bluuebunny/crossref_metadata_2025 huggingface dataset:
PRedicting Outcomes For Crohn’s dIsease using a moLecular biomarkEr (PROFILE): protocol for a multicentre, randomised, biomarker-stratified trial
Authors: Parkes Miles , Noor Nurulamin M , Dowling Francis , Leung Harvey , Bond Simon , Whitehead Lynne , Upponi Sara , Kinnon Paul , Sandham Andrew P , Lyons Paul A , McKinney Eoin F , Smith Kenneth G C , Lee James C
Published: December 2018

Background

The course of Crohn’s disease (CD) varies substantially between individuals, but reliable prognostic markers do not exist. This hinders disease management because patients with aggressive disease are undertreated by conventional ‘step-up’ therapy (in which treatment is gradually escalated in response to refractory or relapsing disease) while those with more indolent disease would be exposed to unnecessary treatment-related toxicity if a more aggressive ‘top-down’ approach was indiscriminately used. The Predicting outcomes for Crohn’s disease using a molecular biomarker trial will assess whether a prognostic transcriptional biomarker, that we have developed and validated, can improve clinical outcomes by facilitating personalised therapy in CD. This represents the first the biomarker-stratified trial in inflammatory bowel disease.

Methods and analysis

This biomarker-stratified trial will compare the relative efficacy of ‘top-down’ and ‘accelerated step-up’ therapy between biomarker-defined subgroups of patients with newly diagnosed CD. 400 participants from ~50 UK centres will be recruited. Subjects within each biomarker subgroup (IBDhior IBDlo) will be randomised (1:1) to receive one of the treatment strategies until trial completion (48 weeks). The primary outcome is the incidence of sustained surgery and steroid-free remission from the completion of induction treatment through to week 48. Secondary outcomes include mucosal healing, quality-of-life assessments and surrogate measures of disease burden including number of flares, cumulative steroid exposure, number of hospital admissions and number of Crohn’s-related surgeries (assessed hierarchically). Analyses will compare the relative benefit of the treatment strategies in each biomarker-defined subgroup, powered as an interaction analysis, to determine whether the biomarker can accurately match patients to the most appropriate therapy.

Ethics and dissemination

Ethical approval has been obtained and recruitment is under way at sites around the UK. Following trial completion and data analysis, the results of the trial will be submitted for publication in peer-reviewed journals and presented at international conferences.

Trial registration number

ISRCTN11808228; Pre-results.
Cultural considerations for informed consent in paediatric research in low/middle-income countries: a scoping review
Authors: Colom Marcela , Rohloff Peter
Published: December 2018

Introduction

Conducting research with children in low/middle-income countries (LMIC) requires consideration of socioeconomic inequalities and cultural and linguistic differences. Our objective was to survey the literature on informed consent in paediatric LMIC research, assessing for practical guidance for culturally and linguistically appropriate procedures.

Methods

We conducted a scoping review on informed consent in paediatric LMIC research searching the PubMed, Web of Science and PsycINFO databases. Eligible articles were published in English, from any date range, of any study design or format.

Results

The search identified 2027 references, of which 50 were included in the analysis following full-text review. Reviewed guidelines emphasised individual, informed and voluntary consent from parents and caregivers. Reviewed articles provided detailed practical guidance on adapting these guiding principles to LMIC settings, including considerations for community engagement, verbal or other alternative consent procedures for low-literacy settings or less commonly spoken languages and guarding against therapeutic misconception by caregivers. There was uncertainty, however, on how to best protect individual autonomy, especially when influenced by gender dynamics, leadership hierarchies or the social status of researchers themselves. There was, furthermore, limited research discussing the special case of research involving adolescents or of procedures for documenting assent by participating children.

Conclusions

A scoping review of paediatric research in LMICs revealed substantial guidance on several features of culturally appropriate informed consent. However, additional research and guidance is needed, especially in the areas of gender imbalances, research with adolescents and children’s own assent to participate in research.
Prognosis and risk stratification in patients with decompensated heart failure receiving inotropic therapy
Authors: Gomes Clara , Terhoch Caíque Bueno , Ayub-Ferreira Silvia Moreira , Conceição-Souza Germano Emilio , Salemi Vera Maria Cury , Chizzola Paulo Roberto , Oliveira Jr Mucio Tavares , Lage Silvia Helena Gelas , Frioes Fernando , Bocchi Edimar Alcides , Issa Victor Sarli
Published: December 2018

Objectives

The prognostic significance of transient use of inotropes has been sufficiently studied in recent heart failure (HF) populations. We hypothesised that risk stratification in these patients could contribute to patient selection for advanced therapies.

Methods

We analysed a prospective cohort of adult patients admitted with decompensated HF and ejection fraction (left ventricular ejection fraction (LVEF)) less than 50%. We explored the outcomes of patients requiring inotropic therapy during hospital admission and after discharge.

Results

The study included 737 patients, (64.0% male), with a median age of 58 years (IQR 48–66 years). Main aetiologies were dilated cardiomyopathy in 273 (37.0%) patients, ischaemic heart disease in 195 (26.5%) patients and Chagas disease in 163 (22.1%) patients. Median LVEF was 26 % (IQR 22%–35%). Inotropes were used in 518 (70.3%) patients. In 431 (83.2%) patients, a single inotrope was administered. Inotropic therapy was associated with higher risk of in-hospital death/urgent heart transplant (OR=10.628, 95% CI 5.055 to 22.344, p<0.001). At 180-day follow-up, of the 431 patients discharged home, 39 (9.0%) died, 21 (4.9%) underwent transplantation and 183 (42.4%) were readmitted. Inotropes were not associated with outcome (death, transplant and rehospitalisation) after discharge.

