorrhage (30%) was the most frequent diagnosis. Neurointensivists performed 130 (65%) of the procedures. Patients underwent tracheostomy 10 (7 to 13) days after intensive care unit admission. Short (ie, 20 mm Hg were observed in 11 cases. Overall, the procedure was associated with an increase in ICP from 7 (4 to 10) to 12 (7 to 18) mm Hg (P

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Opioid exposure safety, superglottic airways and other EMS news of the week

Our co-hosts discuss hot topics related to EMS personnel, from cardiac arrest survival to a DOJ video regarding opioid exposure while on the job

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Incidental Durotomy in Degenerative Lumbar Spine Surgery – A register study of 64,431 operations

Incidental durotomy (ID) is one of the most common intraoperative complications seen in spine surgery. Conflicting evidence has been presented regarding whether or not outcomes are affected by the presence of an ID.

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Information needs of patients in spine surgery: development of a question prompt list to guide informed consent consultations

Informed consent is mandatory before surgery and fundamental in physician–patient interaction. However, communication is sometimes suboptimal.

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Clinical effect of early bisphosphonate treatment for pyogenic vertebral osteomyelitis with osteoporosis: An analysis by the Cox proportional hazard model

Patients with pyogenic vertebral osteomyelitis (PVO) are expected to have an increased risk of bone loss. Therefore, early bisphosphonate therapy would be clinically effective for PVO patients with osteoporosis.

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MicroRNA-494-dependent WDHDI inhibition suppresses epithelial-mesenchymal transition, tumor growth and metastasis in cholangiocarcinoma

Cholangiocarcinoma (CCA) represents a devastating malignancy characterized by high mortality, and notoriously problematic to diagnose. Recently, microRNAs (miRs) have been intensively investigated due to their potential usefulness from a tumor treatment perspective.

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MicroRNA-494-dependent WDHDI inhibition suppresses epithelial-mesenchymal transition, tumor growth and metastasis in cholangiocarcinoma

Cholangiocarcinoma (CCA) represents a devastating malignancy characterized by high mortality, and notoriously problematic to diagnose. Recently, microRNAs (miRs) have been intensively investigated due to their potential usefulness from a tumor treatment perspective.

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Rac1: supports muscle glucose uptake independently of Akt

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Nutritional programming by maternal obesity: Insights into the development of NAFLD

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Recovery of respiratory function in mdx mice co‐treated with neutralizing interleukin‐6 receptor antibodies and Urocortin‐2

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Army Expeditionary Technology Search selects SimpleSense’s first responder technology for Army modernization competition

Playa Vista, Calif. - Otherwise known as xTechSearch, the Army Expeditionary Search is part of a transformation underway in all branches of the military to innovative rapidly to attack problems, like a startup. After reviewing 340 white papers submitted by small businesses and startups that showcased how novel research and technology ideas could benefit the Army's modernization priorities,...

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Genome-wide analysis of Hanwoo and Chikso populations using the BovineSNP50 genotyping array

Abstract

Hanwoo and Chikso are classified as Korean native cattle breeds that are currently registered with the Food and Agriculture Organization. However, there is still a lack of genomic studies to compare Hanwoo to Chikso populations. The objective of this study was to perform genome-wide analysis of Hanwoo and Chikso populations, investigating the genetic relationships between these two populations. We genotyped a total of 319 cattle including 214 Hanwoo and 105 Chikso sampled from Gangwon Province Livestock Technology Research Institute, using the Illumina Bovine SNP50K Beadchip. After performing quality control on the initially generated datasets, we assessed linkage disequilibrium patterns for all the possible SNP pairs within 1 Mb apart. Overall, average r² values in Hanwoo (0.048) were lower than Chikso (0.074) population. The genetic relationship between the populations was further assured by the principal component analysis, exhibiting clear clusters in each of the Hanwoo and Chikso populations, respectively. Overall heterozygosity for Hanwoo (0.359) was slightly higher than Chikso (0.345) and inbreeding coefficient was also a bit higher in Hanwoo (− 0.015) than Chikso (− 0.035). The average F_ST value was 0.036 between Hanwoo and Chikso, indicating little genetic differentiation between those two breeds. Furthermore, we found potential selection signatures including LRP1B and NTRK2 genes that might be implicated with meat and reproductive traits in cattle. In this study, the results showed that both Hanwoo and Chikso populations were not under severe level of inbreeding. Although the principal component analysis exhibited clear clusters in each of the populations, we did not see any clear evidence that those two populations are highly differentiated each other.

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Bilateral independent periodic discharges are associated with electrographic seizures and poor outcome: a case-control study

Publication date: Available online 29 August 2018

Source: Clinical Neurophysiology

Author(s): Gamaleldin Osman, Rahul Rahangdale, Jeffrey W. Britton, Emily J. Gilmore, Hiba Arif Haider, Stephen Hantus, Aline Herlopian, Sara E. Hocker, Jong Woo Lee, Benjamin Legros, Michael Mendoza, Vineet Punia, Nishi Rampal, Jerzy P. Szaflarski, Adam D. Wallace, M. Brandon Westover, Lawrence J. Hirsch, Nicolas Gaspard

Abstract

Objective

To determine the clinical correlates bilateral independent periodic discharges (BIPDs) and their association with electrographic seizures and outcome.

Methods

Retrospective case-control study of patients with BIPDs compared to patients without periodic discharges ("No PDs") and patients with lateralized periodic discharges ("LPDs"), matched for age, etiology and level of alertness.

Results

We included 85 cases and 85 controls in each group. The most frequent etiologies of BIPDs were stroke, CNS infections, and anoxic brain injury. Acute bilateral cerebral injury was more common in the BIPDs group than in the No PDs and LPDs groups (70% vs. 37% vs. 35%). Electrographic seizures were more common with BIPDs than in the absence of PDs (45% vs. 8%), but not than with LPDs (52%). Mortality was higher in the BIPDs group (36%) than in the No PDs group (18%), with fewer patients with BIPDs achieving good outcome (moderate disability or better; 18% vs. 36%), but not than in the LPDs group (24% mortality, 26% good outcome). In multivariate analyses, BIPDs remained associated with mortality (OR: 3.0 [1.4-6.4]) and poor outcome (OR: 2.9 [1.4-6.2]).

Conclusion

BIPDs are caused by bilateral acute brain injury and are associated with a high risk of electrographic seizures and of poor outcome.

Significance

BIPDs are uncommon but their identification in critically ill patients has potential important implications, both in terms of clinical management and prognostication.

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Neurophysiological Monitoring during Cervical Spine Surgeries: Longitudinal Costs and Outcomes

Publication date: Available online 29 August 2018

Source: Clinical Neurophysiology

Author(s): John P. Ney, Daniel P. Kessler

Abstract

Objectives

Well-designed longitudinal studies assessing effectiveness of intraoperative neurophysiologic monitoring (IONM) are lacking. We investigate IONM effects on cost and administrative markers for health outcomes in the year after cervical spine surgery.

Methods

We identified single-level cervical spine surgeries in commercial claims. We constructed linear regression models estimating the effect of IONM (controlling for patient demographics, pre-operative health, services during index admission) on total spending, neurological complications, readmissions, and outpatient opiate usage in the year following index surgery.

Results

IONM was associated with increased spending during index admission of $1,229 (p = 0.001), but decreased spending post-discharge of $1,615 (p = 0.010), for a net -$386 (p = 0.608) for the year after surgery. Shorter length of stay (0.116 days, p = 0.004) and fewer readmissions (20.5 per thousand, p = 0.036) accounted for some post-discharge savings. IONM was associated with decreased rates of nervous system complications (4/1000, p = 0.048) and post-discharge opiate use (17 prescriptions/1000, p = 0.050) in the year after index admission.

Conclusions

IONM was associated with administrative markers suggesting improved health outcomes after cervical spine surgery without greater costs for the year.

Significance

This study suggests IONM may have lasting health and cost benefits.

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Bowel wall healing assessed using magnetic resonance imaging predicts sustained clinical remission and decreased risk of surgery in Crohn’s disease

Abstract

Background

Endoscopic mucosal healing is considered as the best therapeutic target in Crohn's disease (CD) as it is associated with better long-term outcomes. We investigated whether bowel wall healing (BWH) assessed using magnetic resonance imaging (MRI) could predict favorable outcomes and could be a potential therapeutic target.

