Miracle-dz/UniFAR-FTUs huggingface dataset:
West Nile virus‐infected human dendritic cells fail to fully activate invariant natural killer T cells

West Nile virus (WNV) infection is a mosquito‐borne zoonosis with increasing prevalence in the United States. WNV infection begins in the skin, and the virus replicates initially in keratinocytes and dendritic cells (DCs). In the skin and cutaneous lymph nodes, infected DCs are likely to interact with invariant natural killer T cells (iNKTs). Bidirectional interactions between DCs and iNKTs amplify the innate immune response to viral infections, thus controlling viral load and regulating adaptive immunity. iNKTs are stimulated by CD1d‐bound lipid antigens or activated indirectly by inflammatory cytokines. We exposed human monocyte‐derived DCs to WNV Kunjin and determined their ability to activate isolated blood iNKTs. DCs became infected as judged by synthesis of viral mRNA and Envelope and NS‐1 proteins, but did not undergo significant apoptosis. Infected DCs up‐regulated the co‐stimulatory molecules CD86 and CD40, but showed decreased expression of CD1d. WNV infection induced DC secretion of type I interferon (IFN), but no or minimal interleukin (IL)−12, IL‐23, IL‐18 or IL‐10. Unexpectedly, we found that the WNV‐infected DCs stimulated human iNKTs to up‐regulate CD69 and produce low amounts of IL‐10, but not proinflammatory cytokines such as IFN‐γ or tumour necrosis factor (TNF)‐α. Both CD1d and IFNAR blockade partially abrogated this iNKT response, suggesting involvement of a T cell receptor (TCR)–CD1d interaction and type I interferon receptor (IFNAR) signalling. Thus, WNV infection interferes with DC–iNKT interactions by preventing the production of proinflammatory cytokines. iNKTs may be a source of IL‐10 observed in human flavivirus infections and initiate an anti‐inflammatory innate response that limits adaptive immunity and immune pathology upon WNV infection.
Statin therapy in the prevention of recurrent cardiovascular events: a sex-based meta-analysis.

BACKGROUND The effect of statins on the prevention of cardiovascular events is well demonstrated. Whether this protective effect is equal for women and men remains less well established. Our objective was to evaluate if statin therapy is equally effective in decreasing recurrent cardiovascular events in women and men. DATA SOURCES Randomized clinical trials were searched in PubMed using as indexing terms (statins OR cholesterol lowering medications) AND (cardiovascular events OR stroke OR myocardial infarction OR cardiovascular death). STUDY SELECTION We included randomized, double-blinded, placebo-controlled trials evaluating statins for secondary prevention of cardiovascular events. Studies with an open-label design and observational studies were excluded. DATA EXTRACTION The earliest citation was used to determine the characteristic of the studied population and the methodology. All subsequent citations corresponding to the trial were evaluated for outcome rates by sex. DATA SYNTHESIS Eleven trials representing 43,193 patients were included in the analysis. Overall, statin therapy was associated with a reduced risk of cardiovascular events in all outcomes for women (relative risk [RR], 0.81 [95% CI, 0.74-0.89]) and men (RR, 0.82 [95% CI, 0.78-0.85]). However, they did not reduce all-cause mortality in women vs men (RR, 0.92 [95% CI, 0.76-1.13] vs RR, 0.79 [95% CI, 0.720.87]) or stroke (RR, 0.92 [95% CI, 0.76-1.10] vs RR, 0.81 [95% CI, 0.72-0.92]). CONCLUSIONS Statin therapy is an effective intervention in the secondary prevention of cardiovascular events in both sexes, but there is no benefit on stroke and all-cause mortality in women.
Heterologous desensitization of cardiac &bgr;-adrenergic signal via hormone-induced &bgr;AR/arrestin/PDE4 complexes

