Effects of Food Bar Chewing Duration on the Physiologic, Metabolic, and Perceptual Responses to Moderate-Intensity Running

Purpose Chewing duration can affect food particle size, gastric processing, and postprandial glycemia, but these effects have not been investigated with exercise. This study examined how the chewing duration of a food bar impacts glycemic and metabolic responses, gastrointestinal (GI) symptoms, psychological affect, and performance during endurance running. Methods This randomized, unblinded, crossover study had 15 males (35.2 ± 7.4 years, VO2peak: 56.1 ± 5.2 ml/kg/min) attend three laboratory visits. Visit 1 required a VO2peak test, 10 min familiarization run at 60% VO2peak, and familiarization time-to-exhaustion (TTE) test (10 min at 90% VO2peak, followed by TTE at 100% VO2peak). Visits 2 and 3 consisted of a 60 min run at 60% VO2peak, followed by TTE testing. Participants were fed 45 g of a bar (180 kcal, 4 g fat, 33 g carbohydrate, 3 g protein, 1 g fiber) in 9 g servings 30 min before running, and 27 g of bar in 9 g servings at three timepoints during the 60 min run. Participants consumed the servings in 20 (20CHEW) or 40 (40CHEW) masticatory cycles, at 1 chew/second. Outcomes included blood glucose, substrate use, GI symptoms, perceived exertion (RPE), overall feeling, and TTE. Results Post-prandial blood glucose, GI symptoms, and RPE increased over time, but there were no significant between-condition or condition-by-time effects. TTE showed no significant between-condition effect (20CHEW: 288 ± 133 s; 40CHEW: 335 ± 299 s; p = 0.240). Overall feeling demonstrated a time-by-condition effect (p = 0.006), suggesting possible better maintenance over time with 40CHEW. Conclusion Cumulatively, the results suggest that extended chewing minimally impacts physiology, perceptions, and performance during 60 min moderate-intensity running

Blood pressure lowering with alcohol-mediated renal denervation using the Peregrine infusion Catheter is independent of injection site location

Objectives The current analysis utilized core laboratory angiographic data from a prospective, single-arm, open-label, multi-center feasibility study to ascertain whether the location of alcohol infusion within main renal arteries during renal denervation (RDN) had an impact on the BP-lowering effect at 6 months. Background The influence of the location of alcohol infusion during RDN, within the main renal artery (proximal, middle, or distal), on the magnitude of the blood pressure (BP) lowering is unstudied. Methods The Peregrine Catheter was used to perform alcohol-mediated RDN with an infusion of 0.6 mL of alcohol per artery as the neurolytic agent in 90 main arteries and four accessory arteries of 45 patients with hypertension. Results No relationship between the site of alcohol infusion and change from baseline in both office systolic and 24-hour systolic ambulatory BP (ABP) at 6 months was observed. When analyzed at the artery level, the least squares (LS) mean changes ± SEM from baseline to 6 months post-procedure in 24-hour systolic ABP when analyzed by renal arterial location were −11.9 ± 2.4 mmHg (distal), −10 ± 1.6 mmHg (middle), and −10.6 ± 1.3 mmHg (proximal) (all p < 0.0001 for change from baseline within groups). The results were similar for office systolic BP. There was no difference between treated locations (proximal is reference). Conclusion In this post-hoc analysis, the location of alcohol infusion within the main renal artery using the Peregrine system, with alcohol as the neurolytic agent for chemical RDN, did not affect the magnitude of BP changes at 6 months

Comparative Genomic Analysis of the Class \u3ci\u3eEpsilonproteobacteria\u3c/i\u3e and Proposed Reclassification to Epsilonbacteraeota (phyl. nov.)

The Epsilonproteobacteria is the fifth validly described class of the phylum Proteobacteria, known primarily for clinical relevance and for chemolithotrophy in various terrestrial and marine environments, including deep-sea hydrothermal vents. As 16S rRNA gene repositories have expanded and protein marker analysis become more common, the phylogenetic placement of this class has become less certain. A number of recent analyses of the bacterial tree of life using both 16S rRNA and concatenated marker gene analyses have failed to recover the Epsilonproteobacteria as monophyletic with all other classes of Proteobacteria. In order to address this issue, we investigated the phylogenetic placement of this class in the bacterial domain using 16S and 23S rRNA genes, as well as 120 single-copy marker proteins. Single- and concatenated-marker trees were created using a data set of 4,170 bacterial representatives, including 98 Epsilonproteobacteria. Phylogenies were inferred under a variety of tree building methods, with sequential jackknifing of outgroup phyla to ensure robustness of phylogenetic affiliations under differing combinations of bacterial genomes. Based on the assessment of nearly 300 phylogenetic tree topologies, we conclude that the continued inclusion of Epsilonproteobacteria within the Proteobacteria is not warranted, and that this group should be reassigned to a novel phylum for which we propose the name Epsilonbacteraeota (phyl. nov.). We further recommend the reclassification of the order Desulfurellales (Deltaproteobacteria) to a novel class within this phylum and a number of subordinate changes to ensure consistency with the genome-based phylogeny. Phylogenomic analysis of 658 genomes belonging to the newly proposed Epsilonbacteraeota suggests that the ancestor of this phylum was an autotrophic, motile, thermophilic chemolithotroph that likely assimilated nitrogen from ammonium taken up from the environment or generated from environmental nitrate and nitrite by employing a variety of functional redox modules. The emergence of chemoorganoheterotrophic lifestyles in several Epsilonbacteraeota families is the result of multiple independent losses of various ancestral chemolithoautotrophic pathways. Our proposed reclassification of this group resolves an important anomaly in bacterial systematics and ensures that the taxonomy of Proteobacteria remains robust, specifically as genome-based taxonomies become more common