Methods

We performed a post hoc analysis from two prospective studies (n = 174 patients). All the patients with previous objective signs of bowel inflammation and assessed by MRI for therapeutic efficacy had a standardized and blinded evaluation, and underwent MRI. Complete BWH was defined as no segmental MaRIA > 7 or no segmental Clermont score > 8.4 and BWH as no segmental MaRIA > 11 or no segmental Clermont score > 12.5. Clinical corticosteroid-free remission (CFREM) was defined as no reappearance or worsening of clinical manifestation leading to therapeutic modification, hospitalization or CD-related surgery. Multivariate analyses were performed including all the relevant parameters.

Results

Overall, 63 patients with CD were included (mean follow-up = 4.8 ± 3.1 semesters). In multivariate analysis (n = 303 semesters), complete BWH or BWH was associated with sustained CFREM according to MaRIA [OR = 4.42 (2.29–26.54); p = 0.042 and OR = 3.43 (1.02–27.02); p = 0.047, respectively] or Clermont score [OR = 3.09 (1.01–12.91); p = 0.049 and OR = 3.88 (1.40–13.80); p = 0.036, respectively]. In multivariate analysis (n = 63 patients), complete BWH or BWH was associated with decreased risk of surgery using MaRIA [HR = 0.16 (0.043–0.63); p = 0.008 and HR = 0.24 (0.07–0.77); p = 0.017, respectively] or Clermont score [HR = 0.24 (0.07–0.78); p = 0.016 and HR = 0.23 (0.07–0.76); p = 0.016, respectively].

Conclusions

MRI endpoints are predictive of favorable outcomes after medical therapy and could be used as therapeutic target in daily practice and clinical trials.

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Remifentanil suppresses increase in interleukin-6 mRNA in the brain by inhibiting cyclic AMP synthesis

Abstract

Purpose

Neuronal inflammation is caused by systemic inflammation and induces cognitive dysfunction. IL-6 plays a crucial role in therapies for neuronal inflammation and cognitive dysfunction. Remifentanil, an ultra-short-acting opioid, controls inflammatory reactions in the periphery, but not in the brain. Therefore, the anti-inflammatory effects of remifentanil in neuronal tissue and the involvement of cAMP in these effects were investigated in the present study.

Methods

Mice were divided into 4 groups: control, remifentanil, LPS, and LPS + remifentanil. Brain levels of pro-inflammatory cytokine mRNA, and serum levels of corticosterone, catecholamine and IL-6 were measured in the 4 groups. The co-localization of IL-6 and astrocytes in the mouse brain after the LPS injection was validated by immunostaining. LPS and/or remifentanil-induced changes in intracellular cAMP levels in cultured glial cells were measured, and the effects of cAMP on LPS-induced IL-6 mRNA expression levels were evaluated.

Results

Remifentanil suppressed increase in IL-6 mRNA levels in the mouse brain, and also inhibited the responses of plasma IL-6, corticosterone, and noradrenaline in an inflammatory state. In the hypothalamus, IL-6 was localized in the median eminence, at which GFAP immunoreactivity was specifically detected. In cultured cells, remifentanil suppressed increase in IL-6 mRNA levels and intracellular cAMP levels after the administration of LPS, and this enhanced IL-6 mRNA expression in response to LPS.

Conclusion

Remifentanil suppressed increase in IL-6 mRNA levels in the brain in an inflammatory state, and this effect may be attributed to its direct action on neuronal cells through the inhibition of intracellular cAMP rather than corticosterone.

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Randomized comparative study between two different techniques of intercostobrachial nerve block together with brachial plexus block during superficialization of arteriovenous fistula

Abstract

Background

This study compared proximal and distal approaches of intercostobrachial nerve block (ICBNB) combined with infraclavicular brachial plexus block (ICBPB) during superficialization of arteriovenous fistula.

Methods

Seventy adult patients were randomized to receive ICBPB and 6 ml 0.25% bupivacaine at the level of the 3rd rib in the anterior axillary line between pectoralis minor and serratus anterior muscles (group P) or subcutaneously along the medial side of the upper arm (group D). The primary outcome was the achievement of complete sensory block. Secondary outcomes were onset of analgesia, volume of local anesthetic (LA) supplementation, fentanyl administration, success rate, and conversion to general anesthesia (GA).

Results

Complete sensory block in the medial side of the upper arm was achieved in 91% of patients in group P and 51% in group D. Failure rate of ICBNB was higher in group D (49%) than group P (14%). Conversion to GA was determined by the attending anesthesiologist in 26% of patients in group D and 0% in group P. LA supplementation was required in 5 patients in group P and 11 patients in group D, and the mean volume of LA was statistically higher in group D than group P (9.5 ± 1.5, 7.5 ± 2 ml, respectively). Onset of sensory block was faster in group P than group D (8.75 ± 1.67 and 10 ± 2.14 min, respectively). No differences were observed regarding fentanyl administration.

Conclusion

ICBNB proximal approach provides a high success rate with less amount of rescue analgesia compared to the distal approach.

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Identification of the Novel Nup188-brr7 Allele in a Screen for Cold-Sensitive mRNA Export Mutants in Saccharomyces cerevisiae

The maturation and export of mRNA from the nucleus through the nuclear pore complex is critical for maintaining an appropriate proteome in all eukaryotic cells. Here we summarize a previously unpublished screen in S. cerevisiae that utilized an established dT50 in situ hybridization assay to identify cold-sensitive mutants that accumulated bulk poly A RNA in the nucleus. The screen identified seven mutants in six complementation groups, including the brr6-1 strain that we described previously. In addition to brr6-1, we identified novel alleles of the key transport gene GLE1 and NUP188, a component of the Nic96 nucleoporin complex. Notably, we show that the nup188-brr7 allele causes defects in select protein import pathways as well as mRNA export. Given recent structural and functional evidence linking the Nic96 complex to transport components, this mutant may be particularly useful to the transport community.

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Tandem Duplicate Genes in Maize Are Abundant and Date to Two Distinct Periods of Time

Tandem duplicate genes are proximally duplicated and as such occur in similar genomic neighborhoods. Using the maize B73 and PH207 de novo genome assemblies, we identified thousands of tandem gene duplicates that account for ~10% of the annotated genes. These tandem duplicates have a bimodal distribution of ages, which coincide with ancient allopolyploidization and more recent domestication. Tandem duplicates are smaller on average and have a higher probability of containing LTR elements than other genes, suggesting origins in nonhomologous recombination. Within relatively recent tandem duplicate genes, ~26% appear to be undergoing degeneration or divergence in function from the ancestral copy. Our results show that tandem duplicates are abundant in maize, arose in bursts throughout maize evolutionary history under multiple potential mechanisms, and may provide a substrate for novel phenotypic variation.

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Whole Genome Sequence of the Parasitoid Wasp Microplitis demolitor That Harbors an Endogenous Virus Mutualist

Microplitis demolitor (Hymenoptera: Braconidae) is a parasitoid used as a biological control agent to control larval-stage Lepidoptera and serves as a model for studying the function and evolution of symbiotic viruses in the genus Bracovirus. Here we present the M. demolitor genome (assembly version 2.0), with a genome size of 241 Mb, and a N50 scaffold and contig size of 1.1 Mb and 14 Kb, respectively. Using RNA-Seq data and manual annotation of genes of viral origin, we produced a high-quality gene set that includes 18,586 eukaryotic and 171 virus-derived protein-coding genes. Bracoviruses are dsDNA viruses with unusual genome architecture, in which the viral genome is integrated into the wasp genome and is comprised of two distinct components: proviral segments that are amplified, circularized, and packaged into virions for export into the wasp's host via oviposition; and replication genes. This genome assembly revealed that at least two scaffolds contain both nudivirus-like genes and proviral segments, demonstrating that at least some of these components are near each other in the genome on a single chromosome. The updated assembly and annotation are available in several publicly accessible databases; including the National Center for Biotechnology Information and the Ag Data Commons. In addition, all raw sequence data available for M. demolitor have been consolidated and are available for visualization at the i5k Workspace. This whole genome assembly and annotation represents the only genome-scale, annotated assembly from the lineage of parasitoid wasps that has associations with bracoviruses (the 'microgastroid complex'), providing important baseline knowledge about the architecture of co-opted virus symbiont genomes.

