Miracle-dz/UniFAR-FTUs huggingface dataset:
Hormonal contraception and venous thromboembolism

Background. New studies about the influence of hormonal contraception on the risk of venous thromboembolism (VTE) have been published. Aim. To evaluate new epidemiological data and to propose clinical consequences. Design. A literature survey. Methods. Studies assessing the risk of specific types of hormonal contraception were evaluated, compared and set into a clinical perspective. Results. The majority of newer studies have demonstrated a threefold increased risk of VTE in current users of medium‐ and low‐dose combined oral contraceptives (COCs) with norethisterone, levonorgestrel (LNG) or norgestimate compared with non‐users. The same studies have demonstrated a sixfold increased risk of VTE in users of combined pills with desogestrel, gestodene, drospirenone or cyproteroneacetate, and in users of the contraceptive vaginal ring, compared with non‐users. The rate ratio of VTE between users of COCs with newer progestogens compared with users of COCs with LNG was 1.5–2.8 in seven studies and 1.0 in two studies. Progestogen‐only contraception did not confer an increased risk of VTE in any study. The incidence rate of VTE in non‐pregnant women aged 15–49 years using non‐hormonal contraception is three per 10 000 years. Conclusions. For women starting on hormonal contraception, we recommend medium‐ or low‐dose combined pills with norethisterone, LNG or norgestimate as first‐choice preparations. For the many women who are users of COCs with newer progestogens, although the absolute risk of VTE is low, a change to combined pills with norethisterone, LNG or norgestimate may halve their risk of VTE. Finally, we recommend COCs with 20 μg estrogen combined with the older progestogens to be launched in the Scandinavian countries. Women at an increased risk of VTE should consider progestogen‐only contraception or non‐hormonal contraception.
Reciprocal and Coordinate Regulation of Serum Amyloid A Versus Apolipoprotein A-I and Paraoxonase-1 by Inflammation in Murine Hepatocytes

Objectives—During inflammation, the serum amyloid A (SAA) content of HDL increases, whereas apolipoprotein A-I (apoA-I) and paraoxonase-1 (PON-1) decrease. It remains unclear whether SAA physically displaces apoA-I or if these changes derive from coordinated but inverse transcriptional regulation of the HDL apolipoprotein genes. Because cytokines stimulate the hepatic expression of inflammatory markers, we investigated their role in regulating SAA, apoA-I, and PON-1 expression. Methods and Results—A cytokine mixture (tumor necrosis factor [TNF]-&agr;, interleukin [IL]-1&bgr;, and IL-6) simultaneously induced SAA and repressed apoA-I and PON-1 expression levels. These effects were partially inhibited in cells pretreated with either nuclear factor &kgr;B (NF-&kgr;B) inhibitors (pyrrolidine dithiocarbamate, SN50, and overexpression of super-repressor inhibitor &kgr;B) or after exposure to the peroxisome proliferator-activated receptor-&agr; (PPAR&agr;) ligands (WY-14643 and fenofibrate). Consistent with these findings, the basal level of SAA was increased, whereas apoA-I and PON-1 decreased in primary hepatocytes from PPAR&agr;-deficient mice as compared with wild-type mice. Moreover, neither WY-14643 nor fenofibrate had any effect on SAA, apoA-I, or PON-1 expression in the absence of PPAR&agr;. Conclusion—These results suggest that cytokines increase the expression of SAA through NF-&kgr;B transactivation, while simultaneously decreasing the expression of apoA-I and PON-1 by inhibiting PPAR&agr; activation. Inflammation may convert HDL de novo into a more proatherogenic form by coordinate but inverse transcriptional regulation in the liver, rather than by physical displacement of apoA-I by SAA.
A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia.