Aims Cardiac β-adrenergic receptor (βAR) signalling is susceptible to heterologous desensitization by different neurohormonal stimuli in clinical conditions associated with heart failure. We aim to examine the underlying mechanism of cross talk between βARs and a set of G-protein coupled receptors (GPCRs) activated by hormones/agonists. Methods and results Rat ventricular cardiomyocytes were used to determine heterologous phosphorylation of βARs under a series of GPCR agonists. Activation of Gs-coupled dopamine receptor, adenosine receptor, relaxin receptor and prostaglandin E2 receptor, and Gq-coupled α1 adrenergic receptor and angiotensin II type 1 receptor promotes phosphorylation of β1AR and β2AR at putative protein kinase A (PKA) phosphorylation sites; but activation of Gi-coupled α2 adrenergic receptor and activation of protease-activated receptor does not. The GPCR agonists that promote β2AR phosphorylation effectively inhibit βAR agonist isoproterenol-induced PKA phosphorylation of phospholamban and contractile function in ventricular cardiomyocytes. Heterologous GPCR stimuli have minimal to small effect on isoproterenol-induced β2AR activation and G-protein coupling for cyclic adenosine monophosphate (cAMP) production. However, these GPCR stimuli significantly promote phosphorylation of phosphodiesterase 4D (PDE4D), and recruit PDE4D to the phosphorylated β2AR in a β-arrestin 2 dependent manner without promoting β2AR endocytosis. The increased binding between β2AR and PDE4D effectively hydrolyzes cAMP signal generated by subsequent stimulation with isoproterenol. Mutation of PKA phosphorylation sites in β2AR, inhibition of PDE4, or genetic ablation of PDE4D or β-arrestin 2 abolishes this heterologous inhibitory effect. Ablation of β-arrestin 2 or PDE4D gene also rescues β-adrenergic stimuli-induced myocyte contractile function. Conclusions These data reveal essential roles of β-arrestin 2 and PDE4D in a common mechanism for heterologous desensitization of cardiac βARs under hormonal stimulation, which is associated with impaired cardiac function during the development of pathophysiological conditions.
Research in Developmental Disabilities Development and validation of the computerized bilateral motor coordination test

The purpose of this study was to explore the validity of computerized scaling of bilateral, motor coordination in children 4–6 years of age. There were 623 children with an average age of 5, years and 2 months (standard deviation = 6 months) that participated. The 290 girls (46.5%) and 333, boys (53.5%) were from a purposive sample taken from public and private kindergartens in Taiwan. The computerized bilateral motor coordination test included two subtests, bilateral coordination, movements and projected actions. The motion analysis, with mark position and contour motion, was, used to collect important variables from the subtests. Using the judgments of the experts as the, criterion standards, the accuracy, sensitivity, and specificity of the tool were calculated to evaluate the, validity of the computerized bilateral motor coordination test. The accuracy, sensitivity, and, specificity of the bilateral coordination movement subtests were on average 83.9%, 86.4%, and 83.1%, respectively. The accuracy, sensitivity, and specificity of the projected action subtests were on average, 90.5%, 88.1%, and 90.4%, respectively. The computerized bilateral motor coordination tests showed, an average accuracy of 86.3%, a sensitivity of 87.0%, and a specificity of 85.8%. The computerized, bilateral motor coordination test could be a valuable tool when used to identify problems of bilateral, motor coordination and in permitting early intervention to remedy these problems. 2013 Elsevier Ltd. All rights reserved.
Parental Involvement in Higher Education: Understanding the Relationship Among Students, Parents, and the Institution

Helicopter parents have landed on our college campuses! This monograph examines parental involvement in higher education by looking at the history of the relationship between students and institutions and institutional responses to this phenomenon. It explores:OL {list-style:disc}P:{margin-left 60px}* alternative theoretical frameworks that highlight the benefits of strong parental relationships * variables of gender, race and socioeconomic class and how they inform the student-parent relationship* implications for practice and suggestions for policy In this monograph, the authors encourage higher education researchers and practitioners to take their own college experience out of the equation as they consider student-family relationships today. They provide the analysis and background information necessary to think holistically about parents and their involvement so that all parents are included in our institutional efforts, not just the ones making all the noise. This is the sixth issue in the 33rd volume of the Jossey-Bass series ASHE Higher Education Report. Each monograph in the series is the definitive analysis of a tough higher education problem, based on thorough research of pertinent literature and institutional experiences. Topics are identified by a national survey. Noted practitioners and scholars are then commissioned to write the reports, with experts providing critical reviews of each manuscript before publication.
Large CACNA1A deletion in a family with episodic ataxia type 2.