Conclusions

Inotropic drugs are still widely used in patients with advanced decompensated HF and are associated with a worse in-hospital prognosis. In contrast with previous results, intermittent use of inotropes during hospitalisation did not determine a worse prognosis at 180-day follow-up. These data may add to prognostic evaluation in patients with advanced HF in centres where mechanical circulatory support is not broadly available.
Validity of the rheumatoid arthritis MRI score applied to the forefeet using the OMERACT filter: a systematic literature review
Authors: Dakkak Yousra J , van der Heijde Désirée M , Reijnierse Monique , van der Helm-van Mil Annette H M
Published: December 2018

Objective

MRI depicts inflammation and structural damage in rheumatoid arthritis (RA). The validity of MRI-scoring of wrist-joints and metacarpophalangeal-joints according to the RA MRI score(RAMRIS) has been demonstrated. The Outcomes in Rheumatology Clinical Trials (OMERACT) RAMRIS Working Group recently called for validation of the RAMRIS of the metatarsophalangeal (MTP)-joints. Therefore, a systematic literature review was performed to test if the RAMRIS applied to the MTP-joints meets the OMERACT Filter of Truth, Discrimination and Feasibility.

Methods

Medical literature databases up to January 2018 were systematically reviewed for studies reporting on RAMRIS applied to MRI of the MTP-joints in RA. To be included, an article had to contain at least one MRI-feature (synovitis, bone marrow oedema (BME), tenosynovitis, erosion, joint space narrowing (JSN)) and one item from the OMERACT Filter: Truth (face, content and construct validity), Discrimination (test-retest reliability, ability to discriminate in trials, longitudinal construct validity and thresholds of meaning) and Feasibility.

Results

Of the 749 retrieved studies, 13 were included, of which 9 provided data on construct validity, 4 on discrimination (3 on reliability, 2 on longitudinal construct validity and 1 on ability to discriminate in trials) and none on feasibility. Construct validity was suggested for BME and erosions, but lacking for synovitis, tenosynovitis and JSN. Data for discrimination remain to be developed for all outcomes.

Conclusion

According to the OMERACT Filter, the validity of the RAMRIS of the forefeet is insufficient in different aspects. A research agenda was determined.
Effect of methadone and acepromazine premedication on tear production in dogs
Authors: Volk Hayley A , West Ellie , Linn‐Pearl Rose Non , Fricker Georgina V , Panti Ambra , Gould David J
Published: December 2018

Objectives

To evaluate the combined effect of intramuscular acepromazine and methadone on tear production in dogs undergoing general anaesthesia for elective, non‐ocular procedures.

Design

Prospective, non‐randomised, pre‐post treatment study.

Setting

Patients were recruited from a referral practice in the UK.

Methods

Thirty client‐owned dogs were enrolled in this study and received a combined intramuscular premedication of methadone (0.3 mg/kg) and acepromazine (0.02 mg/kg) before general anaesthesia for elective, non‐ocular procedures. Full ophthalmic examination was performed and tear production was quantified using the Schirmer tear test‐1 (STT‐1). On the day of general anaesthesia, an STT‐1 was performed before (STT‐1a) and after (STT‐1b) intramuscular premedication with methadone/acepromazine.

Results

Using a general linear model, a significant effect on STT‐1 results was found for premedication with methadone/acepromazine (P=0.013), but not eye laterality (P=0.527). Following premedication, there was a significant reduction observed in the mean STT‐1 readings of left and right eyes between STT‐1a (20.4±2.8 mm/min) and STT‐1b (16.9±4.1 mm/min; P<0.001). Significantly more dogs had an STT‐1 reading less than 15 mm/min in one or both eyes after premedication (30 per cent; 9/30 dogs) compared with before premedication (6.7 per cent; 2/30 dogs; P=0.042).

Conclusions

An intramuscular premedication of methadone and acepromazine results in a decrease in tear production in dogs before elective general anaesthesia. This may contribute to the risk of ocular morbidities, such as corneal ulceration, particularly in patients with lower baseline tear production.
A Systematic Review of the Medicinal Potential of Mulberry in Treating Diabetes Mellitus
Authors: Wei Helin , Liu Siyuan , Liao Yijun , Ma Chuanhui , Wang Dongying , Tong Jiayun , Feng Jiafu , Yi Tao , Zhu Lin
Published: December 2018

