Miracle-dz/UniFAR-FTUs huggingface dataset:
Interplay of conjugating enzymes with OATP uptake transporters and ABCC/MRP efflux pumps in the elimination of drugs

Background: Biliary excretion is a major elimination route of many drugs and their metabolites. Hepatobiliary elimination is a vectorial process involving uptake transporters in the basolateral hepatocyte membrane, possibly Phase I and Phase II metabolizing enzymes, and ATP-dependent efflux pumps in the apical hepatocyte membrane. Objectives: Because many drugs and their metabolites are anions, this review focuses on transporters involved in their hepatocellular uptake (members of the organic anion transporting polypeptide (OATP) family) and biliary elimination (apical conjugate efflux pump ABCC2/MRP2). Methods: The molecular and functional characteristics of the human OATP and ABCC/MRP transporters are presented, including a detailed overview of endogenous and drug substrates. Examples illustrate the interplay of transporters with Phase II conjugating enzymes. Model systems to study the vectorial transport of organic anions are also discussed. Results/conclusions: OATP uptake transporters, conjugating enzymes, and ABCC2/MRP2 work in concert to enable the hepatobiliary elimination of anionic drugs and their metabolites. It is increasingly important to understand how genetic variants of these transporters and enzymes influence the interindividual variability of drug elimination.
Resistin Stimulation of 17α-Hydroxylase Activity in Ovarian Theca Cells in Vitro: Relevance to Polycystic Ovary Syndrome

Context: A newly discovered hormone resistin has been shown to be increased in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to confirm increased resistinconcentrationsinwomenwithPCOSandtotestthedirecteffect of resistin on human theca cell androgen production. Design: Resistin was measured in fasting serum samples by RIA. To test the direct effects of resistin on ovarian androgen biosynthesis, human theca cells were cultured with resistin fo r3di n thepresence and absence of forskolin and insulin. Patients:Fasting serum samples were obtained from 45 women with PCOS and 74 regularly cycling premenopausal control women in the follicular phase of their menstrual cycles, and ovarian theca cell cultures were established from two control women. Results:Themeanserumresistinconcentrationwasincreased(40%) in women with PCOS. Serum resistin concentrations correlated positivelywithbodymassindexandtestosteroneinPCOSwomenbutnot in controls. There were no significant correlations between resistin and fasting insulin or indicators of insulin resistance when corrected for body mass index. In cultured human theca cells, basal 17-hydroxylase activity was unchanged by resistin alone, but resistin enhanced 17-hydroxylase activity in the presence of forskolin or a combination of forskolin plus insulin. Resistin (1 ng/ml) augmented forskolin and forskolin plus insulin stimulation of CYP17 mRNA expression in a concentration-dependent manner. Conclusion: These data indicate that abnormal resistin secretion in PCOS may play a role in causing ovarian hyperandrogenism. (J Clin Endocrinol Metab 90: 4852–4857, 2005)
Using the postnatal period to help reduce obesity: The midwife's role

The postnatal period represents a key opportunity for education and support to be given surrounding weight loss (Gore et al, 2003; Bastian et al, 2010; Cahill et al, 2010). Midwives, owing to their role and relationship with women, are in a unique position to provide this education and support. In this article, the possibility of providing a 6-week postnatal appointment with a midwife will be explored. This appointment would be aimed at providing weight-loss education and advice and offer further breastfeeding support, in an effort to combat the obesity epidemic. It will also highlight the importance of reflection as a tool for midwives to use in dealing with the issue of obesity.
Control of vascular access device associated bloodstream infection in a large London teaching hospital

