Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional characterization of RNA-dependent DNA polymerase and RNase H activities of a recombinant HIV reverse transcriptase.

The DNA polymerase and RNase H activities of HIV reverse transcriptase are both essential for HIV replication. Although the two activities are both catalyzed by a single polypeptide, they are physically separate; i.e., the DNA polymerase resides in the N-terminal domain whereas the RNase H is localized in the C-terminal domain. The present study was undertaken to characterize the enzymatic properties of these two activities and to determine whether the two catalytic sites are also functionally distinct. We have observed that EGTA specifically stimulates, whereas CaCl2 selectively inhibits, the RNA-dependent DNA polymerase activity but that neither compound has any effect on the RNase H activity of a recombinant HIV reverse transcriptase. The stimulation of the DNA polymerase activity by EGTA is dependent on the Mg2+ concentration; the greatest stimulation is observed at low Mg2+ concentrations. Similarly, the inhibition of DNA polymerase activity by Ca2+ is influenced by Mg2+ concentration. Ca2+ inhibition can be reversed by increasing Mg2+ concentrations, suggesting the possibility that CaCl2 inhibits the reverse transcriptase activity by competing for a metal-binding site on the enzyme. The pyrophosphate analogue phosphonoformate selectively inhibits the polymerase activity but not the RNase H activity of HIV reverse transcriptase. In contrast, the RNase H activity can be selectively inhibited by deoxyadenosine 5'-monophosphate, whereas the DNA polymerase activity is not inhibited. These results suggest that the DNA polymerase and RNase activities are not only physically separate but that they are also functionally distinct.
Rifampin–sirolimus–voriconazole interaction in a hematopoietic cell transplant recipient

Purpose Patients undergoing hematopoietic cell transplantation are treated with multiple medications, potentially complicated by drug–drug interactions. Drug interactions with sirolimus, voriconazole, and rifampin are particularly difficult because of the complex and simultaneous enzyme inhibition and induction mechanisms. We report a hematopoietic cell transplantation patient receiving sirolimus and voriconazole who was given rifampin while being treated for presumed methicillin-resistant Staphylococcus aureus meningitis. Summary A 31 year-old female received a nonmyeloablative allogeneic umbilical cord hematopoietic cell transplantation for myelodysplastic syndrome transformed to acute myeloid leukemia (AML). Her graft versus host disease and antifungal prophylaxis included sirolimus and voriconazole, respectively. Therapeutic drug monitoring prior to admission revealed a stable outpatient sirolimus regimen of 0.4 mg orally daily (trough goal 3–12 mcg/L). She was admitted to the inpatient hematopoietic cell transplantation service and diagnosed with methicillin-resistant Staphylococcus aureus bacteremia and presumed bacterial meningitis 217 days after transplant. Intravenous rifampin and vancomycin were initiated and voriconazole was changed to micafungin. Sirolimus trough concentrations were undetectable two days after starting rifampin. Therapeutic sirolimus concentrations were achieved four days later, at a sirolimus dose of 16–18 mg orally daily. Rifampin was discontinued after nine days and the sirolimus dose was adjusted accordingly, maintaining therapeutic levels throughout follow-up. The patient suffered a flare of chronic skin graft versus host disease requiring etanercept, high-dose systemic steroids, and topical steroids. Conclusion To the best of our knowledge, this is the first report describing the management of sirolimus during the transition from voriconazole inhibition to rifampin induction. Clinicians should be aware of potential drug–drug interactions.
Michael Jackson, Bin Laden and I: Functions of positive and negative, public and private flashbulb memories

