bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycophenolic acid concentrations in peripheral blood mononuclear cells are associated with the incidence of rejection in renal transplant recipients
Authors: Md Dom Zaipul I. , Coller Janet K. , Carroll Robert P. , Tuke Jonathan , McWhinney Brett C. , Somogyi Andrew A. , Sallustio Benedetta C.
Published: July 2018

Aims

Although therapeutic drug monitoring of plasma mycophenolic acid (MPA) concentrations has been recommended to individualize dosage in transplant recipients, little is known regarding lymphocyte concentrations of MPA, where MPA inhibits inosine monophosphate dehydrogenase (IMPDH). This study investigated the utility of measuring predose MPA concentrations in peripheral blood mononuclear cells (C0C) and predose IMPDH activity, as predictors of graft rejection in renal transplant recipients.

Methods

Forty‐eight patients commencing mycophenolate mofetil (1 g twice daily) in combination with tacrolimus and prednisolone were recruited. Blood was collected for determination of trough total (C0P) and unbound (C0u) plasma MPA concentrations. Peripheral blood mononuclear cells were isolated for determination of C0C and IMPDH activity. The incidence of rejection within 2 days of sample collection was determined histologically and classified according to the Banff 2007 criteria.

Results

There was no association between MPA C0C and C0P (rs = 0.28, P = 0.06), however, MPA C0C were weakly correlated with MPA C0u (rs = 0.42, P = 0.013). Multivariate analysis indicated that MPA C0C was the only covariate independently associated with rejection (FDR‐adjusted P = 0.033). The receiver operating characteristic area under the curve (AUC) for the prediction of severe rejection using MPA C0C was 0.75 (P = 0.013), with 73% sensitivity and specificity at a C0C threshold of 0.5 ng 10–7 cells. However, predose IMPDH activity was not a predictor of rejection (P > 0.15).

Conclusions

MPA C0C measurement within the early post‐transplant period may be useful to facilitate early titration of MPA dosing to significantly reduce rejection.
Dorsolateral fibromuscular tissue preservation during artificial urinary sphincter cuff placement is associated with low infection and erosion rates
Authors: Cheung Felix , Fathollahi Ali , Vertosick Emily , Jarvis Thomas R. , Katz Darren , Sandhu Jaspreet S.
Published: July 2018

Objectives

To present a modified technique in artificial urinary sphincter (AUS) placement that is associated with low rates of erosion and infection in a high‐risk population.

Patients and Methods

After Institutional Review Board approval, we identified patients who underwent primary AUS placement using the modified technique between January 2007 and November 2015. Our modification consists of preserving the dorsolateral fibromuscular tissue surrounding the bulbar urethra and horizontally transecting the ventral bulbospongiosus muscle during urethral cuff placement. Preoperative variables such as radiotherapy (RT) and bladder neck contractures were recorded. Effectiveness and complications including infections, erosions, and re‐operations were recorded at follow‐up.

Results

The new technique was used on 208 patients: 40% had a history of RT, including 15% who had had a salvage radical prostatectomy; 26% had had previous bladder neck contractures. No patients developed infection. Overall, erosion occurred in six (2.9%) patients and spontaneous erosions occurred in two (0.9%) during the study period. In all, 21 patients underwent re‐operation for device failure. The probability of re‐operation for ‘any’ reason was 7% (95% confidence interval [CI] 4–12%) at 1 year. The 1‐year social continence rate was 74% (95% CI 67–81%).

Conclusion

Preservation of dorsolateral fibromuscular tissue during AUS placement is an effective means to achieve a low risk of erosions. Our modified technique is safe with low infection and erosion rates, whilst maintaining good functional outcomes despite a high‐risk population.
Mitochondrial function in the heart: the insight into mechanisms and therapeutic potentials
Authors: Nguyen Binh Yen , Ruiz‐Velasco Andrea , Bui Thuy , Collins Lucy , Wang Xin , Liu Wei
Published: July 2018

Mitochondrial dysfunction is considered as a crucial contributory factor in cardiac pathology. This has highlighted the therapeutic potential of targeting mitochondria to prevent or treat cardiac disease. Mitochondrial dysfunction is associated with aberrant electron transport chain activity, reduced ATP production, an abnormal shift in metabolic substrates, ROS overproduction and impaired mitochondrial dynamics. This review will cover the mitochondrial functions and how they are altered in various disease conditions. Furthermore, the mechanisms that lead to mitochondrial defects and the protective mechanisms that prevent mitochondrial damage will be discussed. Finally, potential mitochondrial targets for novel therapeutic intervention will be explored. We will highlight the development of small molecules that target mitochondria from different perspectives and their current progress in clinical trials.

Linked Articles

This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc
Metabolomic and lipidomic analysis of the effect of pioglitazone on hepatic steatosis in a rat model of obese Type 2 diabetes
Authors: Yang Hyekyung , Suh Dong Ho , Kim Dae Hee , Jung Eun Sung , Liu Kwang‐Hyeon , Lee Choong Hwan , Park Cheol‐Young
Published: July 2018

Background and Purpose

Thiazolidinediones, acting as PPAR‐γ ligands, reduce hepatic steatosis in humans and animals. However, the underlying mechanism of this action remains unclear. The purpose of this study was to investigate changes in hepatic metabolites and lipids in response to treatment with the thiazolidinedione pioglitazone in an animal model of obese Type 2 diabetes.

