bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interferon regulatory factors as novel potential targets in the treatment of cardiovascular diseases
Authors: Zhang Xiao‐Jing , Jiang Ding‐Sheng , Li Hongliang 
Published: August 2014

The family of interferon regulatory factors (IRFs) consists of nine members (IRF1–IRF9) in mammals. They act as transcription factors for the interferons and thus exert essential regulatory functions in the immune system and in oncogenesis. Recent clinical and experimental studies have identified critically important roles of the IRFs in cardiovascular diseases, arising from their participation in divergent and overlapping molecular programmes beyond the immune response. Here we review the current knowledge of the regulatory effects and mechanisms of IRFs on the immune system. The role of IRFs and their potential molecular mechanisms as novel stress sensors and mediators of cardiovascular diseases are highlighted.Linked ArticlesThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
Calcium affects OX1 orexin (hypocretin) receptor responses by modifying both orexin binding and the signal transduction machinery
Authors: Putula Jaana , Pihlajamaa Tero , Kukkonen Jyrki P 
Published: August 2014

Background and PurposeOne of the major responses upon orexin receptor activation is Ca2+ influx, and this influx seems to amplify the other responses mediated by orexin receptors. However, the reduction in Ca2+, often used to assess the importance of Ca2+ influx, might affect other properties, like ligand−receptor interactions, as suggested for some GPCR systems. Hence, we investigated the role of the ligand−receptor interaction and Ca2+ signal cascades in the apparent Ca2+ requirement of orexin‐A signalling.Experimental ApproachReceptor binding was assessed in CHO cells expressing human OX1 receptors with [125I]‐orexin‐A by conventional ligand binding as well as scintillation proximity assays. PLC activity was determined by chromatography.Key ResultsBoth orexin receptor binding and PLC activation were strongly dependent on the extracellular Ca2+ concentration. The relationship between Ca2+ concentration and receptor binding was the same as that for PLC activation. However, when Ca2+ entry was reduced by depolarizing the cells or by inhibiting the receptor‐operated Ca2+ channels, orexin‐A‐stimulated PLC activity was much more strongly inhibited than orexin‐A binding.Conclusions and ImplicationsCa2+ plays a dual role in orexin signalling by being a prerequisite for both ligand−receptor interaction and amplifying orexin signals via Ca2+ influx. Some previous results obtained utilizing Ca2+ chelators have to be re‐evaluated based on the results of the current study. From a drug discovery perspective, further experiments need to identify the target for Ca2+ in orexin‐A−OX1 receptor interaction and its mechanism of action.
Development of Category‐Based Induction and Semantic Knowledge
Authors: Fisher Anna V. , Godwin Karrie E. , Matlen Bryan J. , Unger Layla 
Published: August 2014

Category‐based induction is a hallmark of mature cognition; however, little is known about its origins. This study evaluated the hypothesis that category‐based induction is related to semantic development. Computational studies suggest that early on there is little differentiation among concepts, but learning and development lead to increased differentiation based on taxonomic relatedness. This study reports findings from a new task aimed to (a) examine this putative increase in semantic differentiation and (b) test whether individual differences in semantic differentiation are related to category‐based induction in 4‐ to 7‐year‐old children (N = 85). The results provide the first empirical evidence of an age‐related increase in differentiation of representations of animal concepts and suggest that category‐based induction is related to increased semantic differentiation.
Effects of lifestyle modification and metformin on irisin and FGF21 among HIV‐infected subjects with the metabolic syndrome
Authors: Srinivasa Suman , Wong Kimberly , Fitch Kathleen V. , Wei Jeffrey , Petrow Eva , Cypess Aaron M. , Torriani Martin , Grinspoon Steven K. 
Published: August 2014

