bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronically delivered, multicomponent intervention to reduce unnecessary antibiotic prescribing for respiratory infections in primary care: a cluster randomised trial using electronic health records—REDUCE Trial study original protocol
Authors: Juszczyk Dorota , Charlton Judith , McDermott Lisa , Soames Jamie , Sultana Kirin , Ashworth Mark , Fox Robin , Hay Alastair D , Little Paul , Moore Michael V , Yardley Lucy , Prevost A Toby , Gulliford Martin C
Published: August 2016

Introduction

Respiratory tract infections (RTIs) account for about 60% of antibiotics prescribed in primary care. This study aims to test the effectiveness, in a cluster randomised controlled trial, of electronically delivered, multicomponent interventions to reduce unnecessary antibiotic prescribing when patients consult for RTIs in primary care. The research will specifically evaluate the effectiveness of feeding back electronic health records (EHRs) data to general practices.

Methods and analysis

2-arm cluster randomised trial using the EHRs of the Clinical Practice Research Datalink (CPRD). General practices in England, Scotland, Wales and Northern Ireland are being recruited and the general population of all ages represents the target population. Control trial arm practices will continue with usual care. Practices in the intervention arm will receive complex multicomponent interventions, delivered remotely to information systems, including (1) feedback of each practice's antibiotic prescribing through monthly antibiotic prescribing reports estimated from CPRD data; (2) delivery of educational and decision support tools; (3) a webinar to explain and promote effective usage of the intervention. The intervention will continue for 12 months. Outcomes will be evaluated from CPRD EHRs. The primary outcome will be the number of antibiotic prescriptions for RTIs per 1000 patient years. Secondary outcomes will be: the RTI consultation rate; the proportion of consultations for RTI with an antibiotic prescribed; subgroups of age; different categories of RTI and quartiles of intervention usage. There will be more than 80% power to detect an absolute reduction in antibiotic prescription for RTI of 12 per 1000 registered patient years. Total healthcare usage will be estimated from CPRD data and compared between trial arms.

Ethics and dissemination

Trial protocol was approved by the National Research Ethics Service Committee (14/LO/1730). The pragmatic design of the trial will enable subsequent translation of effective interventions at scale in order to achieve population impact.

Trial registration number

ISRCTN95232781; Pre-results.
Ethnographic process evaluation of a quality improvement project to improve transitions of care for older people
Authors: Sutton Elizabeth , Dixon-Woods Mary , Tarrant Carolyn
Published: August 2016

Objectives

Quality improvement projects to address transitions of care across care boundaries are increasingly common but meet with mixed success for reasons that are poorly understood. We aimed to characterise challenges in a project to improve transitions for older people between hospital and care homes.

Design

Independent process evaluation, using ethnographic observations and interviews, of a quality improvement project.

Setting and participants

An English hospital and two residential care homes for older people.

Data

32 hours of non-participant observations and 12 semistructured interviews with project members, hospital and care home staff.

Results

A hospital-based improvement team sought to reduce unplanned readmissions from residential care homes using interventions including a community-based geriatric team that could be accessed directly by care homes and a communication tool intended to facilitate transfer of information between homes and hospital. Only very modest (if any) impacts of these interventions on readmission rates could be detected. The process evaluation identified multiple challenges in implementing interventions and securing improvement. Many of these arose because of lack of consensus on the nature of the problem and the proper solutions: while the hospital team was keen to reduce readmissions and saw the problems as lying in poor communication and lack of community-based support for care homes, the care home staff had different priorities. Care home staff were unconvinced that the improvement interventions were aligned with their needs or addressed their concerns, resulting in compromised implementation.

Conclusions

Process evaluations have a valuable role in quality improvement. Our study suggests that a key task for quality improvement projects aimed at transitions of care is that of developing a shared view of the problem to be addressed. A more participatory approach could help to surface assumptions, interpretations and interests and could facilitate the coproduction of solutions. This finding is likely to have broader applicability.
Attitudes and factors affecting acceptability of self-administered cervicovaginal sampling for human papillomavirus (HPV) genotyping as an alternative to Pap testing among multiethnic Malaysian women
Authors: Ma'som Mahirah , Bhoo-Pathy Nirmala , Nasir Nazrila Hairizan , Bellinson Jerome , Subramaniam Shridevi , Ma Yuntong , Yap Siew-Hwei , Goh Pik-Pin , Gravitt Patti , Woo Yin Ling
Published: August 2016

Objective

The objective of this study was to determine the attitudes and acceptability of self-administered cervicovaginal sampling compared with conventional physician-acquired Papanicolaou (Pap) smear among multiethnic Malaysian women.

Method

A cross-sectional study was carried out via interviewer-administered surveys from August 2013 through August 2015 at five government-run, urban health clinics in the state of Selangor. Subjects were participants from an ongoing community-based human papillomavirus (HPV) prevalence study who answered a standard questionnaire before and after self-sampling. The cervicovaginal self-sampling for HPV genotyping was performed using a simple brush (‘Just for Me’; Preventive Oncology International, Hong Kong). Detailed data on sociodemographics, previous Pap smear experience, and attitudes towards self-administered cervicovaginal sampling were collected and analysed. Acceptability was inferred using a five-item Likert scale that included six different subjective descriptives: experience, difficulty, convenience, embarrassment, discomfort or pain, and confidence in collecting one's own sample.