Experimental Approach

Male Otsuka Long‐Evans Tokushima Fatty (OLETF) rats were orally administered either vehicle (control) or pioglitazone (30 mg·kg−1) and fed a high‐fat diet (60% kcal fat) for 12 weeks. Hepatic metabolites were analysed via metabolomic and lipidomic analyses. Gene expression and PLA2 activity were analysed in livers from pioglitazone‐treated and control rats.

Key Results

OLETF rats that received pioglitazone showed decreased fat accumulation and improvement of lipid profiles in the liver compared to control rats. Pioglitazone treatment significantly altered levels of hepatic metabolites, including free fatty acids, lysophosphatidylcholines and phosphatidylcholines, in the liver. In addition, pioglitazone significantly reduced the expression of genes involved in hepatic de novo lipogenesis and fatty acid uptake and transport, whereas genes related to fatty acid oxidation were up‐regulated. Gene expression and enzyme activity of PLA2, which hydrolyzes phosphatidylcholines to release lysophosphatidylcholines and free fatty acids, were significantly decreased in the livers of pioglitazone‐treated rats compared to control rats.

Conclusions and Implications

Our results present evidence for the ameliorative effect of pioglitazone on hepatic steatosis, largely due to the regulation of lipid metabolism, including fatty acids, lysophosphatidylcholines, phosphatidylcholines and related gene‐expression patterns.
Hypertension: a new treatment for an old disease? Targeting the immune system
Authors: Bomfim Gisele Facholi , Cau Stefany Bruno Assis , Bruno Alexandre Santos , Fedoce Aline Garcia , Carneiro Fernando S
Published: July 2018

Arterial hypertension represents a serious public health problem, being a major cause of morbidity and mortality worldwide. The availability of many antihypertensive therapeutic strategies still fails to adequately treat around 20% of hypertensive patients, who are considered resistant to conventional treatment. In the pathogenesis of hypertension, immune system mechanisms are activated and both the innate and adaptive immune responses play a crucial role. However, what, when and how the immune system is triggered during hypertension development is still largely undefined. In this context, this review highlights scientific advances in the manipulation of the immune system in order to attenuate hypertension and end‐organ damage. Here, we discuss the potential use of immunosuppressants and immunomodulators as pharmacological tools to control the activation of the immune system, by non‐specific and specific mechanisms, to treat hypertension and improve end‐organ damage. Nevertheless, more clinical trials should be performed with these drugs to establish their therapeutic efficacy, safety and risk–benefit ratio in hypertensive conditions.

Linked Articles

This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Biogeography of the freshwater fishes of the Guianas using a partitioned parsimony analysis of endemicity with reappraisal of ecoregional boundaries
Authors: Lemopoulos Alexandre , Covain Raphaël
Published: July 2018

The Guianas are one of the most diverse regions of the Neotropics, hosting a particularly high rate of freshwater fish endemism. The present distributional patterns of freshwater fish species in the major catchments of the Guianas (comprising Guyana, Suriname and French Guiana) were analysed to reveal the faunal relationships between rivers, evaluate different hypotheses concerning biogeographical units, and redefine the boundaries of the Guianese freshwater ecoregions. A parsimony analysis of endemicity was performed using a data partitioning strategy to alleviate some drawbacks inherent to the method (e.g. long branch attraction artefact, heterotachy), and take into account alternative parsimony models assigning different constraints on state changes for the different species. A strong spatial element was present in the data with a structuring of species along a west–east gradient. Two main biogeographical units were highlighted: one to the west, ranging from the Essequibo to the Commewijne rivers and including the Proto Berbice and Surinamese regions, and one to the east ranging from the Maroni to the Oyapock rivers and including the Western, Central and Eastern French Guiana regions. Each ecoregion possessed distinctive fish assemblages, and three to four potential zones of faunal exchanges between Amazonian and Guianese rivers have been confirmed.
An adaptive method for identifying marine areas of high conservation priority
Authors: Afán Isabel , Giménez Joan , Forero Manuela G. , Ramírez Francisco
Published: July 2018

Identifying priority areas for biodiversity conservation is particularly challenging in the marine environment due to the open and dynamic nature of the ocean, the paucity of information on species distribution, and the necessary balance between marine biodiversity conservation and essential supporting services such as seafood provision. We used the Patagonian seabird breeding community as a case study to propose an integrated and adaptive method for delimiting key marine areas for conservation. Priority areas were defined through a free decision‐support tool (Marxan) that included projected at‐sea distributions of seabirds (approximately 2,225,000 individuals of 14 species); BirdLife Important Bird and Biodiversity Areas (IBAs) for pelagic bird species; and the economic costs of potential regulations in fishing practices. The proposed reserve network encompassed approximately 300,000 km2that was largely concentrated in northern and southern inshore and northern and central offshore regions. This reserve network exceeded the minimum threshold of 20% conservation of the abundance of each species proposed by the World Parks Congress. Based on marine currents in the study area, we further identified the 3 primary water masses that may influence areas of conservation priority through water inflow. Our reserve network may benefit from enhanced marine productivity in these highly connected areas, but they may be threatened by human impacts such as marine pollution. Our method of reserve network design is an important advance with respect to the more classical approaches based on criteria defined for one or a few species and may be particularly useful when information on spatial patterns is data deficient. Our approach also accommodates addition of new information on seabird distribution and population dynamics, human activities, and alterations in the marine environment.
Drug‐Drug Interaction Study of Apixaban with Cyclosporine and Tacrolimus in Healthy Volunteers
Authors: Bashir Babar , Stickle Douglas F. , Chervoneva Inna , Kraft Walter K.
Published: July 2018