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Targeted Gene Sequencing in Children with Crohns Disease and Their Parents: Implications for Missing Heritability

Crohn's disease is a complex genetic trait characterized by chronic relapsing intestinal inflammation. Genome wide association studies (GWAS) have identified more than 170 loci associated with the disease, accounting for ~14% of the disease variance. We hypothesized that rare genetic variation in GWAS positional candidates also contribute to disease pathogenesis. We performed targeted, massively-parallel sequencing of 101 genes in 205 children with Crohn's disease, including 179 parent-child trios and 200 controls, both of European ancestry. We used the gene burden test implemented in VAAST and estimated effect sizes using logistic regression and meta-analyses. We identified three genes with nominally significant p-values: NOD2, RTKN2, and MGAT3. Only NOD2 was significant after correcting for multiple comparisons. We identified eight novel rare variants in NOD2 that are likely disease-associated. Incorporation of rare variation and compound heterozygosity nominally increased the proportion of variance explained from 0.074 to 0.089. We estimated the population attributable risk and total heritability of variation in NOD2 to be 32.9% and 3.4%, respectively, with 3.7% and 0.25% accounted for by rare putatively functional variants. Sequencing probands (as opposed to genotyping) to identify rare variants and incorporating phase by sequencing parents can recover a portion of the missing heritability of Crohn's disease.

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Transcriptome Analysis of Four Arabidopsis thaliana Mediator Tail Mutants Reveals Overlapping and Unique Functions in Gene Regulation

The Mediator complex is a central component of transcriptional regulation in Eukaryotes. The complex is structurally divided into four modules known as the head, middle, tail and kinase modules, and in Arabidopsis thaliana, comprises 28-34 subunits. Here, we explore the functions of four Arabidopsis Mediator tail subunits, MED2, MED5a/b, MED16, and MED23, by comparing the impact of mutations in each on the Arabidopsis transcriptome. We find that these subunits affect both unique and overlapping sets of genes, providing insight into the functional and structural relationships between them. The mutants primarily exhibit changes in the expression of genes related to biotic and abiotic stress. We find evidence for a tissue specific role for MED23, as well as in the production of alternative transcripts. Together, our data help disentangle the individual contributions of these MED subunits to global gene expression and suggest new avenues for future research into their functions.

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Optimising Genomic Selection in Wheat: Effect of Marker Density, Population Size and Population Structure on Prediction Accuracy

Genomic selection applied to plant breeding enables earlier estimates of a line's performance and significant reductions in generation interval. Several factors affecting prediction accuracy should be well understood if breeders are to harness genomic selection to its full potential. We used a panel of 10,375 bread wheat (Triticum aestivum) lines genotyped with 18,101 SNP markers to investigate the effect and interaction of training set size, population structure and marker density on genomic prediction accuracy. Through assessing the effect of training set size we showed the rate at which prediction accuracy increases is slower beyond approximately 2,000 lines. The structure of the panel was assessed via principal component analysis and K-means clustering, and its effect on prediction accuracy was examined through a novel cross-validation analysis according to the K-means clusters and breeding cohorts. Here we showed that accuracy can be improved by increasing the diversity within the training set, particularly when relatedness between training and validation sets is low. The breeding cohort analysis revealed that traits with higher selection pressure (lower allelic diversity) can be more accurately predicted by including several previous cohorts in the training set. The effect of marker density and its interaction with population structure was assessed for marker subsets containing between 100 and 17,181 markers. This analysis showed that response to increased marker density is largest when using a diverse training set to predict between poorly related material. These findings represent a significant resource for plant breeders and contribute to the collective knowledge on the optimal structure of calibration panels for genomic prediction.

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A Bayesian Decision Theory Approach for Genomic Selection

Plant and animal breeders are interested in selecting the best individuals from a candidate set for the next breeding cycle. In this paper, we propose a formal method under the Bayesian decision theory framework to tackle the selection problem based on genomic selection (GS) in single- and multi-trait settings. We proposed and tested three univariate loss functions (Kullback-Leibler, KL; Continuous Ranked Probability Score, CRPS; Linear-Linear loss, LinLin) and their corresponding multivariate generalizations (Kullback-Leibler, KL; Energy Score, EnergyS; and the Multivariate Asymmetric Loss Function, MALF). We derived and expressed all the loss functions in terms of heritability and tested them on a real wheat dataset for one cycle of selection and in a simulated selection program. The performance of each univariate loss function was compared with the standard method of selection (Std) that does not use loss functions. We compared the performance in terms of the selection response and the decrease in the population's genetic variance during recurrent breeding cycles. Results suggest that it is possible to obtain better performance in a long-term breeding program using the single-trait scheme by selecting 30% of the best individuals in each cycle but not by selecting 10% of the best individuals. For the multi-trait approach, results show that the population mean for all traits under consideration had positive gains, even though two of the traits were negatively correlated. The corresponding population variances were not statistically different from the different loss function during the 10^th selection cycle. Using the loss function should be a useful criterion when selecting the candidates for selection for the next breeding cycle.

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Tripartite Chromatin Localization of Budding Yeast Shugoshin Involves Higher-Ordered Architecture of Mitotic Chromosomes

The spindle assembly checkpoint (SAC) is key to faithful segregation of chromosomes. One requirement that satisfies SAC is appropriate tension between sister chromatids at the metaphase-anaphase juncture. Proper tension generated by poleward pulling of mitotic spindles signals biorientation of the underlying chromosome. In the budding yeast, the tension status is monitored by the conserved Shugoshin protein, Sgo1p, and the tension sensing motif (TSM) of histone H3. ChIP-seq reveals a unique TSM-dependent, tripartite domain of Sgo1p in each mitotic chromosome. This domain consists of one centromeric and two flanking peaks 3 – 4 kb away, present exclusively in mitosis. Strikingly, this trident motif coincides with cohesin localization, but only at the centromere and the two immediate adjacent loci, despite that cohesin is enriched at numerous regions throughout mitotic chromosomes. Chromosome conformation capture assays reveal apparent looping at the centromeric and pericentric regions. The TSM-Sgo1p-cohesin triad is therefore at the center stage of higher-ordered chromatin architecture for error-free segregation.

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Physiological Starvation Promotes Caenorhabditis elegans Vulval Induction

Studying how molecular pathways respond to ecologically relevant environmental variation is fundamental to understand organismal development and its evolution. Here we characterize how starvation modulates Caenorhabditis elegans vulval cell fate patterning – an environmentally sensitive process, with a nevertheless robust output. Past research has shown many vulval mutants affecting EGF-Ras-MAPK, Delta-Notch and Wnt pathways to be suppressed by environmental factors, such as starvation. Here we aimed to resolve previous, seemingly contradictory, observations on how starvation modulates levels of vulval induction. Using the strong starvation suppression of the Vulvaless phenotype of lin-3/egf reduction-of-function mutations as an experimental paradigm, we first tested for a possible involvement of the sensory system in relaying starvation signals to affect vulval induction: mutation of various sensory inputs, DAF-2/Insulin or DAF-7/TGF-β signaling did not abolish lin-3(rf) starvation suppression. In contrast, nutrient deprivation induced by mutation of the intestinal peptide transporter gene pept-1 or the TOR pathway component rsks-1 (the ortholog of mammalian P70S6K) very strongly suppressed lin-3(rf) mutant phenotypes. Therefore, physiologically starved animals induced by these mutations tightly recapitulated the effects of external starvation on vulval induction. While both starvation and pept-1 RNAi were sufficient to increase Ras and Notch pathway activities in vulval cells, the highly penetrant Vulvaless phenotype of a tissue-specific null allele of lin-3 was not suppressed by either condition. This and additional results indicate that partial lin-3 expression is required for starvation to affect vulval induction. These results suggest a cross-talk between nutrient deprivation, TOR-S6K and EGF-Ras-MAPK signaling during C. elegans vulval induction.

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Disruption of INOS, a Gene Encoding myo-Inositol Phosphate Synthase, Causes Male Sterility in Drosophila melanogaster

Inositol is a precursor for the phospholipid membrane component phosphatidylinositol (PI), involved in signal transduction pathways, endoplasmic reticulum stress, and osmoregulation. Alterations of inositol metabolism have been implicated in human reproductive issues, the therapeutic effects of drugs used to treat epilepsy and bipolar disorder, spinal cord defects, and diseases including diabetes and Alzheimer's. The sole known inositol synthetic enzyme is myo-inositol synthase (MIPS), and the homolog in Drosophilia melanogaster is encoded by the Inos gene. Three identical deletion strains (inos^DF/CyO) were constructed, confirmed by PCR and sequencing, and homozygotes (inos^DF/inos^DF) were shown to lack the transcript encoding the MIPS enzyme. Without inositol, homozygous inos^DF deletion fertilized eggs develop only to the first-instar larval stage. When transferred as pupae to food without inositol, however, inos^DF homozygotes die significantly sooner than wild-type flies. Even with dietary inositol the homozygous inos^DF males are sterile. An inos allele, with a P-element inserted into the first intron, fails to complement this male sterile phenotype. An additional copy of the Inos gene inserted into another chromosome rescues all the phenotypes. These genetic and phenotypic analyses establish D. melanogaster as an excellent model organism in which to examine the role of inositol synthesis in development and reproduction.