Diabetes mellitus (DM) is a serious metabolic disorder which has reached epidemic proportions all over the world. Despite tremendous developments in medicinal chemistry, traditional medicine is still commonly used for the prevention and treatment of DM. Traditional herbal medicines have played a major role in the management of DM in Asian countries. In particular, mulberry has commonly been utilized in China for the treatment of DM for thousands of years. In the last decade, numerous preclinical findings have suggested that mulberry is a promising therapeutic agent for the treatment of DM, and the polyhydroxylated alkaloids, flavonoids and polysaccharides from mulberry may be the potential active components. The present review systematically summarizes the chemical composition of mulberry and the pharmacological effects of different medicinal parts on DM; these effects include influences on glucose absorption, insulin (INS) production/secretion, anti-oxidation and anti-inflammation processes. After summarizing our research findings, we will discuss the challenges and opportunities and explore the direction of future research and the potential for developing mulberry into pharmaceuticals for the widespread treatment of DM.
FRACTAL ANALYSIS OF GAS FLOW THROUGH THE GAS DIFFUSION LAYER IN PROTON EXCHANGE MEMBRANE FUEL CELLS WITH ROUGHENED MICRO-CHANNELS
Authors: ZHENG QIAN , FAN JINTU , LI XIANGPENG , XU CHAO
Published: December 2018

The effective permeability is one of the key parameters for porous fibrous gas diffusion layer (GDL), which plays a crucial role in the proton exchange membrane fuel cells (PEMFCs). However, the effect of the surface morphology of porous fibrous GDL on gas transport behaviors is so far been neglected. In order to take that into consideration, a new analytical model is presented for gas flow in porous fibrous GDL with roughened micro-channels based on the fractal scaling laws. Due to the existence of very small pores in the porous fibrous GDL, gas slippage effects through the small pores are also taken into account. The fractal gas permeability is expressed in terms of the relative roughness, other microstructural parameters as well as gas properties. The proposed fractal model is validated by comparing the model prediction with available experimental data. The effect of relative roughness and other micro-structural parameters of GDL on the permeability is analyzed in detail.
Fuzzy Credit Risk Scoring Rules using FRvarPSO
Authors: Santana Patricia Jimbo , Lanzarini Laura , Bariviera Aurelio F.
Published: December 2018

There is consensus that the best way for reducing insolvency situations in financial institutions is through good risk management, which involves a good client selection process. In the market, there are methodologies for credit scoring, each analyzing a large number of microeconomic and/or macroeconomic variables selected mostly depending on the type of credit to be granted. Since these variables are heterogeneous, the review process carried out by credit analysts takes time. The objective of this article is to propose a solution for this problem by applying fuzzy logic to the creation of classification rules for credit granting. To achieve this, linguistic variables were used to help the analyst interpret the information available from the credit officer. The method proposed here combines the use of fuzzy logic with a neural network and a variable population optimization technique to obtain fuzzy classification rules. It was tested with three databases from financial entities in Ecuador — one credit and savings cooperative and two banks that grant various types of credits. To measure its performance, three benchmarks were used: accuracy, number of classification rules generated, and antecedent length. The results obtained indicate that the hybrid model that is proposed performs better than its previous versions due to the addition of fuzzy logic. At the end of the article, our conclusions are discussed and future research lines are suggested.
DFR
Authors: Bai Kangjun , Yi Yang
Published: December 2018

Neuromorphic computing, which is built on a brain-inspired silicon chip, is uniquely applied to keep pace with the explosive escalation of algorithms and data density on machine learning. Reservoir computing, an emerging computing paradigm based on the recurrent neural network with proven benefits across multifaceted applications, offers an alternative training mechanism only at the readout stage. In this work, we successfully design and fabricate an energy-efficient analog delayed feedback reservoir (DFR) computing system, which is built upon a temporal encoding scheme, a nonlinear transfer function, and a dynamic delayed feedback loop. Measurement results demonstrate its high energy efficiency with rich dynamic behaviors, making the designed system a candidate for low power embedded applications. The system performance, as well as the robustness, are studied and analyzed through the Monte Carlo simulation. The chaotic time series prediction benchmark, NARMA10, is examined through the proposed DFR computing system, and exhibits a 36%−85% reduction on the error rate compared to state-of-the-art DFR computing system designs. To the best of our knowledge, our work represents the first analog integrated circuit (IC) implementation of the DFR computing system.
Energy intake, gastrointestinal transit, and gut hormone release in response to oral triglycerides and fatty acids in men with and without severe obesity
Authors: Dirksen Carsten , Graff Jesper , Fuglsang Stefan , Rehfeld Jens F. , Holst Jens J. , Madsen Jan L.
Published: December 2018

Dietary fat, and particularly fatty acids (FAs) from hydrolyzed triglycerides (TGs), reduces appetite, whereas paradoxically, a high-fat diet leads to excess calorie intake. We therefore hypothesized that the appetite-regulating effects of FAs are perturbed in obesity. Ten men with severe obesity [median body mass index (BMI) of 51.0 kg/m2(range of 47.9–69.0)] and 10 men without obesity [BMI of 24.6 kg/m2(range of 21.7–26.8)] were recruited for a double-blind randomized crossover study. On two occasions, participants were given isocaloric (2,660 kJ) and isovolemic (80 ml) loads of either oleic acid (long-chain FA) or olive oil (TG) containing radiolabeled lipid and water markers. Postload scintigraphy, blood sampling, and assessment of appetite were performed for 10 h, after which an ad libitum meal was served. Compared with olive oil, oleic acid slowed gastric mean emptying time (GMET) for lipids ( P < 0.001), accelerated orocoecal transit time (OCTT; P = 0.005), increased postload cholecystokinin section ( P < 0.001), and suppressed ad libitum energy intake ( P = 0.028) in men with severe obesity, and similar effects were seen in the nonobese group (no group × lipid interactions). However, independent of lipid loads, GMET and OCTT were slower (GMETlipidP = 0.046; GMETwaterP = 0.003; OCTT P = 0.001), and basal and postload secretion of glucagon-like peptide-1 (GLP-1) was attenuated ( P = 0.045 and P = 0.048, respectively) in men with severe obesity compared with men without obesity. We conclude that the more potent appetite-regulating effects of oleic acid versus olive oil are unimpaired in men with severe obesity. However, regardless of lipid formulations, severe obesity is associated with slowed gastrointestinal transit and attenuated GLP-1 secretion.

