Miracle-dz/UniFAR-FTUs huggingface dataset:
Studies on the link between HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in lymph-fistula rats: evidence for both transcriptional and post-transcriptional mechanisms for down-regulation of the two enzymes by bile acids.

The mechanism of down-regulation of hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase by cholic acid (CA) and chenodeoxycholic acid (CDCA) was investigated in rats with a lymph fistula. In accordance with the contention that bile acids are able to down-regulate HMG-CoA reductase by a mechanism independent of their effect on cholesterol absorption, inclusion of the above bile acids in diet (1%, wt/wt) reduced the HMG-CoA reductase specific activity by about 80%. The levels of mRNA were reduced by about 50% and the transcription rate (nuclear run-on) by 27% and 35%, respectively. Thus, HMG-CoA reductase appears to be regulated at both a transcriptional and a post-transcriptional level by bile acids. The cholesterol 7 alpha-hydroxylase activity as well as the corresponding mRNA levels were both reduced by about 50% by the same treatments. The transcription rate of the cholesterol 7 alpha-hydroxylase was not significantly affected by the treatment with CDCA, whereas the CA treatment reduced the transcription rate by about 24%. It is evident that bile acids regulate these two enzymes by different mechanisms in this model, in spite of the fact that the levels of mRNA were affected to about the same degree. The most obvious difference was the marked suppression of HMG-CoA reductase activity by cholic acid with relatively modest effects on transcription rate and level of mRNA. The latter finding is interesting in view of recent reports that dietary cholesterol also seems to down-regulate HMG-CoA reductase predominantly by a post-transcriptional mechanism. (ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of primary Sjögren syndrome: a systematic review.

CONTEXT A variety of topical and systemic drugs are available to treat primary Sjögren syndrome, although no evidence-based therapeutic guidelines are currently available. OBJECTIVE To summarize evidence on primary Sjögren syndrome drug therapy from randomized controlled trials. DATA SOURCES We searched MEDLINE and EMBASE for articles on drug therapy for primary Sjögren syndrome published between January 1, 1986, and April 30, 2010. STUDY SELECTION Controlled trials of topical and systemic drugs including adult patients with primary Sjögren syndrome were selected as the primary information source. RESULTS The search strategy yielded 37 trials. A placebo-controlled trial found significant improvement in the Schirmer and corneal staining scores, blurred vision, and artificial tear use in patients treated with topical ocular 0.05% cyclosporine. Three placebo-controlled trials found that pilocarpine was associated with improvements in dry mouth (61%-70% vs 24%-31% in the placebo group) and dry eye (42%-53% vs 26%). Two placebo-controlled trials found that cevimeline was associated with improvement in dry mouth (66%-76% vs 35%-37% in the placebo group) and dry eye (39%-72% vs 24%-30%). Small trials (<20 patients) found no significant improvement in sicca outcomes for oral prednisone or hydroxychloroquine and limited benefits for immunosuppressive agents (azathioprine and cyclosporine). A large trial found limited benefits for oral interferon alfa-2a. Two placebo-controlled trials of infliximab and etanercept did not achieve the primary outcome (a composite visual analog scale measuring joint pain, fatigue, and dryness); neither did 2 small trials (<30 patients) testing rituximab, although significant results were observed in some secondary outcomes and improvement compared with baseline. CONCLUSIONS In primary Sjögren syndrome, evidence from controlled trials suggests benefits for pilocarpine and cevimeline for sicca features and topical cyclosporine for moderate or severe dry eye. Anti-tumor necrosis factor agents have not shown clinical efficacy, and larger controlled trials are needed to establish the efficacy of rituximab.
Vandetanib for the Treatment of Medullary Thyroid Carcinoma

