Miracle-dz/UniFAR-FTUs huggingface dataset:
Prostaglandin I2 analogs inhibit Th1 and Th2 effector cytokine production by CD4 T cells

An anti‐inflammatory effect of PGI2 has been suggested by increased inflammation in mice that are deficient in the PGI2 receptor (IP) or in respiratory syncytial viral‐ or OVA‐induced CD4 T cell‐associated responses. To determine the mechanism of the anti‐inflammatory effect, we hypothesized that PGI2 analogs inhibit CD4 T cell effector cytokine production. To test this hypothesis, we activated purified CD4 T cells with anti‐CD3 and anti‐CD28 antibodies under Th1 and Th2 polarizing conditions for 4 days and restimulated the T cells with anti‐CD3 in the presence of PGI2 analogs for 2 days. We found that PGI2 analogs (cicaprost and iloprost) inhibited the production of Th1 cytokines (IFN‐γ) and Th2 cytokines (IL‐4, IL‐10, and IL‐13) in a dose‐dependent pattern. The inhibitory effect was partially dependent on the IP receptor signaling and was correlated with elevated intracellular cAMP and down‐regulated NF‐κB activity. Pretreatment of the CD4 T cells with 8‐bromoadenosine‐3′,5′‐cyclic monophosphorothioate, Rp‐isomer, to inhibit a key signaling molecule in the cAMP pathway, protein kinase A (PKA), attenuated the suppressive effect of PGI2 analogs significantly, suggesting that PKA, in part, mediates the inhibition of the cytokine production. These data indicate that PGI2 analogs have an immune‐suppressive effect on previously activated and differentiated CD4 T cells in vitro and suggest that PGI2 may have a similar function in vivo.
Adherence of primary health care physicians to hypertension management guidelines in the Aseer region of Saudi Arabia.

Although there has been significant progress in the management of hypertension, rates for control of this chronic disease in the Kingdom of Saudi Arabia (KSA) has been shown to be very low. This study was aimed to assess the knowledge of primary health care (PHC) physicians and the extent of their adherence to the recommendations of clinical practice guidelines concerning care of hypertensive patients. The assessment was made in the Aseer region of KSA using a modified version of the World Health Organization "Physician Inquiry Questionnaire. " Only 5.6% of the participants measured blood pressure (BP) with the patient in sitting and other postures. Variable sphygmomanometer cuff sizes for different patients were used by 56.5% of the participants, while 74.8% correctly recorded the diastolic BP at Koratkoff sound, phase- 5. Among non- diabetics, the correct diagnosis of systolic and diastolic hypertension was reported by 76.7% and 81.4% respectively, of the PHC physicians. Among diabetics, the correct diagnosis of systolic and diastolic hypertension was reported by 36% and 17.1% of the PHC physicians, respectively. Most physicians inquired about cardiovascular risk factors. Several important items of patients' clinical examination were not completely covered by physicians, e.g., fundus examination (75.2%). PHC physicians missed a few investigations and laboratory tests, e.g., ECG (87.9%), serum creatinine (88.2%) and lipid profile (89.8%). Less than one- fifth of the physicians correctly chose the thiazide diuretics as the preferred initial anti- hypertensive agent (19.9%). Almost two- thirds of the physicians (65.2%) emphasized the importance of BP self- measurement, 89.8% encouraged patients to use a reminder system while 96.3% motivated patients for BP control. Measures for lifestyle modification included weight reduction (98.8%), sodium restriction (97.5%), physical exercise (96.3%) and behavioral improvement (87.6%). Our study suggests that continuing medical education and training courses on guidelines for hypertension management should be arranged for PHC physicians in Aseer.
APOE-epsilon4, depressive symptoms, and cognitive decline in Chinese older adults: Singapore Longitudinal Aging Studies.