NEW & NOTEWORTHY Orally ingested fatty acids more efficiently reduce appetite and energy intake than triglycerides also in men with severe obesity. Men with severe obesity have delayed gastrointestinal transit and attenuated early gut hormone responses after an oral lipid load compared with men without obesity.
A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity
Authors: Zhang C. , Ramsey C. , Berical A. , Yu L. , Leng L. , McGinnis K. A. , Song Y. , Michael H. , McCormack M. C. , Allore H. , Morris A. , Crothers K. , Bucala R. , Lee P. J. , Sauler M.
Published: December 2018

Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT5–8microsatellite repeat) ( rs5844572 ). The role of this polymorphim in mediating disease susceptibility to COPD-related traits remains unknown. We performed a cross-sectional analysis of DNA samples from 641 subjects to analyze MIF-794 CATT5–8( rs5844572 ) polymorphism by standard methods. We generated multivariable logistic regression models to determine the risk of low expressing MIF alleles for airflow obstruction [defined by forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.70] and an abnormal diffusion capacity [defined by a diffusion capacity for carbon monoxide (DLCO) percent predicted <80%]. We then used generalized linear models to determine the association of MIF genotypes with FEV1percent predicted and DLCOpercent predicted. The MIF-794 CATT5allele was associated with an abnormal diffusion capacity in two cohorts [odds ratio (OR): 9.31, 95% confidence interval (CI): 1.97–4.06; and OR: 2.21, 95% CI: 1.03–4.75]. Similarly, the MIF-794 CATT5allele was associated with a reduced DLCOpercentage predicted in these two cohorts: 63.5 vs. 70.0 ( P = 0.0023) and 60.1 vs. 65.4 ( P = 0.059). This study suggests an association between a common genetic polymorphism of an endogenous innate immune gene, MIF, with reduced DLCO, an important measurement of COPD severity.
Separate and interacting effects of the endogenous circadian system and behaviors on plasma aldosterone in humans
Authors: Thosar Saurabh S. , Rueda Jose F. , Berman Alec M. , Lasarev Michael R. , Herzig Maya X. , Clemons Noal A. , Roberts Sally A. , Bowles Nicole P. , Emens Jonathan S. , Ellison David H. , Shea Steven A.
Published: December 2018

Measurements of aldosterone for diagnosis of primary aldosteronism are usually made from blood sampled in the morning when aldosterone typically peaks. We tested the relative contributions and interacting influences of the circadian system, ongoing behaviors, and prior sleep to this morning peak in aldosterone. To determine circadian rhythmicity and separate effects of behaviors on aldosterone, 16 healthy participants completed a 5-day protocol in dim light while all behaviors ranging from sleep to exercise were standardized and scheduled evenly across the 24-h circadian period. In another experiment, to test the separate effects of prior nocturnal sleep or the inactivity that accompanies sleep on aldosterone, 10 healthy participants were studied across 2 nights: 1 with sleep and 1 with maintained wakefulness (randomized order). Plasma aldosterone was measured repeatedly in each experiment. Aldosterone had a significant endogenous rhythm ( P < 0.001), rising across the circadian night and peaking in the morning (~8 AM). Activity, including exercise, increased aldosterone, and different behaviors modulated aldosterone differently across the circadian cycle (circadian phase × behavior interaction; P < 0.001). In the second experiment, prior nocturnal sleep and prior rested wakefulness both increased plasma aldosterone ( P < 0.001) in the morning, to the same extent as the change in circadian phases between evening and morning. The morning increase in aldosterone is due to effects of the circadian system plus increased morning activities and not prior sleep or the inactivity accompanying sleep. These findings have implications for the time of and behaviors preceding measurement of aldosterone, especially under conditions of shift work and jet lag.
Cloning, function, and localization of human, canine, and Drosophila ZIP10 (SLC39A10), a Zn2+ transporter
Authors: Landry Greg M. , Furrow Eva , Holmes Heather L. , Hirata Taku , Kato Akira , Williams Paige , Strohmaier Käri , Gallo Chris J. R. , Chang Minhwang , Pandey Mukesh K. , Jiang Huailei , Bansal Aditya , Franz Marie-Christine , Montalbetti Nicolas , Alexander Mariam P. , Cabrero Pablo , Dow Julian A. T. , DeGrado Timothy R. , Romero Michael F.
Published: December 2018

