bluuebunny/crossref_metadata_2025_split huggingface dataset:
Textured insoles reduce vertical loading rate and increase subjective plantar sensation in overground running
Authors: Wilkinson Michael , Ewen Alistair , Caplan Nicholas , O'leary David , Smith Neil , Stoneham Richard , Saxby Lee 
Published: March 2018

AbstractThe effect of textured insoles on kinetics and kinematics of overground running was assessed. 16 male injury‐free‐recreational runners attended a single visit (age 23 ± 5 yrs; stature 1.78 ± 0.06 m; mass 72.6 ± 9.2 kg). Overground 15‐m runs were completed in flat, canvas plimsolls both with and without textured insoles at self‐selected velocity on an indoor track in an order that was balanced among participants. Average vertical loading rate and peak vertical force (Fpeak) were captured by force platforms. Video footage was digitised for sagittal plane hip, knee and ankle angles at foot strike and mid stance. Velocity, stride rate and length and contact and flight time were determined. Subjectively rated plantar sensation was recorded by visual scale. 95% confidence intervals estimated mean differences. Smallest worthwhile change in loading rate was defined as standardised reduction of 0.54 from a previous comparison of injured versus non‐injured runners. Loading rate decreased (−25 to −9.3 BW s−1; 60% likely beneficial reduction) and plantar sensation was increased (46–58 mm) with the insole. Fpeak (−0.1 to 0.14 BW) and velocity (−0.02 to 0.06 m s−1) were similar. Stride length, flight and contact time were lower (−0.13 to −0.01 m; −0.02 to−0.01 s; −0.016 to −0.006 s) and stride rate was higher (0.01–0.07 steps s−1) with insoles. Textured insoles elicited an acute, meaningful decrease in vertical loading rate in short distance, overground running and were associated with subjectively increased plantar sensation. Reduced vertical loading rate could be explained by altered stride characteristics.
Potential benefits of dietary nitrate ingestion in healthy and clinical populations: A brief review
Authors: McDonagh Sinead T. J. , Wylie Lee J. , Thompson Christopher , Vanhatalo Anni , Jones Andrew M. 
Published: March 2018

AbstractThis article provides an overview of the current literature relating to the efficacy of dietary nitrate (NO3−) ingestion in altering aspects of cardiovascular and metabolic health and exercise capacity in healthy and diseased individuals. The consumption of NO3−‐rich vegetables, such as spinach and beetroot, have been variously shown to promote nitric oxide bioavailability, reduce systemic blood pressure, enhance tissue blood flow, modulate muscle O2 utilisation and improve exercise tolerance both in normoxia and in hypoxia, as is commonly observed in a number of disease states. NO3− ingestion may, therefore, act as a natural means for augmenting performance and attenuating complications associated with limited O2 availability or transport, hypertension and the metabolic syndrome. Recent studies indicate that dietary NO3− might also augment intrinsic skeletal muscle contractility and improve the speed and power of muscle contraction. Moreover, several investigations suggest that NO3− supplementation may improve aspects of cognitive performance both at rest and during exercise. Collectively, these observations position NO3− as more than a putative ergogenic aid and suggest that increasing natural dietary NO3− intake may act as a prophylactic in countering the predations of senescence and certain cardiovascular‐metabolic diseases.
Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8
Authors: Berenguer Jordi , Lagerweij Tonny , Zhao Xi Wen , Dusoswa Sophie , van der Stoop Petra , Westerman Bart , de Gooijer Mark C. , Zoetemelk Marloes , Zomer Anoek , Crommentuijn Matheus H. W. , Wedekind Laurine E. , López‐López Àlan , Giovanazzi Alberta , Bruch‐Oms Marina , van der Meulen‐Muileman Ida H. , Reijmers Rogier M. , van Kuppevelt Toin H. , García‐Vallejo Juan‐Jesús , van Kooyk Yvette , Tannous Bakhos A. , Wesseling Pieter , Koppers‐Lalic Danijela , Vandertop W. Peter , Noske David P. , van Beusechem Victor W. , van Rheenen Jacco , Pegtel D. Michiel , van Tellingen Olaf , Wurdinger Thomas 
Published: March 2018