SummaryObjectiveFew studies have investigated irisin and FGF21 to elucidate the role of these hormones to regulate ‘beiging’ in HIV‐infected patients.DesignFifty HIV‐infected subjects with the metabolic syndrome were previously recruited and randomized to receive lifestyle modification (LSM) and/or metformin over 12 months. In the current study, we assessed FGF21 and irisin at baseline and after intervention. In addition, we assessed circulating FGF21 and irisin in relationship to brown adipose tissue (BAT) gene expression in dorsocervical subcutaneous fat biopsies from 13 HIV‐infected subjects.ResultsAt baseline, prior to intervention, HIV‐infected subjects demonstrated increased log FGF21 (2·13 ± 0·06 vs 1·98 ± 0·05 pg/ml, P = 0·05) and log irisin (0·33 ± 0·02 vs 0·17 ± 0·04 μg/ml, P = 0·003) compared with healthy controls well matched based on waist circumference. After 12 months, HIV‐infected subjects randomized to LSM demonstrated a relative reduction in FGF21 compared with those not randomized to LSM (−10 [−35,22] vs 40 [0,94] %change, P = 0·01). Changes in FGF21 were inversely associated with improved parameters of energy homoeostasis, including increased REE (ρ = −0·34, P = 0·046) and max VO2 (ρ = −0·38, P = 0·02), and reduced RQ (ρ = 0·40, P = 0·02) among all HIV‐infected subjects. Increased UCP‐1 (r = 0·75, P = 0·003), DIO2 (r = 0·58, P = 0·04) and CideA (r = 0·73, P = 0·01) gene expression in dorsocervical fat was significantly associated with FGF21 in HIV‐infected subjects.ConclusionHIV‐infected subjects with metabolic complications demonstrate increases in FGF21 in relationship to BAT gene expression. Relative reductions in FGF21 in those receiving long‐term LSM relate to overall improvements in energy expenditure parameters. In contrast, irisin levels are elevated in HIV‐infected subjects, but are not influenced by LSM nor associated with BAT gene expression.
CD8+ tumour‐infiltrating lymphocytes and COX2 expression may predict relapse in differentiated thyroid cancer
Authors: Cunha Lucas Leite , Marcello Marjory Alana , Nonogaki Suely , Morari Elaine Cristina , Soares Fernando Augusto , Vassallo José , Ward Laura Sterian 
Published: August 2014

SummaryBackground/objectiveThere is an increasing rate of papillary thyroid carcinomas that may never progress to cause symptoms or death. Predicting outcome and determining tumour aggressiveness could help diminish the number of patients submitted to aggressive treatments. We aimed to evaluate whether markers of the immune system response and of tumour‐associated inflammation could predict outcome of differentiated thyroid cancer (DTC) patients.DesignRetrospective cohort study.PatientsWe studied 399 consecutive patients, including 325 papillary and 74 follicular thyroid carcinomas.MeasurementsImmune cell markers were evaluated using immunohistochemistry, including tumour‐associated macrophages (CD68) and subsets of tumour‐infiltrating lymphocytes (TIL), such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also investigated the expression of cyclooxygenase 2 (COX2) in tumour cells and the presence of concurrent lymphocytic infiltration characterizing chronic thyroiditis.ResultsConcurrent lymphocytic infiltration characterizing chronic thyroiditis was observed in 29% of the cases. Among all the immunological parameters evaluated, only the enrichment of CD8+ lymphocytes (P = 0·001) and expression of COX2 (P =0·01) were associated with recurrence. A multivariate model analysis identified CD8+ TIL/COX2 as independent risk factor for recurrence. A multivariate analysis using Cox's proportional‐hazards model adjusted for the presence of concurrent chronic thyroiditis demonstrated that the presence of concurrent chronic thyroiditis had no effect on prognostic prediction mediated by CD8+ TIL and COX2.ConclusionIn conclusion, we suggest the use of a relatively simple pathology tool to help select cases that may benefit of a more aggressive approach sparing the majority of patients from unnecessary procedures.
Genetic, molecular and physiological mechanisms involved in human obesity: Society for Endocrinology Medal Lecture 2012
Authors: Farooqi Sadaf I. 
Published: August 2014

SummaryThe health consequences of obesity represent one of the major public health challenges of our time. Whilst the role of environmental drivers such as reduced physical activity and increased food intake is widely acknowledged, the importance of biological factors which influence individual variation in weight is less readily recognised. Considerable evidence suggests that genetic factors influence a person's weight in a given environment and that these genetic influences are more potent at the extremes of the body mass index (BMI) distribution. The discovery that genetic disruption of certain pathways can lead to severe obesity has informed our current understanding of how body weight is regulated by brain circuits that regulate appetite and energy expenditure. These studies provide a framework for investigating patients and ultimately may guide the development of more rational‐targeted therapies for genetically susceptible individuals with severe obesity.
Quantification and genotyping of lipoprotein lipase in patients with diabetic lipaemia
Authors: Radhakutty A. , Shen J. , Hooper A. J. , Miller S. A. , Burnett J. R. , Mah P. M. , Burt M. G. , Doogue M. P. 
Published: August 2014

