Miracle-dz/UniFAR-FTUs huggingface dataset:
Enantiospecific toxicity of the β‐blocker propranolol to Daphnia magna and Pimephales promelas

Propranolol is a widely prescribed, nonselective β‐adrenergic receptor–blocking agent. Propranolol has been detected in municipal effluents from the ng/L to the low‐μg/L range. Like many therapeutics and other aquatic contaminants, propranolol is distributed as a racemic mixture ((R,S)‐propranolol hydrochloride). Although the (S)‐enantiomer is the most active form in mammals (up to 100‐fold difference), no information is available regarding the enantiospecific toxicity of propranolol to aquatic organisms. Acute and chronic studies were conducted with Daphnia magna and Pimephales promelas to determine enantiospecific toxicity of propranolol to a model aquatic invertebrate and vertebrate, respectively. Also, enantiospecific effects of propranolol on D. magna heart rate were examined. Propranolol treatment levels were verified using high‐performance liquid chromatography/mass spectrometry. Acute (48‐h) responses of both organisms were similar for all enantiomer treatments. Chronic P. promelas responses to propranolol enantiomers followed the hypothesized relationship of (S)‐propranolol being more toxic than (R)‐propranolol, but chronic D. magna responses did not. This is potentially the result of a lack of β‐type receptors in cladocerans. No enantiospecific effects on daphnid heart rate were observed in acute exposures. Interestingly, some propranolol enantiomer treatments produced significant increases in reproduction before causing reproduction to decrease at higher treatment levels. To our knowledge, this research represents the first study of enantiospecific toxicity of chiral pharmaceutical pollutants.
The Game of Monetary Policy, Inflation and Economic Growth

Ghana has been confronted with series of economic problems to the extent of calling on the IMF for a bailout after every eight years. This situation has persisted in spite of various monetary authority stabilization policies. This paper therefore focuses on investigating the games of monetary policy, inflation and economic growth of the Ghanaian economy for the period of 1982-2017. Using Autoregressive Distributed Lag (ARDL) to cointegration model, it was revealed from the study that in the long run interest rate significantly influences economic growth but in a negative direction, implies that a higher interest rate has the tendency to restrained economic growth and inflationary pressures. In relation to exchange rate, the long run result indicates an insignificant negative effect on economic growth. The general results suggest that macroeconomic variable which influences economic growth is interest rate and exchange rate. This is evidence that macroeconomic instabilities have significant effect on economic growth. This therefore calls for fiscal discipline and autonomy power to the Bank of Ghana with less interreference from the government to enable the smooth implementation of monetary policies without any string of politics attached.
Cross‐compartment proteostasis regulation during redox imbalance induced ER stress

Imbalance in protein homeostasis in specific subcellular organelles is alleviated through organelle‐specific stress response pathways. As a canonical example of stress activated pathway, accumulation of misfolded proteins in ER activates unfolded protein response (UPR) in almost all eukaryotic organisms. However, very little is known about the involvement of proteins of other organelles that help to maintain the cellular protein homeostasis during ER stress. In this study, using iTRAQ‐based LC–MS approach, we identified organelle enriched proteins that are differentially expressed in yeast (Saccharomyces cerevisiae) during ER stress in the absence of UPR sensor Ire1p. We have identified about 750 proteins from enriched organelle fraction in three independent iTRAQ experiments. Induction of ER stress resulted in the differential expression of 93 proteins in WT strains, 40 of which were found to be dependent on IRE1. Our study reveals a cross‐talk between ER‐ and mitochondrial proteostasis exemplified by an Ire1p‐dependent induction of Hsp60p, a mitochondrial chaperone. Thus, in this study, we show changes in protein levels in various organelles in response to ER stress. A large fraction of these changes were dependent on canonical UPR signalling through Ire1, highlighting the importance of interorganellar cross‐talk during stress.
Corporate social responsibility, firm performance, and firm risk: the role of firm reputation

ABSTRACT This paper examines the impacts of firms’ corporate social responsibility (CSR) engagements on firm performance and firm risk, and explores the underlying mechanisms. We empirically demonstrate the active effect of CSR activities on firm performance improvement and risk mitigation. We further examine the role of firm reputation with published data from Fortune’s Most Admired Companies list. We document a significant positive association between CSR and firm reputation, and find that firm reputation is positively related to firm performance while negatively related to firm risk. Based on our analyses, firm reputation mediates the effects of CSR on firm performance and firm risk. This study contributes to the CSR literature through exploring CSR-outcomes relationships with published reputation data.
A ten-year review of the effect of OBRA-87 on psychotropic prescribing practices in an academic nursing home.