ABSTRACTCancer cells release extracellular vesicles (EVs) that contain functional biomolecules such as RNA and proteins. EVs are transferred to recipient cancer cells and can promote tumour progression and therapy resistance. Through RNAi screening, we identified a novel EV uptake mechanism involving a triple interaction between the chemokine receptor CCR8 on the cells, glycans exposed on EVs and the soluble ligand CCL18. This ligand acts as bridging molecule, connecting EVs to cancer cells. We show that glioblastoma EVs promote cell proliferation and resistance to the alkylating agent temozolomide (TMZ). Using in vitro and in vivo stem‐like glioblastoma models, we demonstrate that EV‐induced phenotypes are neutralised by a small molecule CCR8 inhibitor, R243. Interference with chemokine receptors may offer therapeutic opportunities against EV‐mediated cross‐talk in glioblastoma.
Genome-scale metabolic modeling of responses to polymyxins in Pseudomonas aeruginosa
Authors: Zhu Yan , Czauderna Tobias , Zhao Jinxin , Klapperstueck Matthias , Maifiah Mohd Hafidz Mahamad , Han Mei-Ling , Lu Jing , Sommer Björn , Velkov Tony , Lithgow Trevor , Song Jiangning , Schreiber Falk , Li Jian 
Published: March 2018

Abstract

Background
Pseudomonas aeruginosa often causes multidrug-resistant infections in immunocompromised patients, and polymyxins are often used as the last-line therapy. Alarmingly, resistance to polymyxins has been increasingly reported worldwide recently. To rescue this last-resort class of antibiotics, it is necessary to systematically understand how P. aeruginosa alters its metabolism in response to polymyxin treatment, thereby facilitating the development of effective therapies. To this end, a genome-scale metabolic model (GSMM) was used to analyze bacterial metabolic changes at the systems level.

Findings
A high-quality GSMM iPAO1 was constructed for P. aeruginosa PAO1 for antimicrobial pharmacological research. Model iPAO1 encompasses an additional periplasmic compartment and contains 3022 metabolites, 4265 reactions, and 1458 genes in total. Growth prediction on 190 carbon and 95 nitrogen sources achieved an accuracy of 89.1%, outperforming all reported P. aeruginosa models. Notably, prediction of the essential genes for growth achieved a high accuracy of 87.9%. Metabolic simulation showed that lipid A modifications associated with polymyxin resistance exert a limited impact on bacterial growth and metabolism but remarkably change the physiochemical properties of the outer membrane. Modeling with transcriptomics constraints revealed a broad range of metabolic responses to polymyxin treatment, including reduced biomass synthesis, upregulated amino acid catabolism, induced flux through the tricarboxylic acid cycle, and increased redox turnover.

Conclusions
Overall, iPAO1 represents the most comprehensive GSMM constructed to date for Pseudomonas. It provides a powerful systems pharmacology platform for the elucidation of complex killing mechanisms of antibiotics.
Differential protein expression and post-translational modifications in metronidazole-resistant Giardia duodenalis
Authors: Emery Samantha J , Baker Louise , Ansell Brendan R E , Mirzaei Mehdi , Haynes Paul A , McConville Malcom J , Svärd Staffan G , Jex Aaron R 
Published: March 2018

Abstract

Background
Metronidazole (Mtz) is the frontline drug treatment for multiple anaerobic pathogens, including the gastrointestinal protist, Giardia duodenalis. However, treatment failure is common and linked to in vivo drug resistance. In Giardia, in vitro drug-resistant lines allow controlled experimental interrogation of resistance mechanisms in isogenic cultures. However, resistance-associated changes are inconsistent between lines, phenotypic data are incomplete, and resistance is rarely genetically fixed, highlighted by reversion to sensitivity after drug selection ceases or via passage through the life cycle. Comprehensive quantitative approaches are required to resolve isolate variability, fully define Mtz resistance phenotypes, and explore the role of post-translational modifications therein.

Findings
We performed quantitative proteomics to describe differentially expressed proteins in 3 seminal Mtz-resistant lines compared to their isogenic, Mtz-susceptible, parental line. We also probed changes in post-translational modifications including protein acetylation, methylation, ubiquitination, and phosphorylation via immunoblotting. We quantified more than 1,000 proteins in each genotype, recording substantial genotypic variation in differentially expressed proteins between isotypes. Our data confirm substantial changes in the antioxidant network, glycolysis, and electron transport and indicate links between protein acetylation and Mtz resistance, including cross-resistance to deacetylase inhibitor trichostatin A in Mtz-resistant lines. Finally, we performed the first controlled, longitudinal study of Mtz resistance stability, monitoring lines after cessation of drug selection, revealing isolate-dependent phenotypic plasticity.