Results

Of the 839 participants, 47.9% were Malays, followed by 30.8% Indians, 18.8% Chinese and 2.5% from other ethnicities. The median age of the participants was 38 years (IQR 30–48). Some 68.2% of participants indicated a preference for self-sampling over the Pap test, with 95% indicating willingness to follow-up a positive result at the hospital. Age, ethnicity and previous Pap test experience were significant independent factors associated with preference for self-sampling. The older the individual, the less likely they were to prefer self-sampling (adjusted OR 0.94, 95% CI 0.90 to 0.98). The Chinese were less likely to prefer self-sampling (72.6%) than the Malays (85.1%) (adjusted OR 0.57, 95% CI 0.33 to 0.98, p=0.004). Participants who had never undergone a Pap smear were also more likely to prefer self-sampling (88.5%) than women who had undergone a previous Pap (80.9%) (adjusted OR 0.06, 95% CI 0.35 to 0.87).

Conclusions

Overall, urban Malaysian women from multiethnic backgrounds found self-sampling to be an acceptable alternative to Pap smear.
Effectiveness and cost-effectiveness of the Salut Programme: a universal health promotion intervention for parents and children—protocol of a register-based retrospective observational study
Authors: Feldman Inna , Eurenius Eva , Häggström Jenny , Sampaio Filipa , Lindkvist Marie , Pulkki-Brännström Anni-Maria , Ivarsson Anneli
Published: August 2016

Introduction

There is inadequate evidence for the effectiveness and cost-effectiveness of health promotion interventions. The Salut Programme aims to reach all parents and children in the Västerbotten County of Sweden with a combination of health promotion interventions initiated during pregnancy and continued over the childhood period. This study protocol describes an effectiveness study and an economic evaluation study, where the ongoing Salut Programme is compared to care-as-usual over the periods of pregnancy, delivery and the child's first 2 years of life.

Methods

A register-based retrospective observational study design will be used with existing data sources with respect to exposures and outcomes. Outcomes of interest are clustered at 3 points: around the child's birth, 1 month after the child's birth and 2 years after the child's birth. We will simulate an experiment by retrospectively identifying and comparing children and their parents in the geographical areas where the Salut Programme was implemented since 2006 and onwards, and the areas where the Programme was not implemented before 2009. Outcomes will be analysed and compared for the premeasure period, and the postmeasure period for both groups. Our analysis combines difference-in-difference estimation with matching. A complementary analysis will be carried out on the longitudinal subsample of mothers who gave birth at least once during each of the time periods. The economic evaluation aims to capture the wider societal costs and benefits of the Salut Programme for the first 2 years of the children's lives. Incremental costs will be compared with incremental health gains and the results will be presented as a cost-consequence analysis.

Ethics and dissemination

The Regional Ethical Review Board in Umeå has given clearance for the Salut Programme research (2010-63-31M). No individual's identity will be revealed when presenting results. This study will provide information that can guide decision-makers to allocate resources optimally.
Study design for a randomised controlled trial to explore the modality and mechanism of Tai Chi in the pulmonary rehabilitation of chronic obstructive pulmonary disease
Authors: Fu Juan-Juan , Min Jie , Yu Peng-Ming , McDonald Vanessa M , Mao Bing
Published: August 2016

Introduction

Although pulmonary rehabilitation (PR) is associated with significant clinical benefits in chronic obstructive pulmonary disease (COPD) and has been recommended by guidelines, PR with conventional exercise training has not been widely applied in the clinic because of its inherent limitations. Alternative exercise such as Tai Chi has been investigated and the results are promising. However, the strengths and weaknesses of the exercise modality of Tai Chi, conventional PR and a combination of Tai Chi and conventional PR and the possible mechanisms underlying Tai Chi exercise remain unclear. This study aims to address the above research gaps in a well-designed clinical trial.

Methods and analysis

This study is a single-blind, randomised controlled trial. Participants with stable COPD will be recruited and randomly assigned to one of four groups receiving Tai Chi exercise, conventional PR using a total body recumbent stepper (TBRS), combined Tai Chi and TBRS, or usual care (control) in a 1:1:1:1 ratio. Participants will perform 30 min of supervised exercise three times a week for 8 weeks; they will receive sequential follow-ups until 12 months after recruitment. The primary outcome will be health-related quality of life as measured by the St George's Respiratory Questionnaire. Secondary outcomes will include 6 min walking distance, pulmonary function, the modified Medical Research Council Dyspnoea Scale, the COPD Assessment Test, the Hospital Anxiety and Depression Scale, the Berg Balance Scale, exacerbation frequency during the study period, and systemic inflammatory and immune markers.

Ethics and dissemination

Ethics approval has been granted by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University (No TCM-2015-82). Written informed consent will be obtained from each participant before any procedures are performed. The study findings will be published in peer-reviewed journals and presented at national and international conferences.