BACKGROUND The precise relationship between depression and cognitive decline in older adults is unclear. We investigated the influence of apolipoprotein E (APOE)-epsilon4 genotype in modulating the effect of depressive symptoms on cognitive decline. METHODS Prospective cohort study of 1,487 cognitively high-functioning Chinese older adults. Depressive symptoms (Geriatric Depression Scale score >/=5) and Mini-Mental State Examination (MMSE) were assessed at baseline, and cognitive decline (at least 1-point drop in MMSE) at 1-2 years after baseline. RESULTS There was no significant difference in cognitive decline between depressed (32.9%) and nondepressed (31.5%) participants in the whole sample or among non-APOE-epsilon4 carriers. Among APOE-epsilon4 carriers, depressed participants showed more cognitive decline (40.0%) than their nondepressed counterparts (28.6%), odds ratio = 2.89, 95% confidence interval: 1.03-8.12; p = . 04, after controlling for age, gender, education, vascular risk factors/events, smoking, alcohol drinking, physical functioning, subjective memory complaint, length of follow-up, and baseline MMSE scores (p for interaction = .03). CONCLUSIONS Our study suggests that the presence of the APOE-epsilon4 allele significantly enhanced the risk of cognitive decline associated with depressive symptoms. This finding should be independently replicated in future studies.
An intensified lifestyle intervention programme may be superior to insulin treatment in poorly controlled Type 2 diabetic patients on oral hypoglycaemic agents: results of a feasibility study

Aims The aims of this study were to assess whether, in Type 2 diabetic patients with inadequate glycaemic control on oral hypoglycaemic agents (OHA), a lifestyle intervention programme based on exercise and diet counselling (i) was as effective as insulin treatment in controlling blood glucose, and (ii) could prevent the weight gain usually accompanying the introduction of insulin treatment.
Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women.

OBJECTIVE To evaluate whether the presence of polymorphisms of peroxisome proliferator-activated receptor gamma PPARγ (Pro 1 2Ala) and PPARGC1B (Ala203Pro) modifies the association between the inorganic arsenic (iAs) methylation capacity and breast cancer (BC). MATERIALS AND METHODS Mexican women were interviewed, and blood and urine samples were collected from them (cases/controls= 197/220). The concentration of urinary arsenic species and the polymorphisms of interest were determined by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and polymerase chain reaction (PCR), respectively. RESULTS In women with a high %MMA (urinary monomethyl arsenic) and high primary methylation ratio (PM = MMA/iAs), the risk of BC was increased (odds ratio [OR]%MMA T3 vs.T1= 3.60: 95% confidence interval [CI] 2.02-6.41, ORPMI T3 vs.T1= 3.47: 95%CI 1.95-6.17), which was maintained after adjusting for polymorphisms. No significant interactions were observed between the polymorphisms and the arsenic variables on the risk of BC. CONCLUSION Pro 12Ala and Ala203Pro polymorphisms did not modify the association between the iAs methylation capacity and BC.
Topical Treatment with Basic Fibroblast Growth Factor Promotes Wound Healing and Barrier Recovery Induced by Skin Abrasion

It has been reported that basic fibroblast growth factor (bFGF) promotes the healing of skin ulceration by inducing fibroblast proliferation, yet the role of bFGF on epidermal barrier function, especially from the perspective of scratch-induced skin abrasion, remains unknown. To this end, we initially developed an epidermal abrasion mouse model induced by scratching with a stainless-steel wire brush, and examined the effects of bFGF on the wound healing induced by skin abrasion. This procedure induced a significant elevation of transepidermal water loss (TEWL) in a scratch-count-dependent manner. This elevated TEWL was significantly decreased following topical application of bFGF to the skin. In addition, bFGF increased the expression of Ki67 in keratinocytes following mechanical scratching. These results suggest that bFGF enhances keratinocyte proliferation, which, in turn, repairs the skin barrier disruption and wounds caused by scratching in mice. Consistently, bFGF stimulated proliferation of normal human epidermal keratinocytes (NHEK). Intriguingly, the effect of bFGF and other growth factors on NHEK proliferation was additive. However, high cell density diminished the effect of bFGF on NHEK proliferation. This particular result can be explained by our observation that FGF receptor mRNA expression in NHEK was low under conditions of high cell density. Our findings suggest that bFGF stimulates keratinocyte proliferation, especially in a lower cell density environment, to repair skin wound in accord with skin barrier recovery.
Trained humans can exercise safely in extreme dry heat when drinking water ad libitum