Conclusions
Our data demonstrate understanding that Mtz resistance must be broadened to post-transcriptional and post-translational responses and that Mtz resistance is polygenic, driven by isolate-dependent variation, and is correlated with changes in protein acetylation networks.
Characteristics of Combat-Associated Small Bowel Injuries
Authors: Skube Mariya E , Mallery Quinn , Lusczek Elizabeth , Elterman Joel , Spott Mary A , Beilman Greg J 
Published: March 2018

AbstractIntroductionAlthough there are multiple studies regarding the management and outcomes of colonic injuries incurred in combat, the literature is limited with regard to small bowel injuries. This study seeks to provide the largest reported review of the characteristics of combat-associated small bowel injuries.Materials and MethodsThe Department of Defense Trauma Registry was queried for U.S. Armed Forces members who sustained hollow viscus injuries in the years 2007–2012 during Operations Enduring Freedom, Iraqi Freedom, and New Dawn. Concomitant injuries, procedures, and complications were delineated. Fisher’s exact test was used to analyze the relationship of bowel injury pattern to rates of repeat laparotomy, fecal diversion, and complications.ResultsOne hundred seventy-one service members had small bowel injuries. The mean age was 25.8 ± 6.6 yr with a mean injury severity score of 27.9 ± 12.4. The majority of injuries were penetrating (94.2%, n = 161) as a result of explosive devices (61.4%, n = 105). The median blood transfusion requirement in the first 24 h was 6.0 units (interquartile range 1.0–17.3 units). The most frequent concomitant injuries were large bowel (64.3%, n = 110), pelvic fracture (35.7%, n = 61), and perineal (26.3%, n = 45). Fifty patients (29.2%) had a colostomy, and nine patients (5.3%) had an ileostomy; 62.6% (n = 107) of soldiers underwent more than one laparotomy. The mortality rate was 1.8% (n = 3). The most common complications were pneumonia (15.2%, n = 26), deep vein thrombosis (14.6%, n = 25), and wound infection (14.6%, n = 25). The need for repeat laparotomy and fecal diversion was found to be significantly associated with injury pattern (p = 0.00052 and p < 0.0001, respectively).ConclusionWe found that two-thirds of service members with small bowel injuries also had a large bowel injury. One-third of the patients required diversion and two-thirds had more than one laparotomy. The pattern of bowel injury significantly affected the need for repeat laparotomy and fecal diversion.
Multiple hit infection and autoimmunity: the dysbiotic microbiota–ACPA connection in rheumatoid arthritis
Authors: Sakkas Lazaros I. , Bogdanos Dimitrios P. 
Published: March 2018

Purpose of review
This review highlights the most recent data obtained in this field and provides clues toward the better understanding of the close interplay between microbiota and host, leading to autoimmune diseases.

Recent findings
A well-described model of microbiota/host interaction of relevance to autoimmunity is linking anti-citrullinated peptide antibody positive rheumatoid arthritis and alterations of microbiota largely concentrating on Porphyromonas gingivalis and more recently of Aggregatibacter actinomycetemcomitans and Prevotella copri.

Summary
The perception of the classical link between microbial infection and development of autoimmune disease has evolved to the more recent concept of the connection between the microbiome/dysbiosis and breaking of immunological tolerance.
Fecal transplants in spondyloarthritis and uveitis: ready for a clinical trial?
Authors: Choi Rene Y. , Asquith Mark , Rosenbaum James T. 
Published: March 2018

Purpose of review
The intestinal microbiome is thought to play a role in the pathogenesis of inflammatory bowel disease (IBD). There are many shared clinical manifestations between IBD and spondyloarthritis (SpA), of which the most common are peripheral arthritis and uveitis. Clinical overlap along with similar genetics between these diseases suggests a possible shared pathogenetic mechanism, which might center on the intestinal microbiota. In this review, we discuss the available evidence that SpA is a microbiome-driven disease and indicate how SpA-associated uveitis could be tied to gut dysbiosis. We conclude by discussing different treatment paradigms targeting the intestinal microbiome for SpA.

Recent findings
Recent studies support the growing evidence of the intestinal microbiome as a crucial player in SpA disease pathogenesis. There is emerging evidence that the gut microbiome may play a causative role in uveitis.

Summary
The field is beginning to discover a new level of understanding how the intestinal microbiome is involved in SpA. Treatment methods to alter intestinal microbiota to treat SpA-related diseases are still in its infancy.
Has the Proportion of Combat-Related Amputations That Develop Heterotopic Ossification Increased?
Authors: Daniels Christopher M. , Pavey Gabriel J. , Arthur Jacob , Noller Michael , Forsberg Jonathan A. , Potter Benjamin K. 
Published: March 2018

Objectives:
To determine what proportion of residual limbs formed heterotopic ossification (HO) in amputations sustained by US service members, the injury profile of these amputations, and what effect the number of limb amputations sustained has on resource utilization.