Trial registration number

ChiCTR-IOR-15006874; Pre-results.
Study protocol: first nationwide comparative audit of acute lower gastrointestinal bleeding in the UK
Authors: Oakland Kathryn , Guy Richard , Uberoi Raman , Seeney Frances , Collins Gary , Grant-Casey John , Mortensen Neil , Murphy Mike , Jairath Vipul
Published: August 2016

Introduction

Acute lower gastrointestinal bleeding (LGIB) is a common indication for emergency hospitalisation worldwide. In contrast to upper GIB, patient characteristics, modes of investigation, transfusion, treatment and outcomes are poorly described. There are minimal clinical guidelines to inform care pathways and the use of endoscopy, including (diagnostic and therapeutic yields), interventional radiology and surgery are poorly defined. As a result, there is potential for wide variation in practice and clinical outcomes.

Methods and analysis

The UK Lower Gastrointestinal Bleeding Audit is a large nationwide audit of adult patients acutely admitted with LGIB or those who develop LGIB while hospitalised for another reason. Consecutive, unselected presentations with LGIB will be enrolled prospectively over a 2-month period at the end of 2015 and detailed data will be collected on patient characteristics, comorbidities, use of anticoagulants, transfusion, timing and modalities of diagnostic and therapeutic procedures, clinical outcome, length of stay and mortality. These will be audited against predefined minimum standards of care for LGIB. It is anticipated that over 80% of all acute hospitals in England and some hospitals in Scotland, Wales and Northern Ireland will participate. Data will be collected on the availability and organisation of care, provision of diagnostic and therapeutic GI endoscopy, interventional radiology, surgery and transfusion protocols.

Ethics and dissemination

This audit will be conducted as part of the national comparative audit programme of blood transfusion through collaboration with specialists in gastroenterology, surgery and interventional radiology. Individual reports will be provided to each participant site as well as an overall report and disseminated through specialist societies. Results will also be published in peer-reviewed journals. The study has been funded by National Health Services (NHS) Blood and Transplant and the Bowel Disease Research Foundation and endorsed by the Association of Coloproctology of Great Britain and Ireland.
Restoration of microRNA-212 Causes a G0/G1 Cell Cycle Arrest and Apoptosis in Adult T-Cell Leukemia/Lymphoma Cells by Repressing CCND3 Expression
Authors: Wang Haihao , Guo Qiannan , Yang Peiwen , Long Guoxian
Published: August 2016

Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive T-cell malignancy. This study was designed to explore the expression and functional significance of microRNA (miR)-212 in ATL. The expression of miR-212 in human ATL tissues and cell lines were investigated. Gain-of-function experiments were carried out to determine the roles of miR-212 in cell proliferation, tumorigenesis, cell cycle progression, and apoptosis. We also identified and functionally characterized the target genes of miR-212 in ATL cells. Compared with normal lymph node biopsies, lymphoma samples from ATL patients displayed underexpression of miR-212 (p=0.0032). Consistently, miR-212 was downregulated in human ATL cell lines, compared with normal T lymphocytes. Restoration of miR-212 significantly (p<0.05) inhibited ATL cell proliferation and tumorigenesis in mice. Overexpression of miR-212 led to an accumulation of G0/G1-phase cells and a concomitant reduction of S-phase cells. Moreover, enforced expression of miR-212-induced significant apoptosis in ATL cells. CCND3, which encodes a cell cycle regulator cyclin D3, was identified as a direct target of miR-212 in ATL cells. Rescue experiments with a miR-212-resistant variant of CCND3 demonstrated that overexpression of CCND3 restored cell-cycle progression and attenuated apoptotic response in miR-212-overexpressing ATL cells. Taken together, miR-212 exerts growth-suppressive effects in ATL cells largely by targeting CCND3 and may have therapeutic potential in ATL.
Acute cocoa flavanol improves cerebral oxygenation without enhancing executive function at rest or after exercise
Authors: Decroix Lieselot , Tonoli Cajsa , Soares Danusa D. , Tagougui Semah , Heyman Elsa , Meeusen Romain
Published: August 2016

Acute exercise-induced improvements in cognitive function are accompanied by increased (cerebral) blood flow and increased brain-derived neurotrophic factor (BDNF) levels. Acute cocoa flavanol (CF) intake may improve cognitive function, cerebral blood flow (in humans), and BNDF levels (in animals). This study investigated (i) the effect of CF intake in combination with exercise on cognitive function and (ii) cerebral hemodynamics and BDNF in response to CF intake and exercise. Twelve healthy men participated in this randomized, double-blind, crossover study. Participants performed a cognitive task (CT) at 100 min after acute 903-mg CF or placebo (PL) intake, followed by a 30-min time-trial. Immediately after this exercise, the same CT was performed. Prefrontal near-infrared spectroscopy was applied during CT and exercise to measure changes in oxygenated (ΔHbO2), deoxygenated (ΔHHb), and total haemoglobin (ΔHbtot) and blood samples were drawn and analyzed for BDNF. Reaction time was faster postexercise, but was not influenced by CF. ΔHbO2 during the resting CT was increased by CF, compared with PL. ΔHbO2, ΔHHb, and ΔHbtot increased in response to exercise without any effect of CF. During the postexercise cognitive task, there were no hemodynamic differences between CF or PL. Serum BDNF was increased by exercise, but was not influenced by CF. In conclusion, at rest, CF intake increased cerebral oxygenation, but not BDNF concentrations, and no impact on executive function was detected. This beneficial effect of CF on cerebral oxygenation at rest was overruled by the strong exercise-induced increases in cerebral perfusion and oxygenation.
An eco-friendly method for analysis of sulfonamides in water samples using a multi-pumping system
Authors: Catelani Tiago Augusto , Castoldi Karine , Tóth Ildikó Vargáné , Santos João Luís Machado , da Costa Lima José Luís Fontes , Pezza Leonardo , Pezza Helena Redigolo
Published: August 2016