This study examined the perceived psychosocial functions of flashbulb memories: It compared positive and negative public flashbulb memories (positive: Bin Laden's death, negative: Michael Jackson's death) with private ones (positive: pregnancy, negative: death of a loved one). A sample of n = 389 young and n = 176 middle-aged adults answered canonical category questions used to identify flashbulb memories and rated the personal significance, the psychological temporal distance, and the functions of each memory (i.e., self-continuity, social-boding, directive functions). Hierarchical regressions showed that, in general, private memories were rated more functional than public memories. Positive and negative private memories were comparable in self-continuity and directionality, but the positive private memory more strongly served social functions. In line with the positivity bias in autobiographical memory, positive flashbulb memories felt psychologically closer than negative ones. Finally, middle-aged adults rated their memories as less functional regarding self-continuity and social-bonding than young adults. Results are discussed regarding the tripartite model of autobiographical memory functions.
Effects of Alchemilla vulgaris and glycerine on epithelial and myofibroblast cell growth and cutaneous lesion healing in rats

Wound‐healing properties have been suggested for Alchemilla vulgaris. Since epithelial and myofibroblast cell growth is required for wound healing, the effects of A. vulgaris on cell growth were investigated in Chang liver and Madin Darby Bovine Kidney (MDBK) epithelial cell lines and rat aortic myofibroblast cultures. Putative healing properties were investigated on dorsal circular 8 mm excisional skin lesions in adult male rats. Cell numbers increased with 0.1–1% A. vulgaris, attaining 21.3 ± 2.1%, 15.5 ± 2.25% and 10.6 ± 0.6% in MDBK, myofibroblast and Chang liver cells, respectively (p < 0.005). No morphological changes or cytotoxicity were noted. In rats A. vulgaris (3%)‐treated lesions were significantly decreased in diameter by 10.0 ± 0.7% (p < 0.005) after 2 days of treatment. On day 3 of treatment, the lesion diameter was significantly reduced by 15.9 ± 1.1% in glycerine vehicle‐treated rats compared with distilled water (p < 0.005), whereas that in A. vulgaris‐treated rats was reduced further by 23.2 ± 1.4% (p < 0.005). Glycerine alone significantly reduced the lesion diameter between days 3 and 5 but complete healing occurred a day earlier in A. vulgaris‐treated rats. The results demonstrate wound‐healing properties of A. vulgaris associated with promitotic activity in epithelial cells and myofibroblasts. Copyright © 2007 John Wiley & Sons, Ltd.
Efficacy and Safety of a Metabolic Modulator Drug in Chronic Stable Angina: Review of Evidence from Clinical Trials

A number of newer antianginal agents, including nicorandil, trimetazidine, and ivabradine, have been synthesized in recent years, but ranolazine, a piperazine derivative that partially inhibits fatty acid oxidation and the late INa current in animal models, is of particular interest mechanistically. Earlier clinical trials with immediate-release ranolazine led to the current sustained-release version tested in the Monotherapy Assessment of Ranolazine In Stable Angina (MARISA) (n = 193) and Combination Assessment of Ranolazine In Stable Angina (CARISA) trials (n = 823) of patients with chronic angina and severe limitation of exercise capacity (ie, < 5 metabolic equivalents). MARISA was a placebo-controlled, randomized trial that compared ranolazine monotherapy (500 mg, 1000 mg, and 1500 mg, twice daily) to placebo. CARISA was a placebo-controlled trial that randomized patients on background 1-blocker or calcium antagonist therapy to placebo or ranolazine (750 mg or 1000 mg, twice daily). Both studies showed a significant increase in total exercise duration, time to angina onset, and time to 1 mm ST segment depression. The average magnitude of increase in exercise duration over placebo was 29 to 56 seconds at peak and 24 to 46 seconds at trough with the 3 doses tested in MARISA, and 24 to 34 seconds greater than placebo with the 2 doses used in CARISA. The beneficial effect was achieved without clinically important changes in rest or exercise heart rate or blood pressure. Weekly angina attack frequency and nitroglycerin usage were significantly reduced in a dose-dependent manner in the 12-week CARISA trial. Reported adverse effects were similar in MARISA and CARISA and consisted of asthenia, nausea, constipation, and dizziness. Syncope, reported in 8 patients at doses of 1000 mg twice daily or more may be related to attenuation of α-1 receptor activity. The mean QTc interval increased with dose and was less than 10 msec on ranolazine at 1000 mg twice daily. The mortality rates at 1 and 2 years in MARISA and CARISA open-label run-on studies were 2% and less than 5%, acceptable for this high-risk population with limited exercise capacity. In conclusion, clinical trial evidence with ranolazine to date is consistent with its proposed mechanism of action and demonstrates an effective antianginal profile that may benefit patients with severe chronic angina.
Comparison between Ropivacaine and Bupivacaine after Subcutaneous Injection in Pigs: Cutaneous Blood Flow and Surgical Bleeding

