bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of rare resistance‐associated variants that are extremely tolerant against NS5A inhibitors during daclatasvir/asunaprevir therapy by a two‐hit mechanism
Authors: Uchida Yoshihito , Kouyama Jun‐ichi , Naiki Kayoko , Sugawara Kayoko , Inao Mie , Imai Yukinori , Nakayama Nobuaki , Mochida Satoshi 
Published: February 2016

AimThe virologic characteristics of resistance‐associated variants (RAVs) developing in patients receiving dual oral therapy with daclatasvir/asunaprevir, including those with previous triple therapy with simeprevir, were evaluated.MethodsA total of 206 patients with genotype‐1b HCV infection, including 5 patients with previous simeprevir therapy, were treated with daclatasvir/asunaprevir for 24 weeks. Resistance‐associated variants in the NS5A regions at baseline and during/after therapy were evaluated using cycling‐probe real‐time polymerase chain reaction combined with direct sequencing. The dynamics of rare RAVs were also assessed using ultra‐deep sequencing.ResultsA sustained virologic response (SVR12) was achieved in 180 patients (87%); the rates were 95% in patients without baseline NS5A‐RAVs and 83%, 59%, and 77% in those with hepatitis C virus (HCV) strains carrying NS5A‐L31M, NS5A‐Y93H/C, and NS5A‐R30Q/H/L mutations, respectively. A multivariate analysis revealed baseline NS5A‐R30Q/H/L mutation and NS5A‐Y93H mutations as significant factors associated with SVR12. Virologic failure developed in all 5 patients with previous simeprevir treatment, and rare RAVs (HCV strains with NS5A‐R30H, NS5A‐A92K, NS5A‐P29del, and NS5A‐P32del) developed at virologic failure. Ultra‐deep sequencing revealed that HCV strains with NS5A‐P29del or NS5A‐P32del were absent at baseline and emerged within 4 weeks of dual oral therapy among the strains appearing after simeprevir administration.ConclusionNS5A‐R30Q/H/L and NS5A‐Y93H mutations at baseline determined the therapeutic efficacy of dual oral therapy with daclatasvir/asunaprevir, but rare NS5A‐RAVs developed frequently in patients with previous simeprevir treatment. Such RAVs may develop in a two‐hit manner, with simeprevir altering the quasispecies of HCV strains in the NS5A regions, leading to the emergence of HCV strains with NS5A‐P29del and NS5A‐P32del during exposure to daclatasvir/asunaprevir.
Strength of recommendation for single‐visit root canal treatment: grading the body of the evidence using a patient‐centred approach
Authors: De‐Deus G. , Canabarro A. 
Published: February 2016

AbstractAimTo identify, search for and critically interpret the results from clinical studies on single‐ versus multiple‐visit root canal treatment in the light of an evidence‐based paradigm. For that purpose, the quality of the available body of evidence was assessed using the SORT ‘grade’ – Strength of Recommendation Taxonomy.MethodologyA protocol was followed including all aspects of the review methods: (i) search strategy, (ii) inclusion criteria for studies, (iii) screening methods, (iv) quality assessment, (v) data synthesis of the selected studies, and (vi) the assessment of quality of the body of evidence available by the means of the SORT ‘grade’. An extensive search of recent biomedical literature was performed in PubMed (up to May, 2014), EMBASE (dating from 1980 to May 2014) and Cochrane databases with appropriate headings and keywords related to single‐ and multiple‐visit root canal treatment. Selected studies were stratified according to their level of evidence using the SORT criteria: (i) quality – Level A high‐quality evidence, Level B medium/low‐quality evidence and Level C no evidence; (ii) degree of consistency – consistent, when most studies found a similar conclusion, or inconsistent, when there was considerable variation amongst study findings.ResultsAfter the digital and manual searches, 246 studies were indentified. Two hundred and seven studies were eliminated by exclusion criteria, resulting in a yield of 39 articles that were selected for retrieval. Of the 39 articles, only 11 could be classified as Level 2 (B); the other 28 articles did not obey the criteria to be considered as real patient‐oriented evidence; thus, they were classified as Level 3 (C). No studies were ranked as Level 1 because they did not obey the minimum standard to be considered as both good‐quality research and patient‐oriented evidence. Despite this, all of the selected Level B studies reported no significant differences between single‐ and multiple‐visit treatments.ConclusionThere is B‐level (mid‐level) evidence to confirm there is no difference between the two different treatments, based on research addressing clinical outcomes and using some consistent but limited‐quality methods of scientific investigation. More studies focused on evaluating patient‐centred outcomes are urgently required.
Thyroid dysfunction and hepatic steatosis in overweight children and adolescents
Authors: Kaltenbach T. E.‐M. , Graeter T. , Oeztuerk S. , Holzner D. , Kratzer W. , Wabitsch M. , Denzer C. 
Published: February 2016