Zinc (Zn2+) is the second most abundant trace element, but is considered a micronutrient, as it is a cofactor for many enzymes and transcription factors. Whereas Zn2+ deficiency can cause cognitive immune or metabolic dysfunction and infertility, excess Zn2+ is nephrotoxic. As for other ions and solutes, Zn2+ is moved into and out of cells by specific membrane transporters: ZnT, Zip, and NRAMP/DMT proteins. ZIP10 is reported to be localized at the apical membrane of renal proximal tubules in rats, where it is believed to play a role in Zn2+ import. Renal regulation of Zn2+ is of particular interest in light of growing evidence that Zn2+ may play a role in kidney stone formation. The objective of this study was to show that ZIP10 homologs transport Zn2+, as well as ZIP10, kidney localization across species. We cloned ZIP10 from dog, human, and Drosophila ( CG10006), tested clones for Zn2+ uptake in Xenopus oocytes and localized the protein in renal structures. CG10006, rather than foi (fear-of-intimacy, CG6817) is the primary ZIP10 homolog found in Drosophila Malpighian tubules. The ZIP10 antibody recognizes recombinant dog, human, and Drosophila ZIP10 proteins. Immunohistochemistry reveals that ZIP10 in higher mammals is found not only in the proximal tubule, but also in the collecting duct system. These ZIP10 proteins show Zn2+ transport. Together, these studies reveal ZIP10 kidney localization, a role in renal Zn2+ transport, and indicates that CG10006 is a Drosophila homolog of ZIP10.
Integrated method for quantitative morphometry and oxygen transport modeling in striated muscle
Authors: Al-Shammari Abdullah A. , Kissane Roger W. P. , Holbek Simon , Mackey Abigail L. , Andersen Thomas R. , Gaffney Eamonn A. , Kjaer Michael , Egginton Stuart
Published: December 2018

Identifying structural limitations in O2transport is primarily restricted by current methods employed to characterize the nature of physiological remodeling. Inadequate resolution or breadth of available data has impaired development of routine diagnostic protocols and effective therapeutic strategies. Understanding O2transport within striated muscle faces major challenges, most notably in quantifying how well individual fibers are supplied by the microcirculation, which has necessitated exploring tissue O2supply using theoretical modeling of diffusive exchange. With capillary domains identified as a suitable model for the description of local O2supply and requiring less computation than numerically calculating the trapping regions that are supplied by each capillary via biophysical transport models, we sought to design a high-throughput method for histological analysis. We present an integrated package that identifies optimal protocols for identification of important input elements, processing of digitized images with semiautomated routines, and incorporation of these data into a mathematical modeling framework with computed output visualized as the tissue partial pressure of O2(Po2) distribution across a biopsy sample. Worked examples are provided using muscle samples from experiments involving rats and humans.

NEW & NOTEWORTHY Progress in quantitative morphometry and analytical modeling has tended to develop independently. Real diagnostic power lies in harnessing both disciplines within one user-friendly package. We present a semiautomated, high-throughput tool for determining muscle phenotype from biopsy material, which also provides anatomically relevant input to quantify tissue oxygenation, in a coherent package not previously available to nonspecialist investigators.
Effects of weight loss on dynamic hyperinflation in obese women asthmatics
Authors: Grandi Silva Aline , Duarte Freitas Patricia , Ferreira Palmira Gabriele , Stelmach Rafael , Carvalho-Pinto Regina Maria , Salge Joao Marcos , Arruda Martins Milton , Carvalho Celso R. F.
Published: December 2018

Obese adults with asthma are more likely to develop dynamic hyperinflation (DH) and expiratory flow limitation (EFL) than nonobese asthmatics, and weight-loss seems to improve the breathing mechanics during exercise. However, studies evaluating the effect of weight loss on DH in obese adults with asthma have not been performed. We sought to evaluate the effect of a weight loss program on DH in obese adults with asthma. Forty-two asthma patients were enrolled in a weight loss program (diet, psychological support, and exercise) and were subsequently divided into two groups according to the percentage of weight loss: a ≥5% group ( n = 19) and a <5% group ( n = 23). Before and after the intervention, DH and EFL (constant load exercise), health-related quality of life (HRQoL), asthma control, quadriceps muscle strength and endurance, body composition, and lung function were assessed. Both groups exhibited a decrease of ≥10% in inspiratory capacity (DH) before intervention, and only the ≥5% group showed clinical improvement in DH compared with the <5% group postintervention (−9.1 ± 14.5% vs. −12.5 ± 13.5%, respectively). In addition, the ≥5% group displayed a significant delay in the onset of both DH and EFL and a clinically significant improvement in HRQoL and asthma control. Furthermore, a correlation was observed between reduced waist circumference and increased inspiratory capacity ( r = −0.45, P = 0.05) in the ≥5% group. In conclusion, a weight-loss of ≥5% of the body weight improves DH, which is associated with waist circumference in obese adults with asthma. In addition, the group with greater weight-loss showed a delayed onset of DH and EFL during exercise and improved asthma clinical control and HRQoL.