Objective: To review the place in therapy of vandetanib for medullary thyroid carcinoma (MTC). Data Sources: Literature searches were performed in Ovid MEDLINE, EMBASE, and Google Scholar using the search terms ZD6474 OR vandetanib OR Caprelsa combined with medullary thyroid carcinoma. Study Selection and Data Extraction: Two phase 2 trials and 1 phase 3 trial were identified. Data Synthesis: Vandetanib is approved for the treatment of unresectable, locally advanced or metastatic MTC in patients with symptomatic or progressive disease. In the phase 3 randomized, double-blind, placebo-controlled trial, vandetanib 300 mg daily (n = 231) was compared with placebo (n = 100). Vandetanib-treated patients experienced a significant improvement in progression-free survival (PFS; hazard ratio [HR] = 0.46; 95% CI = 0.31-0.69; P < .001). No difference in overall survival (OS) was seen at the time of publication. Most adverse effects were grade 1 or 2 and managed by dose interruptions or reductions. The most common grade 3/4 adverse effects were diarrhea, hypertension, QT prolongation, fatigue, and rash. Because of the potential for QT prolongation, torsades de pointes, and sudden death, vandetanib is restricted via a Risk Evaluations and Mitigation Strategy program. Conclusions: Vandetanib prolongs PFS but has not been shown to improve OS. Vandetanib can be considered for patients with unresectable locoregional disease. It is a first-line option for patients with unresectable symptomatic distant metastases as well as an option for advanced disseminated symptomatic metastatic disease. Vandetanib is expected to be an important addition to the formulary of health plans that provide prescription drug benefits.
Plasmodium vivax Chloroquine Resistance and Anemia in the Western Brazilian Amazon

ABSTRACT Data on chloroquine (CQ)-resistant Plasmodium vivax in Latin America is limited, even with the current research efforts to sustain an efficient malaria control program in all these countries where P. vivax is endemic and where malaria still is a major public health issue. This study estimated in vivo CQ resistance in patients with uncomplicated P. vivax malaria, with use of CQ and primaquine simultaneously, in the Brazilian Amazon. Of a total of 135 enrolled subjects who accomplished the 28-day follow-up, parasitological failure was observed in 7 (5.2%) patients, in whom plasma CQ and desethylchloroquine (DCQ) concentrations were above 100 ng/dl. Univariate analysis showed that previous exposure to malaria and a higher initial mean parasitemia were associated with resistance but not with age or gender. In the multivariate analysis, only high initial parasitemia remained significant. Hemoglobin levels were similar at the beginning of the follow-up and were not associated with parasitemia. However, at day 3 and day 7, hemoglobin levels were significantly lower in patients presenting CQ resistance. The P. vivax dhfr (pvdhfr), pvmrp1, pvmdr1, and pvdhps gene mutations were not related to resistance in this small sample. P. vivax CQ resistance is already a problem in the Brazilian Amazon, which could be to some extent associated with the simultaneous report of anemia triggered by this parasite, a common complication of the disease in most of the areas of endemicity.
What drives labor market polarization in advanced countries? The role of China and technology

This article explores the effects of offshoring, technology, and Chinese import competition on labor market polarization in European countries. We find that polarization occurs mostly as a result of polarization within individual industries, while the reallocation of employment away from less polarized industries toward more highly polarized industries contributed only about one-third of the total change. We find that both technological change and Chinese net import competition contributed to labor market polarization, but that they did so in distinct ways. In European manufacturing industries, ICT adoption explains a third of within-industry polarization, while Chinese net import competition contributed to a much smaller extent. The process of between-industry polarization is driven by widespread deindustrialization and servitization in developed countries. We find that Chinese net import competition explains about a fifth of the employment decline in lowly polarized manufacturing industries and was thus an important driver of the reallocation of labor within economies away from lowly polarized manufacturing industries. We present tentative evidence that employment grew faster in initially highly polarized service industries. Moreover, these industries appear unaffected by their indirect input-output-exposure to Chinese net import competition, while this was not the case for initially lowly polarized service industries. While polarization patterns in different European labor markets show considerable heterogeneity, labor market institutions seem to be insufficient to explain these cross-country differences.
Echocardiographic strain imaging and its use in the clinical setting