SummaryBackgroundOvert or subclinical hypothyroidism is a common finding in adult populations affected by non‐alcoholic fatty liver disease (NAFLD). Currently, there are only sparse data available on the association of thyroid dysfunction and NAFLD in obese children and adolescents.ObjectiveThe study aims to investigate the association of thyroid function test values with NAFLD and metabolic risk factors in a population of obese children and adolescents.MethodsA total of 332 overweight and obese children and adolescents (170 girls) aged between 10 and 19 years were analysed. Subjects underwent ultrasound examination of the liver. Thyroid function was evaluated by laboratory determination of thyroid‐stimulating hormone (TSH), total triiodothyronine (T3) and total thyroxine levels. All included subjects were either euthyroid or had subclinical hypothyroidism (TSH > 4 μU mL−1, normal thyroxine). Further metabolic profiling included the determination of lipid status, insulin and liver function tests. Anthropometric parameters body mass index, waist and hip circumference were documented.ResultsThe prevalence of hepatic steatosis was 29.8%. Subjects with NAFLD had significantly higher TSH levels than those without (p = 0.0007). After dividing TSH values into quartiles, both univariate and multivariate analyses (adjusted for age, body mass index–standard deviation scores and stage of puberty) showed a significant association with hepatic steatosis (p < 0.05).ConclusionTaking possible variables into consideration, our results show that there is a significant association between hepatic steatosis and the TSH levels in obese children and adolescents. Mild thyroid dysfunction may therefore have a role in determining an unfavourable metabolic profile in obese children and adolescents.
The case for targeting community pharmacy-led health improvement: Findings from a skin cancer campaign in Wales
Authors: Pearce Sioned , Evans Andrew , Phelps Ceri , Matthews Maura , Hughes Gail , Lewis Ian 
Published: February 2016

AbstractThe use of community pharmacies to deliver health improvement campaigns is well established. Cancer incidence is closely related to increasing levels of deprivation.Because community pharmacies are more prevalent in deprived areas there is potential for them to make an important contribution to health improvement by delivering interventions aimed at reducing cancer incidence amongst those at greatest risk.ObjectivesThe aims of the study were: to examine the association between high risk behaviour and deprivation and contribute evidence to the case for or against targeting cancer prevention campaigns at specific risky behaviour in areas of high deprivation.MethodsThis study has an ecological design and involved retrospective analysis of data derived from 5739 sun-safety quizzes completed by pharmacy users at 714 community pharmacies in Wales during May 2014.ResultsLevels of participation in the campaign and high risk sun-safety behaviours were higher in more deprived areas. Respondents from deprived areas had significantly lower sun-safety knowledge. 3802 (66.2%) respondents reported ‘excellent’ or ‘good’ knowledge of behaviours which promote sun-safety but this did not necessarily translate into how individuals behaved. 3787 (66.1%) respondents considered community pharmacies an acceptable location for the campaign and for discussing the signs and symptoms of skin cancer.Key FindingsResults show association between high risk behaviour and geographically defined deprivation adding to the case for targeting cancer prevention campaigns at specific behaviours and geographies.ConclusionsCommunity pharmacies appear to be acceptable locations from which to deliver health improvement campaigns in terms of participant recruitment, ease of delivery, and pharmacy user feedback.
Brecha salarial étnica en el Perú. ¿A qué obedece la desventaja de las mujeres indígenas?
Authors: KOLEV Alexandre , SUÁREZ ROBLES Pablo 
Published: February 2016