BACKGROUND Episodic ataxia (EA) is an ion channel disorder that manifests as paroxysmal attacks of imbalance and incoordination. Episodic ataxia type 2 (EA2) is characterized by prolonged episodes of ataxia with interictal nystagmus and is caused by mutations in CACNA1A. All mutations identified thus far (to our knowledge) are nonsense or missense point mutations. OBJECTIVE To describe a family with EA2 having a novel mutation deleting several exons of CACNA1A. DESIGN Clinical and molecular study of a family manifesting EA2 attacks. SETTING Academic research. PATIENTS DNA was extracted from blood samples of 3 family members. MAIN OUTCOME MEASURES Microsatellite genotyping of CACNA1A, quantitative multiplex polymerase chain reaction of short fluorescent fragments (QMPSF), and sequencing were performed. RESULTS Genotyping of CACNA1A showed nonmendelian inheritance of a CAG repeat located at the 3' end of the gene in a mother and daughter, suggesting a deletion event, which was subsequently confirmed by QMPSF analysis and sequencing. This 39.5-kilobase deletion removes the last 16 coding exons of the gene. CONCLUSION Deletion of several exons of CACNA1A may cause EA2 and should be assessed in patients having EA2 without a CACNA1A point mutation.
The study of correlation between different factors affecting family planning and various adopted techniques used in the State of Uttarakhand India.

The State of Uttarakhand has experienced fertility decline significantly among couples residing both in rural and urban areas irrespective of their socio-economic conditions. In search of factors influencing fertility decline in the State this study tries to explore family planning use reasons of differentials in general and sterilization use it correlates in particular among rural women in Uttarakhand. Data collected from a random sample of 800 women in the reproductive age group drawn through a random sampling based on the female literacy rate spread over four district of Uttarakhand. It was revealed that the major reasons perceived by rural women for using family planning were ‘less income and high expenditure’ and ‘desire for quality of children. ’ The sterilization use was more by the women with good socio-economic conditions as compared to their counterparts. The different factors which are positively associated with sterilization use are – membership in mahila -sangtan (clubs for rural women) professional desire for sons and daughters educational aspiration for sons and daughters desire to have house and economic constraints for having children.
Why do students abandon programs prior to completion? Case study investigation of dropout students from the Diploma in Hotel and Catering Management DIT

Not only are demographic changes taking place within the Irish population but in addition, significant challenges are being imposed on higher education providers to retain as many students as possible within the higher education system. Yorke (1999) noted that many students leave higher education prematurely and about 50% of these students do so during, or at the end of their first year in college (DIT, 2003). Some non-completion of courses is unavoidable and should not be viewed as failure by the student, tutor or college, but acknowledged that dropping out is likely (Oliver, 2001). However, a lot of non-completion is preventable and it is the responsibility of the college to help retain their students (Yorke, 1999). Retention rates in Universities, DIT and other institutes have been the subject of a number of recent studies (Flanagan et al, 2000; Morgan et al, 2001; Finnegan and Russell, 2000; Morgan and Kelleghan, 2002), and numerous studies by Costello et al. Morgan and Kelleghan (2002) raised the issue of the lack of motivation and lack of preparedness of some students. This survey also highlighted the poor attendance record for some, and that other students were working during term time (McDonagh and Patterson, 2002). With less time on study, little time for reading for pleasure, and more time spent working and watching television, students’ decreased involvement in learning is well established by the time they reach third level (Lindsay and Bolger, 2002). This paper is a case study on the Diploma in Hotel and Catering Management program in the School of Hospitality Management and Tourism, Dublin Institute of Technology.
Highly sensitive and ultrafast read mapping for RNA-seq analysis