OBJECTIVE To compare citalopram and risperidone for the treatment of psychotic symptoms and agitation associated with dementia, with a priori hypotheses that risperidone would be more efficacious for psychosis and citalopram for agitation. METHODS A 12-week randomized, controlled trial in nondepressed patients with dementia hospitalized because of behavioral symptoms (N = 103) was conducted at the University of Pittsburgh Medical Center. Participants were consecutively recruited on an inpatient unit if they had at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions). Once they improved sufficiently, they were discharged to nursing homes, personal care homes, or residential homes for continued treatment. Planned pre-post and mixed model analyses of the main outcome measures of Neurobehavioral Rating Scale and Side Effect Rating Scale at baseline and at weekly/biweekly intervals were conducted. RESULTS Completion rates did not differ for citalopram and risperidone (overall completion rate: 44%). Agitation symptoms (aggression, agitation, or hostility) and psychotic symptoms (suspiciousness, hallucinations, or delusions) decreased in both treatment groups but the improvement did not differ significantly between the two groups. There was a significant increase in side effect burden with risperidone but not with citalopram such that the two groups differed significantly. CONCLUSION No statistical difference was found in the efficacy of citalopram and risperidone for the treatment of either agitation or psychotic symptoms in patients with dementia. These findings need to be replicated before citalopram or other serotonergic antidepressants can be recommended as alternatives to antipsychotics for the treatment of agitation or psychotic symptoms associated with dementia.
Large Scale Meta-Analyses of Fasting Plasma Glucose Raising Variants in GCK, GCKR, MTNR1B and G6PC2 and Their Impacts on Type 2 Diabetes Mellitus Risk

Background The evidence that the variants GCK rs1799884, GCKR rs780094, MTNR1B rs10830963 and G6PC2 rs560887, which are related to fasting plasma glucose levels, increase the risk of type 2 diabetes mellitus (T2DM) is contradictory. We therefore performed a meta-analysis to derive a more precise estimation of the association between these polymorphisms and T2DM. Methods All the publications examining the associations of these variants with risk of T2DM were retrieved from the MEDLINE and EMBASE databases. Using the data from the retrieved articles, we computed summary estimates of the associations of the four variants with T2DM risk. We also examined the studies for heterogeneity, as well as for bias of the publications. Results A total of 113,025 T2DM patients and 199,997 controls from 38 articles were included in the meta-analysis. Overall, the pooled results indicated that GCK (rs1799884), GCKR (rs780094) and MTNR1B (rs10830963) were significantly associated with T2DM susceptibility (OR, 1.04; 95%CI, 1.01–1.08; OR, 1.08; 95%CI, 1.05–1.12 and OR, 1.05; 95%CI, 1.02–1.08, respectively). After stratification by ethnicity, significant associations for the GCK, MTNR1B and G6PC2 variants were detected only in Caucasians (OR, 1.09; 95%CI, 1.02–1.16; OR, 1.10; 95%CI, 1.08–1.13 and OR, 0.97; 95%CI, 0.95–0.99, respectively), but not in Asians (OR, 1.02, 95% CI 0.98–1.05; OR, 1.01; 95%CI, 0.98–1.04 and OR, 1.12; 95%CI, 0.91–1.32, respectively). Conclusions Our meta-analyses demonstrated that GCKR rs780094 variant confers high cross-ethnicity risk for the development of T2DM, while significant associations between GCK, MTNR1B and G6PC2 variants and T2DM risk are limited to Caucasians.
Severe adverse events associated with local anaesthesia in cataract surgery: 1 year national survey of practice and complications in the UK

Background Recent years have seen a major change in practice of local anaesthesia (LA) for cataract surgery. Aims (1) To estimate current usage of LA techniques for cataract surgery, (2) to estimate the incidence of severe adverse events associated with each LA technique, (3) to compare with our previous 2003 study. Methods This was a prospective, observational study of routine practice. For 13 months in 2012–2013, the British Ophthalmological Surveillance Unit sent monthly mailings to all senior British ophthalmologists, asking for reports of ‘potentially sight-threatening or life-threatening complications of LA for cataract surgery’. Current practice was assessed by questionnaire. Results Cataract surgery comprised 3.4% general anaesthesia, 92.5% LA alone and 4.1% LA with sedation. Techniques for the estimated 357 000 LA cataracts were: 8.8% peribulbar, 1.3% retrobulbar, 50.5% sub-Tenon's, 1.4% subconjunctival, 13.8% topical, 24.2% topical-intracameral LA. Severe sight-threatening complications included seven globe perforations, one cilioretinal artery occlusion and one severe corneal oedema. Severe life-threatening complications included one profound vasovagal episode, one silent myocardial infarction, one anaphylactic reaction and one supraventricular tachycardia. Under-reporting means that more complications probably occurred. Conclusions There has been a large swing towards ‘non-injection’ LA in recent years. Serious adverse events were reported with all techniques except topical-intracameral and subconjunctival LA, though the incidence appears lower for ‘non-injection’ LA.
METHYLATION STATUS OF EPIDERMAL GROWTH FACTOR RECEPTOR GENE IN LUNG CARCINOMA CELLS