A new methodology for determination of sulfonamides (sulfaquinoxaline, sulfathiazole, and sulfadimethoxine) in water samples was developed by coupling an automated multi-pumping flow system (MPFS) with a liquid waveguide capillary cell (LWCC; pathlength, 100 cm) and a spectrophotometric detector. The method is based on the reaction between sulfonamides and p-dimethylaminocinnamaldehyde (p-DAC) in the presence of sodium dodecylsulfate (SDS) in dilute acid medium (hydrochloric acid), with measurement of the reaction products at 565 nm. Experimental design methodology was used to optimize the analytical conditions. The linear range obtained was 10.0–130.0 μg/L, and detection and quantification limits were 3.1 and 10.1 μg/L, respectively. The method was successfully applied to the analysis of sulfonamides in water samples. By coupling the MPFS with the LWCC, the sensitivity was enhanced, reagent consumption was low, and waste generation was minimized. The results obtained with the MPFS method were confirmed by LC–MS.
The Minimum Norm Least-Squares Solution in Reduction by Krylov Subspace Methods
Authors: Wang Xinsheng , Wang Chenxu , Yu Mingyan
Published: August 2016

In recent years, model order reduction (MOR) of interconnect system has become an important technique to reduce the computation complexity and improve the verification efficiency in the nanometer VLSI design. The Krylov subspaces techniques in existing MOR methods are efficient, and have become the methods of choice for generating small-scale macro-models of the large-scale multi-port RCL networks that arise in VLSI interconnect analysis. Although the Krylov subspace projection-based MOR methods have been widely studied over the past decade in the electrical computer-aided design community, all of them do not provide a best optimal solution in a given order. In this paper, a minimum norm least-squares solution for MOR by Krylov subspace methods is proposed. The method is based on generalized inverse (or pseudo-inverse) theory. This enables a new criterion for MOR-based Krylov subspace projection methods. Two numerical examples are used to test the PRIMA method based on the method proposed in this paper as a standard model.
On the Heteroclinic Connections in the 1:3 Resonance Problem
Authors: Qin B. W. , Chung K. W. , Fahsi A. , Belhaq M.
Published: August 2016

Analytical predictions of the triangle and clover heteroclinic bifurcations in the problem of self-oscillations stability loss near 1:3 resonance are provided using the method of nonlinear time transformation. The analysis was carried out considering the slow flow of a self-excited nonlinear Mathieu oscillator corresponding to the normal form near this 1:3 strong resonance. Using the Hamiltonian system of the corresponding slow flow near this resonance, the unperturbed zero-order approximation of the heteroclinic connections is established. Conditions of persistence of homoclinic connections in the perturbed first-order approximation of the heteroclinic connections provide close analytical approximations of the triangle and clover heteroclinic bifurcation curves, simultaneously. The analytical predictions are compared to the results obtained by numerical simulations for validation.
Ranking of Z-Numbers and Its Application in Decision Making
Authors: Aliev R. A. , Huseynov O. H. , Serdaroglu R.
Published: August 2016

Real-world decision problems in decision analysis, system analysis, economics, ecology, and other fields are characterized by fuzziness and partial reliability of relevant information. In order to deal with such information, Prof. Zadeh suggested the concept of a Z-number as an ordered pair [Formula: see text] of fuzzy numbers [Formula: see text] and [Formula: see text], the first of which is a linguistic value of a variable of interest, and the second one is a linguistic value of probability measure of the first one, playing a role of reliability of information. Decision making under Z-number based information requires ranking of Z-numbers. In this paper we suggest a human-like fundamental approach for ranking of Z-numbers which is based on two main ideas. One idea is to compute optimality degrees of Z-numbers and the other one is to adjust the obtained degrees by using a human being’s opinion formalized by a degree of pessimism. Two examples and a real-world application are provided to show validity of the suggested research. A comparison of the proposed approach with the existing methods is conducted.
Aminophenyl/carboxyphenylporphyrins as sensitizers for dye-sensitized solar cells
Authors: Rudine Alexander B. , Day Nicholas U. , Tian Xisen , Lee Chang , James Keith E. , Wamser Carl C.
Published: August 2016