Abstract Guidelines to establish safe environmental exercise conditions are partly based on thermal prescriptive zones. Yet there are reports of self-paced human athletic performances in extreme heat. Eighteen participants undertook a 25-km route march in a dry bulb temperature reaching 44.3°C. The mean (± s) age of the participants was 26.0 ± 3.7 years. Their mean ad libitum water intake was 1264 ± 229 mL · h−1. Predicted sweat rate was 1789 ± 267 mL · h−1. Despite an average body mass loss of 2.73 ± 0.98 kg, plasma osmolality and serum sodium concentration did not change significantly during exercise. Total body water fell 1.47 kg during exercise. However, change in body mass did not accurately predict changes in total body water as a 1:1 ratio. There was a significant relationship (negative slope) between post-exercise serum sodium concentration and changes in both body mass and percent total body water. There was no relationship between percent body mass loss and peak exercise core temperature (39 ± 0.9°C) or exercise time. We conclude that participants maintained plasma osmolality, serum sodium concentration, and safe core temperatures by (1) adopting a pacing strategy, (2) high rates of ad libitum water intake, and (3) by a small reduction in total body water to maintain serum sodium concentration. Our findings support the hypothesis that humans are the mammals with the greatest capacity for exercising in extreme heat.
Accessory Gene Regulator Locus of Staphylococcus intermedius

ABSTRACT The accessory gene regulator (agr) locus, a candidate system for the regulation of the production of virulence factors in Staphylococcus intermedius, has been characterized. Using PCR-based genome walking, we have obtained the first complete sequence (3,436 bp) of the accessory gene regulator (agr) gene in this organism. Sequence analysis of the agr gene has identified five open reading frames (ORFs), agrB, agrD, agrC, agrA, and hld. The translated ORF contained amino acid motifs characteristic of the response regulator and histidine protein kinase signal transducer of the classic two-component regulatory system. Sequencing of the agrD PCR products amplified from DNA from 20 different isolates has facilitated detection of genetic variation in the putative autoinducing peptide (AIP) within the agr gene of S. intermedius, revealing the presence of at least three agr specificity groups within this species. Classification of the agr gene from S. intermedius was supported by phylogenetic analysis. Real-time PCR also revealed that the effector molecule of the agr system, RNAIII, was regulated in an autocrine manner in S. intermedius and demonstrated positive correlation with the temporal gene expression patterns of luk and entC. Transcription of RNAIII was also dependent on self secreted cues. Cyclic self and nonself peptides were synthesized on the basis of the novel AIPs produced by S. intermedius, which lack the cysteine necessary to form the thiolactone ring in analogous peptides from Staphylococcus aureus and Staphylococcus epidermidis. Experiments with these synthetic cyclic peptides indicated that self peptides led to up-regulation of RNAIII—findings in support of the assumption that activation of the agr gene is initiated by growth- and species-specific factors generated during bacterial growth.
Effect of the Selective A1 Adenosine Antagonist 8‐Cyclopentyl‐1,3‐dipropylxanthine on Acute Renal Dysfunction Induced by Escherichia coli Endotoxin in Rats

Abstract— The effect of the selective A1 adenosine antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine (CPX), on Escherichia coli endotoxin‐induced acute renal dysfunction was determined in anaesthetized rats. Bolus administration of endotoxin at doses of either 1 or 20 mg kg−1 evoked decreases in inulin clearance, renal blood flow, urine flow and excretion of sodium, potassium and chloride. The changes in renal function produced by 20 mg kg−1 endotoxin were more severe than those noted with 1 mg kg−1 toxin and, by contrast to this lower dose, renal function showed no signs of recovery. Intravenous administration of CPX (0·1 mg kg−1) elicited a statistically significant, although modest, attenuation of the decline in inulin clearance, renal blood flow, urine output and electrolyte excretion induced by 20 mg kg−1 endotoxin. By contrast, treatment with 0·1 mg kg−1 CPX resulted in statistically significant protection against the falls in excretory function evoked by 1 mg kg−1 endotoxin but not against the reductions in renal blood flow and inulin clearance produced by the lower dose of toxin. These results suggest that adenosine may play a role, albeit not a major one, in the pathophysiology of endotoxaemic acute renal failure.
Factors affecting adipose tissue development in chickens: A review