In this randomized, blinded study, we sought to determine whether the vasoconstriction produced by ropivacaine after subcutaneous injection is sufficient to decrease surgical bleeding. Anesthesia was induced in seven piglets (weight, 12.2-20.4 kg) with intraperitoneal thiopental and maintained with intravenous methohexital. Five sites were injected with 10 ml of one of the following solutions: 0.25% ropivacaine, 0.25% bupivacaine, either solution plus 5 μg/ml epinephrine, or saline. Another site was left uninjected for control. Capillary blood flow was measured at each site with a laser Doppler before and ten minutes after the injections. An incision 5 cm in length was then made through the dermis, and blood loss was measured over ten minutes. We found no significant differences in capillary blood flow and blood loss between bupivacaine and ropivacaine. Addition of epinephrine decreased capillary blood flow ( p < 0.05) and tended to decrease blood loss. Capillary blood flow correlated with blood loss (r2 = 0.106; p < 0.05). We conclude that, in contrast to previous studies, ropivacaine did not decrease capillary blood flow in our model. Similarly, ropivacaine did not reduce bleeding from surgical incisions. The reason for these surprising results is not clear but is unlikely to be the larger volume of solutions injected because no such effect was observed with saline alone.
International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer.

PURPOSE To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. METHODS SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. RESULTS GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensity. The panel recommended that the following domains be evaluated in a GA: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and presence of geriatric syndromes. Although several combinations of tools and various models are available for implementation of GA in oncology practice, the expert panel could not endorse one over another. CONCLUSION There is mounting data regarding the utility of GA in oncology practice; however, additional research is needed to continue to strengthen the evidence base.
Blood Glucose and Serum Insulin Levels in Lean and Genetically Obese Mice

Fed and 24 hour fasted lean and genetically obese mice (ob/ob) were given a fixed glucose load per gm body weight by intraperitoneal and intragastric administration. Intraperitoneal glucose injection into the obese mice produced a prolonged elevated blood glucose level with a concomitant significant decrease of circulating insulin. Possible interpretations of this observation are discussed. In those obese animals in which glucose was administered intragastrically the fed obese mice had a blood glucose concentration of 450-500 mg% for a period of one hour but there was no increase in circulating insulin, however, in the fasted obese mice in which the glucose concentration was about 350 mg% for one hour, there was a significant increase in the circulating insulin levels. The fed and fasted lean mice showed normal glucose tolerance curves and the expected increase in circulating insulin following either intraperitoneal orintragastric glucose loads. It is concluded that hyperglycaemia in the ob/ob mice is unlikely to be the principal cause of hyperinsulinaemia.
Intimate partner violence in the Caribbean: State, activist and media responses

Violence in the Caribbean is a major public health and criminal justice problem. In some Caribbean countries, women's share of morbidity and mortality due to violence outstrips men's, which demonstrates a reversal in how gender and violence have been typically and globally understood. This morbidity and mortality among women is frequently a consequence of intimate partner violence (IPV). Using qualitative analysis and feminist discourse and narrative analysis on data from Guyana, St. Vincent and the Grenadines and Barbados, the authors of this paper contribute to the growing research on IPV. The central organising questions are how do state, activist and media responses reproduce and/or challenge asymmetrical relations of power and gender, and what does this mean for women's agency in the context of violent relationships. State, activist and media responses reveal how assumptions about gender and IPV contribute to a contradictory context in which women navigate their desired outcomes.
Cultural and Financial Dollarization of Households in Uruguay