A series of tetraphenyl meso-substituted porphyrins with either p-amino or p-carboxy substituents has been studied as dyes for standard dye-sensitized solar cells (DSSCs). The porphyrins with greater numbers of amino groups generally show greater efficiency, primarily due to higher photocurrents; open-circuit voltage and fill factors are comparable. The most efficient sensitizer was the trans disubstituted zinc porphyrin, with an overall solar energy conversion efficiency of 5.66%, slightly higher than the triamino zinc porphyrin at 5.18%. The improved efficiency is attributed to the well known push–pull effect in porphyrinsensitized DSSCs with electrondonating groups opposite to the electronwithdrawing anchoring (carboxy) groups. It is suggested that porphyrin derivatives with cis diaminophenyl groups show somewhat diminished efficiency due to difficulties with regeneration of the dye from its oxidized form.
DNA Methylation and Demethylation in Plant Immunity
Authors: Deleris A. , Halter T. , Navarro L.
Published: August 2016

Detection of plant and animal pathogens triggers a massive transcriptional reprogramming, which is directed by chromatin-based processes, and ultimately results in antimicrobial immunity. Although the implication of histone modifications in orchestrating biotic stress–induced transcriptional reprogramming has been well characterized, very little was known, until recently, about the role of DNA methylation and demethylation in this process. In this review, we summarize recent findings on the dynamics and biological relevance of DNA methylation and demethylation in plant immunity against nonviral pathogens. In particular, we report the implications of these epigenetic regulatory processes in the transcriptional and co-transcriptional control of immune-responsive genes and discuss their relevance in fine-tuning antimicrobial immune responses. Finally, we discuss the possible yet elusive role of DNA methylation and demethylation in systemic immune responses, transgenerational immune priming, and de novo epiallelism, which could be adaptive.
The Intratumoral Balance between Metabolic and Immunologic Gene Expression Is Associated with Anti–PD-1 Response in Patients with Renal Cell Carcinoma
Authors: Ascierto Maria Libera , McMiller Tracee L. , Berger Alan E. , Danilova Ludmila , Anders Robert A. , Netto George J. , Xu Haiying , Pritchard Theresa S. , Fan Jinshui , Cheadle Chris , Cope Leslie , Drake Charles G. , Pardoll Drew M. , Taube Janis M. , Topalian Suzanne L.
Published: August 2016

Pretreatment tumor PD-L1 expression has been shown to correlate with response to anti–PD-1/PD-L1 therapies. Yet, most patients with PD-L1+ tumors do not respond to treatment. The current study was undertaken to investigate mechanisms underlying the failure of PD-1–targeted therapies in patients with advanced renal cell carcinoma (RCC) whose tumors express PD-L1. Formalin-fixed, paraffin-embedded pretreatment tumor biopsies expressing PD-L1 were derived from 13 RCC patients. RNA was isolated from PD-L1+ regions and subjected to whole genome microarray and multiplex quantitative (q)RT-PCR gene expression analysis. A balance between gene expression profiles reflecting metabolic pathways and immune functions was associated with clinical outcomes following anti–PD-1 therapy. In particular, the expression of genes involved in metabolic and solute transport functions such as UGT1A family members, also found in kidney cancer cell lines, was associated with treatment failure in patients with PD-L1+ RCC. Conversely, tumors from responding patients overexpressed immune markers such as BACH2, a regulator of CD4+ T-cell differentiation, and CCL3 involved in leukocyte migration. These findings suggest that tumor cell–intrinsic metabolic factors may contribute to treatment resistance in RCC, thus serving as predictive markers for treatment outcomes and potential new targets for combination therapy regimens with anti–PD-1. Cancer Immunol Res; 4(9); 726–33. ©2016 AACR.

See related Spotlight by Ohashi, p. 719.
N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia
Authors: Benterud Torkil , Ystgaard Martin B. , Manueldas Sophia , Pankratov Leonid , Alfaro-Cervello Clara , Florholmen Geir , Ahmed Muhammad Shakil , Sandvik Leiv , Norgren Svante , Bjørås Magnar , Baumbusch Lars O. , Solberg Ronnaug , Saugstad Ola Didrik
Published: August 2016

Background: Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs. Objectives: To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-κB in the prefrontal cortex of neonatal pigs. Methods: Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8% oxygen, until the base excess was -20 mmol/l or the mean arterial blood pressure fell to <20 mm Hg (asphyxia with NACA or saline). The pigs were observed for 9.5 h after hypoxia. Samples of prefrontal cortex and plasma were analyzed. Results: Cortex: there was no significant difference in mRNA expression between the intervention groups regarding IL-1β, IL6, TNFα, MMP2, MMP9 or IL18. Pigs exposed to hypoxia-reoxygenation and treatment with NACA (NACA-pigs) had a significantly lower protein concentration of IL-1β than pigs treated with saline (placebo controls), i.e. 8.8 ± 3.9 versus 16.8 ± 10.5 pg/mg protein (p = 0.02). The activation of the transcription factor NF-κB (measured as the fold-change of phosphorylated p65Ser 536), was reduced in the NACA-pigs when compared to the placebo controls (5.2 ± 4.3 vs. 16.0 ± 13.5; p = 0.02). No difference between the intervention groups regarding brain histopathology or in the levels of 8-oxoguanine measured in the prefrontal cortex were observed. Plasma: the NACA-pigs had a stronger reduction of TNFα in the first 30 min following asphyxia compared with the placebo controls, i.e. 36 (30-44) versus 24 (14-32)% (p = 0.01). Conclusion: The reduced levels of the pivotal inflammatory markers IL-1β and TNFα and the transcription factor NF-κB may indicate that NACA has possible neuroprotective effects after perinatal asphyxia.
Increased Activity and Number of Epidermal Melanocytes in Lesional Psoriatic Skin
Authors: Abdel-Naser Mohamed Badawy , Liakou Aikaterini I. , Elewa Rana , Hippe Sabine , Knolle Jürgen , Zouboulis Christos C.
Published: August 2016