&NA; The intense genetic selection for rapid growth in broilers has resulted in an increase in voluntary feed intake and growth rate, accompanied by increased fat deposition in adipose tissue depots throughout the body. Adipose tissue expansion is a result of the formation of adipocytes (several processes collectively referred to as adipogenesis) and cellular accumulation of triacylglycerols inside lipid droplets. In mammals, different anatomical depots are metabolically distinct. The molecular and cellular mechanisms underlying adipose tissue development have been characterized in mammalian models, whereas information in avian species is scarce. The purpose of this review is to describe factors regulating adipogenesis in chickens, with an emphasis on dietary factors and the broiler. Results from many studies have demonstrated effects of dietary nutrient composition on adipose tissue development and lipid metabolism. Transcription factors, such as peroxisome proliferator‐activated receptor &ggr;, CCAAT/enhancer‐binding proteins &agr; and &bgr;, and sterol regulatory element binding proteins orchestrate a series of cellular events that lead to an increase in activity of fatty acid transport proteins and enzymes that are responsible for triacylglycerol synthesis. Understanding the mechanisms underlying adipose tissue development may provide a practical strategy to affect body composition of the commercial broiler while providing insights on diets that maximize conversion into muscle rather than fat and affect depot‐dependent deposition of lipids. Because of the propensity to overeat and become obese, the broiler chicken also represents an attractive biomedical model for eating disorders and obesity in humans.
Defining and Analyzing Retention-in-Care Among Pregnant and Breastfeeding HIV-Infected Women: Unpacking the Data to Interpret and Improve PMTCT Outcomes

Abstract:The prevent mother-to-child transmission (PMTCT) “cascade” describes the programmatic steps for pregnant and breastfeeding women that influence HIV transmission rates. To this end, HIV-infected pregnant women and mothers need access to health services and adhere to antiretroviral (ARV) prophylaxis or lifetime treatment. Within the cascade, the concept of “retention-in-care” is commonly used as a proxy for adherence to ARV interventions and, even, viral suppression. Yet surprisingly, there is no standard definition of retention-in-care either for the purposes of HIV surveillance or implementation research. Implicit to the concept of retention-in-care is the sense of continuity and receipt of care at relevant time points. In the context of PMTCT, the main challenge for surveillance and implementation research is to estimate effective coverage of ARV interventions over a prolonged period of time. These data are used to inform program management and also to estimate postnatal MTCT rates. Attendance of HIV-infected mothers at clinic at 12-month postpartum is often equated with full retention in PMTCT programs over this period. Yet, measurement approaches that fail to register missed visits, or inconsistent attendance or other missing data in the interval period, fail to capture patterns of attendance and care received by mothers and children and risk introducing systematic errors and bias. More importantly, providing only an aggregated rate of attendance as a proxy for retention-in-care fails to identify specific gaps in health services where interventions to improve retention along the PMTCT cascade are most needed. In this article, we discuss how data on retention-in-care can be understood and analyzed, and what are the implications and opportunities for programs and implementation research.
Families in home care--a resource or a burden? District nurses' beliefs.

BACKGROUND Caring for families in home care is a growing part of Swedish district nurses' professional work. District nurses' facilitative and constraining beliefs about families guide the extent to which families are acknowledged and engaged in the care. AIMS AND OBJECTIVES The aim of the study was to explore district nurses' beliefs about families in home care. DESIGN Explorative, descriptive. METHODS Five district nurses participated in focus group interviews on three separate occasions. Each interview lasted approximately 90 minutes, was audio taped and transcribed verbatim. A thematic content analysis was used for analyses of the data. RESULTS The result revealed two underpinning beliefs held by the district nurses towards families in home care: families are a resource and Families are a burden. Families could be a resource for the patient, for the other family members as well as for the district nurses themselves. Families could be a resource for the patient both practically and emotionally by e.g. being present and listening. Being open in communication with other family members and district nurses was also considered as a resource. The district nurses considered families as a burden when they were experienced as demanding in various ways, for example, when family members did not act in a way that pleased the district nurses or when family members showed their suffering. CONCLUSIONS This study highlight some facilitating and constraining beliefs held by district nurses: families can be both a resource and a burden. RELEVANCE TO CLINICAL PRACTICE It is important that district nurses are aware of what beliefs they hold as their beliefs guide their actions towards the families.
Endothelial Nitric Oxide Synthase Polymorphism Is Not Associated with Placental Abruption in Finnish Women

