bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concentration‐dependent response to pioglitazone in nonalcoholic steatohepatitis
Authors: Kawaguchi‐Suzuki M. , Bril F. , Kalavalapalli S. , Cusi K. , Frye R. F. 
Published: May 2017

SummaryBackgroundPioglitazone is a safe and effective option to manage patients with type 2 diabetes and nonalcoholic steatohepatitis (NASH). However, there is marked variability in treatment response.AimTo evaluate the relationship between concentrations of pioglitazone and its active metabolites and treatment outcomes in patients with NASH.MethodsPioglitazone concentrations were measured in patients with NASH treated with pioglitazone 45 mg/day for 18 months; liver biopsy samples were obtained at baseline and after treatment. The primary outcome was a ≥2‐point reduction in NAFLD activity score (NAS) with at least one‐point improvement in more than one liver histology category and without worsening of fibrosis. A novel marker, the pioglitazone exposure index, was calculated to consider the concentrations of pioglitazone as well as the two active metabolites.ResultsThe response to pioglitazone was concentration‐dependent as evidenced by the significant relationship between both pioglitazone concentration and pioglitazone exposure index with changes in NAS (r=.48, P=.0002 and r=.51, P<.0001, respectively), steatosis (r=.41, P=.002 and r=.46, P=.0005), and inflammation (r=.44, P=.0009 and r=.40, P=.0003). The pioglitazone exposure index was also associated with a change in ballooning (P=.04). The pioglitazone exposure index was higher in patients with NASH resolution (2.85±1.38 vs 1.78±1.48, P=.018). A predictive model for the primary outcome was developed that incorporated baseline NAS and pioglitazone exposure index (AUC=0.77).ConclusionsThis study demonstrates the importance of pioglitazone exposure to variable response in patients with NASH, and indicates potential factors that may identify patients most likely to benefit from chronic pioglitazone treatment.
Systematic assessment of environmental risk factors for bipolar disorder: an umbrella review of systematic reviews and meta‐analyses
Authors: Bortolato Beatrice , Köhler Cristiano A. , Evangelou Evangelos , León‐Caballero Jordi , Solmi Marco , Stubbs Brendon , Belbasis Lazaros , Pacchiarotti Isabella , Kessing Lars V. , Berk Michael , Vieta Eduard , Carvalho André F. 
Published: May 2017

ObjectivesThe pathophysiology of bipolar disorder is likely to involve both genetic and environmental risk factors. In our study, we aimed to perform a systematic search of environmental risk factors for BD. In addition, we assessed possible hints of bias in this literature, and identified risk factors supported by high epidemiological credibility.MethodsWe searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases up to 7 October 2016 to identify systematic reviews and meta‐analyses of observational studies that assessed associations between putative environmental risk factors and BD. For each meta‐analysis, we estimated its summary effect size by means of both random‐ and fixed‐effects models, 95% confidence intervals (CIs), the 95% prediction interval, and heterogeneity. Evidence of small‐study effects and excess of significance bias was also assessed.ResultsSixteen publications met the inclusion criteria (seven meta‐analyses and nine qualitative systematic reviews). Fifty‐one unique environmental risk factors for BD were evaluated. Six meta‐analyses investigated associations with a risk factor for BD. Only irritable bowel syndrome (IBS) emerged as a risk factor for BD supported by convincing evidence (k=6; odds ratio [OR]=2.48; 95% CI=2.35−2.61; P<.001), and childhood adversity was supported by highly suggestive evidence. Asthma and obesity were risk factors for BD supported by suggestive evidence, and seropositivity to Toxoplasma gondii and a history of head injury were supported by weak evidence.ConclusionsNotwithstanding that several environmental risk factors for BD were identified, few meta‐analyses of observational studies were available. Therefore, further well‐designed and adequately powered studies are necessary to map the environmental risk factors for BD.
The effects of early institutionalization on emotional face processing: evidence for sparing via an experience‐dependent mechanism
Authors: Young Audrey , Luyster Rhiannon J. , Fox Nathan A. , Zeanah Charles H. , Nelson Charles A. 
Published: May 2017

