bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatigue in chronic liver disease: New insights and therapeutic approaches
Authors: Swain Mark G. , Jones David E. J. 
Published: June 2018

AbstractThe management of fatigue associated with chronic liver disease is a complex and major clinical challenge. Although fatigue can complicate many chronic diseases, it is particularly common in diseases with an inflammatory component. Fatigue can have both peripheral (i.e., neuromuscular) and central (i.e., resulting from changes in neurotransmission within the brain) causes. However, fatigue in chronic liver disease has strong social/contextual components and is often associated with behavioural alterations including depression and anxiety. Given the increasing awareness of patient‐reported outcomes as important components of treatment outcomes and clinical research, there is a growing need to better understand and manage this poorly understood yet debilitating symptom. Although several pathophysiological mechanisms for explaining the development of fatigue have been generated, our understanding of fatigue in patients with chronic liver disease remains incomplete. A better understanding of the pathways and neurotransmitter systems involved may provide specific directed therapies. Currently, the management of fatigue in chronic liver disease can involve a combined use of methods to beneficially alter behavioural components and pharmacological interventions, of which several treatments have potential for the improved management of fatigue in chronic liver disease. However, evidence and consensus are lacking on the best approach and the most appropriate biochemical target(s) whilst clinical trials to address this issue have been few and limited by small sample size. In this review, we outline current understanding of the impact of fatigue and related symptoms in chronic liver disease, discuss theories of pathogenesis, and examine current and emerging approaches to its treatment.
Genetic polymorphisms of the hepatic pathways of fatty liver disease after living donor liver transplantation
Authors: Chiu King‐Wah , Goto Shigeru , Nakano Toshiaki , Hu Tsung‐Hui , Chen Ding‐Wei , Huang Kuang‐Tzu , Hsu Li‐Wen , Chen Chao‐Long 
Published: June 2018

AbstractBackground & AimsFatty liver disease is an important complication associated with liver transplantation, and the cytochrome P‐450 system of the donor liver may be involved in its pathogenesis. To explore the effects of the CYP27A1, CYP27B1, CYP2R1, and vitamin D receptor pathways on vitamin D maintenance after living donor liver transplantation, we investigated the interplay between serum 25(OH)D and common variants in 60 paired donors and recipients who underwent living donor liver transplantation.MethodsWe prospectively collected 60 donor/recipient pairs from our liver transplantation programmes and extracted serum DNA to evaluate single nucleotide polymorphisms in CYP27A1 rs4674344, CYP27B1 rs10877012, CYP2R1 rs10741657, and VDR rs2228530 alleles using real‐time polymerase chain reaction. We measured serum 25(OH)D concentrations of donors (D‐D0) and recipients before (R‐D0) and after (R‐D30) living donor liver transplantation for comparison with repeated‐measures analysis of variance in generalized estimating equations analysis.ResultsFatty liver disease was noted in 28.3% of the cases after living donor liver transplantation, and the graft rejection rate was 25%. There were significant differences in low serum 25(OH)D concentrations between D‐D0 and R‐D0 and between R‐D0 and R‐30 groups. Significant associations were observed for serum CYP27A1 rs4674344 in recipients and donors as well as for graft liver tissue with VDR rs2228530. There was no significant relationship with serum CYP27B1 rs10877012 in recipients and donors or with graft liver tissue with CYP2R1 rs10741657.ConclusionsDonor/recipient CYP27A1 rs4674344 and graft VDR rs2228570 may be related to low serum 25(OH)D and may play a major role in the development of fatty liver disease in recipients after living donor liver transplantation.
Metformin inhibits TGF‐beta 1‐induced MCP‐1 expression through BAMBI‐mediated suppression of MEK/ERK1/2 signalling
Authors: Liang Diefei , Song Zijiao , Liang Weiwen , Li Yan , Liu Shanying 
Published: June 2018