The use of echocardiography has grown tremendously over the past several years. It is used routinely for diagnosis, prognosis and monitoring changes of cardiac function in coronary artery disease, heart failure, pulmonary hypertension, arrhythmias, pericardial disease and valvular disease, as well as congenital conditions. In recent years, the advancing technology used to evaluate the heart by ultrasound has allowed physicians to understand the mechanics of the heart muscle and the contribution of abnormalities in myocardial movement to heart disease. This review will discuss novel echocardiographic strain imaging techniques, placing them in the context of myocardial mechanics and describing current and future applications.
On-screen vector-based ultrasound assessment of vesical neck movement.

OBJECTIVE We sought to develop a vector-based assessment to determine the magnitude and direction of bladder neck movements, as well as to assess whether probe movement relative to the pubis needs to be taken into account. STUDY DESIGN Ten nulliparous continent, 10 primiparous continent, and 10 primiparous stress-incontinent women were recruited. Perineal ultrasound scanning was performed in standing women while they were resting, performing the Valsalva maneuver, coughing, and performing Kegel exercises. A direct on-screen assessment of bladder neck displacement from rest to the peak of dynamic activity relative to the pubic axis was made. Transducer movement was assessed by measuring the displacement of the pubic bone. RESULTS The method was feasible because measurements were possible in all 30 subjects. Vesical neck and pubic point movement in millimeters (+/- SD) and the percentage error if pubic point movement is not accounted for are as follow: strain, vesical neck 16.9 +/- 6.1 and pubic point 4.8 +/- 3.9, 28%; cough, vesical neck 10.2 +/- 5.4, pubic point 2.9 +/- 3.4, 33%; Kegel exercise, vesical neck 7.0 +/- 3.6 and pubic point 0.7 +/- 1.4, 37%. Similar discrepancies in angle were found and are presented. Uncorrected direction of vesical neck and pubic point movement in degrees and the percentage error if pubic point movement is not accounted for are as follow: strain, vesical neck 169.4 +/- 18.5 and pubic point 214.0 +/- 56.7, 18%; cough, vesical neck 162.0 +/- 12.8, pubic point 238.4 +/- 27.4, 22%; Kegel exercise, vesical neck -0.9 +/- 12.7 and pubic point -4.8 +/- 20.6, 87%. Test-retest reliability correlations were more than an r value of 0.7 in all measures and 86% of the measurements greater than 0.8. CONCLUSION The vector-based system provides a simple method for quantifying distance and direction of vesical neck motion, as well as localizing the resting vesical neck position.
Cognitive Predictors of Alcohol Involvement and Alcohol Consumption–Related Consequences in a Sample of Drunk-Driving Offenders

Motivational theories of alcohol involvement emphasize a wide range of cognitive factors as precursors to “heavy” or high-risk drinking. Central to this consideration has been expectancies, drinking urges, triggers, and situational cues, all of which can synergistically or independently stimulate drinking. Unfortunately, empirical studies have scrutinized low-level or moderate drinkers drawn from the general population, and less is known about the role of cognitive factors as precursors to high-risk drinking. The present study examines the unique contribution of several measures of cognitive motivation to harmful alcohol use in a sample of convicted drunk drivers. Confirmatory factor analysis indicated the psychometric soundness of a model positing four latent predictor constructs assessing drinking urges/triggers, situational cues, positive and negative expectancies and outcome constructs assessing harmful alcohol use and perceived consequences of harmful drinking. A structural equation model indicated that each motivational construct was associated uniquely with both drinking and perceived consequences, with the largest overall effect in both cases associated with situational cues. Results are discussed in terms of identifying prominent cognitive factors that may foster harmful drinking among high-risk populations and their implications for treatment.
Polymerase Amplification, Cloning, and Gene Expression of Benzo‐Homologous “yDNA” Base Pairs