Apixaban is metabolized by cytochrome P450 (CYP) 3A4 in the liver and intestine, undergoes direct intestinal excretion, and is a substrate to permeability glycoprotein (P‐gp) and breast cancer resistance protein (BCRP) transporters. We examined the drug interactions between cyclosporine and tacrolimus (combined inhibitors of CYP3A4, P‐gp, and BCRP) with apixaban in 12 healthy adult male volunteers. Apixaban 10 mg was administered orally alone, in combination with 100 mg cyclosporine or 5 mg tacrolimus. Co‐administration with cyclosporine resulted in increase in apixaban maximum plasma concentration (Cmax) and area under the plasma concentration‐time curve from time zero to the last quantifiable concentration (AUC(0‐tlast)) with associated geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of 143% (112, 183) and 120% (97, 148), respectively. Co‐administration with tacrolimus resulted in reduction in apixaban Cmax and AUC(0‐tlast) with associated GMRs (90% CI) of 87% (69, 112) and 78% (63, 97), respectively. The observed changes in apixaban exposure margins with cyclosporine or tacrolimus are within the range of the historical clinical development program, therefore, apixaban dose adjustments are not warranted.
Examining the factor structure of the Motives for Playing Drinking Games measure among Australian university students
Authors: George Amanda M. , Zamboanga Byron L. , Martin Jessica L. , Olthuis Janine V.
Published: July 2018

Introduction and Aims

Given the prevalence of drinking games among university students and the health risks associated with playing drinking games, it is important to consider motivations for participation. The psychometric properties of the Motives for Playing Drinking Games (MPDG) measure have been examined among US college student samples, but mixed findings have been reported regarding the number of factors in the measure. This is the first study to examine the factor structure and applicability of the MPDG measure among a sample of Australian university students.

Design and Methods

University students (N = 254; aged 18–46 years; 62% female) with prior drinking experience completed an online survey which included questions pertaining to demographics, drinking game frequency and consumption, drinking game consequences and the MPDG measure.

Results

Confirmatory factor analyses demonstrated that the originally proposed 8‐factors within the MPDG measure were problematic in the current sample and a revised 7‐factor solution was preferred. Analyses examining the relations of the revised 7 MPDG factors with drinking game behaviours (e.g. gaming‐specific consequences and amount consumed during play) highlighted the importance of some MPDG (enhancement/thrills, conformity and sexual pursuit motives).

Discussion and Conclusions

While the MPDG measure shows promise for assessing drinking game‐specific motives, the need to consider the applicability of MPDG subscales across different samples was apparent.
Barriers or enablers? Chiefs, elite capture, disasters, and resettlement in rural Malawi
Authors: Kita Stern Mwakalimi
Published: July 2018

Chiefs are at the centre of household and community development efforts in most low‐income countries around the world. Yet, researchers and scholars have paid limited attention to the institution of chieftaincy and to understanding its role in the management of climate change adaptation and disaster risk reduction. This paper draws on a micro ethnographic evaluation conducted in two predominantly rural districts of Malawi in southeast Africa to assess two different manifestations of elite control. In the first case, a resettlement programme was implemented where chiefs were co‐opted and took the lead. In the second case, a food insecurity response programme was designed to exclude chiefs. The study finds that neither co‐opting nor countering chiefs prevents elite capture. Rather, the majority of chiefs oscillate between malevolent and benevolent capture. The findings require that states focus on the cultural and political dimensions of rural life when designing climate change adaptation and disaster risk reduction programmes.
Stability of retrospective self‐reports of childhood trauma in first‐episode psychosis
Authors: Simpson Samantha , Phillips Lisa , Baksheev Gennady , Garner Belinda , Markulev Connie , Phassouliotis Christina , Alvarez‐Jimenez Mario , McGorry Patrick , Bendall Sarah
Published: July 2018

Aim

Childhood trauma (CT), abuse and neglect are commonly reported by individuals experiencing psychosis. However, there are concerns that acute psychotic symptoms, in particular delusions, may contribute to inaccurate reporting of CT. As a result, individuals experiencing psychosis may not be asked about their experiences of abuse when they are being seen in psychiatric settings. This lack of attention can directly impact on the tailoring of their clinical care. This study aimed to investigate the stability of reports of CT by young people experiencing a first psychotic episode (FEP) compared to healthy comparison subjects.

Methods

Responses of 24 young people during the acute FEP and 3 months later to items on the Childhood Trauma Questionnaire (CTQ) were compared to 30 non‐psychiatric controls. All participants were aged 15 to 25 years.