NEW & NOTEWORTHY This is the first study to evaluate dynamic hyperinflation (DH) after a weight loss program in obese patients with asthma. Our results demonstrate that moderate weight loss can improve DH in obese patients with asthma that is associated with a decrease in abdominal fat. Moreover, a minimum of 5% in weight loss delays the onset of DH and expiratory flow limitation besides inducing a clinical improvement in asthma quality of life and clinical control.
Effect of net gas volume changes on alveolar and arterial gas partial pressures in the presence of ventilation-perfusion mismatch
Authors: Korman Ben , Dash Ranjan K. , Peyton Philip J.
Published: December 2018

The second gas effect (SGE) occurs when nitrous oxide enhances the uptake of volatile anesthetics administered simultaneously. Recent work shows that the SGE is greater in blood than in the gas phase, that this is due to ventilation-perfusion mismatch, that as mismatch increases, the SGE increases in blood but is diminished in the gas phase, and that these effects persist well into the period of nitrous oxide maintenance anesthesia. These modifications of the SGE are most pronounced with the low soluble agents in current use. We investigate further the effect of net gas volume loss during nitrous oxide uptake on low concentrations of other gases present using partial pressure-solubility diagrams. The steady-state equations of gas exchange were solved assuming a log-normal distribution of ventilation-perfusion ratios using Lebesgue-Stieltjes integration. It was shown that under these conditions the classical partial pressure-solubility diagram must be modified, that for currently used volatile anesthetic agents the alveolar-arterial partial pressure difference is less than that predicted in the past, and that the alveolar-arterial partial pressure difference may even be reversed during uptake in the case of highly insoluble gases such as sulfur hexafluoride. Comparing this with the situation described previously for nitrogen in steady-state air breathing, we show that for nitrogen, the direction of the alveolar-arterial gradient is opposite to the direction of net gas volume movement. Although gas uptake with ventilation-perfusion inequality exceeding that when matching is optimal is shown to be possible, it is less likely than alveolar-arterial partial pressure reversal.

NEW & NOTEWORTHY Net uptake of gases administered with nitrous oxide may proceed against an alveolar-arterial partial pressure gradient. The alveolar-arterial gradient for nitrogen in the steady-state breathing air depends not only on the existence of a distribution of ventilation-perfusion ratios in the lung but also on the presence of a net change in gas volume and is opposite in direction to the direction of net gas volume uptake.
Titin as a force-generating muscle protein under regulatory control
Authors: Freundt Johanna K. , Linke Wolfgang A.
Published: December 2018

Titin has long been recognized as a mechanical protein in muscle cells that has a main function as a molecular spring in the contractile units, the sarcomeres. Recent work suggests that the titin spring contributes to muscle contraction in a more active manner than previously thought. In this review, we highlight this property, specifically the ability of the immunoglobulin-like (Ig) domains of titin to undergo unfolding-refolding transitions when isolated titin molecules or skeletal myofibrils are held at physiological force levels. Folding of titin Ig domains under force is a hitherto unappreciated, putative source of work production in muscle cells, which could work in synergy with the actomyosin system to maximize the energy delivered by a stretched, actively contracting muscle. This review also focuses on the mechanisms shown to modulate titin-based viscoelastic forces in skeletal muscle cells, including chaperone binding, titin oxidation, phosphorylation, Ca2+binding, and interaction with actin filaments. Along the way, we discuss which of these modulatory mechanisms might contribute to the phenomenon of residual force enhancement relevant for eccentric muscle contractions. Finally, a brief perspective is added on the potential for the alterations in titin-based force to dynamically alter mechano-chemical signaling pathways in the muscle cell. We conclude that titin from skeletal muscle is a determinant of both passive and active tension and a bona fide mechanosensor, whose stiffness is tuned by various independent mechanisms.
Paraganglioma Presenting as a Nasal Septal Mass: Case Report and Literature Review
Authors: Kim James H. , Tu Nathan , Wrobel Bozena Barbara
Published: December 2018

Objectives. To describe a rare case of a paraganglioma arising from the nasal septum and review the diagnosis and management of paragangliomas in the nasal cavity and paranasal sinuses.Methods. We present a case of a 70-year-old female presenting with persistent nasal congestion and obstruction. Nasal endoscopy revealed a posterior septal mass approaching the sphenoid sinuses and partially obstructing the nasopharynx. A biopsy of the mass was taken, and histologic analysis confirmed a diagnosis of paraganglioma.Results. The patient underwent an endoscopic resection of the tumor. There has been no evidence of disease recurrence after 3 months of follow‐up.Conclusions. Paragangliomas arising from the nasal septum are exceedingly rare, but should be considered in the differential diagnosis in patients presenting with nasal septal masses. These tumors are typically benign, although few cases of malignant sinonasal paragangliomas have been reported. Treatment requires surgical excision with close follow-up as several cases of tumor recurrence have been reported.
Clinical Utility of Neutrophil CD64 to Detect Extrapulmonary Tuberculosis in Three Patients with Rheumatoid Arthritis Undergoing Treatment with Biologics
Authors: Nogi Shinichi , Arinuma Yoshiyuki , Komiya Akiko , Hashimoto Atsushi , Matsui Toshihiro , Tohma Shigeto
Published: December 2018

Biologics play a key role in the treatment of rheumatoid arthritis (RA), while RA-related serious infection remains an unsettled clinical problem. Detection of tuberculosis (TB) is challenging due to the difficulty in distinguishing symptoms such as fever and elevation of inflammatory markers from other infections or a disease flare of RA. The expression of the CD64 molecule on neutrophils (neutrophil CD64) was upregulated by various infections including TB. However, it was not affected by disease activity of RA or by any therapy against RA. The present article reports three cases of extrapulmonary TB which occurred in patients with RA undergoing treatment with biologics. The marked increase in the levels of neutrophil CD64 may provide important insight into the diagnosis of TB.
Ultrasound Improves Antimicrobial Effect of Sodium Hypochlorite and Instrumental Texture on Fresh-Cut Yellow Melon
Authors: Rosario Denes K. A. , Duarte Ana Lucia A. , Madalao Marina C. M. , Libardi Manoela C. , Teixeira Luciano J. Q. , Conte-Junior Carlos A. , Bernardes Patricia C.
Published: December 2018