ResumenLa desigualdad étnica profesional figura desde antiguo en la agenda política de América Latina. Con datos de la Encuesta Nacional de Hogares, los autores analizan la brecha salarial étnica por sexo en el Perú en 2005–2011. La brecha de género es menor que la étnica, pero las mujeres indígenas sufren ambas. Los autores interpretan el componente inexplicado de la brecha como la medida máxima de la discriminación étnica, y descomponen el explicado para determinar los efectos de las características individuales, las del empleo y la situación geográfica. Como estos efectos explican gran parte de la brecha salarial étnica que afecta a las mujeres, se concluye con propuestas de política al efecto.
Cultural immersion through international experiences among Japanese nurses: Present status, future intentions, and perceived barriers
Authors: Chiba Yoko , Nakayama Takeo 
Published: February 2016

AbstractAimGiven limited exposure to various ethnicities, languages, and cultures, providing health care to an increasing foreign population in Japan will likely be challenging for Japanese nurses. This study aimed to examine past and intended future international experiences of Japanese nurses to assess their cultural immersion level.MethodsA cross‐sectional electronic survey was conducted among 2029 nurses in 2010. Participants were categorized by travel purpose, and the frequency of non‐holiday travel was analyzed. To examine participants' desire for and perceived feasibility of future non‐holiday international experiences by background characteristics, logistic regression analyses were performed.ResultsOf 1039 participants, 10.1% had past non‐holiday international experiences, with 80% having traveled to high‐income, English‐speaking countries. The median value for travel frequency was once, and the median duration of travel was less than 1 month. The most common purpose of travel was participation in short‐term programs (e.g. professional training, language study). Fifty‐one percent of female nurses reported a desire for future non‐holiday international experiences. Of these, 37.2% considered such experiences feasible. Age of the youngest child, having nursing specialization, English proficiency, and past international experience were significant predictors for feasibility.ConclusionJapanese nurses with foreign experience were considered valuable human resources for culturally appropriate care. Efforts should be made to integrate them into the Japanese healthcare setting. The present study revealed room for improvement in foreign language proficiency and cross‐cultural training with a focus on non‐English‐speaking and developing countries. A supportive workplace environment should be created that allows nurses to pursue the international experiences they desire.
Hyperammonemia alters glycinergic neurotransmission and modulation of the glutamate‐nitric oxide‐cGMP pathway by extracellular glycine in cerebellum in vivo
Authors: Cabrera‐Pastor Andrea , Taoro‐Gonzalez Lucas , Felipo Vicente 
Published: February 2016

AbstractThe glutamate‐nitric oxide (NO)‐cGMP pathway modulates some forms of learning. How glycine modulates this pathway is unclear. Glycine could modulate the pathway biphasically, enhancing its function through NMDA receptor activation or reducing it through glycine receptor activation. Chronic hyperammonemia impairs the glutamate‐NO‐cGMP pathway in the cerebellum and induces cognitive impairment. The possible alterations in hyperammonemia of glycinergic neurotransmission and of glutamate‐NO‐cGMP pathway modulation by glycine remain unknown. The aims were to assess, by in vivo microdialysis in cerebellum: (i) the effects of different glycine concentrations, administered through the microdialysis probe, on the glutamate‐NO‐cGMP pathway function; (ii) the effects of tonic glycine receptors activation on the pathway function, by blocking them with strychnine; (iii) whether hyperammonemia alters the pathway modulation by glycine; (iv) and whether hyperammonemia alters extracellular glycine concentration and/or glycine receptor membrane expression. In control rats, low glycine levels reduce the pathway function, likely by activating glycine receptors, while 20 μM glycine enhances the pathway function, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine did not reduce the pathway function, but enhanced it when administered at 1–20 μM. Hyperammonemia reduces extracellular glycine concentration by approximately 50% and glycine receptor membrane expression. However, tonic glycine receptor activation seems to be enhanced in hyperammonemic rats, as indicated by the larger increase in extracellular cGMP induced by strychnine. These data show that glycine modulates the glutamate‐NO‐cGMP pathway biphasically and that hyperammonemia strongly alters glycinergic neurotransmission and modulation by glycine of the glutamate‐NO‐cGMP pathway. These alterations may contribute to the cerebellar aspects of cognitive alterations in hyperammonemia.
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The findings reported in this study show that hyperammonemia alters glycinergic neurotransmission and the glutamate‐NO‐cGMP pathway modulation by glycine. In control rats, low glycine levels reduced the pathway function, likely by activating glycine receptors, while 20 μM glycine enhanced the pathway, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine (administered at 1–20 μM) enhances the pathway, likely by activating NMDA receptors.
Nutritional screening of patients at a memory clinic – association between patients’ and their relatives’ self‐reports
Authors: Lyngroth Anne Liv , Hernes Susanne Miriam Sørensen , Madsen Bengt‐Ove , Söderhamn Ulrika , Grov Ellen Karine 
Published: February 2016