The methylation status of the epidermal growth factor receptor (EGFR) gene was compared in cell lines from four major types of lung carcinoma, small cell lung carcinoma (SCLC), large cell lung carcinoma, squamous cell carcinoma and adenocarcinoma, in order to examine whether DNA methylation is responsible for the suppression of EGFR gene in SCLC cells. Southern blot analysis revealed that the structural region of the EGFR gene is methylated to various degrees regardless of the expression of EGF receptor on the surface. An 8‐kilobase EcoRI fragment which contains the EGFR gene promoter region is readily digested with various methylation‐sensitive restriction enzymes in all types of cells, indicating that the EGFR gene 5’region is barely methylated. Thus, a mechanism other than DNA methylation appears to control EGFR gene expression and the lack of EGFR gene expression in SCLC cells may be caused by a paucity of some transcription regulatory factor(s).
Perceptual display: exceeding display limitations by exploiting the human visual system

Existing displays have a number of limitations, which make it difficult to realistically reproduce real-world appearance; discrete pixels are used to represent images, which are refreshed only a limited number of times per second, the output luminance range is much smaller than in the real world, and only two dimensions are available to reproduce a three-dimensional scene. While in some cases technology advanced and higher frame rates, higher resolution, higher luminance, and even disparity-based stereo is possible, these solutions are often costly and, further, it is challenging to produce adequate content. On the other hand, the human visual system has certain limitations itself, such as the density of photoreceptors, imperfections in the eye optics, or the limited ability to discern high-frequency information. The methods presented in this dissertation show that taking these properties into account can improve the efficiency and perceived quality of displayed imagery. More precisely, those techniques make use of perceptual effects, which are not measurable physically, that will allow us to overcome the physical limitations of display devices in order to enhance apparent image qualities.
Interventions to Improve Adherence to Antiretroviral Therapy

Summary: Recent research has shown that very high levels of adherence are required to obtain the maximum benefit of highly active antiretroviral therapy (HAART). This situation justifies the importance of developing efficient strategies to improve adherence to drugs against HIV. A comprehensive range of factors are the targets of the most effective interventions to improve adherence, including cognitive, behavioral, emotional, and social aspects. The authors describe three theoretical models that can help identify barriers and guide interventions. Most of the interventions are complex and may include more convenient care, provision of information, counseling, reminders, reinforcement, self‐monitoring, family therapy, or additional supervision or attention. The authors suggest aspects that should be included in interventions to promote adherence based on a review of the literature and clinical experience. Limited evidence suggests that interventions to enhance adherence to antiretroviral therapy in people with HIV are most likely to be successful when they are comprehensive, longitudinal, and tailored to the person.
Inhibitory Effects of GHRH Antagonists on Human GH-Secreting Adenoma Tissue

Experimental data indicate that antagonists of growth hormone-releasing hormone (GHRH) could be used clinically in disorders characterized by excessive GHRH/growth hormone (GH) secretion, but direct evidence for the effectiveness of GHRH antagonists on human pituitary tissue is still lacking. In this study, we investigated the inhibitory effect of our GHRH antagonists MZ-4-71 and JV-1-36 and the somatostatin (SST) analog RC-160 on superfused pituitary cells obtained from a human GH-secreting adenoma. Using Western blot analysis and immunohistochemistry, we demonstrated profuse expression of the GHRH receptor and its major splice variant SV1 and an increase in the expression of Gsa protein in the adenoma tissue. Exposure of the tumor cells to exogenous pulses of GHRH induced definite GH responses, causing a 3- to 5-fold elevation of the basal GH level. The antagonists MZ-4-71 and JV-1-36 did not alter basal GH secretion, indicating that the adenoma cells did not secrete GHRH in an autocrine manner. However, both antagonists prevented the stimulatory effect of exogenous GHRH. Similarly to the GHRH antagonists, neither SST-14 nor the SST analog RC-160 had an effect on the basal GH secretion of the tumor cells, but both peptides inhibited the stimulatory effect of exogenous GHRH, with RC-160 being more potent than SST. Our study provides direct evidence for the effectiveness of potent GHRH antagonists such as MZ-4-71 and JV-1-36 on human pituitary GH-secreting adenoma tissue and strongly suggests that these drugs could be used for therapy of GHRH-associated forms of acromegaly, particularly for those patients in whom surgery fails or is not an option.
From Hospital to Home After Cardiac Surgery: Evaluation of a Community Nursing Care Management Model