AbstractAimsTo determine if diabetic lipaemia is caused by loss of function mutations in the lipoprotein lipase gene, LPL.MethodsWe conducted a case–control study over 2 years in two tertiary care hospitals in South Australia. Six patients with a history of diabetic lipaemia and 12 control subjects, with previous diabetic ketoacidosis and peak triglyceride concentrations < 2.4 mmol/l were included. Participants were well at the time of study investigations.ResultsOnly one patient with lipaemia had a loss of function mutation in LPL and no functional mutations in APOC2 or GPIHBP1 were identified. The mean lipoprotein lipase concentration was lower in patients with diabetic lipaemia than in control subjects (306 vs 484 μg/l, P = 0.04). The mean fasting C‐peptide concentration was higher in patients with diabetic lipaemia than in control subjects (771 vs 50 pmol/l; P = 0.001).ConclusionsLipoprotein lipase deficiency in patients with a history of diabetic lipaemia was predominantly quantitative, rather than secondary to mutations in LPL, APOC2 or GPIHBP1. The majority of patients with severe hypertriglyceridaemia in diabetic ketoacidosis may have ketosis‐prone Type 2, rather than Type 1, diabetes.
Depression, anxiety and self‐care behaviours of young adults with Type 2 diabetes: results from the International Diabetes Management and Impact for Long‐term Empowerment and Success (MILES) Study
Authors: Browne J. L. , Nefs G. , Pouwer F. , Speight J. 
Published: August 2014

AbstractAimYoung adults with Type 2 diabetes have higher physical morbidity and mortality than other diabetes sub‐groups, but differences in psychosocial outcomes have not yet been investigated. We sought to compare depression and anxiety symptoms and self‐care behaviours of young adults with Type 2 diabetes with two matched control groups.MethodsUsing cross‐sectional survey data from the Australian and Dutch Diabetes Management and Impact for Long‐term Empowerment and Success (MILES) studies, we matched 93 young adults (aged 18–39 years) with Type 2 diabetes (case group) with: (i) 93 older adults ( ≥ 40 years) with Type 2 diabetes (Type 2 diabetes control group; matched on country, gender, education, diabetes duration and insulin use) and (ii) 93 young adults with Type 1 diabetes (Type 1 diabetes control group; matched on country, gender, age and education). Groups were compared with regard to depression symptoms (nine‐item Patient Health Questionnaire), anxiety symptoms (seven‐item Generalised Anxiety Disorder questionnaire) and frequency of selected self‐care behaviours (single item per behaviour).ResultsParticipants in the case group had higher depression scores (Cohen's d = 0.40) and were more likely to have clinically meaningful depressive symptoms (Cramer's V = 0.23) than those in the Type 2 diabetes control group. Participants in the case group had statistically equivalent depression scores to the Type 1 diabetes control group. The groups did not differ in anxiety scores. Those in the case group were less likely than both control groups to take insulin as recommended (Cramer's V = 0.24–0.34), but there were no significant differences between the groups in oral medication‐taking. The case group were less likely than the Type 2 diabetes control group to eat healthily (Cramer's V = 0.16), and less likely than the Type 1 diabetes control group to be physically active (Cramer's V = 0.15).ConclusionsOur results suggest that Type 2 diabetes is as challenging as Type 1 diabetes for young adults and more so than for older adults. Young adults with Type 2 diabetes may require more intensive psychological and self‐care support than their older counterparts.
Reversal of Type 2 diabetes after bariatric surgery is determined by the degree of achieved weight loss in both short‐ and long‐duration diabetes
Authors: Steven S. , Carey P. E. , Small P. K. , Taylor R. 
Published: August 2014