Results

FEP participants reported higher CT than controls at both time points. Reliability analyses (interclass correlation coefficients [ICCs]) suggested strong agreement between CT reports at baseline and follow‐up for FEP participants (.81) and controls (.91). Positive psychotic symptoms were unrelated to CT reports. Although the severity of CT reports fluctuated between assessments, complete retractions of severe abuse claims occurred rarely.

Conclusions

The results suggest that retrospective self‐report can be used to reliably assess CT in young people experiencing acute psychosis.
Long‐term improvements after mindfulness‐based group therapy of depression, anxiety and stress and adjustment disorders: A randomized controlled trial
Authors: Sundquist Jan , Palmér Karolina , Memon Ashfaque A. , Wang Xiao , Johansson Leena M. , Sundquist Kristina
Published: July 2018

Background

Although mindfulness‐based group therapies (MGTs) for depressive, anxiety or stress and adjustment disorders are promising, there is a substantial lack of knowledge regarding the long‐term improvements after such therapies in these common psychiatric disorders.

Methods

Two hundred and fifteen patients were randomized in a randomized clinical trial (RCT) (ClinicalTrials.gov ID: NCT01476371) conducted in 2012 at 16 primary healthcare centres in southern Sweden. The patients were randomized to MGT or treatment as usual (TAU) and completed four psychometric self‐rated scales after 8 weeks of treatment. Approximately 12 months after the completion of the 8‐week treatment, the same scales were repeated. Ordinal and generalized linear‐mixed models, adjusted for cluster effects, were used for the analysis.

Results

For all four psychometric scales (MADRS‐S [Montgomery‐Åsberg Depression Rating Scale‐S], HADS‐D, HADS‐A [Hospital Anxiety and Depression Scale A and D] and PHQ‐9 [Patient Health Questionnaire‐9]) the scores at the 1‐year follow‐up were significantly improved (all P values <0.001) in both groups. Furthermore, there were no significant differences between the MGT and TAU in the psychometric scores at the 1‐year follow‐up.

Conclusions

To the best of our knowledge, this is the first RCT comparing the long‐term improvements after MGT with TAU. Although it cannot be excluded that our findings are a result of the natural course of common psychiatric disorders or other factors, they suggest a long‐term positive improvement after both MGT and TAU.
When is an alternative possibility robust?
Authors: Kittle Simon
Published: July 2018

According to some, free will requires alternative possibilities. But not any old alternative possibility will do. Sometimes, being able to bring about an alternative does not bestow any control on an agent. In order to bestow control, and so be directly relevant qua alternative to grounding the agent's moral responsibility, alternatives need to be robust. Here, I investigate the nature of robust alternatives. I argue that Derk Pereboom's latest robustness criterion is too strong, and I suggest a different criterion based on the idea that what agents need to be able to do is keep open the possibility of securing their blamelessness, rather than needing to directly ensure their own blamelessness at the time of decision.
Reflections on, and visions for, the changing field of pollination ecology
Authors: Knight T. M. , Ashman T.‐L. , Bennett J. M. , Burns J. H. , Passonneau S. , Steets J. A.
Published: July 2018

Since the launch ofEcology Lettersin 1998, the field of Pollination Ecology has changed considerably in its focus. In this review, we discuss the major discoveries across the past two decades. We quantitatively synthesise the frequency by which different concepts and topics appeared in the peer‐reviewed literature, as well as the connections between these topics. We then look forward to identify pressing research frontiers and opportunities for additional integration in the future. We find that there has been a shift towards viewing plant–pollinator interactions as networks and towards understanding how global drivers influence the plants, pollinators and the ecosystem service of pollination. Future frontiers include moving towards a macroecological view of plant–pollinator interactions, understanding how ecological intensification and urbanisation will influence pollination, considering other interactions, such as plant–microbe–pollinator networks, and understanding the causes and consequences of extinctions. Pollination Ecology is poised to advance our basic understanding of the ecological and evolutionary factors that shape plant–animal interactions and to create applied knowledge that informs conservation decision making.
Theoderic goes to the promised land: accidental propaganda in Jordanes's Gothic history?
Authors: Wilkinson Ryan
Published: July 2018

Claims that Jordanes's Getica advanced Justinianic propaganda often point to its (alleged) critique of Theoderic the Ostrogoth. I argue instead that Jordanes intended a positive reading – but one point of praise was likely accidental. The Getica links Theoderic to the biblical figure of Moses, using narrative parallels between their careers and a specific biblical allusion. Although competent, Jordanes may never have recognized that Cassiodoran comparison, thanks to subtle divisions within the scriptural Latinity to which he and Cassiodorus belonged. Whatever his aims, Jordanes could not fully control Cassiodorus's rhetoric; the allusion's survival points to limits on conscious intertextuality in a diverse textual milieu.
Competition lifespan survival analysis in the Norwegian‐Swedish Coldblooded Trotter racehorse
Authors: Velie B. D. , Jäderkvist Fegraeus K. , Ihler C. F. , Lindgren G. , Strand E.
Published: July 2018

Background

Studies of large racing populations have established clear differences in the career profile of stallions, mares and geldings. Multiple studies have also demonstrated positive effects on racing careers for horses that commence racing at a younger age. However, the applicability of these studies to small, native racing populations is unknown and warrants investigation.