Hyperactive gp130/STAT3-driven gastric tumourigenesis promotes submucosal tertiary lymphoid structure development

Tertiary lymphoid structures (TLSs) display phenotypic and functional characteristics of secondary lymphoid organs, and often develop in tissues affected by chronic inflammation, as well as in certain inflammation-associated cancers where they are prognostic of improved patient survival. However, the mechanisms that govern the development of tumour-associated TLSs remain ill-defined. Here, we observed tumour-associated TLSs in a preclinical mouse model (gp130F/F) of gastric cancer, where tumourigenesis is dependent on hyperactive STAT3 signalling through the common IL-6 family signalling receptor, gp130. Gastric tumourigenesis was associated with the development of B and T cell-rich submucosal lymphoid aggregates, containing CD21+ cellular networks and high endothelial venules. Temporally, TLS formation coincided with the development of gastric adenomas and induction of homeostatic chemokines including Cxcl13, Ccl19 and Ccl21. Reflecting the requirement of gp130-driven STAT3 signalling for gastric tumourigenesis, submucosal TLS development was also STAT3-dependent, but independent of the cytokine IL-17 which has been linked with lymphoid neogenesis in chronic inflammation and autoimmunity. Interestingly, upregulated lymphoid chemokine expression and TLS formation were also observed in a chronic gastritis model induced by Helicobacter felis infection. Tumour-associated TLSs were also observed in patients with intestinal-type gastric cancer, and a gene signature linked with TLS development in gp130F/F mice was associated with advanced clinical disease, but was not prognostic of patient survival. Collectively, our in vivo data reveal that hyperactive gp130-STAT3 signalling closely links gastric tumourigenesis with lymphoid neogenesis, and while a TLS gene signature was associated with advanced gastric cancer in patients, it did not indicate a favourable prognosis

Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial

Background Left atrial appendage (LAA) occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. Objective EWOLUTION was designed to provide data in routine practice from a prospective multicenter registry. Methods A total of 1025 patients scheduled for a WATCHMAN implant were prospectively and sequentially enrolled at 47 centers. Indication for LAA closure was based on European Society of Cardiology guidelines. Follow-up and transesophageal echocardiography (TEE) were performed per local practice. Results The baseline CHA 2 DS 2 -VASc score was 4.5 ± 1.6; the mean age was 73.4 ± 9 years; previous transient ischemic attack/ischemic stroke was present in 312 (30.5%), 155 (15.1%) had previous hemorrhagic stroke, and 320 (31.3%) had a history of major bleeding; and 750 (73%) were deemed unsuitable for oral anticoagulation therapy. WATCHMAN implant succeeded in 1005 (98.5%) of patients, without leaks >5 mm in 1002 (99.7%) with at least 1 TEE follow-up in 875 patients (87%). Antiplatelet therapy was used in 784 (83%), while vitamin K antagonists were used in only 75 (8%). At 1 year, mortality was 98 (9.8%), reflecting the advanced age and comorbidities in this population. Device thrombus was observed in 28 patients at routine TEE (3.7%) and was not correlated with the drug regimen ( P = .14). Ischemic stroke rate was 1.1% (relative risk 84% vs estimated historical data); the major bleeding rate was 2.6% and was predominantly (2.3%) nonprocedure/device related. Conclusion LAA closure with the WATCHMAN device has a high implant and sealing success. This method of stroke risk reduction appears to be safe and effective with an ischemic stroke rate as low as 1.1%, even though 73% of patients had a contraindication to and were not using oral anticoagulation

Intermediate follow-up following intravascular stenting for treatment of coarctation of the aorta