We describe a quality improvement programme used in a large teaching hospital trust to reduce the number of hospital acquired blood stream infections (HA-BSI) relating to vascular devices. Our strategy included the appointment of a lead nurse whose role was to engage with clinicians, to develop guidelines, to standardise and facilitate good practice, to train to uniform standards, and to retain local ownership, while working to avoid risk compensation. Information was gathered using our laboratory data search system, as well as observation and audit of vascular access device practice. Vascular access device training became part of all induction and update programmes for clinical staff.The results showed a significant and sustained decline in frequency of patient episodes of HA-BSI. The numbers of patients from whom coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus spp. , Klebsiella and Enterobacter spp. were isolated in any given month all declined significantly. The numbers of patients with positive blood cultures with Escherichia coli did not decline. The improvement has been sustained for more than 3.5 years. This study shows that when standardisation, facilitation and education are developed with stakeholder involvement, it is possible to achieve a sustained reduction in the incidence of vascular device associated infections.
Dietary folate intake and food sources of children and adolescents in Chungcheong area - Using nutrient database revised by measured folate in selected foods *

Purpose: The purpose of this study was to estimate dietary folate intake and food sources of children and adolescents using a nutrient database revised based on measured folate in selected foods. Methods: Folate content in 51 foods known as folate sources was measured by microbiological assay after trienzyme extraction. Folate intake was estimated from a part of the data of ‘Dietary Intake Survey of Infants, Children and Adolescents in 2007~2008’ conducted by the Korea Food and Drug Administration (KFDA) and the Korea Health Industry Development Institute (KHIDI). The study subjects were 567 children aged 1~19 years living in the Chungcheong area who completed two 24-hour recalls. Results: Folate values were revised by replacing the values in the current database with the analyzed values except when the value in the current database was between the analytical values or was not different from the mean analytical value by more than 10%. Among the revised values of 40 food items, folate values of 36 foods were lower than the current values. Mean folate intakes estimated with the revised database were approximately 70~80% lower than those estimated with the current database. Mean folate intakes of males aged 12~14 and females aged 12~19 were lower than the 2010 Recommended Nutrient Intakes (RNIs). Chicken's eggs, Kimchi, rice, mandarin, and laver were found to be main food sources of folate. Conclusion: In this study, mean dietary folate intakes were lower than those estimated with the current database. Further analyses for folate content especially in cooked foods commonly consumed in Korea are needed using a reliable assay in order to accurately assess folate intake of the Korean population. In addition, nutrition education should be provided for adolescent females in order to increase consumption of folate-rich foods.
Intramyocardial bone marrow stem cell treatment for myocardial regeneration

Transplantation of stem cells has been shown by substantial experimental evidence as well as by initial clinical studies to improve cardiac function in patients with post-infarction myocardial injury. Both angiogenic and myogenic properties of bone-marrow-derived stem cells have been evidenced to be involved in its beneficial effect on heart function after transplantation into area of ischaemic injury. This paper summarizes the current knowledge on the mechanisms involved in regenerative potential of bone-marrow-derived stem cells, with special attention to the clinical experience with cell transplantation during cardiac surgery.
Involvement of tumor necrosis factor‐α, interleukin‐I β, interleukin‐8, and interleukin‐I receptor antagonist in acute lung injury caused by local Shwartzman reaction

A local Shwartzman reactlon (LSR) was prepared in rabbit lung as a model of acute lung injury. To induce LSR, intratracheal injection of lipopolysaccharide (LPS) 10 μg into the lower lobe of the right lung, followed 24 h later by I.v. injectlon of LPS (10 μg/kg). In the lung with the LSR, myeloperoxidase activity, representing neutrophil accumulation, peaked at 1–2 h and was sustained for 48 h after challenge with i.v. LPS. The lung water content peaked at 12 h, and decreased gradually. Histological findings showed diffuse interstitial widenlng, lntra‐alveolar leukocyte infiltration with hemorrhage, and alveolar exudate formation. The production of tumor necrosis factor‐α (TNF‐α), interleukin‐1 β (IL‐1β), interleukin 8 (IL‐8), and IL‐1 receptor antagonist (IL‐1Ra) in the lung was analyzed. TNF‐α first elevated and peaked at 0.5h (66.±16.7ng/g.lung), subsequently, 11–1β and 11–8 increased and peaked at 2h (17.8 ± 3.4 ng/g. lung and 336.9±49.6ng/g.lung, respectively). IL‐1Ra was present even before the challenge, and the production increased to show a dual peak (0.5 h, 1.5±0.2 μg/g.lung; and 2h, 1.6±0.1 μg/g.lung), and a large concentration of IL‐1 Ra was sustained for 48 h. lmmunohistochemistry showed that the cellular source of these cytokines was alveolar macrophages and infiltrating neutrophils. Thus, disclosing the kinetics of the generation of cytokines led to a better understanding of thelr roles, namely TNF‐α as an initiator, IL‐1 and IL‐8 as amplitier and effector, and IL‐1 Ra as regulator of the intensity of acute inflammation.
Socioeconomic inequalities in cancer survival in the Netherlands and Great Britain: small-area based studies usiug cancer registry data