OBJECTIVE The Omnibus Budget Reconciliation Act of 1987 (OBRA-87) included provisions for regulating the use of psychotropic medication, particularly antipsychotics, in long-term-care facilities. The study examined the effect of OBRA-87 on patterns of prescribing of psychotropic medication in a 514-bed nursing home affiliated with a large medical school. METHODS Computerized pharmacy records for the ten-year period from March 1984 through July 1994 were retrospectively reviewed to identify orders written for psychotropic medications and to determine the percentage of nursing home residents who received prescriptions for those agents and the average daily dose of the most frequently prescribed agents. RESULTS During the period before implementation of the regulations, the percentages of residents who received antidepressants, anxiolytic and sedative-hypnotic medications, and antipsychotic medications were stable. After implementation, prescription of antidepressants increased significantly, coinciding with a reduction in prescription of anxiolytics and sedative-hypnotics and a substantial decrease in prescription of antipsychotics. The total number of residents who received any type of psychotropic medication decreased, and over time a trend toward prescription of agents recommended for geriatric use, such as short-acting benzodiazepines and tertiary tricyclic antidepressants, emerged. CONCLUSIONS The changes that resulted from the OBRA-87 regulations reffect both the restrictions placed on classes of medication and the prevalence of psychiatric disorders in the nursing home. In this facility, OBRA-87 appears to have served as an impetus for clinical review and change in practice style.
Press–pulse interactions: effects of warming, N deposition, altered winter precipitation, and fire on desert grassland community structure and dynamics

Global environmental change is altering temperature, precipitation patterns, resource availability, and disturbance regimes. Theory predicts that ecological presses will interact with pulse events to alter ecosystem structure and function. In 2006, we established a long‐term, multifactor global change experiment to determine the interactive effects of nighttime warming, increased atmospheric nitrogen (N) deposition, and increased winter precipitation on plant community structure and aboveground net primary production (ANPP) in a northern Chihuahuan Desert grassland. In 2009, a lightning‐caused wildfire burned through the experiment. Here, we report on the interactive effects of these global change drivers on pre‐ and postfire grassland community structure and ANPP. Our nighttime warming treatment increased winter nighttime air temperatures by an average of 1.1 °C and summer nighttime air temperature by 1.5 °C. Soil N availability was 2.5 times higher in fertilized compared with control plots. Average soil volumetric water content (VWC) in winter was slightly but significantly higher (13.0% vs. 11.0%) in plots receiving added winter rain relative to controls, and VWC was slightly higher in warmed (14.5%) compared with control (13.5%) plots during the growing season even though surface soil temperatures were significantly higher in warmed plots. Despite these significant treatment effects, ANPP and plant community structure were highly resistant to these global change drivers prior to the fire. Burning reduced the cover of the dominant grasses by more than 75%. Following the fire, forb species richness and biomass increased significantly, particularly in warmed, fertilized plots that received additional winter precipitation. Thus, although unburned grassland showed little initial response to multiple ecological presses, our results demonstrate how a single pulse disturbance can interact with chronic alterations in resource availability to increase ecosystem sensitivity to multiple drivers of global environmental change.
United States Anesthesiologists over 50: Retirement Decision Making and Workforce Implications

Background:Anesthesiology is among the medical specialties expected to have physician shortage. With little known about older anesthesiologists’ work effort and retirement decision making, the American Society of Anesthesiologists participated in a 2006 national survey of physicians aged 50–79 yr. Methods:Samples of anesthesiologists and other specialists completed a survey of work activities, professional satisfaction, self-defined health and financial status, retirement plans and perspectives, and demographics. A complex survey design enabled adjustments for sampling and response-rate biases so that respondents’ characteristics resembled those in the American Medical Association Physician Masterfile. Retirement decision making was modeled with multivariable ordinal logistic regression. Life-table analysis provided a forecast of likely clinical workforce trends over an ensuing 30 yr. Results:Anesthesiologists (N = 3,222; response rate = 37%) reported a mean work week of 49.4 h and a mean retirement age of 62.7 yr, both values similar to those of other older physicians. Work week decreased with age, and part-time work increased. Women worked a shorter work week (mean, 47.9 vs. 49.7 h, P = 0.024), partly due to greater part-time work (20.2 vs. 13.1%, P value less than 0.001). Relative importance of factors reported among those leaving patient care differed by age cohort, subspecialty, and work status. Poor health was cited by 64% of anesthesiologists retiring in their 50s as compared with 43% of those retiring later (P = 0.039). Conclusions:This survey lends support for greater attention to potentially modifiable factors, such as workplace wellness and professional satisfaction, to prevent premature retirement. The growing trend in part-time work deserves further study.
Polymorphic Alu insertions in human populations of Bosnia and Herzegovina