Objectives

To provide summary statistics for performance outcomes for the Norwegian‐Swedish Coldblooded Trotter and to document and provide evidence on the current differences in racing careers across age at first start groups, sexes and country of birth.

Study design

Cohort study.

Methods

Performance data on the population of Norwegian‐Swedish Coldblooded Trotters born between 2000 and 2009 (n = 14,548) were acquired and used to describe and compare the racing careers of this native racing breed. Career length, career starts and career earnings were evaluated. Kaplan–Meier survival curves, stratified by sex, age group and country of birth were produced for career length. A Cox proportional hazards model was fitted to assess factors influencing the hazard rate of retirement from racing.

Results

Log‐rank test for equality of career length survival functions showed significant differences (P<0.001) across sexes, countries of birth and age at first start groups. An increased age at first start increased the hazard rate of retirement from racing.

Main limitations

Racing career length is influenced by many factors. While this study accounts for some of the known influences on career length, the analysis would be strengthened by the inclusion of additional information, such as trainer and reasons for retirement.

Conclusions

The results of this study suggest no adverse effects to the racing of young Norwegian‐Swedish Coldblooded trotters. The study also establishes significant differences in career length based on sex and identifies that these differences are the opposite of what is seen in many other horse racing breeds.

The Summary is available in Spanish – see Supporting Information
Cross‐species systems analysis of evolutionary toolkits of neurogenomic response to social challenge
Authors: Saul Michael C. , Blatti Charles , Yang Wei , Bukhari Syed A. , Shpigler Hagai Y. , Troy Joseph M. , Seward Christopher H. , Sloofman Laura , Chandrasekaran Sriram , Bell Alison M. , Stubbs Lisa , Robinson Gene E. , Zhao Sihai D. , Sinha Saurabh
Published: July 2018

Social challenges like territorial intrusions evoke behavioral responses in widely diverging species. Recent work has showed that evolutionary “toolkits”—genes and modules with lineage‐specific variations but deep conservation of function—participate in the behavioral response to social challenge. Here, we develop a multispecies computational‐experimental approach to characterize such a toolkit at a systems level. Brain transcriptomic responses to social challenge was probed via RNA‐seq profiling in three diverged species—honey bees, mice and three‐spined stickleback fish—following a common methodology, allowing fair comparisons across species. Data were collected from multiple brain regions and multiple time points after social challenge exposure, achieving anatomical and temporal resolution substantially greater than previous work. We developed statistically rigorous analyses equipped to find homologous functional groups among these species at the levels of individual genes, functional and coexpressed gene modules, and transcription factor subnetworks. We identified six orthogroups involved in response to social challenge, including groups represented by mouse genes Npas4 and Nr4a1, as well as common modulation of systems such as transcriptional regulators, ion channels, G‐protein‐coupled receptors and synaptic proteins. We also identified conserved coexpression modules enriched for mitochondrial fatty acid metabolism and heat shock that constitute the shared neurogenomic response. Our analysis suggests a toolkit wherein nuclear receptors, interacting with chaperones, induce transcriptional changes in mitochondrial activity, neural cytoarchitecture and synaptic transmission after social challenge. It shows systems‐level mechanisms that have been repeatedly co‐opted during evolution of analogous behaviors, thus advancing the genetic toolkit concept beyond individual genes.
Deficiency of the basic helix‐loop‐helix transcription factor DEC1 prevents obesity induced by a high‐fat diet in mice
Authors: Noshiro Mitsuhide , Kawamoto Takeshi , Nakashima Ayumu , Ozaki Noritsugu , Ueno Toshinori , Saeki Masayumi , Honda Kiyomasa , Fujimoto Katsumi , Kato Yukio
Published: July 2018

Obesity is a major public health problem in developed countries resulting from increased food intake and decreased energy consumption and usually associated with abnormal lipid metabolism. Here, we show that DEC1, a basic helix‐loop‐helix transcription factor, plays an important role in the regulation of lipid consumption in mouse brown adipose tissue (BAT), which is the major site of thermogenesis. Homozygous Dec1 deletion attenuated high‐fat‐diet‐induced obesity, adipocyte hypertrophy, fat volume and hepatic steatosis. Furthermore, DEC1 deficiency increased body temperature during daytime and enhanced the expression of uncoupler protein 1, a key factor of thermogenesis, and various lipolysis‐related genes in interscapular BAT. In vitro experiments suggested that DEC1 suppresses the expression of various lipolysis‐related genes induced by the heterodimer of peroxisome proliferator‐activated receptor γ and retinoid X receptor α (RXRα) through direct binding to RXRα. These observations suggest that enhanced lipolysis in BAT caused by DEC1 deficiency leads to an increase in lipid consumption, thereby decreasing lipid accumulation in adipose tissues and the liver. Thus, DEC1 may serve as an energy‐saving factor that suppresses lipid consumption, which may be relevant to managing obesity.
Clinical significance of PDEF factor expression and its relation to androgen receptor in ER− breast cancer
Authors: Cao Lu , Li Congying , Xu Cong , Xiang Guomin , Liu Fang , Liu Xiaozhen , Jiao Jiao , Lv Shuhua , Niu Yun
Published: July 2018

Aims

The mechanism of androgen receptor (AR) promoting tumour growth in oestrogen receptor‐negative (ER−) breast cancer (BC) is undetermined. Prostate‐derived ETS factor (PDEF) is highly restricted to the hormone‐regulated tissues of epithelial cells, such as those in the prostate, breast and other tissues. It has been demonstrated that PDEF expression is associated with AR in prostate cancer. In this research, we aimed to investigate the relationship between PDEF and AR in ER− BC.