In this paper, we analyze factors associated with the financial and cultural dollarization of households in Uruguay. We estimate cultural dollarization with data from the 2013 financial survey of Uruguayan households, particularly using the currency reporting option available to respondents. Financial dollarization, meanwhile, is estimated as the share of US dollar-denominated bank assets in total assets. We find that the level of dollarization of bank savings is mainly explained by the size of savings and household wealth. We also observe that our proxy variable for cultural dollarization is associated with wealth and home ownership. Other factors that influence cultural dollarization are age and years of formal education, which are positively and significantly correlated with the use of the US dollar as a unit of account and asset valuation. Larger households, on the other hand, are less culturally dollarized. The evidence points to the key role played by the pricing system in the dollarization culture.
Insights into Left Ventricular Function from the Time Course of Regional and Global Rotation by Speckle Tracking Echocardiography

Background: Description and quantification of regional left ventricular (LV) rotation and the time course of LV rotation might provide further insight into LV function. Methods: The study comprised 60 healthy volunteers (age 39 ± 15 years, 31 men) in whom complete global and regional LV rotation could be assessed at both the basal and apical LV level with speckle tracking echocardiography, using QLAB advanced quantification software version 6.0 (Philips, Best, The Netherlands). Results: At the LV basal level, a brief counterclockwise rotation from aortic valve opening until 25% ejection was seen in the anterior segments (anterior, anteroseptal, anterolateral) only. Clockwise rotation in the anterior segments at the basal level was decreased as compared to the posterior segments (inferior, inferoseptal, inferolateral) from 25% ejection until aortic valve closure. At the LV apical level, all segments showed a brief clockwise rotation during the isovolumic contraction phase. Also, at this level there were no differences in regional LV rotation at any other moment during the cardiac cycle. There was a marked de‐rotation from the moment of maximal rotation until E‐peak at the LV basal level (79 ± 18%) whereas de‐rotation during this interval was less pronounced at the LV apical level (55 ± 21%). Only at the LV basal level significant linear relationships were seen between the E/A ratio and de‐rotation extent and velocity from mitral valve opening until E‐peak (R2= 0.42 and R2= 0.40, respectively, both P < 0.001). Conclusion: In the normal human heart significant regional differences in LV rotation and de‐rotation exist.
Peritoneal cancer and occupational exposure to asbestos: results from the application of a job-exposure matrix.

BACKGROUND Because of the rarity of peritoneal mesothelioma, occupational risks associated with it have seldom been studied, particularly among women. In this respect, death certificates databases may provide numbers large enough for analysis, although the International Classification of Diseases, 9th revision (ICD-9) does not single out mesothelioma from the rest of peritoneal cancers. The aim of this paper is twofold: to explore occupational risks of peritoneal cancer among men and women, and to test the performance of a job-exposure matrix in detecting its association with asbestos exposure using the occupation and industry reported in the death certificate. METHODS From a large database containing information on the 1984-1992 death certificates of 24 U.S. states, we identified 657 deaths from peritoneal cancer and 6,570 controls who died from non-malignant diseases, 1:10 matched by region, gender, race, and 5-year age group. RESULTS Occupations at risk included insulators among men, and machine operators among women. Among men, we found a significant increase in risk associated with employment in manufacturing industries, such as industrial and miscellaneous chemicals; miscellaneous non-metallic mineral and stone products; construction and material handling machines; and electrical machinery, equipment, and supplies; as well as in services to dwellings and other buildings. Industries at increased risk among women included elementary and secondary schools; miscellaneous retail stores; and publishing and printing. Our job-exposure matrix classified 17 male cases and 3 controls in the high probability category of exposure to asbestos (OR = 61.6). Among men, risk of peritoneal cancer increased significantly by probability and intensity of exposure to asbestos. No such pattern was observed among women. The job-exposure matrix did not classify any female subjects in the high probability or intensity of asbestos exposure. DISCUSSION This study provides evidence that death certificate data and job-exposure matrices are useful tools to observe well-established associations, such as the one existing between peritoneal cancer and asbestos exposure among men, in spite of crude information, disease misclassification, and occupational misclassification. These factors are more likely to preclude meaningful results among women.
Prevalence, Characteristics and Perinatal Outcome of Fetal Ventriculomegaly in 29,000 Pregnancies Followed at a Single Institution