Early psychosocial deprivation has profound adverse effects on children's brain and behavioural development, including abnormalities in physical growth, intellectual function, social cognition, and emotional development. Nevertheless, the domain of emotional face processing has appeared in previous research to be relatively spared; here, we test for possible sleeper effects emerging in early adolescence. This study employed event‐related potentials (ERPs) to examine the neural correlates of facial emotion processing in 12‐year‐old children who took part in a randomized controlled trial of foster care as an intervention for early institutionalization. Results revealed no significant group differences in two face and emotion‐sensitive ERP components (P1 and N170), nor any association with age at placement or per cent of lifetime spent in an institution. These results converged with previous evidence from this population supporting relative sparing of facial emotion processing. We hypothesize that this sparing is due to an experience‐dependent mechanism in which the amount of exposure to faces and facial expressions of emotion children received was sufficient to meet the low threshold required for cortical specialization of structures critical to emotion processing.
Statement of contribution

What is already known on this subject?

Early psychosocial deprivation leads to profoundly detrimental effects on children's brain and behavioural development.

With respect to children's emotional face processing abilities, few adverse effects of institutionalized rearing have previously been reported.

Recent studies suggest that ‘sleeper effects’ may emerge many years later, especially in the domain of face processing.

What does this study add?

Examining a cumulative 12 years of data, we found only minimal group differences and no evidence of a sleeper effect in this particular domain.

These findings identify emotional face processing as a unique ability in which relative sparing can be found.

We propose an experience‐dependent mechanism in which the amount of social interaction children received met the low threshold required for cortical specialization.
Hydroxyeicosapentaenoic acids and epoxyeicosatetraenoic acids attenuate early occurrence of nonalcoholic fatty liver disease
Authors: Wang Chunjiong , Liu Wenli , Yao Liu , Zhang Xuejiao , Zhang Xu , Ye Chenji , Jiang Hongfeng , He Jinlong , Zhu Yi , Ai Ding 
Published: May 2017

Background and PurposeThe ω‐3 polyunsaturated fatty acids (PUFAs) mediate protective effects on several metabolic disorders. However, the functions of their metabolites in the early stage of nonalcoholic fatty liver disease (NAFLD) are largely unknown.Experimental ApproachMice were fed a control diet, high‐fat diet (HFD) or ω‐3 PUFA‐enriched HFD (ω3HFD) for 4 days and phenotypes were analysed. LC–MS/MS was used to determine the eicosanoid profiles. Primary hepatocytes and peritoneal macrophages were used for the mechanism study.Key ResultsIn short‐term HFD‐fed mice, the significantly increased lipid accumulation in the liver was reversed by ω‐3 PUFA supplementation. Metabolomics showed that the plasma concentrations of hydroxyeicosapentaenoic acids (HEPEs) and epoxyeicosatetraenoic acids (EEQs) were reduced by a short‐term HFD and markedly increased by the ω3HFD. However, HEPE/EEQ treatment had no direct protective effect on hepatocytes. ω3HFD also significantly attenuated HFD‐induced adipose tissue inflammation. Furthermore, the expression of pro‐inflammatory cytokines and activation of the JNK pathway induced by palmitate were suppressed by HEPEs and EEQs in macrophages. 17,18‐EEQ, 5‐HEPE and 9‐HEPE were identified as the effective components among these metabolites, as indicated by their greater suppression of the palmitate‐induced expression of inflammatory factors, chemotaxis and JNK activation compared to other metabolites in macrophages. A mixture of 17,18‐EEQ, 5‐HEPE and 9‐HEPE significantly ameliorated the short‐term HFD‐induced accumulation of macrophages in adipose tissue and hepatic steatosis.Conclusion and Implications17,18‐EEQ, 5‐HEPE and 9‐HEPE may be potential approaches to prevent NAFLD in the early stage by inhibiting the inflammatory response in adipose tissue macrophages via JNK signalling.
Vitamin D treatment modulates immune activation in cystic fibrosis
Authors: Pincikova T , Paquin-Proulx D , Sandberg J K , Flodström-Tullberg M , Hjelte L 
Published: May 2017