Methods and results

We immunohistochemically evaluated the correlation between PDEF and AR expression in 246 cases of ER− invasive BC, and investigated their relationship in ER− BC cell lines. The expression of PDEF was associated with the positive expression of AR (P < 0.001) and a worse survival rate (P = 0.006). PDEF+ tumours were significantly more often AR+ (P < 0.001). AR and PDEF were more often co‐expressed and the series of AR+PDEF+ (126 of 246, 51.2%) had a poor survival rate (P = 0.046). In Cox models, PDEF expression (P = 0.028) was an independent predictor for overall survival (OS). At the cellular protein and mRNA levels, our experiments also showed a statistically significant positive correlation between PDEF and AR, and that PDEF may be regulated by AR.

Conclusions

PDEF is associated with markers of bad prognosis, supporting its role as a growth promoter in ER− BC. Our findings also provide evidence that PDEF is strongly correlated with AR expression in ER− breast cancer; it may be a downstream target gene of AR and a potential prognostic factor in ER− BC.
TFE3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis
Authors: Lee Hyun Jung , Shin Dong Hoon , Kim So Young , Hwang Chung Su , Lee Jung Hee , Park Won Young , Choi Kyung Un , Kim Jee Yeon , Lee Chang Hun , Sol Mee Young , Rha Seo Hee , Park Sung Woo
Published: July 2018

Aims

Since Xp11.2 translocation‐associated renal cell carcinoma (TRCC) was first recognised, its morphological features and the clinical significance of TFE3 expression, frequency of gene translocation and diagnostic criteria have been the subject of limited studies. The present retrospective analysis aimed to evaluate the correlation between TFE3 immunoreactivity and its gene translocation status using fluorescence in‐situ hybridisation (FISH) and determine how TFE3 translocation and expression affect patient prognosis differently.

Methods and results

We enrolled 303 consecutive renal cell carcinoma cases. Immunohistochemical staining for TFE3 was performed in 303 cases, and FISH analysis was performed for molecular testing. The TCGA data set of renal cell carcinoma was evaluated to validate TFE3 expression and survival analysis. TFE3 expression was associated significantly with the nested alveolar pattern, papillary pattern, eosinophilic cytoplasm, voluminous expansile cytoplasm, nuclear grade, tumour necrosis, sarcomatoid pattern and picket fence appearance. FISH analysis showed break‐apart signals in 26 of 32 (81.25%) cases expressing strong or moderate nuclear TFE3 immunoreactivity. Thirteen of 56 samples that showed no or weak TFE3 expression with morphologically suspicious cases were translocation‐positive in the FISH assay. The TFE3‐translocation group (harbouring TFE3 translocation regardless of TFE3 expression) showed the poorest progression‐free survival (PFS), and the TFE3‐expressing group (expressing TFE3 but negative for translocation) was correlated significantly with decreased PFS.

Conclusion

Increased TFE3 expression in RCC was associated with poor PFS regardless of the gene translocation status. Moreover, morphological analysis should help to select candidates who would benefit from TFE3 staining and FISH analysis.
Interorganizational Performance Management: A Co‐evolutionary Model
Authors: van Fenema Paul C. , Keers Bianca M.
Published: July 2018

Making interorganizational cooperation successful proves a daunting task. While current approaches to interorganizational performance management (PM) highlight why interorganizational cooperation matters and which phases are required, it remains silent on the dynamics of interorganizational PM. That is, how can PM evolve with and contribute to interorganizational cooperation. The purpose of this paper is to increase understanding of interorganizational PM. To this end, it develops a structure and process foundation of interorganizational value creation, and it provides a model that shows how processes of organizational and interorganizational PM co‐evolve. The study starts by providing insight into differences between organizational and interorganizational PM. It then presents five approaches pertaining to performance in interorganizational cooperation. The paper distinguishes strategic–economic, PM, supply‐chain management, organizational and marketing approaches. These approaches are related from a structure and process angle and are used to develop a co‐evolutionary model of interorganizational PM. The resulting conceptualization has implications for research on new modes of complex and heterogeneous interorganizational value creation. The paper elaborates on these implications, pointing to new directions for future PM research.
Reviewing and Theorizing the Unintended Consequences of Performance Management Systems
Authors: Franco‐Santos Monica , Otley David
Published: July 2018