AbstractAimTo define the impact of duration of diabetes and extent of weight loss on the reversibility of Type 2 diabetes after bariatric surgery.MethodsComplete data were collated from 89 individuals with Type 2 diabetes mellitus undergoing any bariatric surgical procedure in a specialist bariatric centre. People with a preoperative HbA1c < 43 mmol/mol (6.1%) were excluded. Diabetes duration was defined as: short, < 4 years; medium, 4–8 years; and long, > 8 years.ResultsAn HbA1c of <43mmol/mol (6.1%) was achieved by 62% of patients in the short‐duration group and 26% of patients in the long‐duration group. Normoglycaemia was rarely achieved in the long‐duration group if weight loss was < 25kg. In the whole cohort there was a clear relationship of greater weight loss with lower HbA1c levels (Rs = −0.53; P < 0.0001).ConclusionsThe study shows that the degree of achieved weight loss is the major determinant of return to normal blood glucose levels after bariatric surgery. Normoglycaemia can be achieved in long‐duration Type 2 diabetes, but a greater degree of weight loss is required than for short‐duration diabetes.
Similarity between generic and brand‐name antihypertensive drugs for primary prevention of cardiovascular disease: evidence from a large population‐based study
Authors: Corrao Giovanni , Soranna Davide , Merlino Luca , Mancia Giuseppe 
Published: August 2014

AbstractBackgroundAlthough generic and earlier brand‐name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern.ObjectiveTo compare effectiveness of generic and brand‐name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes.Design and subjectsA population‐based, nested case–control study was carried out by including the cohort of 78 520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand‐name agents.ResultsThere was no evidence that patients who started on generics experienced different CV risk than those on brand‐name product (OR 0·86; 95% CI 0·63–1·17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand‐name agents (OR 1·19; 95% CI 0·86–1·63). Compared with patients who kept initial brand‐name therapy, those who experienced brand‐to‐generic or generic‐to‐brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1·18 (0·96–1·47), 0·87 (0·63–1·21) and 1·08 (0·80–1·46).ConclusionsOur findings do not support the notion that brand‐name antihypertensive agents are superior to generics for preventing CV outcomes in the real‐world clinical practice.
The Impact of the Oral Proficiency Interview on One Foreign Language Teacher Education Program
Authors: Kissau Scott 
Published: August 2014

AbstractThe Oral Proficiency Interview (OPI) has been increasingly used in academia. However, while multiple studies have documented the growth in OPI implementation across the United States and the proficiency rates of its completers, few have focused specifically on foreign language teacher candidates, and even fewer have investigated the impact that this proficiency assessment may have on language teacher training programs. To better understand the impact of the OPI on foreign language teacher education programs and help guide programmatic decision making, a case study was conducted of one such program that recently implemented the OPI as part of its licensure requirements. The results confirmed earlier research with respect to expected proficiency outcomes of foreign language teacher candidates. The results also suggested that the OPI requirement did not negatively affect program enrollment, nor did teacher trainees negatively perceive the OPI requirement. Finally, the study provided evidence of the positive impact the OPI may have on a foreign language teacher education program. Recommended practices for implementing the OPI in teacher training programs and ways to support foreign language teacher candidates who must complete the assessment are discussed.
Evaluation of a fine sediment biomonitoring tool across a wide range of temperate rivers and streams
Authors: Turley Matt D. , Bilotta Gary S. , Extence Chris A. , Brazier Richard E. 
Published: August 2014

Summary

Elevated levels of fine sediment (suspended and deposited) are a common cause of ecological degradation in freshwater ecosystems. However, it is time‐consuming and expensive to monitor these parameters to support national and international water resource legislation.

The Proportion of Sediment‐sensitive Invertebrates (PSI) index is a biomonitoring tool that is designed to identify the degree of sedimentation in rivers and streams. Despite having a sound biological basis, until now, the PSI index has only been tested against observed fine sediment data in two catchments; other published applications of the PSI index have relied on inferred fine sediment values.

In this study, we report the results of a comprehensive analysis of the performance of the PSI index across a wide range of reference condition temperate stream and river ecosystems, including 835 sites with data on deposited sediment and 451 sites with data on suspended solids (>12 500 data points measured between 1978 and 2002).