Background: From a demographic and genetic perspective, Bosnia and Herzegovina is interwoven with a number of differentially isolated local populations of indigenous people with different population and religious backgrounds. Aim: In order to estimate their genetic structure, this study investigated the frequencies of 10 Alu polymorphic loci in 10 regional populations distributed across Bosnia and Herzegovina. Genetic differentiation among the three major population groups in Bosnia and Herzegovina was estimated. Subjects and methods: DNA from 506 unrelated individuals was extracted from buccal swabs using the salting-out extraction method. Each DNA sample was PCR-amplified using locus-specific primers. Results: Gene diversity values showed similarity in all analysed populations and ranged from 0.305–0.328. FST values for all loci showed that most variability is found within populations. Overall FST for all loci and AMOVA indicated that most variability was detected within populations. Conclusion: Results of this study are in agreement with the previous studies, indicating that the three populations in Bosnia and Herzegovina have the same genetic background. There is no significant differentiation among regional populations, pointing to absence of geographic influence. The Bosnian population is clearly located within the European gene pool.
Rural Residence Is Associated With Delayed Care Entry and Increased Mortality Among Veterans With Human Immunodeficiency Virus Infection

Context:Rural persons with human immunodeficiency virus (HIV) face many barriers to care, but little is known about rural-urban variation in HIV outcomes. Objective:To determine the association between rural residence and HIV outcomes. Design, Setting, and Patients:Retrospective cohort study of mortality among persons initiating HIV care in Veterans Administration (VA) during 1998–2006, with mortality follow-up through 2008. Rural residence was determined using Rural Urban Commuting Area codes. We identified 8489 persons initiating HIV care in VA with no evidence of combination antiretroviral therapy (cART) use at care entry, of whom 705 (8.3%) were rural. Outcome Measure:All-cause mortality. Results:At care entry, rural persons were less likely than urban persons to have drug use problems (10.6% vs. 19.5%, P < 0.001) or hepatitis C (34.3% vs. 41.2%, P = 0.001), but had more advanced HIV infection (median CD4: 186 vs. 246, P < 0.001). By 2 years after care entry, 5874 persons had initiated cART (528 rural [74.9%] and 5346 urban [68.7%], P = 0.001), and there were 1022 deaths (108 rural [15.3%] and 914 urban [11.7%], P = 0.004). The mortality hazard ratio for rural persons compared with urban was 1.34 (95% confidence interval: 1.05–1.69). The hazard ratio decreased to 1.18 (95% confidence interval: 0.93–1.50) after adjustment for HIV severity (CD4 and AIDS-defining illnesses) at care entry, and was 1.17 (95% confidence interval: 0.92–1.50) in a model adjusting for age, HIV severity at care entry, substance use, hepatitis B or C diagnoses, and cART initiation. Conclusions:Later entry into care drives increased mortality for rural compared with urban veterans with HIV. Future studies should explore the person, care system, and community-level determinants of late care entry for rural persons with HIV.
Pregnancy outcome among grand multiparous women at the University of Maiduguri Teaching Hospital: A case control study

Summary Grand multiparity has been described as an independent risk factor for a variety of obstetric complications, especially in developing countries with inadequate health facilities. This case control study compares the pregnancy outcomes of grand multiparas with that of multiparas at the University of Maiduguri Teaching Hospital over a period of 1 year. The labour ward records and patients' case notes were used to extract information. Multivariate analysis created a model of the adverse factors that were independently associated with grand multiparity after control for confounding effects of age and other variables. During the period of study, there were 1,865 deliveries, out of which 350 were grandmultiparas, a rate of 18.8%. Out of the 350 grandmultiparas, 91 were excluded, leaving 259 (74%) patients which were used for the study. The multivariate analysis shows that compared with the multiparas, the grand multiparas were more likely to be uneducated, have abruptio placentae, precipitate labour and stillbirth but were less likely to have prolonged labour, episiotomy, placenta praevia, require operative deliveries or be anaemic at booking. Grandmultiparity was found to be associated with adverse pregnancy outcome. This finding has implications for practitioners caring for these women in our environment.
Okadaic acid and phorbol esters: comparative effects of these tumor promoters on cell transformation, intercellular communication and differentiation in vitro.