ABSTRACTAimsMetformin is a biguanide derivative widely used for the treatment of type 2 diabetes mellitus. Recent evidence demonstrates that this anti‐hyperglycaemic drug exerts renal protective effects, yet the mechanisms remain poorly understood. monocyte chemoattractant protein 1 (MCP‐1) has been recognized as a key mediator of renal fibrosis in chronic kidney diseases, including diabetic nephropathy. This study aimed to investigate the effects of metformin on transforming growth factor beta 1 (TGF‐β1)‐induced MCP‐1 expression and the underlying mechanisms in rat renal tubular epithelial cells.MethodsRat renal tubular epithelial cell line NRK‐52E cells were stimulated with TGF‐β1 and/or metformin. The messenger RNA (mRNA) of MCP‐1 and bone morphogenetic protein and activin membrane‐bound inhibitor (BAMBI) was evaluated by real‐time quantitative polymerase chain reaction. MCP‐1 protein was measured by enzyme linked immunosorbent assay (ELISA). Total and phosphorylated extracellular signal‐regulated kinases 1/2 (ERK1/2) was evaluated by western blot. Down‐ and upregulation of BAMBI were achieved by RNA interference targeting BAMBI and lentiviral vector‐mediated overexpression of the BAMBI gene, respectively. Cell viability was analysed using Cell Counting Kit 8 (CCK‐8) reagents.ResultsStimulation with TGF‐β1 resulted in the increased expression of MCP‐1 and decreased expression of BAMBI in NRK‐52E cells. Metformin inhibited the expression of MCP‐1 in NRK‐52E cells. Pretreatment with metformin suppressed upregulation of MCP‐1 and downregulation of BAMBI, as well as phosphorylation of ERK1/2 induced by TGF‐β1. U0126, a specific inhibitor for mitogen‐activated and extracellular signal‐regulated kinase kinases 1/2 (MEK‐1/2), completely blocked TGF‐β1‐induced MCP‐1 expression. Knockdown of the BAMBI gene promoted phosphorylation of ERK1/2 and TGF‐β1‐induced expression of MCP‐1. Overexpression of BAMBI inhibited phosphorylation of ERK1/2 and TGF‐β1‐induced upregulation of MCP‐1.ConclusionIn rat renal tubular epithelial cells, metformin prevents TGF‐β1‐induced MCP‐1 expression, in which BAMBI‐mediated inhibition of MEK/ERK1/2 might be involved.
Effect of radiofrequency on epicardial myocardium after ablation of ventricular arrhythmias from within coronary sinus
Authors: Candemir Basar , Ozyurek Elif , Vurgun Kutay , Turan Nazli , Duzen Veysel , Goksuluk Huseyin , Ozyuncu Nil , Kurklu Seda , Altin Timucin , Akyurek Omer , Erol Cetin 
Published: June 2018

AbstractBackgroundRadiofrequency (RF) ablation of idiopathic ventricular arrhythmias (IVA) from the coronary venous system (CVS) has been increasingly performed, but real effect of ablation lesions from CVS on epicardial myocardium has not been studied.ObjectiveTo compare effects of RF delivered inside the distal CVS during ablation of IVAs originating from left ventricular summit (LVS) with IVAs ablated from right ventricular outflow tract (RVOT) using cardiac magnetic resonance imaging (CMRI).MethodsTwenty consecutive patients with IVAs who underwent acutely successful RF ablation at initial appropriate sites, i.e., distal CVS (Group 1, n = 10) or RVOT (Group 2; n = 10) were enrolled. Detailed contrast‐enhanced CMRI of each patient was performed 3 months later. Presence and location of scars, distance of CVS to epicardial ventricular myocardium were measured and analyzed.ResultsGroup 1 consisted of 10 and Group 2 consisted of 10 patients. Three months after the ablation, only three patients in Group 1 had detectable late gadolinium enhancement (LGE) on CMRI while nine out of 10 patients in Group 2 had evident LGE on CMRI (P: 0.02). The mean distance of distal CVS to epicardial anterobasal myocardium was measured to be 8.8 ± 1.6 mm in Group 1. In three cases that had detectable scar on superior anterobasal LV epicardium, the mean distance was 7.4 ± 1.1 mm.ConclusionsRF delivery inside the CVS is less likely to produce detectable LGE on CMRI compared to RVOT. This may partially explain less than ideal long‐term results after ablation of LVS IVAs from within the great cardiac vein/anterior interventricular vein.
Significant age‐ and gender‐related variability of main lymphocyte subsets in paediatric patients: Latvian data
Authors: Nikulshin Sergey , Kundzina Linda , Tolstikova Iveta , Gravele Dagne , Prokofjeva Tatjana , Gardovska Dace 
Published: June 2018