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The Sleep Inbred Panel, a Collection of Inbred Drosophila melanogaster with Extreme Long and Short Sleep Duration

Understanding how genomic variation causes differences in observable phenotypes remains a major challenge in biology. It is difficult to trace the sequence of events originating from genomic variants to changes in transcriptional responses or protein modifications. Ideally, one would conduct experiments with individuals that are at either extreme of the trait of interest, but such resources are often not available. Further, advances in genome editing will enable testing of candidate polymorphisms individually and in combination. Here we have created a resource for the study of sleep with 39 inbred lines of Drosophila—the Sleep Inbred Panel (SIP). SIP lines have stable long- and short-sleeping phenotypes developed from naturally occurring polymorphisms. These lines are fully sequenced, enabling more accurate targeting for genome editing and transgenic constructs. This panel facilitates the study of intermediate transcriptional and proteomic correlates of sleep, and supports genome editing studies to verify polymorphisms associated with sleep duration.

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Event Analysis: Using Transcript Events To Improve Estimates of Abundance in RNA-seq Data

Alternative splicing leverages genomic content by allowing the synthesis of multiple transcripts and, by implication, protein isoforms, from a single gene. However, estimating the abundance of transcripts produced in a given tissue from short sequencing reads is difficult and can result in both the construction of transcripts that do not exist, and the failure to identify true transcripts. An alternative approach is to catalog the events that make up isoforms (splice junctions and exons). We present here the Event Analysis (EA) approach, where we project transcripts onto the genome and identify overlapping/unique regions and junctions. In addition, all possible logical junctions are assembled into a catalog. Transcripts are filtered before quantitation based on simple measures: the proportion of the events detected, and the coverage. We find that mapping to a junction catalog is more efficient at detecting novel junctions than mapping in a splice aware manner. We identify 99.8% of true transcripts while iReckon identifies 82% of the true transcripts and creates more transcripts not included in the simulation than were initially used in the simulation. Using PacBio Iso-seq data from a mouse neural progenitor cell model, EA detects 60% of the novel junctions that are combinations of existing exons while only 43% are detected by STAR. EA further detects ~5,000 annotated junctions missed by STAR. Filtering transcripts based on the proportion of the transcript detected and the number of reads on average supporting that transcript captures 95% of the PacBio transcriptome. Filtering the reference transcriptome before quantitation, results in is a more stable estimate of isoform abundance, with improved correlation between replicates. This was particularly evident when EA is applied to an RNA-seq study of type 1 diabetes (T1D), where the coefficient of variation among subjects (n = 81) in the transcript abundance estimates was substantially reduced compared to the estimation using the full reference. EA focuses on individual transcriptional events. These events can be quantitate and analyzed directly or used to identify the probable set of expressed transcripts. Simple rules based on detected events and coverage used in filtering result in a dramatic improvement in isoform estimation without the use of ancillary data (e.g., ChIP, long reads) that may not be available for many studies.

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Maternal Proteins That Are Phosphoregulated upon Egg Activation Include Crucial Factors for Oogenesis, Egg Activation and Embryogenesis in Drosophila melanogaster

Egg activation is essential for the successful transition from a mature oocyte to a developmentally competent egg. It consists of a series of events including the resumption and completion of meiosis, initiation of translation of some maternal mRNAs and destruction of others, and changes to the vitelline envelope. This major change of cell state is accompanied by large scale alteration in the oocyte's phosphoproteome. We hypothesize that the cohort of proteins that are subject to phosphoregulation during egg activation are functionally important for processes before, during, or soon after this transition, potentially uniquely or as proteins carrying out essential cellular functions like those they do in other (somatic) cells. In this study, we used germline-specific RNAi to examine the function of 189 maternal proteins that are phosphoregulated during egg activation in Drosophila melanogaster. We identified 53 genes whose knockdown reduced or abolished egg production and caused a range of defects in ovarian morphology, as well as 51 genes whose knockdown led to significant impairment or abolishment of the egg hatchability. We observed different stages of developmental arrest in the embryos and various defects in spindle morphology and aberrant centrosome activities in the early arrested embryos. Our results, validated by the detection of multiple genes with previously-documented maternal effect phenotypes among the proteins we tested, revealed 15 genes with newly discovered roles in egg activation and early embryogenesis in Drosophila. Given that protein phosphoregulation is a conserved characteristic of this developmental transition, we suggest that the phosphoregulated proteins may provide a rich pool of candidates for the identification of important players in the egg-to-embryo transition.

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Acute Effects of Drugs on Caenorhabditis elegans Movement Reveal Complex Responses and Plasticity

Many drugs act very rapidly — they can turn on or off their targets within minutes in a whole animal. What are the acute effects of drug treatment and how does an animal respond to these? We developed a simple assay to measure the acute effects of drugs on C. elegans movement and examined the effects of a range of compounds including neuroactive drugs, toxins, environmental stresses and novel compounds on worm movement over a time period of 3 hr. We found a wide variety of acute responses. Many compounds cause rapid paralysis which may be permanent or followed by one or more recovery phases. The recoveries are not the result of some generic stress response but are specific to the drug e.g., recovery from paralysis due to a neuroactive drug requires neurotransmitter pathways whereas recovery from a metabolic inhibitor requires metabolic changes. Finally, we also find that acute responses can vary greatly across development and that there is extensive natural variation in acute responses. In summary, acute responses are sensitive probes of the ability of biological networks to respond to drug treatment and these responses can reveal the action of unexplored pathways.

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BGGE: A New Package for Genomic-Enabled Prediction Incorporating Genotype x Environment Interaction Models

One of the major issues in plant breeding is the occurrence of genotype x environment (GE) interaction. Several models have been created to understand this phenomenon and explore it. In the genomic era, several models were employed to improve selection by using markers and account for GE interaction simultaneously. Some of these models use special genetic covariance matrices. In addition, the scale of multi-environment trials is getting larger, and this increases the computational challenges. In this context, we propose an R package that, in general, allows building GE genomic covariance matrices and fitting linear mixed models, in particular, to a few genomic GE models. Here we propose two functions: one to prepare the genomic kernels accounting for the genomic GE and another to perform genomic prediction using a Bayesian linear mixed model. A specific treatment is given for sparse covariance matrices, in particular, to block diagonal matrices that are present in some GE models in order to decrease the computational demand. In empirical comparisons with Bayesian Genomic Linear Regression (BGLR), accuracies and the mean squared error were similar; however, the computational time was up to five times lower than when using the classic approach. Bayesian Genomic Genotype x Environment Interaction (BGGE) is a fast, efficient option for creating genomic GE kernels and making genomic predictions.

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Complex Haplotypes of GSTM1 Gene Deletions Harbor Signatures of a Selective Sweep in East Asian Populations

The deletion of the metabolizing Glutathione S-transferase Mu 1 (GSTM1) gene has been associated with multiple cancers, metabolic and autoimmune disorders, as well as drug response. It is unusually common, with allele frequency reaching up to 75% in some human populations. Such high allele frequency of a derived allele with apparent impact on an otherwise conserved gene is a rare phenomenon. To investigate the evolutionary history of this locus, we analyzed 310 genomes using population genetics tools. Our analysis revealed a surprising lack of linkage disequilibrium between the deletion and the flanking single nucleotide variants in this locus. Tests that measure extended homozygosity and rapid change in allele frequency revealed signatures of an incomplete sweep in the locus. Using empirical approaches, we identified the Tanuki haplogroup, which carries the GSTM1 deletion and is found in approximately 70% of East Asian chromosomes. This haplogroup has rapidly increased in frequency in East Asian populations, contributing to a high population differentiation among continental human groups. We showed that extended homozygosity and population differentiation for this haplogroup is incompatible with simulated neutral expectations in East Asian populations. In parallel, we found that the Tanuki haplogroup is significantly associated with the expression levels of other GSTM genes. Collectively, our results suggest that standing variation in this locus has likely undergone an incomplete sweep in East Asia with regulatory impact on multiple GSTM genes. Our study provides the necessary framework for further studies to elucidate the evolutionary reasons that maintain disease-susceptibility variants in the GSTM1 locus.