Purpose/objectives This quasi-experimental research aims to (1) evaluate the implementation process of a community nursing care management model and (2) assess the effects of this model on patients followed at home. Primary practice setting Two community healthcare centers had introduced a community nursing care management model in their practice (experimental groups), whereas another health community care center with no experience with such a model served as a control group. The community nursing care management model included clinical pathways designed for a clientele who had been hospitalized for cardiac surgery. Findings/conclusions Even though the implementation process was challenging, the community nursing care management model was found useful enough to be integrated into routine nursing home care practice after cardiac surgery. Although the effects produced by this systematic home care program on the clientele did not differ significantly from those produced by usual nursing care, there was a positive effect for the clientele recorded on all measurement indicators used. Implications for case management practice The introduction of the nursing care management model enabled nurses to structure the care provided and reduced interindividual variation. The application of this program also proved to be an opportunity to initiate and assimilate new professional roles. Additional studies should be conducted to assess its effectiveness in home care for other health problems.
African Migrant Patients’ Trust in Chinese Physicians: A Social Ecological Approach to Understanding Patient-Physician Trust

Background Patient trust in physicians is a critical determinant of health seeking behaviors, medication adherence, and health outcomes. A crisis of interpersonal trust exists in China, extending throughout multiple social spheres, including the healthcare system. At the same time, with increased migration from Africa to China in the last two decades, Chinese physicians must establish mutual trust with an increasingly diverse patient population. We undertook a qualitative study to identify factors affecting African migrants’ trust in Chinese physicians and to identify potential mechanisms for promoting trust. Methods / Principal Findings We conducted semi-structured, in-depth interviews with 40 African migrants in Guangzhou, China. A modified version of the social ecological model was used as a theoretical framework. At the patient-physician level, interpersonal treatment, technical competence, perceived commitment and motive, and language concordance were associated with enhanced trust. At the health system level, two primary factors influenced African migrants’ trust in their physicians: the fee-for-service payment system and lack of continuity with any one physician. Patients’ social networks and the broader socio-cultural context of interactions between African migrants and Chinese locals also influenced patients’ trust of their physicians. Conclusions These findings demonstrate the importance of factors beyond the immediate patient-physician interaction and suggest opportunities to promote trust through health system interventions.
Cardiovascular and Renal Effects of Birdseed Associated with Aerobic Exercise in Rats.

INTRODUCTION Phalaris canariensis L. (Pc), known as birdseed, is rich in tryptophan. The aqueous extract of Pc (AEPc) treatment reduced systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR) via mechanisms mediated by the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Hypertension is a risk factor to cardiovascular and renal diseases. Considering that physical exercise improves hypertension and cardiovascular function, the aim of this study was to evaluate whether the benefits of exercise (Ex) would be enhanced by concomitant AEPc treatment (400 mg·kg·d p.o.). METHODS Vascular reactivity was assessed in aorta rings from SHR treated with AEPc for 4 wk. Training intensity was based on maximal lactate steady state obtained during the 2-wk adaptation period in a treadmill running. Then exercised (60 min running, five times per week during 8 wk) or sedentary SHR were untreated or treated with AEPc during 8 wk. SBP was estimated by plethysmograph. Heart mass and body mass were used to obtain the index of cardiac hypertrophy. Glucose tolerance test was evaluated by oral glucose overload, and the mRNA expressions of indoleamine 2,3-dioxygenase, interleukin 1β (IL-1β), and IL-10 in the kidney were obtained by real time polymerase chain reaction. RESULTS AEPc induced endothelial-mediated vascular relaxation. AEPc or Ex alone reduced SBP, the index of cardiac hypertrophy and ventricular fibrosis, improved glucose metabolism, and attenuated proteinuria and the renal expression of the proinflammatory IL-1β with an overexpression in the anti-inflammatory IL-10. AEPc potentiated the benefits of the Ex on the cardiovascular system, metabolic parameters, and renal inflammation. CONCLUSION Birdseed reduced cardiovascular risk related to hypertension and had positive effects when associated to physical exercise.
Successful definition of nanowire and porous Si regions of different porosity levels by regular positive photoresist using metal-assisted chemical etching