As sequencing technologies progress, the amount of data produced grows exponentially, shifting the bottleneck of discovery towards the data analysis phase. In particular, currently available mapping solutions for RNA-seq leave room for improvement in terms of sensitivity and performance, hindering an efficient analysis of transcriptomes by massive sequencing. Here, we present an innovative approach that combines re-engineering, optimization and parallelization. This solution results in a significant increase of mapping sensitivity over a wide range of read lengths and substantial shorter runtimes when compared with current RNA-seq mapping methods available.
Development of a tool to define the population of emergency medical care users in South Africa

Prehospital emergency medical service (EMS) data is essential for understanding the functioning of the services as well as the community's health. Being able to clearly and accurately define the patient population in terms of demographics and clinical condition may guide the EMS in resource management, clinical governance, research, education and political decisions. However, such data is limited in South Africa. This research, therefore, aimed to develop a data collection tool to determine the population of prehospital emergency medical care patients in South Africa. The objectives were: (i) determination of what data needed to be collected, (ii) development of a tool to collect the data, and (iii) testing the tool for ease and appropriateness of use and completeness of data collection in an authentic environment. A mixed-method, predominantly qualitative methodological design was used, with some elements of grounded theory. There were three phases corresponding to the objectives. The first two were qualitative and the third was both qualitative and quantitative. In the first phase expert consensus was sought, using a focus group discussion and Delphi study, to develop a minimum data set (MDS) to describe the patient population. The resultant MDS consisted of 18 data elements which could be categorised into demographics, time and location of EMS use, the clinical reasons for EMS use, and the actual use of the EMS. A tool and associated user instructions, based on the findings of Phase One, were developed and refined during Phase Two. Phase Three was used for testing the tool in an authentic environment. The tool was found to be acceptable and user-friendly. Further testing of the tool for accuracy and reliability is recommended.
TH1 and TH2 response to Campylobacter jejuni antigen in Guillain-Barre syndrome.

OBJECTIVES To determine the expression of proinflammatory and anti-inflammatory cytokines in lymphocytes from the progressive and recovery phases of Guillain-Barré syndrome (GBS) after stimulation with Campylobacter jejuni outer membrane proteins. DESIGN Case-control study. SETTING Sanjay Gandhi Postgraduate Institute of Medical Sciences. PARTICIPANTS Sixty-five patients with GBS, 60 age- and sex-matched disease control individuals, and 68 healthy control individuals were included in the study. MAIN OUTCOME MEASURES Lymphocytes from patients with GBS were stimulated with C jejuni outer membrane proteins, and the levels of different proinflammatory (T(H)1 [helper T cell, subtype 1]) and anti-inflammatory (T(H)2) cytokines were determined by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS In the progressive phase of the disease, the expressions of interferon γ (IFN-γ), interleukin 1β (IL-1β), tumor necrosis factor (TNF), IL-6, IL-10, and the IFN-γ:IL-4 ratio were significantly upregulated, but expressions of transforming growth factor (TGF)-β1 and IL-4 were lower in patients compared with disease and healthy controls. In contrast, the levels of IFN-γ, IL-1β, TNF, IL-6, IL-10, and the IFN-γ:IL-4 ratio were significantly lower, but TGF-β1 and IL-4 were upregulated in the recovery phase of GBS patients compared with controls. CONCLUSIONS Upregulation of T(H)1 cytokines in the early disease course may be associated with immune-mediated disease progression due to neuronal inflammation, but upregulation of T(H)2 immune response during the later phase aids recovery from the disease.
Prevention of exuberant granulation tissue and neovascularization in the rat cornea by naltrexone.