Ultrasound combined with sanitizers is efficient for the reduction of microbiological contaminants in fruits and vegetables. However, the physicochemical changes remain to be elucidated. Therefore, the isolated and combined effect of ultrasound (40 kHz, 500 W) and sodium hypochlorite (NaOCl) (100 mg/L) for 5 min in the bacterial microbiota and physicochemical changes on yellow melon (Cucumis melo L.) were evaluated. Mesophilic aerobic bacteria (MAB), pH, total titratable acidity (TTA), and texture profile were performed. No changes in pH and TTA (p>0.05) were obtained. Firmness, chewiness, cohesiveness, and gumminess increased (p<0.05) after the ultrasound application. A synergistic effect between ultrasound and NaOCl in the MAB reduction was achieved. Therefore, ultrasound improves the antimicrobial effect of NaOCl and texture profile without undesirable chemical changes.
Spleen‐Kidney Supplementing Formula Alleviates Renal Fibrosis in Diabetic Rats via TGF‐β1‐miR‐21‐PTEN Signaling Pathway
Authors: Tian Chunyu , Wang Ya , Chang Hong , Li Ji’an , La Xiaojin
Published: December 2018

Background. Spleen‐Kidney Supplementing Formula (SKSF), composed of 6 raw Chinese herbs and proposed based on the therapeutic principle of supplementing spleen‐kidney and clearing the extra heat of stomach‐lung, is effective in the treatment of type 2 diabetes mellitus (T2DM). Aim. This study aims to investigate the mechanism of SKSF to alleviate renal fibrosis in diabetic rats. Methods. T2DM model was induced by high‐fat diet and multiple injections of low‐dose streptozotocin. After 8‐week intervention, samples were collected for detection. Results. SKSF decreased fasting blood glucose, glycosylated hemoglobin A1c, blood urea nitrogen, uric acid, urea, 24‐hour urine protein, and KW/BW ratio, while it increased creatinine clearance rate of T2DM rats. Meanwhile, SKSF attenuated the renal fibrosis and improved the morphology and structure of renal tissue. Furthermore, SKSF significantly reduced the expression level of plasma miR‐21 and TGF‐β1 protein level and increased PTEN protein level. Conclusion. SKSF could attenuate the renal damage and renal fibrosis induced in T2DM, which may be related to its regulation on the expressions of TGF‐β1, PTEN, and miR‐21.
Automated, Noncontact Intraocular Pressure Home Monitoring after Implantation of a Novel Telemetric Intraocular Pressure Sensor in Patients with Glaucoma: A Feasibility Study
Authors: Koutsonas Antonis , Walter Peter , Kuerten David , Plange Niklas
Published: December 2018

Purpose. Reliable and regular assessment of intraocular pressure (IOP) is important for the monitoring of patients with glaucoma. The purpose of this study was to evaluate the feasibility of a novel system for the automated, noncontact measurement of IOP. Patients and Methods. A first-generation telemetric IOP sensor was previously implanted in the ciliary sulcus of six patients with open-angle glaucoma during cataract surgery. Using this technology, automated noninvasive tonometry may be performed in a home setting. In the present study, a modified sleep mask and a modified eyepatch with incorporated coil antennae for measurements during nighttime and daytime, respectively, were tested on a single patient. Results. In this feasibility study, the 24 h wear of the prototype measuring apparatus was well tolerated. Three sequences of 24 h IOP measurements with at least 200 IOP measurements per day were performed (Sequence 1: mean 19.6 ± 2.7 mmHg, range 13.4–28.7 mmHg; Sequence 2: mean 21.0 ± 3.0 mmHg, range 13.1–30.5 mmHg; Sequence 3: mean 19.9 ± 2.4 mmHg, range 12.6–27 mmHg). Conclusions. For the first time, repeated and automated 24-hour measurements are possible using a prototype noncontact reading system after implantation of a novel telemetric IOP sensor in patients with glaucoma.
Ultrashort Long-Period Fiber Gratings Inscribed on a Single-Mode Fiber for Torsion Sensing Applications
Authors: Nespereira Marta , Coelho João M. P. , Rebordão José Manuel
Published: December 2018

The response of ultrashort-length CO2-induced long-period fiber grating (LPFG) sensors to torsion is reported. While engraving using CO2 laser radiation, the fiber is submitted to high tension allowing the obtainment of gratings with shorter lengths, down to 2.4 mm, which is almost one order of magnitude lower than the usual. Also, the fiber is only irradiated in one side, creating an asymmetrical profile leading to highly birefringent gratings. Sensitivity to axial twists is demonstrated, with values up to 0.15 nm/(rad/m) for the resonant wavelength shift and higher than 0.03 dBm/(rad/m) for the variation in the intensity (attenuation). Discrimination between rotation directions, clockwise and counterclockwise, was observed.
Effect of Neoadjuvant Hormone Therapy on Resection Margin and Survival Prognoses in Locally Advanced Prostate Cancer after Prostatectomy Using Propensity-Score Matching
Authors: Kim Sung Han , Park Eun Young , Joo Jungnam , Joung Jae Young , Seo Ho Kyung , Chung Jinsoo , Lee Kang Hyun
Published: December 2018