Design:
Retrospective review.

Setting:
A tertiary military medical center.

Patients:
Four-hundred seventy-one consecutive patients with 714 combat-related amputations were treated at our institution between September 2009 and August 2014. Four-hundred thirty-nine amputations had radiographic follow-up beyond 2 months of injury and met the criteria for study inclusion.

Main Outcome Measure:
Formation and grade of HO.

Results:
HO was present in 399 of 439 (91%) residual limbs, including 211 of 216 (98%) transfemoral amputations. Dismounted improvised explosive device blast injury resulted in HO development in 346 of 372 (93%) residual limbs compared with 36 of 44 (82%) in mounted improvised explosive device blast injury [P = 0.014; odds ratio (OR) 2.96, 95% confidence interval (CI), 1.25–7.04]. As the number of amputations per patient increased, so too did blood product utilization [including packed red blood cells (P < 0.001), fresh frozen plasma (P < 0.001), and platelets (P < 0.001)]; the number of days on a ventilator (P < 0.001), in the intensive care unit (P < 0.001), and in the hospital (P = 0.007).

Conclusions:
HO prevalence in the traumatic amputations of war wounded has increased compared with earlier studies, which is temporally associated with higher rates of increasingly severe injuries due to dismounted blast.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Phenotyping Cardiac Arrest: Bench and Bedside Characterization of Brain and Heart Injury Based on Etiology
Authors: Uray Thomas , Lamade Andrew , Elmer Jonathan , Drabek Tomas , Stezoski Jason P. , Missé Amalea , Janesko-Feldman Keri , Garman Robert H. , Chen Niel , Kochanek Patrick M. , Dezfulian Cameron 
Published: March 2018

Objectives:
Cardiac arrest etiology may be an important source of between-patient heterogeneity, but the impact of etiology on organ injury is unknown. We tested the hypothesis that asphyxial cardiac arrest results in greater neurologic injury than cardiac etiology cardiac arrest (ventricular fibrillation cardiac arrest), whereas ventricular fibrillation cardiac arrest results in greater cardiovascular dysfunction after return of spontaneous circulation.

Design:
Prospective observational human and randomized animal study.

Setting:
University laboratory and ICUs.

Patients:
Five-hundred forty-three cardiac arrest patients admitted to ICU.

Subjects:
Seventy-five male Sprague-Dawley rats.

Interventions:
We examined neurologic and cardiovascular injury in Isoflurane-anesthetized rat cardiac arrest models matched by ischemic time. Hemodynamic and neurologic outcomes were assessed after 5 minutes no flow asphyxial cardiac arrest or ventricular fibrillation cardiac arrest. Comparison was made to injury patterns observed after human asphyxial cardiac arrest or ventricular fibrillation cardiac arrest.

Measurements and Main Results:
In rats, cardiac output (20 ± 10 vs 45 ± 9 mL/min) and pH were lower and lactate higher (9.5 ± 1.0 vs 6.4 ± 1.3 mmol/L) after return of spontaneous circulation from ventricular fibrillation cardiac arrest versus asphyxial cardiac arrest (all p < 0.01). Asphyxial cardiac arrest resulted in greater early neurologic deficits, 7-day neuronal loss, and reduced freezing time (memory) after conditioned fear (all p < 0.05). Brain antioxidant reserves were more depleted following asphyxial cardiac arrest. In adjusted analyses, human ventricular fibrillation cardiac arrest was associated with greater cardiovascular injury based on peak troponin (7.8 ng/mL [0.8–57 ng/mL] vs 0.3 ng/mL [0.0–1.5 ng/mL]) and ejection fraction by echocardiography (20% vs 55%; all p < 0.0001), whereas asphyxial cardiac arrest was associated with worse early neurologic injury and poor functional outcome at hospital discharge (n = 46 [18%] vs 102 [44%]; p < 0.0001). Most ventricular fibrillation cardiac arrest deaths (54%) were the result of cardiovascular instability, whereas most asphyxial cardiac arrest deaths (75%) resulted from neurologic injury (p < 0.0001).