AbstractAge‐ and gender‐related variability of main lymphocyte subsets (T, B and NK cell absolute counts and percentages from Ly; T4, T8 and DN cell absolute counts and percentages from lymphocytes and from T cells; T4:T8 and T:B ratios) was studied in a large cohort of paediatric patients (2 days‐17 years) at yearly intervals. A total of 4128 six‐color TBNK tests performed on BD FACSCanto II flow cytometer were assessed; patients with immune deficiencies and tumours were not included. The study revealed significant age‐ and gender‐related changes in all subsets. Absolute counts of T, B, T4 cells dropped from neonates to adolescents, decrease in T8 and NK cells was milder; relative count of T cells increased with age and that of B cells decreased; T4:T8 ratio went down and T:B ratio grew. Total T, T4 cells and T4:T8 ratio were significantly higher in girls, while T8, NK and DN cells were significantly higher in boys; significantly higher relative and absolute B cell counts in boys appeared in adolescence. We compared our results with reference values for healthy children (Tosato et al, Cytometry A. 2015;87:81); there was a good concordance, except for DN cells. Advantages of using patient cohort instead of healthy children as reference, possibilities for adjusting age‐ and gender‐specific reference ranges and potential international data pooling are discussed.
Molecular mimicry: An explanation for autoimmune diseases and infertility
Authors: Thaper Deepali , Prabha Vijay 
Published: June 2018

AbstractMicroorganisms execute an enthralling range of adjustments to survive in the host. Among the various strategies employed by microorganisms to surmount the host immune response, the phenomenon of molecular mimicry empowers the microorganisms to manoeuvre host physiology and cellular functions for their own advantage by mimicking the host proteins and initiating autoimmunity. This phenomena, by and large, has been studied in context of autoimmune diseases; however, its implications have also been reported in infertility. Hence, in this article, we provide a review of the various instances of molecular mimicry initiated by bacteria, parasites and viruses in the world of autoimmune diseases and infertility.
Critical micelle concentration and particle size determine adjuvanticity of cyclic lipopeptides
Authors: Yoshino Naoto , Takeshita Ryosuke , Kawamura Hanae , Murakami Kazuyuki , Sasaki Yutaka , Sugiyama Ikumi , Sadzuka Yasuyuki , Kagabu Masahiro , Sugiyama Toru , Muraki Yasushi , Sato Shigehiro 
Published: June 2018

AbstractCyclic lipopeptides such as surfactin and polymyxin have potent mucosal adjuvant properties. Cyclic lipopeptides are tensioactive compounds, but the relationship between adjuvanticity and surface activity is unknown. Here, we show that the critical micelle concentration (cmc) of surfactant and particle size of the surfactant‐protein complex are important determinants of cyclic lipopeptide adjuvanticity. We found that the diameter of cyclic lipopeptide‐ovalbumin (OVA) complex particles was significantly larger than that in the solutions of OVA alone at cyclic lipopeptide concentrations above the cmc. OVA‐specific antibody titres in mice immunized intranasally with OVA and a cyclic lipopeptide at concentrations above its cmc were significantly higher than those in mice immunized with OVA plus the same dose of the cyclic lipopeptide but administered with formulations in which cyclic lipopeptide concentration was below the cmc. Thus, the concentration of the cyclic lipopeptide in the formulation at immunization, but not its overall dose, was critical for its adjuvanticity. Furthermore, two types of aggregates, the cyclic lipopeptide simplex micelles and the cyclic lipopeptide‐OVA complex micelles, were found in formulations with SF concentrations above its cmc. Degranulation of mast cells exposed to SF simplex micelles was more pronounced when SF concentration was above the cmc. In conclusion, our study showed that surface activity properties, such as the cmc and the size of surfactant‐protein complex, contribute to the adjuvanticity of cyclic lipopeptides. Our study proposes a novel idea that cmc is a key parameter for tensioactive adjuvants.
Identifying the best body‐weight‐status index associated with metabolic risk in youth
Authors: Gomes Thayse Natacha , Nevill Alan , Katzmarzyk Peter T. , Pereira Sara , dos Santos Marcos Moura , Buranarugsa Rojapon , dos Santos Fernanda Karina , Souza Michele , Chaves Raquel , Maia José 
Published: June 2018

This study investigated the association of six different anthropometric markers with metabolic syndrome to find the most suited to predict children at risk. Sample comprises 1324 Portuguese youth (701 girls, 623 boys), aged 10‐17 years. Six anthropometric markers were included: body mass index (BMI), BMI z‐score, tri‐ponderal index (TPI), waist circumference (WC), WC/height ratio (WC/H), and WC/H adjusted ratio (WC/Hadj). A standardized metabolic risk score (zMR) was computed by summing of standardized values for fasting glucose, triglycerides, high‐density lipoprotein cholesterol, and mean arterial blood pressure. The associations between zMR and anthropometric markers were assessed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal values that best predict metabolic risk of each anthropometric marker. Among the studied predictors, BMI z‐score, followed by BMI and WC, was most highly associated with zMR, while WC/Hadj was the weakest predictor. ROC analyses showed significant AUCs for all markers, yet the discrimination was poor (AUCs from 0.60 to 0.68), with sensitivity ranging from 45.5% to 67.5% and specificity from 72.6% to 81.9%. The optimal cut‐off values to predict metabolic risk were 1.62, 23.1 kg/m2, 71.0 cm, 18.0 kg/m3, 0.47, and 0.50, for BMI z‐score, BMI, WC, TPI, WC/H, and WC/Hadj, respectively. BMI z‐score, followed by BMI and WC, were the most relevant anthropometric markers to predict metabolic risk in youth, while WC/Hadj was the worst predictor. Results suggest that anthropometric markers should continue to be used as clinical tools to identify youth at risk.
Epidemiology of injuries in outdoor and indoor hockey players over one season: a prospective cohort study
Authors: Hollander Karsten , Wellmann Kai , Eulenburg Christine zu , Braumann Klaus-Michael , Junge Astrid , Zech Astrid 
Published: June 2018