Aims and objectivesTo compare individual reports by patients and relatives (proxy) of the Nutritional Form For the Elderly and relate the Nutritional Form For the Elderly scores to Mini Mental Status Examination scores, weight loss, Body Mass Index, five‐point Clock Drawing Test and background variables.BackgroundUndernutrition or risk of undernutrition is a significant problem among people with dementia. A poor nutritional state increases the risk of infections, delayed convalescence after acute illness and reduced quality of life.DesignA cross‐sectional study.MethodApplication of the Nutritional Form For the Elderly in addition to clinical nutrition parameters and cognitive tests in a memory clinic among 213 persons referred for assessment due to possible cognitive impairment or dementia.ResultsPatients’ and proxy Nutritional Form For the Elderly scores yielded comparative results. Nutritional Form For the Elderly scores ≥6 (medium to high risk of undernutrition) were found in 32% of the patients vs. 43% of proxy. Mean Mini Mental Status Examination score was 23·2 (SD 4·5) and 50% failed the Clock Drawing Test. Involuntary weight loss was reported by 42% of the patients, and in 26% of the patients, Body Mass Index values were below 22 kg/m2, indicating undernutrition. By regression analysis, Clock Drawing Test (p = 0·019) and Mini Mental Status Examination (p = 0·04) might predict the risk of reduced nutritional status.ConclusionThe study demonstrates that a significant proportion of patients at our memory clinic were at nutritional risk. Corresponding results exist between patients’ and proxy Nutritional Form For the Elderly scores; however, the patients assessed themselves more well‐nourished as compared to proxy assessment. The discrepancies seem to increase with more severe cognitive impairment. Females and single‐dwelling individuals were at higher risk of undernutrition compared to males and cohabitants.Relevance to clinical practiceSelf‐reporting and proxy‐rating seem both applicable for nutritional screening among moderate cognitive impaired. Cognitive decline seems to affect the accuracy when patients rate themselves. A reduced Mini Mental Status Examination and/or failed Clock Drawing Test might predict the risk of undernutrition.
Applying an ecological restoration approach to study patient safety culture in an intensive care unit
Authors: Gimenes Fernanda Raphael Escobar , Torrieri Mayara Carvalho Godinho Rigobello , Gabriel Carmen Silvia , Rocha Fernanda Ludmilla Rossi , Silva Ana Elisa Bauer de Camargo , Shasanmi Rebecca O , Cassiani Silvia Helena De Bortoli 
Published: February 2016