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GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data

Intermediate phenotypes such as gene expression values can be used to elucidate the mechanisms by which genetic variation causes phenotypic variation, but jointly analyzing such heterogeneous data are far from trivial. Here we extend a so-called mediation model to handle the confounding effects of genetic background, and use it to analyze flowering time variation in Arabidopsis thaliana, focusing in particular on the central role played by the key regulator FLOWERING TIME LOCUS C (FLC). FLC polymorphism and FLC expression are both strongly correlated with flowering time variation, but the effect of the former is only partly mediated through the latter. Furthermore, the latter also reflects genetic background effects. We demonstrate that it is possible to partition these effects, shedding light on the complex regulatory network that underlies flowering time variation.

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Whole Genome Sequencing, de Novo Assembly and Phenotypic Profiling for the New Budding Yeast Species Saccharomyces jurei

Saccharomyces sensu stricto complex consist of yeast species, which are not only important in the fermentation industry but are also model systems for genomic and ecological analysis. Here, we present the complete genome assemblies of Saccharomyces jurei, a newly discovered Saccharomyces sensu stricto species from high altitude oaks. Phylogenetic and phenotypic analysis revealed that S. jurei is more closely related to S. mikatae, than S. cerevisiae, and S. paradoxus. The karyotype of S. jurei presents two reciprocal chromosomal translocations between chromosome VI/VII and I/XIII when compared to the S. cerevisiae genome. Interestingly, while the rearrangement I/XIII is unique to S. jurei, the other is in common with S. mikatae strain IFO1815, suggesting shared evolutionary history of this species after the split between S. cerevisiae and S. mikatae. The number of Ty elements differed in the new species, with a higher number of Ty elements present in S. jurei than in S. cerevisiae. Phenotypically, the S. jurei strain NCYC 3962 has relatively higher fitness than the other strain NCYC 3947^T under most of the environmental stress conditions tested and showed remarkably increased fitness in higher concentration of acetic acid compared to the other sensu stricto species. Both strains were found to be better adapted to lower temperatures compared to S. cerevisiae.

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mTOR Complex 1 Implicated in Aphid/Buchnera Host/Symbiont Integration

Obligate nutritional endosymbioses are arguably the most intimate of all interspecific associations. While many insect nutritional endosymbioses are well studied, a full picture of how two disparate organisms, a bacterial endosymbiont and a eukaryotic host, are integrated is still lacking. The mTOR pathway is known to integrate nutritional conditions with cell growth and survival in eukaryotes. Characterization and localization of amino acid transporters in aphids suggest the mTOR pathway as a point of integration between an aphid host and its amino acid-provisioning endosymbiont Buchnera aphidicola. The mTOR pathway is unannotated in aphids and unstudied in any nutritional endosymbiosis. We annotated mTOR pathway genes in two aphid species, Acyrthosiphon pisum and Myzus persicae, using both BLASTp searches and Hidden Markov Models. Using previously collected RNAseq data we constructed new reference transcriptomes for bacteriocyte, gut, and whole insect tissue for three lines of M. persicae. Annotation of the mTOR pathway identified homologs of all known invertebrate mTOR genes in both aphid species with some duplications. Differential expression analysis showed that genes specific to the amino acid-sensitive mTOR Complex 1 were more highly expressed in bacteriocytes than genes specific to the amino acid-insensitive mTOR Complex 2. Almost all mTOR genes involved in sensing amino acids showed higher expression in bacteriocytes than in whole insect tissue. When compared to gut, the putative glutamine/arginine sensing transporter ACYPI000333, an ortholog of SLC38A9, showed 6.5 times higher expression in bacteriocytes. Our results suggest that the mTOR pathway may be functionally important in mediating integration of Buchnera into aphid growth and reproduction.

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CORL Expression and Function in Insulin Producing Neurons Reversibly Influences Adult Longevity in Drosophila

CORL proteins (known as SKOR in mice, Fussel in humans and fussel in Flybase) are a family of CNS specific proteins related to Sno/Ski oncogenes. Their developmental and adult roles are largely unknown. A Drosophila CORL (dCORL) reporter gene is expressed in all Drosophila insulin-like peptide 2 (dILP2) neurons of the pars intercerebralis (PI) of the larval and adult brain. The transcription factor Drifter is also expressed in the PI in a subset of dCORL and dILP2 expressing neurons and in several non-dILP2 neurons. dCORL mutant virgin adult brains are missing all dILP2 neurons that do not also express Drifter. This phenotype is also seen when expressing dCORL-RNAi in neurosecretory cells of the PI. dCORL mutant virgin adults of both sexes have a significantly shorter lifespan than their parental strain. This longevity defect is completely reversed by mating (lifespan increases over 50% for males and females). Analyses of dCORL mutant mated adult brains revealed a complete rescue of dILP2 neurons without Drifter. Taken together, the data suggest that dCORL participates in a neural network connecting the insulin signaling pathway, longevity and mating. The conserved sequence and CNS specificity of all CORL proteins imply that this network may be operating in mammals.

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Editorial Board

Publication date: October 2018

Source: Journal of Human Evolution, Volume 123

Author(s):

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Genetic variants in components of the NALCN–UNC80–UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies)

Abstract

NALCN is a conserved cation channel, which conducts a permanent sodium leak current and regulates resting membrane potential and neuronal excitability. It is part of a large ion channel complex, the "NALCN channelosome", consisting of multiple proteins including UNC80 and UNC79. The predominant neuronal expression pattern and its function suggest an important role in neuronal function and disease. So far, biallelic NALCN and UNC80 variants have been described in a small number of individuals leading to infantile hypotonia, psychomotor retardation, and characteristic facies 1 (IHPRF1, OMIM 615419) and 2 (IHPRF2, OMIM 616801), respectively. Heterozygous de novo NALCN missense variants in the S5/S6 pore-forming segments lead to congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD, OMIM 616266) with some clinical overlap. In this study, we present detailed clinical information of 16 novel individuals with biallelic NALCN variants, 1 individual with a heterozygous de novo NALCN missense variant and an interesting clinical phenotype without contractures, and 12 individuals with biallelic UNC80 variants. We report for the first time a missense NALCN variant located in the predicted S6 pore-forming unit inherited in an autosomal-recessive manner leading to mild IHPRF1. We show evidence of clinical variability, especially among IHPRF1-affected individuals, and discuss differences between the IHPRF1- and IHPRF2 phenotypes. In summary, we provide a comprehensive overview of IHPRF1 and IHPRF2 phenotypes based on the largest cohort of individuals reported so far and provide additional insights into the clinical phenotypes of these neurodevelopmental diseases to help improve counseling of affected families.

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Rare coding variant analysis in a large cohort of Ashkenazi Jewish families with inflammatory bowel disease

Abstract

Rare variants are thought to contribute to the genetics of inflammatory bowel disease (IBD), which is more common amongst the Ashkenazi Jewish (AJ) population. A family-based approach using exome sequencing of AJ individuals with IBD was employed with a view to identify novel rare genetic variants for this disease. Exome sequencing was performed on 960 Jewish individuals including 513 from 199 multiplex families with up to eight cases. Rare, damaging variants in loci prioritized by linkage analysis and those shared by multiple affected individuals within the same family were identified. Independent evidence of association of each variant with disease was assessed. A number of candidate variants were identified, including in genes involved in the immune system. The ability to achieve statistical significance in independent case/control replication data was limited by power and was only achieved for variants in the well-established Crohn's disease gene, NOD2. This work demonstrates the challenges of identifying disease-associated rare damaging variants from exome data, even amongst a favorable cohort of familial cases from a genetic isolate. Further research of the prioritized rare candidate variants is required to confirm their association with the disease.