Conclusions:
In transcending rat and human studies, we find a consistent phenotype of heart and brain injury after cardiac arrest based on etiology: ventricular fibrillation cardiac arrest produces worse cardiovascular dysfunction, whereas asphyxial cardiac arrest produces worsened neurologic injury associated with greater oxidative stress.
Parkin Mediates Mitophagy to Participate in Cardioprotection Induced by Late Exercise Preconditioning but Bnip3 Does Not
Authors: Yuan Yang , Pan Shan-Shan 
Published: March 2018

Background:
Late exercise preconditioning (LEP) is confirmed to have a protective effect on acute cardiovascular stress. However, the mechanisms by which mitophagy participates in exercise preconditioning (EP)-induced cardioprotection remain unclear. LEP may involve mitophagy mediated by the receptors PARK2 gene–encoded E3 ubiquitin ligase (Parkin) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) to scavenge damaged mitochondria.

Methods:
Our EP protocol involved four 10-minute periods of running, separated by 10-minute recovery intervals, plus a period of exhaustive running at 24 hours after EP. We assessed this late protective effect by injection of the autophagy inhibitor wortmannin, transmission electron microscopy, laser scanning confocal microscopy, and other molecular biotechnology methods; we simultaneously detected related markers, analyzed the specific relationships between mitophagy proteins, and assessed mitochondrial translocation.

Results:
Exhaustive exercise (EE) causes serious injuries to cardiomyofibrils, inducing hypoxia–ischemia and changing the ultrastructure. EE fails to clear excessively generated mitochondria to link with LC3 accumulation. After EP, increased autophagy levels at 30 minutes were converted to mitophagy within 24 hours. We found that LEP significantly suppressed EE-induced injuries, which we confirmed by observing decreased levels of the mitochondria-localized proteins COX4/1 and TOM20. LEP to exhaustion caused mitochondrial degradation by increasing the efficiency of LC3–outer mitochondrial membrane translocation in a Parkin-mediated manner, in which activated protein kinase and TOM70 may play both key roles. However, we did not observe mitophagy to be associated with Bnip3 mediation in LEP-induced cardioprotection. However, Bnip3 may play a role in inducing mitochondrial LC3-II increases. Wortmannin had no effect on LC3 translocation; instead, it influenced LC3-I to convert to LC3-II. Thus, suppressing mitophagy led to the attenuation of EP-induced cardioprotection.
Effects of dietary and exercise intervention on weight loss and body composition in obese postmenopausal women: a systematic review and meta-analysis
Authors: Cheng Chao-Chun , Hsu Ching-Yun , Liu Jen-Fang 
Published: March 2018

Abstract

Objective:
This study examined the effects of dietary and exercise interventions on weight loss and body composition in overweight/obese peri- and postmenopausal women.

Methods:

Medline, Central, Embase, and Google Scholar databases were searched for relevant trials conducted until December 31, 2016. Randomized controlled trials (RCTs) and prospective studies of overweight/obese peri- or postmenopausal women that examined the effects of dietary or exercise interventions, alone or combined, on weight loss were included. The primary outcome was percentage reduction in body weight.

Results:
From 292 studies initially identified, 11 studies with 12 sets of participants were included. Both dietary and exercise intervention groups had significantly greater weight loss than control groups (diet vs control: difference in means = −6.55, 95% CI, −9.51 to −3.59, P < 0.001; exercise vs control: difference in means = −3.49, 95% CI, −6.96 to −0.02, P = 0.049). Combined dietary and exercise interventions resulted in greater weight loss than dietary interventions alone (diet plus exercise vs diet: difference in means = −1.22, 95% CI, −2.14 to −0.29, P = 0.010). Diet plus exercise resulted in greater fat loss (difference in means = −0.44, 95% CI, −0.67 to −0.20, P < 0.001) and greater lean mass loss (difference in means = −0.84, 95% CI, −1.13 to −0.55, P < 0.001) than diet alone.

Conclusions:
Dietary interventions reduced body weight and body composition profile parameters in peri- and postmenopausal women more than exercise alone. The addition of exercise reinforced the effect of dietary interventions on changing body weight and composition.
Improvement of Symptoms after Lymphaticovenous Anastomosis in Patients with Abdominal Wall Lymphedema
Authors: Ewalds Lotte , Cornelissen Anouk J. M. , van der Hulst René R. W. J. , Qiu Shan S. 
Published: March 2018

Summary:
At our institution, we performed a lymphaticovenous anastomosis in patients with primary or secondary abdominal lymphedema. Patients report good outcomes and feel relieved of their complaints. To obtain good results, it is important to have decent knowledge on the anatomical state of the lymphatic system. In general, the lymphatic system of the lower abdomen can be compared with the system of the upper legs. According to our current case results, the abdominal area might be susceptible to lymphaticovenous anastomosis procedure. Further research should be performed to confirm the effect of the intervention and the imaging techniques to monitor the improvements.