Background : We report a multiinstitutional study on intermediate-term outcome of intravascular stenting for treatment of coarctation of the aorta using integrated arch imaging (IAI) techniques. Methods and Results : Medical records of 578 patients from 17 institutions were reviewed. A total of 588 procedures were performed between May 1989 and Aug 2005. About 27% (160/588) procedures were followed up by further IAI of their aorta (MRI/CT/repeat cardiac catheterization) after initial stent procedures. Abnormal imaging studies included: the presence of dissection or aneurysm formation, stent fracture, or the presence of reobstruction within the stent (instent restenosis or significant intimal build-up within the stent). Forty-one abnormal imaging studies were reported in the intermediate follow-up at median 12 months (0.5–92 months). Smaller postintervention of the aorta (CoA) diameter and an increased persistent systolic pressure gradient were associated with encountering abnormal follow-up imaging studies. Aortic wall abnormalities included dissections ( n = 5) and aneurysm ( n = 13). The risk of encountering aortic wall abnormalities increased with larger percent increase in CoA diameter poststent implant, increasing balloon/coarc ratio, and performing prestent angioplasty. Stent restenosis was observed in 5/6 parts encountering stent fracture and neointimal buildup ( n = 16). Small CoA diameter poststent implant and increased poststent residual pressure gradient increased the likelihood of encountering instent restenosis at intermediate follow-up. Conclusions : Abnormalities were observed at intermediate follow-up following IS placement for treatment of native and recurrent coarctation of the aorta. Not exceeding a balloon:coarctation ratio of 3.5 and avoidance of prestent angioplasty decreased the likelihood of encountering an abnormal follow-up imaging study in patients undergoing intravascular stent placement for the treatment of coarctation of the aorta. We recommend IAI for all patients undergoing IS placement for treatment of CoA. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57392/1/21191_ftp.pd

TMEM161B modulates radial glial scaffolding in neocortical development.

TMEM161B encodes an evolutionarily conserved widely expressed novel 8-pass trans- membrane protein of unknown function in human. Here we identify TMEM161B homozygous hypomorphic missense variants in our recessive polymicrogyria (PMG) cohort. Patients carrying TMEM161B mutations exhibit striking neocortical PMG and intellectual disability. Tmem161b knockout mice fail to develop midline hem- ispheric cleavage, whereas knock-in of patient mutations and patient-derived brain organoids show defects in apical cell polarity and radial glial scaffolding. We found that TMEM161B modulates actin filopodia, functioning upstream of the Rho-GTPase CDC42. Our data link TMEM161B with human PMG, likely regulating radial glia apical polarity during neocortical development

Treating symptoms and reversing remodelling: clinical and echocardiographic 1‐year outcomes with percutaneous mitral annuloplasty for mild to moderate secondary mitral regurgitation

Aims- To determine the effects of percutaneous mitral annuloplasty on symptoms, walk distance and left ventricular (LV) structure and function in patients with mild or moderate secondary mitral regurgitation (SMR). Methods and results- This was a pooled analysis of patients (n = 68) who, despite guideline-directed medical therapy had symptomatic heart failure (HF) with mild (n = 25) or moderate (n = 43) SMR treated with percutaneous mitral annuloplasty as part of the TITAN, TITAN II, or REDUCE-FMR trials. Primary outcomes were changes in symptoms, 6-min walk distance, and quality of life assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) after 1 year. Secondary analyses included changes in LV structure and function. At 1 year, New York Heart Association class status was maintained (48%) or improved (46%) in most patients, mean KCCQ scores increased from baseline by 10 units [95% confidence interval (CI) 3 to17; P < 0.01] and mean 6-min walk test distance increased by 34 m (95% CI 12 to 57; P < 0.01). SMR grade improved in 25% of patients and was maintained in 58% of patients with changes in mean regurgitant volume of −7 mL (95% CI −11 to −3; P < 0.001), vena contracta −0.11 cm (95% CI −0.20 to −0.02; P < 0.05), and effective regurgitant orifice area −0.03 cm2 (95% CI −0.06 to −0.01; P < 0.05). There were non-significant improvements in LV ejection fraction and volumes. Survival over 1 year was 89% with no difference between mild (96%) and moderate (86%) SMR (log-rank P = 0.22). Progression-free survival was 70% (82% in mild vs. 63% in moderate SMR; P = 0.16). Freedom from HF hospitalization was 73% (87% in mild SMR vs. 66% in moderate SMR; P = 0.07). Conclusion- Among patients with symptomatic HF and mild or moderate SMR on guideline-directed medical therapy, percutaneous mitral annuloplasty was associated with improvements in symptoms, SMR, a stabilization of LV structure and function, and high survival rates

What Makes a Top-Performing Precision Medicine Search Engine? Tracing Main System Features in a Systematic Way

From 2017 to 2019 the Text REtrieval Conference (TREC) held a challenge task on precision medicine using documents from medical publications (PubMed) and clinical trials. Despite lots of performance measurements carried out in these evaluation campaigns, the scientific community is still pretty unsure about the impact individual system features and their weights have on the overall system performance. In order to overcome this explanatory gap, we first determined optimal feature configurations using the Sequential Model-based Algorithm Configuration (SMAC) program and applied its output to a BM25-based search engine. We then ran an ablation study to systematically assess the individual contributions of relevant system features: BM25 parameters, query type and weighting schema, query expansion, stop word filtering, and keyword boosting. For evaluation, we employed the gold standard data from the three TREC-PM installments to evaluate the effectiveness of different features using the commonly shared infNDCG metric.Comment: Accepted for SIGIR2020, 10 page