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Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability

Abstract

Identification of Mendelian genes for neurodevelopmental disorders using exome sequencing to study autosomal recessive (AR) consanguineous pedigrees has been highly successful. To identify causal variants for syndromic and non-syndromic intellectual disability (ID), exome sequencing was performed using DNA samples from 22 consanguineous Pakistani families with ARID, of which 21 have additional phenotypes including microcephaly. To aid in variant identification, homozygosity mapping and linkage analysis were performed. DNA samples from affected family member(s) from every pedigree underwent exome sequencing. Identified rare damaging exome variants were tested for co-segregation with ID using Sanger sequencing. For seven ARID families, variants were identified in genes not previously associated with ID, including: EI24, FXR1 and TET3 for which knockout mouse models have brain defects; and CACNG7 and TRAPPC10 where cell studies suggest roles in important neural pathways. For two families, the novel ARID genes CARNMT1 and GARNL3 lie within previously reported ID microdeletion regions. We also observed homozygous variants in two ID candidate genes, GRAMD1B and TBRG1, for which each has been previously reported in a single family. An additional 14 families have homozygous variants in established ID genes, of which 11 variants are novel. All ARID genes have increased expression in specific structures of the developing and adult human brain and 91% of the genes are differentially expressed in utero or during early childhood. The identification of novel ARID candidate genes and variants adds to the knowledge base that is required to further understand human brain function and development.

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Rapid method for determination of 90Sr in biological samples by liquid scintillation counting after separation on synthesized column

Publication date: October 2018

Source: Journal of Environmental Radioactivity, Volumes 193–194

Author(s): Xiangyin Kong, Lei Dang, Xianzhang Shao, Liangliang Yin, Yanqin Ji

Abstract

A simple, rapid and cost-efficient method for determination of activity concentration of ⁹⁰Sr in biological samples with an extraction chromatographic column (crown ether on teflon powder) and following counted by liquid scintillation counting was developed in this paper. The column retained most of ⁹⁰Sr while almost all of matrix ions were removed during rinsing steps with 8M nitric acid and finally ⁹⁰Sr was eluted with deionized water, the chemical recovery of strontium is greater than 60%, almost all of matrix ions were removed by the procedure we reported. Finally the uncertainty was evaluated and minimum detectable activity of this method is 1.28Bq/kg.

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A Systematic Review of Mobile Health Applications in Rehabilitation

Publication date: Available online 29 August 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Ryan Nussbaum, Christopher Kelly, Eleanor Quinby, Ami Mac, Bambang Parmanto, Brad E. Dicianno

Abstract

Objective

To conduct systematic review to better define how medical mobile applications (apps) have been utilized in environments relevant to Physical Medicine and Rehabilitation.

Data Sources

PUBMED, IEEE, ACM Digital Library, SCOPUS, INSPEC, and EMBASE

Study Selection

A 10-year date limit was utilized, spanning publication dates from June 1, 2006 to June 30, 2016. Terms related to Physical Medicine and Rehabilitation as well as mobile apps were used in ten individual search strategies.

Data Extraction

Two investigators screened abstracts and applied inclusion and exclusion criteria. Full-length articles were retrieved. Duplicate articles were removed. If a study met all criteria, the manuscript was reviewed in full.

Data Synthesis

Specific variables of interest were extracted and added to summary tables. Summary tables were used to categorize studies according themes, and a list of app features was generated.

Conclusions

The search yielded abstracts from 8,116 studies, and 102 studies were included in the systematic review. Approximately one-third of the studies evaluated apps as interventions while the remaining two-third of the studies assessed functioning of the app or participant interaction with the app. Some apps may have positive benefits when used to deliver exercise or gait training interventions, as self-management systems, or as measurement tools.

Registration

The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) network (no. CRD42016046672).

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Relationships between Specific Functional Abilities and Health-Related Quality of Life in Chronic Traumatic Spinal Cord Injury

Objective The objective of this study is to explore the relationships between specific functional abilities assessed from the 3rd version of the Spinal Cord Injury Measure (SCIM), and health-related quality of life (HRQoL) following a traumatic spinal cord injury (tSCI). Design A prospective cohort of 195 patients that had sustained a tSCI from C1 to L1, and consecutively admitted to a single Level 1 SCI-specialized trauma center between April 2010 and September 2016 was studied. Correlation coefficients were calculated between SCIM scores and SF-36v2 summary scores (Physical component score, PCS; Mental component score, MCS). Results The total SCIM score correlated moderately with the PCS in the entire cohort, correlated strongly with PCS in tetraplegics, did not correlate with PCS in paraplegics, and did not correlate with MCS. Mobility subgroup and individual items scores showed the strongest correlations with the PCS in the entire cohort, followed by self-care and sphincter management. Conclusion This work is significant being the first to determine which specific functional abilities are mostly related to HRQoL, and highlights the differences between tetraplegic and paraplegic patients. Our findings could help clinicians to guide rehabilitation plan based on importance of specific functional abilities in relationship with the HRQoL. Funding sources: Fonds de recherche du Québec – Santé / Rick Hansen Spinal Cord Injury Registry Program / USAMRMC, USA Medical Research and Material Command, Dep. of Defense, Grant # GRANT11235843 Corresponding author: Jean-Marc Mac-Thiong, MD, PhD, Hôpital du Sacré-Coeur de Montréal, Department of Surgery, 5400 Boulevard Gouin Ouest, Montreal, Québec, Canada H4J 1C5 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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DeLisa Lecture. Evidence in Rehabilitation Medicine: between facts and prejudices

The relationship between evidence based medicine (EBM) and rehabilitation medicine (RM) is somewhat controversial. The motto "there is no evidence in RM" is at times a real burden on the shoulders of RM. There are a lot of ideas around EBM in RM: some are correct, while others are probably prejudices only. In this paper it is first discussed what EBM is, its origin and meaning, giving some notes about Cochrane – arguably, the gold standard of EBM. The relationship between RM and EBM is then faced, to try to understand why these difficulties exist: it is considered what RM is, comparing RM to the other "classical" medical specialties; the problems with evidence generation and the actual state of research in RM. The implementation of EBM in RM is also introduced, including a brief discussion of knowledge translation, what it is and why it is important, paying particular attention to Cochrane Rehabilitation – the new global RM body that is facing these issues. Finally some solutions for EBM in RM are proposed. Correspondence: Stefano Negrini, Largo Paolo VI, +390307245282, rbettinsoli@dongnocchi.it Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Validation of Simple Methods to Select a Suitable Nostril for Nasotracheal Intubation.

Related Articles

Validation of Simple Methods to Select a Suitable Nostril for Nasotracheal Intubation.

Anesthesiol Res Pract. 2018;2018:4910653

Authors: Thongrong C, Thaisiam P, Kasemsiri P

Abstract
Background: Nasotracheal intubation is a blind procedure that may lead to complications; therefore, several tests were introduced to assess a suitable nostril for nasotracheal intubation. However, the value of simple tests in clinical practice was insufficient to evaluate.
Method: A diagnostic prospective study was conducted in 42 patients, ASA classes I-III, undergoing surgery requiring nasotracheal intubation for general anesthesia. Two simple methods for assessing the patency of nostrils were investigated. Firstly, the occlusion test was evaluated by asking for the patient's own assessment of nasal airflow during occlusion of each contralateral nostril while in a sitting posture. Secondly, patients breathed onto a spatula held 1 cm below the nostrils while in a sitting posture. All patients were assessed using these two simple tests. Nasal endoscopic examination of each patient was used as a gold standard.
Results: The diagnostic value of the occlusion test (sensitivity of 91.7%, specificity of 61.1%, PPV of 75.9%, NPV of 84.6%, LR+ of 2.36, and LR- of 0.14) seemed better than that of the spatula test (sensitivity of 95.8%, specificity of 25.0%, PPV of 63.0%, NPV of 81.8%, LR+ of 1.28, and LR- of 0.17). When both tests were combined in series, the diagnostic value increased (sensitivity of 87.9%, specificity of 70.8%, PPV of 80.1%, NPV of 81.4%, LR+ of 3.01, and LR- of 0.17).
Conclusion and Recommendations: The simple occlusion test is more useful than the spatula test. However, combining the results from both tests in series helped to improve the diagnostic value for selecting a suitable nostril for nasotracheal intubation.