A widened DNA base‐pair architecture is studied in an effort to explore the possibility of whether new genetic system designs might possess some of the functions of natural DNA. In the “yDNA” system, pairs are homologated by addition of a benzene ring, which yields (in the present study) benzopyrimidines that are correctly paired with purines. Here we report initial tests of ability of the benzopyrimidines yT and yC to store and transfer biochemical and biological information in vitro and in bacterial cells. In vitro primer extension studies with two polymerases showed that the enzymes could insert the correct nucleotides opposite these yDNA bases, but with low selectivity. PCR amplifications with a thermostable polymerase resulted in correct pairings in 15–20 % of the cases, and more successfully when yT or yC were situated within the primers. Segments of DNA containing one or two yDNA bases were then ligated into a plasmid and tested for their ability to successfully lead the expression of an active protein in vivo. Although active at only a fraction of the activity of fully natural DNA, the unnatural bases encoded the correct codon bases in the majority of cases when singly substituted, and yielded functioning green fluorescent protein. Although the activities with native polymerases are modest with these large base pairs, this is the first example of encoding protein in vivo by an unnatural DNA base pair architecture.
BILATERAL AND BIMODAL BENEFITS AS A FUNCTION OF AGE FOR ADULTS FITTED WITH A COCHLEAR IMPLANT.

BACKGROUND Both bilateral cochlear implants (CIs) and bimodal (electric plus contralateral acoustic) stimulation can provide better speech intelligibility than a single CI. In both cases patients need to combine information from two ears into a single percept. In this paper we ask whether the physiological and psychological processes associated with aging alter the ability of bilateral and bimodal CI patients to combine information across two ears in the service of speech understanding. MATERIALS The subjects were 61 adult, bilateral CI patients and 94 adult, bimodal patients. The test battery was composed of monosyllabic words presented in quiet and the AzBio sentences presented in quiet, at +10 and at +5 dB signal-to-noise ratio (SNR). METHODS The subjects were tested in standard audiometric sound booths. Speech and noise were always presented from a single speaker directly in front of the listener. RESULTS Age and bilateral or bimodal benefit were not significantly correlated for any test measure. CONCLUSIONS Other factors being equal, both bilateral CIs and bimodal CIs can be recommended for elderly patients.
Left Atrial Posterior Wall Isolation Does Not Improve the Outcome of Circumferential Pulmonary Vein Ablation for Atrial Fibrillation: A Prospective Randomized Study

Background—Ablation of the pulmonary veins (PVs) for atrial fibrillation treatment is often combined with linear radiofrequency lesions along the left atrium (LA) to improve the success rate. The study was designed to assess the contribution of LA posterior wall isolation to the outcome of circumferential pulmonary vein ablation (CPVA). Methods and Results—CPVA consisted of continuous radiofrequency lesions encircling both ipsilateral PVs plus an ablation line along the mitral isthmus. Patients were then randomized into 2 groups. In the first group, superior PVs were connected by linear lesions along the LA roof (CPVA-1 group). In the second group, the LA posterior wall was isolated by adding a second line connecting the inferior aspect of the 2 inferior PVs (CPVA-2 group). The study included 120 patients (53±11 years, 77% male, 60% paroxysmal atrial fibrillation, LA of 41.3±5.4 mm, 46% with hypertension, and 22% with structural heart disease). After a single ablation procedure and a mean follow-up of 10±4 months, 24 (40%) patients of the CPVA-1 group had atrial fibrillation recurrences and 3 (5%) had new-onset LA flutter. In the CPVA-2 group, recurrences were due to atrial fibrillation episodes in 23 patients (38%) and LA flutter in 4 (7%). Freedom from arrhythmia recurrences was not statistically different in the CPVA-1 group as compared with the CPVA-2 group (log rank P=0.943). Conclusion—Isolation of the LA posterior wall did not increase the success rate of CPVA.
Aortic Graft at Coronary Artery Bypass Surgery as a Source of Human Aortic Smooth Muscle Cells