Different design choices in the controls used to manage performance often lead to a range of unintended consequences, which have profound effects on individuals and organizations. This paper presents a mixed review (both systematic and eclectic) of the literature on the unintended consequences of performance management systems, and develops a typology to explain how and why they occur. It finds that the most salient unintended consequences of directive performance management systems are gaming, information manipulation, selective attention, illusion of control and relationships transformation. It argues that these consequences exist as a result of limiting factors such as ignorance, error, short‐term concerns, fundamental values, self‐fulfilling forecasts and changes in social relationships. The emerging typology‐based theory suggests that the choice of control mechanisms is based on two key assumptions concerning goal‐alignment and goal‐uncertainty that relate back to ideas in agency theory and stewardship theory. It concludes that, in the design of performance management systems, the more the ‘assumed’ reality about the state of goal‐alignment and goal‐uncertainty diverges from the ‘real’ state of affairs, the more the resultant system is likely to create perverse unintended consequences, leading to poor organizational outcomes.
Peyer's patches‐derived CD11b+ B cells recruit regulatory T cells through CXCL9 in dextran sulphate sodium‐induced colitis
Authors: Wang Zhiming , Zhang Hushan , Liu Ronghua , Qian Tingting , Liu Jiajing , Huang Enyu , Lu Zhou , Zhao Chujun , Wang Luman , Chu Yiwei
Published: July 2018

Regulatory T (Treg) cells play an essential role in the maintenance of intestinal homeostasis. In Peyer's patches (PPs), which comprise the most important IgA induction site in the gut‐associated lymphoid tissue, Treg cells promote IgA isotype switching. However, the mechanisms underlying their entry into PPs and isotype switching facilitation in activated B cells remain unknown. This study, based on the dextran sulphate sodium (DSS)‐induced colitis model, revealed that Treg cells are significantly increased in PPs, along with CD11b+ B‐cell induction. Immunofluorescence staining showed that infiltrated Treg cells were located around CD11b+ B cells and produced transforming growth factor‐β, thereby inducing IgA+ B cells. Furthermore, in vivo and in vitro studies revealed that CD11b+ B cells in PPs had the capacity to recruit Treg cells into PPs rather than promoting their proliferation. Finally, we found that Treg cell recruitment was mediated by the chemokine CXCL9 derived from CD11b+ B cells in PPs. These findings demonstrate that CD11b+ B cells induced in PPs during colitis actively recruit Treg cells to accomplish IgA isotype switch in a CXCL9‐dependent manner.
Accuracy of pen‐type laser fluorescence device and radiographic methods in detecting approximal carious lesions in primary teeth – an in vivo study
Authors: Souza Luana Alves de , Cancio Viviane , Tostes Mônica Almeida
Published: July 2018

Background

The diagnosis of approximal lesions is limited due to the difficulty of direct examination of these areas.

Aim

To determine the accuracy of pen‐type laser fluorescence (LFpen) device, compared to digital bitewing (BW) radiography, in diagnosing approximal carious lesions in posterior primary teeth at cavitation and non‐cavitation thresholds.

Design

A total of 46 children (aged 3–9 years) were assessed and 195 approximal surfaces of 184 primary molars were examined by digital BW and LFpen. Visual‐tactile inspection based on the International Caries Detection and Assessment System (ICDAS‐II) was used as the reference standard. All examinations were performed by the same examiner. Sensitivity, specificity, and accuracy were calculated. Spearman's correlation coefficients were calculated between LFpen and BW readings and the reference standard.

Results

Sensitivity, specificity and AUC were 81.8, 86.7, and 0.84 for BW and 49.1, 87.9, and 0.69 for LFpen both at non‐cavitation thresholds. At cavitation thresholds, BW showed higher specificity (96.0), sensitivity (93.0), and AUC (0.98) than did LFpen (72.0, 86.9, and 0.82, respectively), but a lower correlation was indicated by LFpen readings.

Conclusion

Bitewing had a better diagnostic accuracy and significantly outperformed LFpen in the detection of non‐cavitated lesions. Similar results were obtained by the two methods at the cavitation threshold.
Carrier frequencies of hearing loss variants in newborns of China: A meta‐analysis
Authors: Fu Yali , Zha Shuwei , Lü Nianqing , Xu Haoqin , Zhang Xuening , Shi Wenhui , Zha Ji
Published: July 2018

Objective

The objective of this study was to review the carrier frequencies of hearing loss gene variants, such as GJB2, SLC26A4, and MT‐RNR1 in newborns of China.

Design

PubMed, Embase, BioCentral, CNKI, WanFang, and VIP databases were used for searching relevant literature studies published during the period of January 2007 and January 2016. Meta‐analysis was performed by using the R software. The estimated rate and its 95% confidence intervals (CI) of the relevant indexes in newborns were collected and calculated using a fixed‐effects model or a random‐effects model when appropriate.

Results

In total, 35 of 958 published literature studies in Chinese and English were selected. The overall results showed that in newborns of China, the carrier frequencies of GJB2 variants (235 delC, 299 delAT) were 1.64% (95% CI 1.52% to 1.77%) and 0.33% (95% CI 0.19% to 0.51%); SLC26A4 variants (IVS7‐2 A > G, 2168 A > G) were 1.02% (95% CI 0.91% to 1.15%) and 0.14% (95% CI 0.06% to 0.25%); MT‐RNR1 variants (1555 A > G, 1449 C > T) were 0.20% (95% CI 0.17% to 0.23%) and 0.03% (95% CI 0.02% to 0.05%).