Aims and objectivesTo gain an understanding of medication safety culture and other quality issues in a Brazilian intensive care unit using a restorative approach.BackgroundPatient safety should be considered one of the pillars of quality in health care. Thus, patient safety culture is increasingly being explored as a guide for quality improvement efforts.DesignA qualitative approach.MethodsParticipatory photographic research methods from the field of ecological restoration were adapted in this study. This study used focus groups, then subsequent nurse‐led photo‐narrated walkabouts, and photo elicitation with 23 nurses and one physician in interactive phases of data collection and analysis over an eight‐month timeframe.ResultsThe core themes identified were: the ‘medication system shapes patient safety’ and the ‘feeling of helplessness in the face of the prevailing organization culture’. Participants discussed supports exiting in the intensive care unit that shape medication safety, the barriers that impede safe medication management, the solutions to improve medication safety and the creation of a better medication safety culture.ConclusionsThe methods used allowed participants to visualise sound practices as well as key safety issues, reflect on their day‐to‐day work, re‐think potential improvements, and enact changes to improve medication safety and medication safety culture. However, the patient safety culture is also marked by administrative pressure. The hospital needs to adopt participatory management, where the health professionals can act together with the organisational leaders to promote a just culture.Relevance to clinical practiceThe participatory photographic research methods from the field of ecological restoration provided participants with a tool to promote patient safety culture and engage policy change dialogue. However, it will be important in future restorative research to track‐specific safety outcomes over time to assess the cost‐benefit of the adoption of participatory management models.
Experiments link competition and climate change responses
Authors: Alexander Jake M. 
Published: February 2016

AbstractSpecies interactions can have a larger impact on plant performance than direct effects of climate change itself, as shown by Rysavy et al. in this issue of the Journal of Vegetation Science. Their study illustrates different ways in which plant–plant interactions can change following climate change, stressing the need for experiments to disentangle direct and indirect impacts of climate change.
A Trichoderma atroviride stress‐activated MAPK pathway integrates stress and light signals
Authors: Esquivel‐Naranjo Edgardo Ulises , García‐Esquivel Mónica , Medina‐Castellanos Elizabeth , Correa‐Pérez Víctor Alejandro , Parra‐Arriaga Jorge Luis , Landeros‐Jaime Fidel , Cervantes‐Chávez José Antonio , Herrera‐Estrella Alfredo 
Published: February 2016

SummaryCells possess stress‐activated protein kinase (SAPK) signalling pathways, which are activated practically in response to any cellular insult, regulating responses for survival and adaptation to harmful environmental changes. To understand the function of SAPK pathways in T. atroviride, mutants lacking the MAPKK Pbs2 and the MAPK Tmk3 were analysed under several cellular stresses, and in their response to light. All mutants were highly sensitive to cellular insults such as osmotic and oxidative stress, cell wall damage, high temperature, cadmium, and UV irradiation. Under oxidative stress, the Tmk3 pathway showed specific roles during development, which in conidia are essential for tolerance to oxidant agents and appear to play a minor role in mycelia. The function of this pathway was more evident in Δpbs2 and Δtmk3 mutant strains when combining oxidative stress or cell wall damage with light. Light stimulates tolerance to osmotic stress through Tmk3 independently of the photoreceptor Blr1. Strikingly, photoconidiation and expression of blue light regulated genes was severally affected in Δtmk3 and Δpbs2 strains, indicating that this pathway regulates light responses. Furthermore, Tmk3 was rapidly phosphorylated upon light exposure. Thus, our data indicate that Tmk3 signalling cooperates with the Blr photoreceptor complex in the activation of gene expression.
Investigation of mental health in Indonesian health workers immigrating to Japan under the Economic Partnership Agreement
Authors: Sato Fumiko , Hayakawa Kazuo , Kamide Kei 
Published: February 2016

AbstractThe aim of this study was to assess the mental health status of Indonesian nurses and care workers who immigrated to Japan after the Economic Partnership Agreement was signed by the governments of Japan and Indonesia in 2008. From November 2012 to March 2013, questionnaires were mailed to 206 workers in 87 medical and caregiving facilities that openly accept Indonesian EPA immigrant workers. Responses were received from 71 workers in 35 facilities. Responses from 22.5% of workers suggested that they were at risk of developing mental health problems, and “gender” and “acquisition state of national qualifications” were the main factors influencing their mental health status. The results suggest that support after obtaining national qualifications is inadequate and that mid and long‐term support systems that focus on the needs of immigrant healthcare workers after passing national examinations are necessary.