Summary
Persistent inflammatory response in cystic fibrosis (CF) airways is believed to play a central role in the progression of lung damage. Anti-inflammatory treatment may slow lung disease progression, but adverse side effects have limited its use. Vitamin D has immunoregulatory properties. We randomized 16 CF patients to receive vitamin D2, vitamin D3 or to serve as controls, and investigated the effect of vitamin D supplementation on soluble immunological parameters, myeloid dendritic cells (mDCs) and T cell activation. Three months of vitamin D treatment were followed by two washout months. Vitamin D status at baseline was correlated negatively with haptoglobin, erythrocyte sedimentation rate and immunoglobulin A concentration. Total vitamin D dose per kg bodyweight correlated with the down-modulation of the co-stimulatory receptor CD86 on mDCs. Vitamin D treatment was associated with reduced CD279 (PD-1) expression on CD4+ and CD8+ T cells, as well as decreased frequency of CD8+ T cells co-expressing the activation markers CD38 and human leucocyte antigen D-related (HLA-DR) in a dose-dependent manner. There was a trend towards decreased mucosal-associated invariant T cells (MAIT) cell frequency in patients receiving vitamin D and free serum 25-hydroxyvitamin D (free-s25OHD) correlated positively with CD38 expression by these cells. At the end of intervention, the change in free-s25OHD was correlated negatively with the change in CD279 (PD-1) expression on MAIT cells. Collectively, these data indicate that vitamin D has robust pleiotropic immunomodulatory effects in CF. Larger studies are needed to explore the immunomodulatory treatment potential of vitamin D in CF in more detail.
Modified method of intravenous immunoglobulin administration for patients with intractable multifocal motor neuropathy: A case report
Authors: Mukaino Akihiro , Nagaoka Atsushi , Yoshimura Shunsuke , Nakajima Hideki , Shiraishi Hirokazu , Motomura Masakatsu , Morikawa Miyuki , Kusunoki Susumu , Nakane Shunya , Ando Yukio , Tsujino Akira 
Published: May 2017

AbstractBackgroundWe report a case of a 64‐year‐old Japanese man who was diagnosed with definite multifocal motor neuropathy and successfully treated with administration of intravenous immunoglobulin (IVIg) spread over two separate weeks.Case presentationAfter IVIg administration (30 g/day, five consecutive days), motor function was improved, but it was not possible to maintain the muscle strength just a few months after treatment. Although plasma exchange and cyclosporine were combined, the patient developed muscle weakness just 2 weeks after initial IVIg treatment. His grip strength decreased to 0 kg, proximal upper‐limb muscle strength reduced to 2/5 according to manual muscle testing, and muscle weakness developed in the proximal lower limb muscle. We modified IVIg administration protocol from five consecutive days to two separate weeks: 3 days in the first week and 2 days in the third week without changing the total dose per month. After initiation of divided IVIg protocol, muscle weakness dramatically improved, and muscle power could be kept normal. Corrected optical density value of immunoglobulin M antibodies against GM1 elevated in the all clinical course did not correlate with muscle strength improvement. Serum immunoglobulin G levels became stable in ≥2000 mg/dL, and were associated with muscle strength improvement.ConclusionAdministration of IVIg over two separate weeks might be a treatment option in intractable patients with multifocal motor neuropathy.
High‐intensity interval training using whole‐body exercises: training recommendations and methodological overview
Authors: Machado Alexandre F. , Baker Julien S. , Figueira Junior Aylton J. , Bocalini Danilo S. 
Published: May 2017