Conclusions

There are high carrier frequencies of GJB2 variants among newborns in China, followed by SLC26A4 and MT‐RNR1 variants. In order to achieve “early detection, early diagnosis and early treatment” and reduce the incidence of hereditary hearing loss in offspring, a comprehensive combination of neonatal hearing screening and deafness gene detection should be recommended and implemented in China.
“She doesn't want to go to hospital. That's one thing she hates”: Collective performativity in avoidable nursing home to hospital transfers
Authors: Mäkelä Petra
Published: July 2018

Older people who live with a combination of conditions experience fluctuations over time, which others may interpret as a need for medical attention. For some nursing home residents, this results in transitions in and out of hospital. Such transfers may be arranged without expectation of improved quality of life, can be associated with significant morbidity and mortality, and may preclude end‐of‐life preferences. Factors affecting avoidable hospitalization for nursing home residents are not well understood. I aim to explore potential drivers, moving beyond deficit explanations relating to funding, training, and resources. I use a framework of analysis that firstly considers medicalization of frailty, as a state of vulnerability that provides focus for others' action. I then draw on Judith Butler's theory of performativity, to explore nursing homes as sites of identity work for staff, residents and families. I consider ways subjectivities can be effected through reiterative practice that is compelled by normative conventions. Trouble may arise when citational practice of health care staff, and performative acquiescence of residents and families, culminates in an inevitability of hospitalization when navigating grey areas of assumed clinical risk. Principles of coproduction could present a disruptive opening, to rework power asymmetries, and move toward aspirations for residents and their relatives to be at the centre of decisions about care.
EPA plays multiple roles in regulating lipid accumulation of grass carp Ctenopharyngodon idella adipose tissue in vitro and in vivo
Authors: Lei Cai X. , Tian Jing J. , Ji Hong , Li Yang
Published: July 2018

This study was conducted to assess the effect of eicosapentaenoic acid (20:5n‐3, EPA) on lipid accumulation in grass carp Ctenopharyngodon idella adipose tissue both in vitro and in vivo. EPA was observed to inhibit the adipocyte viability in a time and dose‐dependent manner. EPA was also found to induce reactive oxygen species accumulation in vitro. The mRNA levels of caspase 3a and caspase 3b, as well as the activity of Caspase 3 increased significantly in vitro and in vivo, whereas the value of B cell leukemia 2–Bcl‐2 associated X protein decreased significantly. Besides, the pro‐apoptotic effect was relieved by α‐tocopherol. Dietary 0.52% EPA had no apparent effect on intraperitoneal fat index. Moreover, EPA promoted the hydrolytic gene expressions in vitro and in vivo, including adipose triglyceride lipase and hormone sensitive lipase‐a. Meanwhile, the lipogenic gene expressions of liver X receptor α, sterol regulatory element binding protein‐1c and fatty‐acid synthase were down‐regulated by EPA in vitro and in vivo. However, EPA also acted to promote the marker gene expressions of adipogenesis, including peroxisome proliferator‐activated receptor γ and lipoprotein lipase in vitro and in vivo. Contents of EPA increased significantly in the treatment groups in vitro and in vivo. These results support that EPA affects multiple aspects of lipid metabolism, including hydrolysis, lipogenesis, adipogenesis and apoptosis. However, it barely functioned in decreasing the lipid accumulation of Ctenopharyngodon idella under the current culture conditions.
Efficacy and safety of fixed‐dose combination of drotaverine hydrochloride (80 mg) and paracetamol (500 mg) in amelioration of abdominal pain in acute infectious gastroenteritis: A randomized controlled trial
Authors: Narang Shiva , Koli Jitender
Published: July 2018

Background and Aim

This randomized controlled trial was undertaken to assess efficacy and safety of fixed‐dose combination of drotaverine hydrochloride (80 mg) and paracetamol (PCM) (500 mg). This was performed by comparison of mean pain intensity difference, total pain relief at 2 h, onset of pain relief, decrease in number of pain episodes, global improvement, and adverse effects.

Methods

A randomized double‐blind controlled trial for adults between 18 and 59 years of either gender with acute infectious diarrhea (≥ 3 unformed, watery, or soft stools with symptoms at least within the last 24 h preceding randomization with duration of illness not more than 72 h) with moderate‐to‐severe abdominal pain. Participants were treated with either a fixed‐dose combination of oral drotaverine hydrochloride (80 mg) and PCM (500 mg) or oral PCM (500 mg) three times a day for 3 days.

Results

Of 252 (126 in each group) participants, all received at least one dose of medication. Two hundred forty‐two completed the study. Mean pain intensity difference at 60 min after administration of study medication by Visual Analogue Scale (VAS) and total pain relief at 2 h using both VAS and Verbal Rating Scale showed statistically significant improvement in drotaverine hydrochloride (80 mg) and PCM (500 mg) group. The onset of pain relief was also significantly better in drotaverine hydrochloride (80 mg) and PCM (500 mg) group when using VAS.

Conclusion

Fixed‐dose combination of drotaverine hydrochloride (80 mg) and PCM (500 mg) is an effective and safe antispasmodic agent in abdominal pain associated with acute infectious gastroenteritis.