Objective: To study whether genetic variability in the gene encoding endothelial nitric oxide synthase (eNOS) affects individual susceptibility to the development of placental abruption during pregnancy. Methods: One hundred and sixteen pregnant women with placental abruption and 113 healthy controls were genotyped for Glu298Asp polymorphism in the eNOS gene. Chi-square analysis was used to assess the differences in genotype and allele frequencies between the two groups. Results: A statistically similar allelic distribution of eNOS Glu298Asp polymorphism was observed in the two groups, with the frequency of the variant G allele being 66.8% in the abruption group and 68.1% in the control group (OR 0.94, 95% CI: 0.64–1.39; p = 0.76). The genotype distribution of the eNOS polymorphism was also found to be statistically similar (p = 0.72). Conclusions: The observed genotype data in subjects from eastern Finland suggest that the Glu298Asp polymorphism of the eNOS gene does not contribute to placental abruption in this population.
Three-Dimensional Hysterosalpingo-Contrast-Sonography for the Assessment of Tubal Patency in Women with Infertility: A Systematic Review with Meta-Analysis

Background/Aims: We aimed at performing a systematic review to determine the diagnostic accuracy of three-dimensional (3D) hysterosalpingo-contrast-sonography (HyCoSy) for detecting tubal occlusion. Methods: A systematic review in Medline database search from January 1989 to October 2015 to identify relevant studies evaluating 3D-HyCoSy. Eligibility criteria were studies assessing the role of 3D-HyCoSy for diagnosing tubal occlusion in infertile women. Index test was 3D-HyCoSy. Reference standard was laparoscopy with dye test or X-ray hysterosalpingography. Quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity and specificity for the method were estimated. Results: A total number of 88 papers were identified. After exclusions, nine studies were ultimately included. Pooled estimated sensitivity was 98% (95% CI 91-100) with a moderate heterogeneity (I2: 64.8%, 95% CI 39.6-89.9; and Cochran Q 22.7, p < 0.001). Pooled estimated specificity was 90% (95% CI 83-95) with significant heterogeneity (I2: 80.3%, 95% CI 68.1-92.5; and Cochran Q 40.6, p < 0.001). Positive likelihood ratio was 10.3 (95% CI 5.6-18.7) and negative likelihood ratio was 0.02 (95% CI 0.00-0.21). Conclusion: 3D-HyCoSy is an accurate test for diagnosing tubal occlusion in women with infertility.
HOST-RANGE EVOLUTION IN APHIDIUS PARASITOIDS: FIDELITY, VIRULENCE AND FITNESS TRADE-OFFS ON AN ANCESTRAL HOST

Abstract The diversity of parasitic insects remains one of the most conspicuous patterns on the planet. The principal factor thought to contribute to differentiation of populations and ultimately speciation is the intimate relationship parasites share with hosts and the potential for disruptive selection associated with using different host species. Traits that generate this diversity have been an intensely debated topic of central importance to the evolution of specialization and maintenance of ecological diversity. A fundamental hypothesis surrounding the evolution of specialization is that no single genotype is uniformly superior in all environments. This “trade-off” hypothesis suggests that negative fitness correlations can lead to specialization on different hosts as alternative stable strategies. In this study we demonstrate a trade-off in the ability of the parasitoid, Aphidius ervi, to maintain a high level of fitness on an ancestral and novel host, which suggests a genetic basis for host utilization that may limit host-range expansion in parasitoids. Furthermore, behavioral evidence suggests mechanisms that could promote specialization through induced host fidelity. Results are discussed in the context of host-affiliated ecological selection as a potential source driving diversification in parasitoid communities and the influence of host species heterogeneity on population differentiation and local adaptation.