A simple and efficient method for selective formation of porous Si areas using regular photoresist as a masking layer is presented. Such a simple masking layer is sufficient to create a wide range of porosity levels through metal-assisted chemical etching (MaCE) using platinum, palladium and silver nanoparticles. Reproducible porous areas with a minimum feature size of 5 µm were produced on Si wafers. The pore size and height are the functions of the etching time and type of nanoparticles. Using Ag nanopaticles we have been able to obtain Si nanowires of about 30 µm height. Based on these results, a combination of positive photoresist and MaCE seems to be a reliable way for micron and submicron patterning of nanowire and porous areas on Si wafers, which is simple, inexpensive and compatible with integrated circuit fabrication techniques.
Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei

The majority of cloned animals derived by nuclear transfer from somatic cell nuclei develop to the blastocyst stage but die after implantation. Mouse embryos that lack an Oct4 gene, which plays an essential role in control of developmental pluripotency, develop to the blastocyst stage and also die after implantation, because they lack pluripotent embryonic cells. Based on this similarity, we posited that cloned embryos derived from differentiated cell nuclei fail to establish a population of truly pluripotent embryonic cells because of faulty reactivation of key embryonic genes such as Oct4. To explore this hypothesis, we used an in silico approach to identify a set of Oct4-related genes whose developmental expression pattern is similar to that of Oct4. When expression of Oct4 and 10 Oct4-related genes was analyzed in individual cumulus cell-derived cloned blastocysts, only 62% correctly expressed all tested genes. In contrast to this incomplete reactivation of Oct4-related genes in somatic clones, ES cell-derived cloned blastocysts and normal control embryos expressed these genes normally. Notably, the contrast between expression patterns of the Oct4-related genes correlated with efficiency of embryonic development of somatic and ES cell-derived cloned blastocysts to term. These observations suggest that failure to reactivate the full spectrum of these Oct4-related genes may contribute to embryonic lethality in somatic-cell clones.
Single-channel basis for the slow activation of the repolarizing cardiac potassium current, IKs

Coassembly of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with potassium voltage-gated channel, Isk-related family, member 1 (KCNE1) the delayed rectifier potassium channel IKs. Its slow activation is critically important for membrane repolarization and for abbreviating the cardiac action potential, especially during sympathetic activation and at high heart rates. Mutations in either gene can cause long QT syndrome, which can lead to fatal arrhythmias. To understand better the elementary behavior of this slowly activating channel complex, we quantitatively analyzed direct measurements of single-channel IKs. Single-channel recordings from transiently transfected mouse ltk− cells confirm a channel that has long latency periods to opening (1.67 ± 0.073 s at +60 mV) but that flickers rapidly between multiple open and closed states in non-deactivating bursts at positive membrane potentials. Channel activity is cyclic with periods of high activity followed by quiescence, leading to an overall open probability of only ∼0.15 after 4 s under our recording conditions. The mean single-channel conductance was determined to be 3.2 pS, but unlike any other known wild-type human potassium channel, long-lived subconductance levels coupled to activation are a key feature of both the activation and deactivation time courses of the conducting channel complex. Up to five conducting levels ranging from 0.13 to 0.66 pA could be identified in single-channel recordings at 60 mV. Fast closings and overt subconductance behavior of the wild-type IKs channel required modification of existing Markov models to include these features of channel behavior.