OBJECTIVE To determine whether topical application of naltrexone prevents exuberant granulation tissue formation with neovascularization in diabetic rat corneas. METHODS Diabetes was induced with streptozotocin. A 5-mm corneal abrasion at 9 or 11 weeks was treated topically for 7 days (4 times daily) with naltrexone or a sterile vehicle. RESULTS Within 2 to 5 days after reepithelialization, diabetic rats given the sterile vehicle had a 41% incidence of corneal lesions represented by exuberant granulation tissue with corneal neovascularization extending from the limbus. These lesions exhibited edema, cellular and vascular inflammation, and disruption of stromal lamella by fibrovascular tissue and calcium mineralization, but infection was not detected. No corneal lesions were recorded in the diabetic group treated with naltrexone or the control group given the sterile vehicle. Diabetic rats with corneal lesions given the sterile vehicle reepithelialized more slowly than diabetic rats given the sterile vehicle without such lesions, but no difference in blood glucose levels were noted. CONCLUSIONS Using a minimally invasive model in diabetic rats, topical naltrexone normalizes corneal wound healing and prevents neovascularization. CLINICAL RELEVANCE Direct application of naltrexone may serve as an important strategy for facilitating corneal healing and inhibiting corneal neovascularization.
MODIFIED 2-STAGE ILEAL POUCH-ANAL ANASTOMOSIS RESULTS IN LOWER RATE OF ANASTOMOTIC LEAK COMPARED TO TRADITIONAL 2-STAGE SURGERY FOR ULCERATIVE COLITIS Short title : Anastomotic leak in 2-Stage IPAA for UC

BACKGROUND AND AIMS: There is a paucity of evidence in ulcerative colitis (UC) comparing the traditional 2-stage (total proctocolectomy with ileal pouch-anal anastomosis (IPAA) and diverting ileostomy, followed by ileostomy closure) versus the modified 2-stage restorative proctocolectomy (subtotal colectomy with end ileostomy, followed by completion proctectomy and IPAA, without diverting ileostomy). This study examines the risk of anastomotic leak following IPAA in traditional vs. modified 2-stage IPAA for UC patients. METHODS: This was a single institution, retrospective study of all UC patients who underwent a traditional or modified 2-stage IPAA between 2002 and 2013. The primary outcome was anastomotic leak following IPAA. RESULTS: 460 patients had a 2-stage IPAA procedure. 223 (48.5%) patients underwent traditional 2-stage IPAA and 237 (51.5%) patients received the modified 2-stage procedure. There was more pre-operative enteral corticosteroid use (44.7 vs. 33.2%, p 0.04) prior to the first surgery in the modified 2-stage group compared to the traditional 2-stage group. The modified 2-stage group had higher UC disease severity at presentation (86.9% patients with moderate/severe UC vs. 73.1%, p <0.01). However, the modified 2stage group had a lower rate of anastomotic leak following IPAA (4.6 vs. 15.7%, p by gest on M arch 0, 2016 http://eccoxfordjournals.org/ D ow nladed from
Service user-professional interaction in health and care settings

This thesis is comprised of three chapters written as articles for publication. The theme linking the chapters is the focus on interaction between service users and professionals working in health and care settings. Chapter one reviews discursive research on health and care professional interaction with people with a learning disability. The focus is on how professionals talk with and about people with a learning disability. Citations are explored which describe professional talk in research interviews, interactions with people with a learning disability in everyday settings, questionnaire-based interviews, therapeutic interactions and meetings. Certain practices have been found to work well in particular contexts and some not so well. There is potential to use practices across contexts, however there is no guarantee that a particular practice will perform the same action in a different interactional setting. Future research in the area could look at the effects of trying to increase the use of some of the more successful practices through staff training. Chapter two details an empirical study on how questions are used by participants in care programme approach (CPA) review meetings in the NHS. Questions were found to be asked by the professionals at the meeting in a manner that followed the format of a semi-structured interview. Six question types are described in the paper that perform a range of actions; switching topic, prompting the service user, avoiding overt disagreement, bringing the meeting back on topic, offering the service user the opportunity to ask questions and ensuring a particular structure is followed. The analysis suggests that government guidance on CPA regarding service user participation is not being realised in the way that the process is conducted on an interactional level. Chapter three contains a reflective piece about my experiences conducting discursive research in an NHS setting. It describes the challenges faced in doing research using this methodology and makes suggestions on how some of these potential issues might be tackled.