PMID: 30154839 [PubMed]

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Comment on: “Exercise Prescription in Patients With Different Combinations of Cardiovascular Disease Risk Factors: A Consensus Statement From the EXPERT Working Group”

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Coffee and wine consumption is associated with reduced mortality from alcoholic liver disease: Follow-up of 219 279 Norwegian men and women aged 30-67 years

Annals of Epidemiology

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Beneficial Intervertebral Disc and Muscle Adaptations

PURPOSE Cycling is widely practiced as a mode of transportation, a leisurely pursuit and a competitive sport. Approximately half of cyclists experience low back pain. Yet, there has been limited study of spine tissue adaptations due to cycling. METHODS To investigate potential risk factors for spinal pain, we compared 18 high-volume cyclists (>150 km per week for ≥5 years) to 18 height-matched non-sporting referents. Participants had no history of spinal pathology. Magnetic resonance imaging was used to quantify intervertebral disc (IVD) morphology and hydration; and psoas, erector spinae, quadratus lumborum and multifidus muscle size and fat content. Endurance of trunk muscles (flexors and extensors) were measured and physical activity levels assessed objectively using accelerometry. RESULTS Cyclists IVD showed prolonged T2-time (+10.0(17.3)%; p=0.021), implying better IVD hydration and glycosaminoglycan content, compared to referents. Lower thoracic and upper lumbar IVD T2 time were longer in cyclists (p≤0.029) but not at the lower lumbar spine. T2-time differences were larger in the nucleus pulposus compared to the annulus fibrosus. Cyclists showed larger psoas muscles with less fat content compared to referents. Cyclists also exhibited longer isometric trunk endurance times (p≤0.036) and higher physical activity levels (osteogenic index, p=0.038). CONCLUSION Despite previous studies reporting higher than average prevalence of back pain in cyclists, the high-volume road cyclists in our cohort showed no anatomical or functional deficiency in spinal structures. In contrast, we found evidence for beneficial adaptations to the intervertebral discs and psoas muscles in high-volume cyclists compared to referents. These data support the notion that cycling is not detrimental to the spine; rather, in contrast, may be associated with beneficial changes at the spine. Corresponding Author: Daniel L. Belavy BPhty, PhD; Deakin University, Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Geelong, Victoria, Australia. Tel: +61 3 9244 6606; E-mail: d.belavy@deakin.edu.au, belavy@gmail.com. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and statement that results of the present study do not constitute endorsement by ACSM. DLB, MQ, NDR, YL, DC, GT and TR declare no competing interests. This project was supported by the School of Exercise and Nutrition Sciences, Deakin University (Grant ID: Belavy 2014-2017). © 2018 American College of Sports Medicine

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O2 Pulse Patterns in Male Master Athletes with Normal and Abnormal Exercise Tests

Purpose The clinical relevance of abnormal exercise testing (ET) results (at least 0.1 mV ST-segment depression measured during exercise or recovery in three consecutive beats) in athletes without obstructive coronary artery disease (CAD) is not well understood. It is unknown whether this phenomenon reflects a physiological adaptation to sport or a truly ischemic response and a concomitant attenuated stroke volume (SV) response. The aim of this study was to investigate if athletes with abnormal ET results without obstructive CAD showed signs of an attenuated SV response using cardiopulmonary exercise testing (CPET) parameters. Methods 78 male master athletes with abnormal ET results without obstructive CAD underwent CPET. [INCREMENT]O2 pulse/[INCREMENT]Work rate (WR), [INCREMENT]VO2/[INCREMENT]WR and [INCREMENT]Heart rate (HR)/[INCREMENT]WR were assessed and compared with data from 78 male master athletes with normal ET results, matched for age, sports characteristics and exercise capacity. Results The [INCREMENT]O2 pulse/[INCREMENT]WR ratio beyond AT in athletes with abnormal ET results was lower than in athletes with normal ET results (0.73 ± 0.41 versus 1.12 ± 0.54 respectively, p

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Brain-derived Neurotrophic Factor Pathway after Downhill and Uphill Training in Rats

Introduction Elevation of brain-derived neurotrophic factor (BDNF) levels in the brain and subsequent phosphorylation of its cognate tropomyosin-related kinase B (TrkB) receptors at tyrosine 816 (pTrkBtyr816) are largely involved in the positive effect of aerobic exercise on brain functioning. While BDNF levels were reported to increase in proportion with exercise intensity, the effect of the type of contraction is unknown. Therefore, the cerebral BDNF/TrkB pathway was investigated after uphill and downhill treadmill activities at equivalent intensity to preferentially induce eccentric and concentric contractions, respectively. Methods A treadmill activity (30 min/day for 7 consecutive days) either in a horizontal position at two different speeds to modulate intensity (experiment 1) or at three different inclinations (null, -10%, +5%) but at equivalent intensity to modulate the type of contraction (experiment 2) was induced in rats. Both experiments included sedentary rats. Levels of BDNF, pTrkBtyr816, synaptophysin (marker of synaptogenesis), endothelial nitric oxide synthase phosphorylated at serine 1177 (peNOSser1177) and c-fos levels (indicators of elevation in blood flow in the cerebrovasculature and neuronal activity, respectively) were measured in motor- and cognition-related brain regions using western blotting analysis. Results Experiment 1 indicated that treadmill activity induces an intensity-dependent increase in peNOSser1177, c-fos and BDNF levels. Experiment 2 showed that intensity of exercise as well as activation of the cerebral BDNF pathway and synaptogenesis did not differ among horizontal, uphill and downhill treadmill activities. Conclusion The cerebral response of the BDNF pathway to a treadmill activity is dependent on exercise intensity, but not on the type of contraction (eccentric vs concentric). Corresponding author: Martin PEDARD, INSERM U1093, UFR des Sciences de Santé, 7 boulevard Jeanne d'Arc, 21000 DIJON, FRANCE. Tel: (33) 3 80 39 32 25, E-mail address: martinpedard@gmail.com The authors thank Suzanne Rankin for English revision. Authors declare that the results are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation and state that results of the present study do not constitute endorsement by ACSM. Conflict of interest and source of funding: There is no conflict of interest with regard to the work that was supported by funding from the University of Bourgogne and Franche Comté and INSERM. Submitted for publication May 2018. Accepted for publication August 2018. © 2018 American College of Sports Medicine

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Mediating Effect of Muscle on the Relationship of Physical Activity and Bone

Purpose This study analyzed prospective associations between distinct trajectories of objectively measured physical activity (PA) and late adolescent bone parameters and explored the mediating effects of lean soft tissue (LST), a surrogate of muscle mass to associations. Methods PA was measured by accelerometry starting at age 5 and continuing at 8, 11, 13, 15 and 17 years in approximately 524 participants from the Iowa Bone Development Study. Gender-specific group-based trajectory modeling was used to construct developmental trajectories of moderate-and-vigorous intensity PA (MVPA) from childhood to late adolescence. At age 17, proximal femur bone mineral density (aBMD) was assessed by dual X-ray energy absorptiometry, and its distribution was calculated by aBMD ratios. Specific geometric measures of the proximal femur were assessed using Hip Structural Analysis. Results A significant portion of the total effect of MVPA from age 5 to 17 yr on bone parameters at age 17 was explained by an increase in leg LST in both sexes. For males and females, indirect effects were observed on the total and all regional proximal femur aBMDs, and on the ratio between the inferomedial and superolateral neck aBMD. The effect on the ratio between the trochanter and the total proximal femur was specific to females, while the effect on the hip axis length was specific to males. Direct effects of MVPA on aBMDs were identified only in males. Conclusions Using robust mediation analysis, this is the first study addressing the indirect effect (through muscle) of PA across childhood and adolescence on proximal femur bone parameters. To improve bone health at the proximal femur, the results suggest PA interventions during growth that increase muscle mass, particularly in females. Corresponding author: Vera Zymbal, Postal address: Department of Sports and Health, Faculdade de Motricidade Humana, Universidade de Lisboa, Estrada da Costa, 1499-002 - Cruz Quebrada, Lisbon, Portugal, E-mail: verazymbal@fmh.ulisboa.pt, Telephone: +351 96192383 This work was supported by the Portuguese Science and Technology Foundation (FCT) (SFRH/BD/79828/2011 and PTDC/DES/115607/2009). It is also supported by the National Institute of Dental and Craniofacial Research grants R01-DE12101, R01-DE09551, and P30-DE10126, and the General Clinical Research Centers Program from the National Center for Research Resources, M01-RR00059 and UL1-RR024979. No potential conflict of interest was reported by the authors. The authors have no conflicts of interest to disclose in relation to this study. The results of the present study do not constitute endorsement by American College of Sports Medicine. The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Submitted for publication November 2017. Accepted for publication August 2018. © 2018 American College of Sports Medicine

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Differences in Hip and Knee Landing Moments across Female Pubertal Development