ObjectivesTo determine the incidence and characteristics of hockey (‘field hockey’) injuries over the course of one outdoor and indoor season. Comparisons of female versus male players, outdoor versus indoor season and match versus practice were performed.MethodsFemale and male teams of the first, second, third, regional and youth divisions were recruited among a local hockey association in Northern Germany, and followed over an indoor and an outdoor season. Exposure times and location, type, severity and cause of injuries during practice and matches were documented by the coaches or medical staff and collected weekly. Prevalence and incidence rates were calculated.ResultsOf the 232 players (mean±SD age 20.7±4.7 years, 68.1% male, 31.9% first division), 84 players (36.2%) suffered 108 new injuries during the season. The overall incidence rate was 3.7 injuries per 1000 player hours (95% CI 3.0 to 4.4). The injury incidence was lower in practice (2.7 per 1000 player practice hours, 95% CI 2.0 to 3.3) than in matches (9.7 per 1000 player match hours, 95% CI 6.8 to 12.7), and was similar for female and male players as well as during the outdoor and the indoor season. Most injuries affected the lower limb (thigh, knee and ankle) and occurred without contact (58.3%). Severe injuries (n=34; 31.5%) were predominantly located at the knee and hand/finger.ConclusionHockey players have a high prevalence and incidence of injuries, especially at the lower limb.
Understanding changes in dyspnoea perception in obstructive lung disease after mindfulness training
Authors: Malpass Alice , Feder Gene , Dodd James W 
Published: June 2018

IntroductionDyspnoea has been defined as a ‘subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity’. However, the majority of available dyspnoea measures treat it as a single entity and rely on quantitative methodology. We propose that qualitative research can enhance our understanding of dyspnoea, in particular, how perception varies so much among patients with similar disease states. In this paper, we focus on how a specific type of inner attention—mindfulness—may alter perceptions of dyspnoea. The aim is to characterise mindfulness attention, which impacts on perceptions of dyspnoea and relate these to the multidimensional model of dyspnoea. We explore how an individual can change their perception and therefore relationship to similar disease states.Method22 patients with asthma or chronic obstructive pulmonary disease were recruited from primary and secondary care to an 8-week course in mindfulness-based cognitive therapy (MBCT). 12 patients took part in an in-depth qualitative interview 2 months after completing the MBCT course. Data were recorded, transcribed and then analysed using a framework approach, drawing on components of the multidimensional model of dyspnoea (multidimensional dyspnoea profile, MDP).ResultsWe found that MBCT training involves developing three types of mindful attention (broad attention, informative attention and re-directive attention), which impact on perceptions of the sensory dimension of dyspnoea. MBCT appears to target affective and sensory perceptions articulated in the MDP model.ConclusionMore research is needed into how mindfulness-based interventions may mediate the relationship between affective experience and the sensory perception of dyspnoea symptoms.
Changes in autonomy, job demands and working hours after diagnosis of chronic disease: a comparison of employed and self-employed older persons using the English Longitudinal Study of Ageing (ELSA)
Authors: Fleischmann Maria , Carr Ewan , Xue Baowen , Zaninotto Paola , Stansfeld Stephen A , Stafford Mai , Head Jenny 
Published: June 2018