textabstractCancer is the second most impOltant cause of death in the Netherlands, as it is in many developed countries. In 1990 about 30% of all deaths in the Netherlands could be ascribed to cancer. I In general, survival from cancer is rather poor but it varies by such characteristics as the organ of origin of the tumour and age of the patient. Socioeconomic status is another factor which has been found to be of prognostic importance for cancer patients. ' In general, cancer patients fi'om lower socioeconomic groups have a lower survival rate than patients fi'om higher socioeconomic groups. The subject of this thesis is the association between socioeconomic status and cancer survival in the southeastern Netherlands and the area covered by the South Thames Regional Health Authority (RHA) in South East England. Both a description of and explanations for variation in survival by socioeconomic status in these two areas are given. The studies reported in this thesis, can be placed within a broader framework of research on socioeconomic inequalities in health (paragraph 1.1) as well as within a narrower framework of research on socioeconomic inequalities in cancer (paragraph 1.2). In the final paragraph of this introduction, the aims of the studies reported in this thesis are presented (paragraph 1.3).
Mental Illness Stereotypes and Clinical Care: Do People Avoid Treatment Because of Stigma?

Abstract Despite evidence that pharmacological and psychosocial treatments yield significant benefits for many psychiatric disorders, many people who might otherwise profit from treatment fail to access care or do not fully adhere to services once they are begun. One interpretation of a health belief model suggests that the stigma of mental illness and corresponding treatments is a significant, perceived cost that undermines participation. Evidence that supports this assumption is reviewed in this paper. We begin with a brief summary of empirical models that describe stigma. We then review research studies that suggest how perceived stigma may undermine treatment participation. Despite the presence of a few studies that support the connection between stigma and treatment avoidance, research in this area is remarkably sparse, especially given assertions about the importance of this point in the Surgeon General's 1999 Report. Possible directions for future research are outlined as a result. Finally, we provide a review of stigma-change strategies and their hypothetical effects on treatment use.
e0072 Cardioprotective effect of β3 adrenocepter agonism in pressure overload induced hypertrophy

Objective β3-adrenergic receptors (β3-AR) and its downstream signalling are recognised as novel modulators of heart function. We have recently shown impaired cardiac functional compensation in a model of pressure overload. We therefore hypothesised that the selective β3-AR agonist, BRL37344 (BRL), would protect the heart from pressure overload induced cardiac remodelling. Methods and results C57BL/6J mice underwent transverse aortic constriction (TAC) for 3 weeks, resulting in increased cardiac hypertrophy and dysfunction assessed by echocardiography. 3 weeks of BRL treatment (0.1 mg/kg/day via subcutaneous osmotic infusion pump) starting from 1 day post TAC reduced hypertrophy, with lower heart weight normalised to tibia length (100±4 vs 120±7 mg/cm), LV mass (136±7 vs 163±8 mg), wall thickness (1.08±0.02 vs 1.16±0.02 mm) and systolic dimension (1.36±0.09 vs 12.08±0.23 mm; p<0.05 for all), and completely restored systolic function back to normal (58±2 vs 62±1%; p=NS vs sham, p<0.05 vs TAC). BRL reduced myocyte width by H&E staining, but had no effect on fibrosis scale. These benefits from β3-AR stimulation were associated with increased nitric oxide (NO) production (13.73±1.84 vs 5.03±0.52 μM/mg protein) and suppressed superoxide generation (14017±838 vs 21459±783 CPM/mg tissue; p<0.01 vs TAC for both). Neuronal NO synthase (nNOS) protein expression was up-regulated ∼3 fold by BRL treatment (1.11±0.22 vs 0.39±0.17; p<0.05). More interestingly, the suppressive effect of BRL on superoxide generation was abolished by acute nNOS inhibition by specific nNOS inhibitor N5-(1-imino-3-butenyl)-L-ornithine, monohydrochloride) (L-VNIO). Conclusions These results are the first to show in vivo the cardioprotective effect of β3-AR specific agonism in pressure overload hypertrophy and heart failure, and support nNOS as a downstream molecule favouring NO and reactive oxygen species (ROS) balance in this pathologic process in the failing heart.
Changing Minds campaign