This study aimed to investigate the effect of neoadjuvant hormone therapy (NHT) on resection margin positivity, biochemical-recurrence- (BCR-) free survival, and overall survival (OS) in 176 patients with locally advanced prostate cancer (LAPC) treated with radical prostatectomy using propensity-score matching, including 79 (44.9%) patients treated with the NHT. Fifty pairs of one-to-one propensity-score matching were matched to investigate the pure effect of NHT on resection margin positivity, BCR, and OS with a statistical significance of p<0.050. Before matching, NHT, tumor volume percentage, and extracapsular extension were significant factors for resection margin positivity (p≤0.001); however, after matching, NHT became insignificant in the multivariate analysis (p=0.084). In the survival analysis, NHT was not associated with BCR or OS before and after matching (BCR: hazard ratio, 1.35 and 0.84, respectively; OS: hazard ratio, 1.05 and 0.77, respectively; p≥0.539 for all). Conversely, PSA level (HR, 2.23), extracapsular extension (HR, 2.10), and lymphovascular invasion (HR, 1.85) were significant factors for BCR (p≤0.001 for all), but none were significant factors for OS in the propensity-score matching analysis (p≥0.948). Therefore, NHT was not a significant factor for resection margin positivity, BCR-free survival, and OS before and after propensity-score matching in patients with LAPC.
MicroRNA Expression Profiles Identify Biomarker for Differentiating the Embolic Stroke from Thrombotic Stroke
Authors: Chen Lai-Te , Jiang Chen-Yang
Published: December 2018

In order to identify potential biomarkers that distinguish the embolic stroke (ES) from thrombotic stroke (TS), a profile of microRNA expression was analyzed. The GSE60319 expression profile was downloaded from the Gene Expression Omnibus (GEO) database. The GEO2R was applied to screen for differentially expressed microRNAs (DEmiRNAs) between the embolic stroke group and thrombotic stroke group. The miRWalk was utilized to predict the target genes of DEmiRNAs. Genes associated with embolic stroke were downloaded from the Comparative Toxicogenomics Database. Cross reference of target genes to disease related genes was conducted to construct the DEmiRNA-gene network. The protein-protein interaction (PPI) network of overlapping genes was evaluated by STRING, using the MCODE and CytoHubba plugin of Cytoscape to identify the modules and hub genes. The enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) in modules was performed. There were 30 microRNAs in total identified as DEmiRNAs between embolic stroke and thrombotic stroke groups, of which 8 were upregulated and 22 were downregulated. Among these differentially expressed miRNAs, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were significantly associated with an ES to TS. Using the miRWalk 3.0 online tool, target genes regulated by DEmiRNAs were predicted. In addition, disease related genes were predicted and compared with target genes of DEmiRNAs. 166 overlapped genes regulated by miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were identified, suggesting their association with diseases that contributed to ES, mainly including atrial fibrillation, mitral valve stenosis, myocardial infarction, and aortic dissection. Therefore, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were promising candidate biomarkers for differentiating an ES from TS. The PPI network demonstrated that miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were associated with an ES by mainly regulating “CCND1, E2F2, E2F3, ITCH, UBE4A, UBE3C, RBL2, FBXO31, EIF2C4, and EIF2C1”. Furthermore, miR-15a-5p and miR-17-5p may function through “cell cycle, prostate cancer, and small cell lung cancer” while miR-19b-3p and miR-20a-5p function through “insulin resistance, hepatitis B, and viral carcinogenesis” and “vasopressin-regulated water reabsorption”, respectively. However, these results were approached in the manner of bioinformatics analysis; therefore, further verification is required.
Laparoscopic Repair for Recurrent Bilateral Inguinal Bladder Hernia following Bilateral Transabdominal Preperitoneal Repair
Authors: Umemura Akira , Suto Takayuki , Fujuwara Hisataka , Nakamura Seika , Nitta Hiroyuki , Takahara Takeshi , Hasegawa Yasushi , Sasaki Akira
Published: December 2018

Introduction. Although a recurrent inguinal hernia is sometimes observed as a supravesical hernia, it is extremely rare to encounter a bilateral bladder sliding hernia recurrence. In this report, we describe an extremely rare case of a recurrent bilateral supravesical bladder hernia after bilateral transabdominal preperitoneal repair (B-TAPP). Case Presentation. A 69-year-old man visited our hospital with complaints of bilateral groin swelling and frequent voiding after B-TAPP. A plain CT revealed that the urinary bladder was herniating into the bilateral supravesical hernias. He underwent laparoscopic bilateral supravesical bladder hernia repair using a bladder takedown approach and median TAPP. Discussion. In Japan, the current mainstream method of hernioplasty is TAPP. However, an immature surgical technique and inadequate mesh placement may increase the risk of recurrent hernias. We successfully repaired this patient’s recurrent bilateral supravesical bladder hernias laparoscopically. Conclusion. This rare condition (recurrent bilateral supravesical bladder hernias after B-TAPP) was successfully treated by using the bladder takedown approach and median TAPP. During surgical training and later in clinical practice, surgeons should master a surgical technique for this procedure in order to reduce recurrent hernias.