SummaryHIIT whole body (HWB)‐based exercise is a new calisthenics exercise programme approach that can be considered an effective and safe method to improve physical fitness and body composition. HWB is a method that can be applied to different populations and ages. The purpose of this study was to describe possible methodologies for performing physical training based on whole‐body exercise in healthy subjects. The HWB sessions consist of a repeated stimulus based on high‐intensity exercise that also include monitoring time to effort, time to recuperation and session time. The exercise intensity is related to the maximal number of movements possible in a given time; therefore, the exercise sessions can be characterized as maximal. The intensity can be recorded using ratings of perceived exertion. Weekly training frequency and exercise selection should be structured according to individual subject functional fitness. Using this simple method, there is potential for greater adherence to physical activity which can promote health benefits to all members of society.
Follow‐up of patients with refractory or relapsed multiple myeloma after allogeneic hematopoietic cell transplantation
Authors: Schneidawind Corina , Duerr‐Stoerzer Silke , Faul Christoph , Kanz Lothar , Weisel Katja , Bethge Wolfgang , Schneidawind Dominik 
Published: May 2017

AbstractBackgroundThe role of allogeneic hematopoietic cell transplantation (HCT) for the treatment of multiple myeloma is controversial. However, the introduction of proteasome inhibitors and immunomodulatory drugs might influence outcomes in case of relapse or refractory disease after allogeneic HCT.MethodsWe report 41 consecutive patients that underwent allogeneic HCT for the treatment of relapsed or refractory multiple myeloma.ResultsThree‐year event‐free survival (EFS) and overall survival (OS) of the whole cohort were 15% and 51%, respectively. In a subgroup analysis, allogeneic HCT after a second high‐dose chemotherapy with autologous stem cell support was associated with a decreased 3‐year EFS (6% vs 24%, P=.04) and OS (35% vs 64%, P=.09). In case of relapse or refractory disease after allogeneic HCT, the treatment with proteasome inhibitors or immunomodulatory drugs significantly improved survival (1‐year OS 79% vs 29%, P=.001).ConclusionThe incorporation of proteasome inhibitors and immunomodulatory drugs into transplant protocols has the potential to improve outcomes and refine the role of allogeneic HCT for the treatment of multiple myeloma as a platform for long‐term disease control.
The relationship between initial route of heroin administration and speed of transition to daily heroin use
Authors: Hines Lindsey A. , Lynskey Michael , Morley Katherine I. , Griffiths Paul , Gossop Michael , Powis Beverly , Strang John 
Published: May 2017

AbstractIntroduction and Aims. The effect of heroin administration route on speed of transition to regular use is unknown. This paper aims to determine whether the speed of transition from initiation of heroin use to daily heroin use differs by route of administration (injecting, chasing/inhaling or snorting). Design and Methods. Privileged access interviewer survey of purposively selected sample of 395 current people who use heroin (both in and not in treatment) in London, UK (historical sample from 1991). Data on age and year of initiation, time from initiation to daily use and routes of administration were collected by means of a structured questionnaire. Generalised ordered logistic models were used to test the relationship between route of initial administration of heroin and speed of transition to daily heroin use. Analyses were adjusted for gender, ethnicity, daily use of other drug(s) at time of initiation, year of initiation and treatment status at interview. Results. After adjustment, participants whose initial administration route was injecting had a 4.71 (95% confidence interval 1.34–16.5) increase in likelihood of progressing to daily use within 1–3 weeks of initiation, compared to those whose initial administration route was non‐injecting. Discussion and Conclusions. The speed of transition from first use to daily heroin use is faster if the individual injects heroin at initiation of use. Those who initiate heroin use through injecting have a shorter time frame for intervention before drug use escalation. [Hines LA, Lynskey M, Morley KI, Griffiths P, Gossop M, Powis B, Strang J. The relationship between initial route of heroin administration and speed of transition to daily heroin use. Drug Alcohol Rev 2017;00:000‐000]
Defining Health Research for Development: The perspective of stakeholders from an international health research partnership in Ghana and Tanzania
Authors: Ward Claire Leonie , Shaw David , Anane‐Sarpong Evelyn , Sankoh Osman , Tanner Marcel , Elger Bernice 
Published: May 2017