Sir: Professor Crisp ( Psychiatric Bulletin , November 2001, 25 , 444-446) gave an update on the Changing Minds campaign, and concluded by urging all areas of the College to participate actively in this campaign. As someone who has helped to run one of the Stigma Alert educational roadshows aimed at
A review of the health leadership and management capacity in Papua New Guinea

This report by Dr Augustine Asante and John Hall describes the current situation of health leadership and management capacity in Papua New Guinea. PNG has some of the worst health indicators in the Asia-Pacific region and unless health delivery is drastically scaled up, will miss several of its Millennium Development Goal (MDG) targets. Areas covered by this report include access to health care, financing the health system, human resources for health, health management structure, number and distribution of managers, competence of district health managers, management working environment, functioning of management support systems and the socio-cultural context. Image: Youth With A Mission-International / flickr
Dental Students’ Perceptions on Restorative Dentistry Education in Shahid Beheshti Dental School

3 General Practitioner. Abstract Objective: Numerous studies have emphasized on the importance of developing an ideal educational system for high-quality dental education. The present study sought to assess the perception of dental students on operative dentistry education in Department of Restorative Dentistry, Shahid Beheshti Dental School, Tehran, Iran. Methods: In this descriptive cross-sectional study, 220 students were selected and given a questionnaire including demographic , grades in operative dentistry clinical and didactic courses, the efficacy of preclinical courses in preparing students for clinical practice, ways to improve competency and expertise of students for clinical setting, student's opinion on relating the assessment tests with the taught topics, required instructional resources for assessment of students' proficiency in restorative dentistry and satisfaction rate of students with clinical courses offered in the current curriculum. Data were analyzed using descriptive statistics (SPSS 18). Results: The Clinical Operative Dentistry 3 and Preclinical Dental Anatomy received a mean satisfaction score of 3.31 and 2.74, respectively. Furthermore, 57.3% of students highly emphasized the necessity of studying textbooks of restorative dentistry. 50.5% of students believe that lectures by instructors along with active participation of students were the best method for didactic operative dentistry courses. In addition, 60.5% were in favor of using a combination of textbooks, lectures, and class notes for the assessment of students' learning. Conclusion: The present study revealed that Department of Restorative Dentistry in Shahid Beheshti Dental School is successful in its teaching and achieving students' satisfaction. However, some revisions need to be made in educational methods and contents and active participation of students in class discussions should be encouraged as well.
Therapeutic patents for the treatment of pre-eclampsia

Pre-eclampsia (PE) is a pregnancy-specific syndrome that is a principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy-associated deaths. In its mild form, PE most commonly presents with the features of maternal hypertension and proteinuria but can swiftly and unpredictably become severe with many extensive and life-threatening complications. The diverse symptoms of PE have made it a difficult disease not only to define, but also to identify a causative agent for the symptoms. It has therefore proved difficult to develop specific drugs that can be used to manage the condition. This review examines the patent literature to reveal current findings that exhibit the potential to target the effects of PE with the aim of either preventing or altering the course of this life-threatening disease of pregnancy.
Hyaluronidase-1 expression is not a predictor of biochemical recurrence in radical prostatectomy specimens