Background: Psoriatic lesions may resolve with hypo- or hyperpigmentation. The involvement of melanocytes in this dichotomous clinical outcome is not fully investigated. Objectives: Qualitative and quantitative assessment of melanocytes in untreated lesional and non-lesional psoriatic skin (n = 15) and healthy controls (n = 10). Methods: Skin biopsies were labelled immunohistochemically (APAAP technique) with the antimelanocyte monoclonal antibodies (MoAbs) HMB45, Melan A, tyrosinase and microphthalmia-associated transcription factor (MITF). The labelled melanocytes were evaluated by an independent investigator with a digital image analyser. Results: Lesional melanocytes, in contrast to those in non-lesional and healthy skin, exhibited features of activation in the form of dilatation, prominent and long dendrites and intense labelling. The number of melanocytes was significantly increased in psoriatic lesions in comparison with non-lesional psoriatic and healthy skin as shown by counts of cells labelled with the MoAbs HMB45 (3-fold; p < 0.001), Melan A (1.6-fold; p < 0.01) and tyrosinase (1.5-fold; p < 0.01). In contrast, labelling with MITF revealed no significant difference (1.2-fold increase; p > 0.05). Likewise, no significant difference between non-lesional psoriatic and healthy skin control was found (p > 0.05). Furthermore, no positively labelled dermal cells were detected, apart from few only detected with Melan A. Conclusions: Epidermal melanocyte activity and numbers are increased in the epidermal compartment of psoriatic lesions providing an explanation for postinflammatory hyperpigmentation.
LEFTY2 Controls Migration of Human Endometrial Cancer Cells via Focal Adhesion Kinase Activity (FAK) and miRNA-200a
Authors: Alowayed Nour , Salker Madhuri S. , Zeng Ni , Singh Yogesh , Lang Florian
Published: August 2016

Background: LEFTY2, a suppressor of cell proliferation, tumor growth, regulator of stemness and embryonic differentiation, is a negative regulator of cancer cell reprogramming. Malignant transformation may lead to migration requiring loss of adhesion and gain of migratory activity. Signaling involved in the orchestration of migration, proliferation and spreading of cells include focal adhesion kinase (FAK) and adhesion molecule E-cadherin. Aims: The present study explored whether LEFTY2 influences the proliferation marker MKi67, FAK activity, E-cadherin abundance and migration of Ishikawa human endometrial carcinoma cells. Moreover, the study explored the involvement of microRNA-200a (miR-200a), which is known to regulate cellular adhesion by targeting E-Cadherin. Methods: FAK activity was estimated from FAK phosphorylation quantified by Western blotting, migration utilizing a wound healing assay, miR-200a and MKi67 expression levels utilizing qRT-PCR, cell proliferation and apoptosis using BrdU and Annexin V staining, respectively, and E-Cadherin (E-Cad) abundance, using confocal microscopy. Results: LEFTY2 (25 ng/ml, 48 hours) treatment was followed by decrease of MKi67 expression, FAK activity and migration. LEFTY2 upregulated miRNA-200a and E-Cad protein level in Ishikawa cells. The effect of LEFTY2 on migration was mimicked by FAK inhibitor PF 573228 (50 µM). Addition of LEFTY2 in the presence of PF-573228 did not result in a further significant decline of migration. Conclusion: In conclusion, LEFTY2 down-regulates MKi67 expression and FAK activity, up-regulates miR-200a and E-cadherin, and is thus a powerful negative regulator of endometrial cell proliferation and migration.
Down-Regulation of MicroRNA-137 Improves High Glucose-Induced Oxidative Stress Injury in Human Umbilical Vein Endothelial Cells by Up-Regulation of AMPKα1
Authors: Li Jie , Li Junfeng , Wei Tingting , Li Junhua
Published: August 2016