BackgroundModifications in working conditions can accommodate changing needs of chronically ill persons. The self-employed may have more possibilities than employees to modify their working conditions. We investigate how working conditions change following diagnosis of chronic disease for employed and self-employed older persons.MethodsWe used waves 2–7 from the English Longitudinal Study of Ageing (ELSA). We included 1389 participants aged 50–60 years who reported no chronic disease at baseline. Using fixed-effects linear regression analysis, we investigated how autonomy, physical and psychosocial job demands and working hours changed following diagnosis of chronic disease.ResultsFor employees, on diagnosis of chronic disease autonomy marginally decreased (−0.10, 95% CI −0.20 to 0.00) and physical job demands significantly increased (0.13, 95% CI 0.01 to 0.25), whereas for the self-employed autonomy did not significantly change and physical job demands decreased on diagnosis of chronic disease (−0.36, 95% CI −0.64 to –0.07), compared with prediagnosis levels. Psychosocial job demands did not change on diagnosis of chronic disease for employees or the self-employed. Working hours did not change for employees, but dropped for self-employed (although non-significantly) by about 2.8 hours on diagnosis of chronic disease (−2.78, 95% CI −6.03 to 0.48).ConclusionImprovements in working conditions after diagnosis of chronic disease were restricted to the self-employed. This could suggest that workplace adjustments are necessary after diagnosis of chronic disease, but that the self-employed are more likely to realise these. Policy seeking to extend working life should consider work(place) adjustments for chronically ill workers as a means to prevent early exit from work.
Cause-specific mortality by partnership status: simultaneous analysis using longitudinal data from England and Wales
Authors: Franke Sebastian , Kulu Hill 
Published: June 2018

BackgroundThis paper examines cause-specific mortality by partnership status. Although non-marital cohabitation has spread rapidly in industrialised countries, only a few studies have investigated mortality by partnership status and no recent study has investigated cause-specific mortality by partnership status.MethodsWe use data from the Office for National Statistics Longitudinal Study and apply competing risks survival models.ResultsThe simultaneous analysis shows that married individuals have lower mortality than non-married from circulatory, respiratory, digestive, alcohol and accident related causes of deaths, but not from cancer. The analysis by partnership status reveals that once we distinguish premarital and postmarital cohabitants from other non-married groups, the differences between partnered and non-partnered individuals become even more pronounced for all causes of death; this is largely due to similar cause-specific mortality levels between married and cohabiting individuals.ConclusionsWith declining marriage rates and the spread of cohabitation and separation, a distinction between partnered and non-partnered individuals is critical to understanding whether and how having a partner shapes the individuals’ health behaviour and mortality. The cause-specific analysis supports both the importance of selection into partnership and the protective effect of living with someone together.
Anti‐TIM‐1 Monoclonal Antibody (RMT1‐10) Attenuates Atherosclerosis By Expanding IgM‐producing B1a Cells
Authors: Hosseini Hamid , Yi Li , Kanellakis Peter , Cao Anh , Tay Christopher , Peter Karlheinz , Bobik Alex , Toh Ban‐Hock , Kyaw Tin 
Published: June 2018

Background

Peritoneal B1a cells attenuate atherosclerosis by secreting natural polyclonal immunoglobulin M (IgM). Regulatory B cells expressing T‐cell immunoglobulin mucin domain‐1 (
TIM
‐1) expanded through
TIM
‐1 ligation by anti‐
TIM
‐1 monoclonal antibody (
RMT
1‐10) induces immune tolerance.

Methods and Results

We examined the capacity of
RMT
1‐10 to expand peritoneal B1a cells to prevent atherosclerosis development and retard progression of established atherosclerosis.
RMT
1‐10 treatment selectively doubled peritoneal B1a cells, tripled
TIM
‐1
+
B1a cells and increased
TIM
‐1
+
IgM
+
interleukin (IL)‐10
+
by 3‐fold and
TIM
‐1
+
IgM
+
IL‐10
−
B1a cells by 2.5‐fold. Similar expansion of B1a B cells was observed in spleens. These effects reduced atherosclerotic lesion size, increased plasma IgM and lesion IgM deposits, and decreased oxidatively modified low‐density lipoproteins in lesions. Lesion
CD
4
+
and
CD
8
+
T cells, macrophages and monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1, expression of proinflammatory cytokines monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1,
IL
1β, apoptotic cell numbers and necrotic cores were also reduced.
RMT
1‐10 treatment failed to expand peritoneal B1a cells and reduce atherosclerosis after splenectomy that reduces B1a cells, indicating that these effects are B1a cell‐dependent. Apolipoprotein E‐
KO
mice fed a high‐fat diet for 6 weeks before treatment with
RMT
1‐10 also increased
TIM
‐1
+
IgM
+
IL
‐10
+
and
TIM
‐1
+
IgM
+
IL
‐10
−
B1a cells and IgM levels and attenuated progression of established atherosclerosis.

Conclusions

RMT
1‐10 treatment attenuates atherosclerosis development and progression by selectively expanding IgM producing atheroprotective B1a cells. Antibody‐based in vivo expansion of B1a cells could be an attractive approach for treating atherosclerosis.