Aim: Th e purposes of this study were to evaluate the rate of biochemical recurrence among patients who underwent radical prostatectomy due to localized prostate cancer, assess the risk factors of biochemical recurrence, and investigate its relation with hyaluronidase-1 (HYAL-1). Materials and methods: We retrospectively evaluated the data of 112 patients who underwent radical retropubic prostatectomy. HYAL-1 expression was evaluated immunohistochemically and staining was graded as mild, moderate, and severe. Two blinded pathologists evaluated the specimens. Th e relation among preoperative pathologic fi ndings that were detected in transrectal ultrasound (TRUS) guided biopsy, specimens of radical prostatectomy in the fi nal stage, and biochemical recurrence rate were also evaluated. Mean follow-up time was 59.8 months (range: 20 to 92 months). Results: Tumor recurrence was detected in 29 patients. Th ere was no relation between HYAL-1 expression and recurrence. In multivariate analysis, the percentage of tumors detected in TRUS biopsy specimens, positive surgical margin, capsular involvement, and seminal vesicle invasion detected in the fi nal pathology were correlated with recurrence. Th e sensitivity, specifi city, positive predictive value, and negative predictive value of HYAL-1 expression were respectively 38%, 63%, 30%, and 71%. Conclusion: HYAL-1 expression was not found to be predictive for recurrence. Further molecular markers and genetic studies are necessary to predict the biochemical recurrence aft er radical prostatectomy.
Optical sharper focusing in an anisotropic crystal.

Optical super-resolution technique through tight focusing is a widely used technique to image material samples with anisotropic optical properties. The knowledge of the field distribution of a tightly focused beam in anisotropic media is both scientifically interesting and technologically important. In this paper, the optical properties of a uniaxial crystal with the optic axis perpendicular to the interface under a tight focusing configuration are studied with rigorous theoretical and numerical analysis. The significant effect of the Poynting vector on the focal position introduces an obvious displacement of the focal spot formed by the extraordinary waves (e-ray). Moreover, a sharper focus with a lateral size of 0. 22λ is obtained as a result of the effective separation of the ordinary waves (o-ray) and the e-ray. It provides a new tool to fabricate optical structures with higher resolutions than that in an isotropic medium through the far-field method.
Thai Cultural Understandings of Active Ageing from the Perspectives of Older Adults: A Qualitative Study

Activeageing is an important aspect facilitating life quality for older adults. Researchon active ageing has grown over recent decades but the knowledge base of activeageing continues to be based overwhelmingly on Western studies. Asian eldersmay have a distinctly different perspective from Westerners concerning themeaning of active ageing. Little is known about the ways older persons view ordefine active ageing in Thai context. This study focused on the characteristicsof active ageing among older Thai adults. A descriptive, qualitative approach was employed and datacollected in focusgroups and in-depth interviews with 64 community-dwelling adults aged 60 andover. Participants were recruited from four provinces in the four regions ofThailand, that is North, Northeast, Central, and South. Data were analyzedusing content analysis. Thisstudy helped build an understanding of what active ageing means by asking thisof older adults. Six themes of active ageing were identified as beingself-reliant; being actively engaged with society; growing spirituality;maintaining healthy lifestyle; being active learners; and managing later lifesecurity. The perceptions of active ageing among the Thai elderly involvedhealth, social participation, and security in life, which are also the three key pillars ofactive ageing suggested by World Health Organization. When compared to researchin a Western context, some of the dimensions of Thai active ageing weredistinct, specifically growing spirituality and managing later life security,while others were overlapping.
Husband-Wife Communication About Family Planning and Contraceptive Use in Kenya

one or both partners know of at least one modern method, and among 85% of couples both partners approve of family planning. Discussion with the partner about family planning was reported in 82% of couples. However, only 67% of wives and 75% of husbands correctly predicted their spouse’s approval of family planning. Knowledge and approval of family planning, husband-wife communication, desire for more children and ideal family size are all significantly associated with current use. Multiple logistic regression analyses show that husband-wife communication, particularly the wife’s perception of her husband’s approval of family planning, is highly associated with current contraceptive use (odds ratio of 4.2). Dialogue appears to increase the effectiveness of communication: Specifically, one spouse’s perception of the other spouse’s approval is more likely to be correct if they have discussed family planning than if they have not, and this relationship significantly affects contraceptive use.