Background/Aims: To investigate the effects of miR-137 on high glucose (HG)-induced vascular injury, and to establish the mechanism underlying these effects. Methods: Human umbilical vein endothelial cells (HUVECs) were transfected with miR-137 inhibitor or mimic, and then treated with normal or high glucose. Cell viability and apoptosis were detected by using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected by fluorescent probe (DCFH-DA), thiobarbituric acid reaction, and the nitroblue tetrazolium assay, respectively. The mRNA and protein expressions of AMPKα1 were determined by qRT-PCR and Western blotting. Results: Down-regulation of miR-137 dramatically reverted HG-induced decreases in cell viability and SOD levels and increases in apoptosis, ROS and MDA levels. Moreover, bioinformatics analysis predicted that the AMPKα1 was a potential target gene of miR-137. Luciferase reporter assay demonstrated that miR-137 could directly target AMPKα1. AMPKα1 overexpression had the similar effect as miR-137 inhibition. Down-regulation of AMPKα1 in HUVECs transfected with miR-137 inhibitor partially reversed the protective effect of miR-137 inhibition on HG-induced oxidative stress in HUVECs. Conclusion: Down-regulation of miR-137 ameliorates HG-induced injury in HUVECs by overexpression of AMPKα1, leading to increasing cellular reductive reactions and decreasing oxidative stress. These results provide further evidence for protective effect of miR-137 inhibition on HG-induced vascular injury.
Mineralocorticoid Receptor Blockade Improves Insulin Sensitivity in the Rat Heart and a Possible Molecular Mechanism
Authors: Wang Mei , Li Yongjun , Zhou Kun , Zhang Guoru , Wang Yaling , Liu Tao , Zhang Yang , Guo Anjun , An Yu
Published: August 2016

Background/Aims: Extensive research has explored the role of aldosterone in insulin resistance. Recent evidence suggests that the mineralocorticoid receptor (MR) mediates aldosterone-induced dysregulation of cytokines, and most of this research has focused on adjustments in fat tissue and adipocytes. However, the direct effect of MR blockade on insulin resistance in cardiomyocytes remains largely unknown. In the present study, we investigated whether MR blockade improves insulin-sensitizing factors in insulin-resistant rats and attenuates the dysregulation of the aldosterone-related transport of adiponectin and glucose in cardiomyocytes and examined the underlying mechanisms. Methods: The effects of aldosterone, MR inhibitors (e.g., eplerenone), a peroxisome proliferator-activated receptor (PPAR) α agonist, and a p38 mitogen-activated protein kinase (MAPK) inhibitor on adiponectin and glucose transport were studied at the mRNA and protein levels in vitro and in vivo. Results: Our data revealed that aldosterone reduced the expression of adiponectin and inhibited the transport of glucose in cardiomyocytes and that MR blockade reversed these affects. In vivo, MR blockade improved insulin-sensitive parameters and increased adiponectin expression in the myocardia of high-fat diet rats. Furthermore, aldosterone promoted p38MAPK expression but negatively affected PPARα expression, and the downregulation of adiponectin by aldosterone was reversed by MR blockade, a PPARα agonist, and a p38 MAPK inhibitor. Conclusion: The above results suggested that aldosterone promoted insulin resistance in the heart and that this effect could be partly reversed by MR blockade through signal transduction in the P38 MAPK pathway and PPARα.
Magnetically Controlled Growing Rod in Early-Onset Scoliosis: A Minimum of 2-Year Follow-Up
Authors: Yılmaz Baran , Ekşi Murat Şakir , Işik Semra , Özcan-Ekşi Emel Ece , Toktaş Zafer Orkun , Konya Deniz
Published: August 2016

Purpose: The magnetically controlled growing rod technique decreases complications, costs, and loss of functionality by avoiding successive surgical corrections every 6 months in patients with early-onset scoliosis. However, only a few studies have presented clinical experience with the magnetically controlled growing rod. In this study we aimed to present our single-center experience in patients with early-onset scoliosis who underwent the magnetically controlled growing rod technique and follow-up for at least 2 years. Materials and Methods: We made an observational study by evaluating patients with early-onset scoliosis who underwent the magnetically controlled growing rod technique between February 2012 and December 2013. Demographic and clinical data were obtained from the patients charts. We included patients who were followed up for at least 2 years. Radiological data were obtained from plain anterior-posterior and lateral scoliosis X-rays. Results: Eight patients with early-onset scoliosis who underwent surgery using the magnetic system were treated with dual rods. None of the spines were fused to the sacrum. We observed no intra- and/or postsurgical complications. The average number of external rod lengthenings was 7.6. The average amount of lengthening was 30.6 mm on the right side and 27.8 mm on the left side by the time of last clinical follow-up. The average coronal and sagittal Cobb values at the final clinical evaluation were 10.5° (thoracic coronal), 13.75° (lumbar coronal), 6.25° (lumbosacral coronal), 24.5° (thoracic sagittal), and 40° (lumbar sagittal), respectively. Conclusions: The magnetically controlled growing rod is beneficial in early-onset scoliosis, since it enables spinal growth and decreases additional surgeries, complications, and costs. Even though we had a small sample size, our follow-up period was enough to declare long-term outcomes of our patients. Multicenter and large sample-sized studies are needed to make more conclusive statements regarding this promising scoliosis treatment approach.
Quantification of Gait Abnormalities in Healthy-Looking Multiple Sclerosis Patients (with Expanded Disability Status Scale 0-1.5)
Authors: Novotna Klara , Sobisek Lukas , Horakova Dana , Havrdova Eva , Lizrova Preiningerova Jana
Published: August 2016