AbstractObjectivesThe study uses a qualitative empirical method to define Health Research for Development. This project explores the perspectives of stakeholders in an international health research partnership operating in Ghana and Tanzania.MethodsWe conducted 52 key informant interviews with major stakeholders in an international multicenter partnership between GlaxoSmithKline (GSK, Vaccine Developer) and the global health nonprofit organisation PATH and its Malaria Vaccine Initiative program (PATH/MVI, Funder‐Development Partner), (RTS, S) (NCT00866619). The respondents included teams from four clinical research centres (two centres in Ghana and two in Tanzania) and various collaborating partners. This paper analyses responses to the question: What is Health Research for Development?ResultsBased on the stakeholders’ experience the respondents offered many ways of defining Health Research for Development. The responses fell into four broad themes: i) Equitable Partnerships; ii) System Sustainability; iii) Addressing Local Health Targets, and iv) Regional Commitment to Benefit Sharing.ConclusionThrough defining Health Research for Development six key learning points were generated from the four result themes: 1) Ensure there is local research leadership working with the collaborative partnership, and local healthcare system, to align the project agenda and activities with local research and health priorities; 2) Know the country‐specific context ‐ map the social, health, legislative and political setting; 3) Define an explicit development component and plan of action in a research project; 4) Address the barriers and opportunities to sustain system capacity. 5) Support decentralised health system decision‐making to facilitate the translation pathway; 6) Govern, monitor and evaluate the development components of health research partnerships. Overall, equity and unity between partners are required to deliver health research for development.
A critique of the principle of ‘respect for autonomy’, grounded in African thought
Authors: Behrens Kevin G. 
Published: May 2017

AbstractI give an account how the principle of ‘respect for autonomy’ dominates the field of bioethics, and how it came to triumph over its competitors, ‘respect for persons’ and ‘respect for free power of choice’. I argue that ‘respect for autonomy’ is unsatisfactory as a basic principle of bioethics because it is grounded in too individualistic a worldview, citing concerns of African theorists and other communitarians who claim that the principle fails to acknowledge the fundamental importance of understanding persons within the nexus of their communal relationships. I defend the claim that ‘respect for persons’ is a more appropriate principle, as it is able to acknowledge both individual decision making and the essential relationality of persons. I acknowledge that my preference for ‘respect for persons’ is problematic because of the important debate around the definition of ‘personhood’ in bioethics discourse. Relying on Thaddeus Metz's conception of moral status, I propose a relational definition of personhood that distinguishes between persons with agency and persons without agency, arguing that we have different moral obligations to these distinct categories of persons. I claim that this conception of personhood is better able to accommodate our moral intuitions than conventional approaches, and that it is able to do so without being speciesist or question‐begging.
H3Africa: An Africa exemplar? Exploring its framework on protecting human research participants
Authors: Nnamuchi Obiajulu 
Published: May 2017

AbstractThe Human Heredity and Health in Africa (H3Africa) Consortium is a conglomeration of research and infrastructure projects spread throughout Africa whose aim is to apply genomic methodology to diseases affecting the people in the region. Its operation is innovative in the sense that it is doing something new; that is, filling a hitherto existing void in genomic research capability of African scientists and infusing resources and manpower to institutions and investigators across Africa. But aside from developing and sustaining capacity in genomic research and biorepositories, H3Africa is also invested in developing appropriate ethical regulatory regime to govern research in these areas. This latter concern –research ethics governance – is the major subject of this paper. Specifically, the paper discusses protection of research participants as envisaged by H3Africa in the area of consent, safeguarding privacy, maintaining confidentiality of health information and sharing of data/biospecimens. The ultimate goal is to determine whether H3Africa initiatives and processes are consistent or at odds with international guidelines and best practices.
An Examination of European Firms’ Derivatives Usage: The Importance of Model Selection
Authors: Carroll Anthony , O'Brien Fergal , Ryan James 
Published: May 2017

AbstractThis paper investigates the determinants of foreign currency (FX) and interest rate (IR) derivatives usage for European non‐financial firms. We employ a Tobit model and a two‐part model which allows the determinants of the usage decision to differ from the extent of usage decision. We find FX derivatives usage is motivated by economies of scale and FX exposure, while IR derivatives usage is motivated by the magnitude and nature of firms’ debt. We also find that for IR derivatives the determinants of the usage decision differ from the determinants of the extent of usage decision.