Objective: Our purpose was to assess the impact of prenatally diagnosed ventriculomegaly (VM) on the course of advancing pregnancy and the postnatal outcome of affected fetuses. Methods: In this retrospective survey 109/28,935 (3.8 per 1,000) singleton pregnancies with abnormal width of the fetal lateral ventricle system diagnosed by antenatal ultrasound examination at the University Hospital of Schleswig-Holstein, Campus Lübeck, were reviewed between 1993 and 2007. Clinical data and pregnancy outcome information were derived from a standardized parental questionnaire or from hospital records. Postnatal follow-up was obtained in >90%. Results: Forty-seven cases with isolated VM (IVM; 43%) and 62 fetuses (57%) with nonisolated VM were diagnosed. In the IVM group 19 cases had mild and 28 fetuses severe VM. Of 62 cases with non-IVM there were 32 with mildly dilated ventricles and 30 had severe enlargements. Chromosomal aberrations were present in 5 fetuses (4.6%) of the non-IVM group. Thirty-four pregnancies (31%) were terminated on parental request (10 IVM/24 non-IVM). The risk of abnormal neurodevelopmental outcome was highest in the presence of associated anomalies (irrespective of the extent of dilatation) and in cases with severe IVM (91 and 68%, respectively). In contrast, 13/14 children with mild IVM showed an age-related normal psychomotor behavior. Fetuses with severe VM had a 2.2- (IVM) to 3.6-fold (non-IVM) elevated risk of progressive dilatations compared to mild VM. In our study the fetuses with asymmetrical bilateral IVM tended to have severe ventricular enlargements more often. Conclusions: As reported previously we found a positive association between neurodevelopmental delay and the degree of lateral ventricular dilatation. The presence of additional abnormalities is generally a poor prognostic sign and accompanied by a nonfavorable postnatal outcome.
[Evaluation of bacterial contamination in disinfectants for domestic use].

OBJECTIVE To evaluate disinfectants for domestic use for the presence of bacteria, identify them, and determine their tolerance level to benzalkonium chloride. METHODS Fifty-two samples of commercially available disinfectants for domestic use were acquired at random in the metropolitan area of São Paulo, Brazil, and analyzed to detect the presence of bacterial contaminants. The isolated organisms were identified and their tolerance level to benzalkonium chloride was determined by broth macrodilution method. RESULTS Sixteen (30.77%) of fifty-two disinfectants sampled were contaminated by Gram-negative bacteria, with counts varying between 10(4) and 10(6) UFC/ml. Alcaligenes xylosoxidans, Burkholderia cepacia and Serratia marcescens were the predominant organisms found. The minimum inhibitory concentration (MIC: mg/ml) of benzalkonium chloride for these bacteria were 2.48, 1.23 and 0.30 to S. marcescens, A. xylosoxidans and B. cepacia, respectively. CONCLUSIONS The disinfectant formulation containing quaternary ammonium compounds (QACs) may be exposed to contamination by Gram-negative bacteria. The MICs of benzalkonium chloride against the isolated bacteria were low, indicating that the bacteria grown in culture media without QACs lost their tolerance to this biocide.