Background: Gait impairment is a common symptom in multiple sclerosis (MS) patients, but there is a lack of evidence about gait performance in the group of MS patients with no apparent disability. The aim of our study was to evaluate gait characteristics in MS patients with no apparent impairment of walking and with an Expanded Disability Status Scale (EDSS 0-1.5), and to determine whether any abnormalities are detectable by common clinical tests. Methods: This was an observational study of 64 MS patients with an EDSS 0-1.5 and 47 age- and sex-matched healthy controls. We measured their performance in the timed 25-foot walk test (T25FWT) and the 2-minute walk test (2MWT). The spatiotemporal parameters of gait were measured using a GAITRite instrument. Results: MS patients with no apparent disability (EDSS 0-1.5) performed worse in T25FWT and 2MWT than normal controls. During the self-selected walking speed test on GAITRite, MS patients had a prolonged double support phase, and during the fast walking speed test, they had lower cadence and decreased step length.
Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology)
Authors: Kaplan Muhammet A. , Arslan Ulku Y. , Işıkdogan Abdurrahman , Dane Faysal , Oksuzoglu Berna , Inanc Mevlude , Akman Tulay , Kucukoner Mehmet , Cinkir Havva Y. , Rzazade Rashad , Ozkan Metin , Yilmaz Ugur , Bayoglu Ibrahim V. , Gunaydin Yusuf , Baykara Meltem , Yazilitas Dogan , Cubukcu Erdem , Suner Ali , Ersoy Ugur , Bilici Mehmet , Yazici Ozan , Cayır Kerim , Demirci Umut , Uysal Mukremin
Published: August 2016

Purpose: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. Methods: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. Results: The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). Conclusions: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.
Language Impairment Resulting from a de novo Deletion of 7q32.1q33
Authors: Jiménez-Romero María S. , Barcos-Martínez Montserrat , Espejo-Portero Isabel , Benítez-Burraco Antonio
Published: August 2016

We report on a girl who presents with hearing loss, behavioral disturbances (according to the Inventory for Client and Agency Planning) as well as motor and cognitive delay (according to Battelle Developmental Inventories) which have a significant impact on her speech and language abilities [according to the Peabody Picture Vocabulary Test (ed 3), and the Prueba de Lenguaje Oral de Navarra-Revisada (Navarra Oral Language Test, Revised)]. Five copy number variations (CNVs) were identified in the child: arr[hg18] 7q32.1q33(127109685-132492196)×1, 8p23.1(7156900-7359099) ×1, 15q13.1(26215673-26884937)×1, Xp22.33(17245- 102434)×3, and Xp22.33(964441-965024)×3. The pathogenicity of similar CNVs is mostly reported as unknown. The largest deletion is found in a hot spot for cognitive disease and language impairment and contains several genes involved in brain development and function, many of which have been related to developmental disorders encompassing language deficits (dyslexia, speech-sound disorder, and autism). Some of these genes interact with FOXP2. The proband's phenotype may result from a reduced expression of some of these genes.
Gluten Intolerance and Neurodevelopmental Disorders: Is Nitric Oxide the Common Biomarker Linking These Conditions?
Authors: Fluegge Keith
Published: August 2016

Cruchet et al. attempt to tease out the myths and facts surrounding the growing popularity of certain dietary approaches in the management of neurodevelopmental disorders, like attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs). The authors identify a particular exclusionary-type approach that seeks to eliminate dietary gluten. Although the relationship between celiac disease (CD) and ADHD/ASD is not well established, a repeated clinical feature noted in CD is the elevated levels of nitric oxide in serum and urine. Elevated oxidative stress has also been observed in neurodevelopmental conditions, and the author of this correspondence has been the first to propose that chronic, environmental exposure to the air pollutant, nitrous oxide may contribute to these oxidative stress profiles through neural cholinergic perturbation. Therefore, the purpose of this correspondence is to highlight this biochemical connection between these conditions so as to identify the clinical populations who may realize the greatest benefit of these dietary approaches, while minimizing any potential risk of nutrient deficiencies.
O que é "sindicalismo verde"? Reconfigurações da "luta de classes" sob a crise ecológica do capitalismo
Authors: Souza Luiz Enrique Vieira de
Published: August 2016

SHANTZ, Jeff. Green Syndicalism: An Alternative Red/Green Vision. New York: Syracuse University Press, 2012.
A hipótese pigmentocrática
Authors: Alves Benno Warken
Published: August 2016

TELLES, Edward. The Project on Ethnicity and Race in Latin America (PERLA). Pigmentocracies: ethnicity, race and color in Latin America. Chapel Hill: The University of North Carolina Press, 2014. 297 p.
Reparações, direitos humanos e cidadania: uma gramática para o conflito racial no Brasil?
Authors: Rios Flavia
Published: August 2016

SAILLANT, Francine. Le mouvement noir au Brésil (2000-2010): Réparations, droits et citoyenneté. Collection Anthropologie prospective. France: Academia L ́Harmattan S.A, 2014.
Aspectos aculturativos da festa do Divino Espírito Santo no Brasil, de Emílio Willems
Authors: Santiago Filho Elio Roberto Pinto
Published: August 2016

Traduzido do original: WILLEMS, Emílio. Acculturative aspects of the feast of the Holy Gost in Brazil. American Anthropologist, v. 51, p. 400-408, 1949.