The effect of taxonomic level and taxonomic resolution on the performance of the PSI index was also examined, as was the performance of the PSI index against other non‐sediment‐specific indices, including Average Score Per Taxon (ASPT), Lotic‐invertebrate Index for Flow Evaluation (LIFE), Ephemeroptera, Plecoptera and Trichoptera (EPT) abundance, % EPT abundance, EPT richness and % EPT richness.

The results of this study show that the PSI index was more correlated with fine sediment metrics than the other biological indices tested: rs = −0.64, (P < 0.01, n = 2502) for deposited sediment and rs = −0.50 (P < 0.01, n = 1353) for suspended solids.

We highlight the optimal conditions for applying the PSI index, in its current form. Given the variability in the relationship between PSI and fine sediment metrics, we propose that the use of data from more objective, quantitative methods of measuring deposited fine sediment may help to enhance the performance of the model for future applications and advance understanding of fine sediment dynamics and the pressure–response relationship.
Grazing management and tussock distribution in elephant grass
Authors: Pereira L. E. T. , Paiva A. J. , Geremia E. V. , da Silva S. C. 
Published: August 2014

AbstractSoil occupation capacity via lateral expansion of tussocks in elephant grass (Pennisetum purpureum Schum.) may be associated with basal tillering. As grazing management alters the proportion of basal and aerial tillers in a tiller population, the hypothesis of this work was that grazing management affects tussock size and distribution with implications for plant population stability. The objective of this study was to evaluate the tiller population stability index, the proportion of basal and aerial tillers, tussock size, and the frequency of tussocks and bare ground in rotationally managed elephant grass cv. Napier. Treatments resulted from the combination of two post‐grazing heights (35 and 45 cm) and two pre‐grazing conditions (95% and maximum canopy light interception during regrowth – LI0·95 and LIMax) and were allocated to experimental units (850 m2 paddocks) according to a 2 × 2 factorial arrangement in a randomized complete block design, with four replications. Measurements were taken from January 2011 to April 2012. The post‐grazing height treatments affected the tiller population stability index, but did not influence the pattern of tussock distribution. On the other hand, the different grazing frequencies (targets of LI pre‐grazing) altered the pattern of tussock distribution and the proportion of bare ground. In general, the tiller population stability index and frequency of tussocks were higher and the frequency of bare ground lower on swards managed with the LI0·95 target relative to those managed with the LIMax target, regardless of the post‐grazing height used, indicating a larger soil occupation capacity of plants under the more frequent defoliation regime. Such responses were associated with larger population of basal tillers and highlight the importance of tiller category and perennation pathway in defining patterns of plant growth and tussock distribution.
Role of turmeric in oxidative modulation in end‐stage renal disease patients
Authors: Pakfetrat Maryam , Akmali Masoumeh , Malekmakan Leila , Dabaghimanesh Mojtaba , Khorsand Marjan 
Published: August 2014

AbstractOxidative stress is considered as a major player in uremia‐associated morbidity and mortality in hemodialysis (HD) patients. The aim of this study was to evaluate the effects of turmeric on oxidative stress markers in HD patients. This study was a prospective and double‐blind randomized clinical trial. Fifty HD patients aged 18–60 years were recruited after fulfilling the inclusion criteria. Patients were randomly categorized into 2 groups: trial group received turmeric and control group received placebo for 8 weeks. Each patient in the trial group received turmeric, whereas the control group received starch for the same 8 weeks. Plasma malondialdehyde (MDA), red blood cell (RBC) antioxidant enzyme activities as glutathione peroxidase (GPX), glutathione reductase (GR), and catalase (CAT), cholesterol, high‐density lipoprotein‐cholesterol, low‐density lipoprotein‐cholesterol, triglyceride, albumin, and hemoglobin were also measured before and after study. Although MDA level was reduced in both groups, the ratio of decrease was significantly higher in the turmeric group (0.2 vs. 0.1, P = 0.040). Three enzymes of GPX, GR, and CAT levels were increased in both groups; the ratio of increased was significantly higher in the turmeric group for the CAT enzyme (0.73 vs. 0.54; P = 0.02). Also, significant elevation of albumin level in the turmeric group compared with the control group was observed (P = 0.001). Regular ingestion of turmeric reduces plasma MDA and increases RBC CAT activity and plasma albumin levels in HD patients. Turmeric showed no adverse effects.