One of the serious obstacles of the aortopathies research is a considerable shortage of human aortic smooth muscle cells (SMCs), which can be used to model the disease. SMC in most cases come from the whole aorta of transplant donors, which are rather difficult to access. In the course of coronary artery bypass graft (CABG) surgery, a fragment of aortic tissue is excised to make a bypass root. In this study, we show a possibility to use CABG leftover fragments of thoracic aorta as a source of human SMC for in vitro research. We isolated SMC from the fragments of aortic tissues obtained during CABG procedure and compared these cells to the cells that were isolated from aortic tissue of transplant donors. The content of key SMC contractile markers (SMA, SM22α, and vimentin) as well as proliferation and migration rates, metalloproteases MMP-2 and MMP-9 activities were similar in CABG-derived SMC and in transplant donor–derived SMC. In conclusion, leftovers of ascending thoracic aorta obtained during CABG can be used as a source of human aortic SMCs for in vitro research.
Alternate use of divergent forms of an ancient exon in the fructose-1,6-bisphosphate aldolase gene of Drosophila melanogaster

The fructose-1,6-bisphosphate aldolase gene of Drosophila melanogaster contains three divergent copies of an evolutionarily conserved 3' exon. Two mRNAs encoding aldolase contain three exons and differ only in the poly(A) site. The first exon is small and noncoding. The second encodes the first 332 amino acids, which form the catalytic domain, and is homologous to exons 2 through 8 of vertebrates. The third exon encodes the last 29 amino acids, thought to control substrate specificity, and is homologous to vertebrate exon 9. A third mRNA substitutes a different 3' exon (4a) for exon 3 and encodes a protein very similar to aldolase. A fourth mRNA begins at a different promoter and shares the second exon with the aldolase messages. However, two exons, 3a and 4a, together substitute for exon 3. Like exon 4a, exon 3a is homologous to terminal aldolase exons. The exon 3a-4a junction is such that exon 4a would be translated in a frame different from that which would produce a protein with similarity to aldolase. The putative proteins encoded by the third and fourth mRNAs are likely to be aldolases with altered substrate specificities, illustrating alternate use of duplicated and diverged exons as an evolutionary mechanism for adaptation of enzymatic activities.
Barrett's, blood groups and progression to oesophageal cancer: is nitric oxide the link?

Introduction Incidence of oesophageal adenocarcinoma (OAC) is increasing rapidly. OAC arises in columnar-lined oesophagus (CLO), a metaplastic change affecting some patients with gastro-oesophageal reflux disease (GORD). As yet there is no reliable method of identifying those at highest risk. Our earlier observation of an association between OAC and blood group O Rhesus negative, if confirmed, may help identify those at greatest risk. Aim and methods To assess the distribution of blood group and Rhesus D (RhD) factor in patients with GORD compared with the blood donating general population. GORD was categorized as nonerosive reflux (NER), erosive oesophagitis, CLO and OAC. The Rotherham Hospital database holds details of all GORD, CLO and OAC patients seen in the Gastroenterology Unit. Blood group information for patients with GORD was obtained from patients' records and the hospital's blood transfusion service. The blood group distribution in the general population was obtained from the National Blood Transfusion Service. The number of expected to observed patients in each blood group for each subtype was compared. Results Two thousand six hundred and ten NER, 2813 erosive oesophagitis, 568 CLO and 73 OAC patients had a recorded blood group. For RhD positive patients observed proportions in each blood group were similar to expected. The most striking difference was the marked excess of OAC in blood group O, Rhesus negative (P=0.002). Conclusion CLO patients with blood group O, RhD negative carry a disproportionately higher risk of developing OAC. The mechanism is unknown but the finding has practical application in guiding risk stratification and intensity of surveillance.