Purpose The higher prevalence of knee injuries amongst adolescent females may be related to female pubertal development. The aim of this study was to determine whether girls exhibit higher tri-planar knee and hip moments with more advanced pubertal development during a single limb landing. Methods Lower limb biomechanics of 93 females grouped according to pre-pubertal (n=31), early/mid-pubertal (n=31) and late/post-pubertal (n=31) development performed a single-limb drop lateral jump. Peak tri-planar knee moments and hip moments at the time of peak knee moments were derived from a Vicon motion analysis system and concealed force plate. Joint moments were normalized to body mass (Nm/kg), height (Nm/kg/m) and body mass by height (Nm/kg/m). Between-group differences were analysed using a one-way ANOVA with Pearson correlations used to explore relationships between joint moments and anthropometrics. Results Girls at latter stages of puberty landed with higher tri-planar knee moments and hip flexion moment at time of peak knee flexion moment when normalized separately to body mass and to height (p

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Does Exercise Alter Gut Microbial Composition?—A Systematic Review

Purpose The objective of this systematic review of literature was to evaluate and summarize published research that has investigated the association between exercise and gut microbial composition in mammals. Methods This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The databases searched for this review included: PubMed; PubMed Central; Medline; Cumulative Index of Nursing and Allied Health Literature; Web of Science; Commonwealth Agricultural Bureaux Direct; Health Source: Nursing Academic Edition; Clinicaltrials.gov; PROSPERO; and The Cochrane Library. Results Twenty-five articles met the inclusion criteria: 17 rodent, 1 canine, 2 equine, and 5 human studies. All studies in rodents and equines included control groups; whereas, only one study in humans included a control group. The remaining were cross-sectional or cohort studies. All studies in rodents controlled for dietary intake and one study in humans implemented a 3-d dietary control. Eleven studies assessed voluntary exercise and 13 studies utilized forced exercise. Diversification within the Firmicutes phylum was consistently observed in exercise groups across studies. There were no consistent trends within Bacteroidetes, Actinobacteria, or Proteobacteria phyla. In general, the potential interactions between exercise and diet composition and their respective influences on the intestinal microbiome were not well characterized. Conclusion Exercise was associated with changes in gut microbial composition, an increase in butyrate producing bacteria and an increase in fecal butyrate concentrations independent of diet in rodents and humans. The overall quality of evidence in the studies in humans was low and the risk of bias was unclear. Future studies with standardized reporting and rigorous dietary control in larger samples are needed to further determine the influence of exercise on gut microbial composition. CORRESPONDING AUTHOR: Kevin P. Davy, Virginia Tech, Department of Human Nutrition, Foods, and Exercise, 215 War Memorial Hall, Blacksburg, VA 24061, USA This project was internally supported by the department of Human Nutrition, Foods, and Exercise at Virginia Tech. CMM was supported in part by the Translational Obesity Research Interdisciplinary Graduate Education Program at Virginia Tech. The authors have no conflicts of interest to declare. The results of this study do not constitute an endorsement by ACSM. All results are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Submitted for publication April 2018. Accepted for publication August 2018. © 2018 American College of Sports Medicine

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Critical Velocity during Intermittent Running with Changes of Direction

Purpose We tested the hypothesis that critical velocity (CV) during intermittent running with changes of direction (Int/CoD) is reliably and accurately identified from a simple shuttle field test. We also tested the hypothesis that CV during Int/CoD running is not equivalent to continuous linear running. Methods Young adults performed a custom shuttle test of intermittent sprint running to reveal critical velocity. Sprints were 18.3 meters per direction, with rest between sprints of 15 seconds for 3 minutes, 10 seconds for 2 minutes and no rest for 2 minutes (7 minutes total). To test reliability, the CV shuttle test (CVST) was performed twice. To test validity, blood lactate was assessed during two separate trials inclusive of 5% above or below CVST end velocity. To explore task specificity, CV during CVST was compared to CV obtained from 3 linear running time trials. Results Total distance and CSVT end test velocity were similar between visits (864 ± 21 m and 3.23 ± 0.13 m/s vs 900 ± 30m and 3.21 ± 0.15 m/s, respectively). At 5% above CVST end velocity, all subjects failed to complete 20 minutes and had unstable blood lactate values. A steady state blood lactate profile was observed during trials 5% below end velocity and all subjects completed the trial. The CV from the CVST was lower than the CV from linear running ([INCREMENT] -17 ± 6 %), highlighting the importance of test specificity for threshold determination. Conclusion The CVST provides a reliable and accurate determination of CV and can be used by coaches, athletes, and trainers to better understand the physiological impact specific to practice or competitions involving intermittent change of direction running. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and the results of the present study do not constitute endorsement by ACSM. Conflicts of Interest and Source of Funding: No conflicts of interest are declared. This project was supported by internal Nike, Inc funding mechanisms. © 2018 American College of Sports Medicine

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Walking Ground Reaction Force Post-ACL Reconstruction: Analysis of Time and Symptoms

Purpose The association between lower-extremity loading and clinically-relevant knee symptoms at different time points following anterior cruciate ligament reconstruction (ACLR) is unclear. Vertical ground reaction force (vGRF) from walking was compared between individuals with and without clinically-relevant knee symptoms in three cohorts: 24 months post-ACLR. Methods 128 individuals with unilateral ACLR were classified as symptomatic or asymptomatic, based on previously-defined cutoff values for the Knee Osteoarthritis and Injury Outcome Score (24 months post-ACLR [symptomatic n=13, asymptomatic n=33]). vGRF exerted on the ACLR limb was collected during walking gait, and functional analyses of variance were used to evaluate the effects of symptoms and time post-ACLR on vGRF throughout stance phase (α=0.05). Results Symptomatic individuals, 24 months post-ACLR, exhibited greater vGRF during both peaks, but lesser vGRF during midstance, compared to asymptomatic individuals. Conclusion Relative to asymptomatic individuals, symptomatic individuals are more likely to underload the ACLR limb early following ACLR (i.e., 24 months). We propose these differences in lower extremity loading during walking might have implications for long-term knee health, and should be considered when designing therapeutic interventions for individuals with an ACLR. Corresponding Author: Brian Pietrosimone PhD, Associate Professor, Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, 210 South Road Fetzer Hall, Chapel Hill, NC 27599, Phone: 919-962-3617, Email: brian@unc.edu The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. None of the authors involved with the current study have any competing interests related to the current project. The research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (1R03AR066840-01A1), the United States Army (MR140103), North Carolina Translational and Clinical Sciences (TraCS) Institute and National Athletic Trainers Association Research and Education Foundation (14NewInv001). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, TraCS Institute or the National Athletic Trainers Association Research and Education Foundation. © 2018 American College of Sports Medicine

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No Difference Between Spray Dried Milk and Native Whey Supplementation with Strength Training

Background A rapid digestibility and high leucine content are considered important for maximal stimulation of muscle protein synthesis. Consequently, with these properties, native whey may hold greater anabolic potential than milk, when supplemented in combination with strength training. Our aim was to compare the effects of supplementation with milk or native whey, during a 12-week strength training period, on gains in muscle mass and strength in young adults. Methods In this double-blinded, randomized, controlled study a total of 40 untrained young men and women received two daily servings of either milk or native whey containing 20 g of protein, during a 12-week strength training intervention. Muscle strength, lean mass, thigh muscle cross sectional area, m. vastus lateralis thickness and muscle fiber cross sectional area were assessed before and after the training period. In addition, the acute phosphorylation of the anabolic kinases p70S6K, 4E-BP1 and eEF-2 in response to a standardized workout and supplementation was investigated before and after the 12-week training period. Results Muscle mass and strength increased, by all measures applied (5-16%, P 0.25). p70S6K phosphorylation increased (~1000%, P 0.40). No correlation between these acute measures and changes in muscle mass or strength were observed. Conclusion Supplementation with milk or native whey during a 12-week strength training period did not differentially affect muscle mass and strength in young untrained individuals. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Correspondence to: Håvard Hamarsland, Department of Physical Performance, Norwegian School of Sport Sciences, P.O. Box 4014 Ullevål Stadion, 0806 Oslo, Norway, Tel: +47 93445916. Havard.hamarsland@gmail.com The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. Financial support: TINE SA funded the study. TINE SA was not involved in design of the study, data collection, analyses, interpretation of data or writing of the manuscript. Disclosures: The authors declare no conflict of interest. Submitted for publication April 2018. Accepted for publication August 2018. © 2018 American College of Sports Medicine

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