Okadaic acid is a non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoter in the mouse skin carcinogenesis system. Here we report on the in vitro activity of okadaic acid in 3 assay systems: BALB/c 3T3 cell transformation, gap junctional intercellular communication (GJIC) in various cell types, and inhibition of induction of differentiation of Friend virus-transformed murine erythroleukemia (MEL) cells. The activity of okadaic acid was compared to that of the phorbol ester tumor promoters TPA and phorbol-12,13-didecanoate (PDD). In a test system involving a 2-week exposure of BALB/c 3T3 cells following 3-methylcholanthrene initiation, okadaic acid at a concentration of 10 ng/ml was equipotent to PDD as a promoter of cell transformation (4.9 and 3.7 foci/dish, respectively). Longer exposures to okadaic acid resulted in cytotoxicity. Okadaic acid-generated as well as PDD-generated transformed foci displayed a selective lack of GJIC between focus cells and surrounding normal cells, i.e., transformed cells communicate among themselves but not with surrounding cells. However, in contrast to TPA, there was no inhibition by okadaic acid, except at toxic doses, of homologous GJIC in BALB/c 3T3 cells or human and mouse keratinocytes. Furthermore, okadaic acid, unlike TPA, did not inhibit MEL cell differentiation. Together, these results indicate that okadaic acid acts as a promoter of cell transformation but that its mechanism of action is different from that of the phorbol ester tumor promoters.
Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

The aim of the present review is to synthesise and summarise our recent knowledge on the involvement of cholecystokinin (CCK) and gastrin peptides and their receptors in the control of digestive functions and more generally their role in the field of nutrition in mammals. First, we examined the release of these peptides from the gut, focusing on their molecular forms, the factors regulating their release and the signalling pathways mediating their effects. Second, general physiological effects of CCK and gastrin peptides are described with regard to their specific receptors and the role of CCK on vagal mucosal afferent nerve activities. Local effects of CCK and gastrin in the gut are also reported, including gut development, gastrointestinal motility and control of pancreatic functions through vagal afferent pathways, including NO. Third, some examples of the intervention of the CCK and gastrin peptides are exposed in diseases, taking into account intervention of the classical receptor subtypes (CCK1 and CCK2 receptors) and their heterodimerisation as well as CCK-C receptor subtype. Finally, applications and future challenges are suggested in the nutritional field (performances) and in therapy with regards to the molecular forms or in relation with the type of receptor as well as new techniques to be utilised in detection or in therapy of disease. In conclusion, the present review underlines recent developments in this field: CCK and gastrin peptides and their receptors are the key factor of nutritional aspects; a better understanding of the mechanisms involved may increase the efficiency of the nutritional functions and the treatment of abnormalities under pathological conditions.
Childhood Head Injury and Metacognitive Processes in Language and Memory

We studied the metacognitive functioning of children with severe and mild traumatic brain injury (TBI) and typically developing children. To test metacognition for memory, children were tested on a modified Judgment of Learning task. We found that children with severe TBI were impaired in their ability to predict recall of specific items prior to study-recall trials, but were unimpaired in predicting recall on a delayed test when the judgment was made after study-recall trials. Metacognitive knowledge impairment for memorial abilities was also demonstrated in children with severe TBI by poor estimation of memory span and exaggerated overconfidence in performance. To test metacognition within the language domain, we gave children a sentence anomaly detection and repair task in which spoken sentences were monitored for semantic anomalies. Children with severe TBI were impaired on the detection of semantic anomalies, especially under conditions of high memory load. However, metalinguistic knowledge in the form of adequate repairs of anomalous sentences, was preserved. Results are discussed in terms of effects of age at test and injury severity.
Heterogeneous expression of Wnt/β‐catenin target genes within colorectal cancer

Invasion of common colorectal adenocarcinomas is coupled with a transient loss of epithelial differentiation of tumor cells. Previously, we have shown that dedifferentiated tumor cells at the invasive front (IF) accumulate the transcriptional activator β‐catenin in the nucleus, in contrast to cells of the tumor center. To characterize the cells of these two morphogenic tumor areas, gene expression profiling was performed. Our study demonstrates that intratumorous heterogeneity in colorectal cancer correlates with differential expression of 510 genes between the central tumor region (TC) and the IF. Many genes differentially expressed at the IF are involved in cellular invasion processes like cell motility, cell adhesion and extracellular matrix interaction. This in vivo analysis shows overexpression of known Wnt/β‐catenin target genes either in the entire tumor tissue (compared to normal mucosa) or specifically at the IF. Thus, even though all tumor cells overexpress β‐catenin, the existence of at least 2 groups of Wnt/β‐catenin target genes selectively activated in different tumor regions is suggested. The concomitant high expression of inflammation‐ and tissue repair‐related genes at the IF supports the hypothesis that an inflammation‐activated microenvironment may trigger selective Wnt/β‐catenin target gene expression and contribute to the malignant progression of colorectal cancer. © 2007 Wiley‐Liss, Inc.
Detection of hepatitis C virus RNA in hepatocellular carcinoma by in situ hybridization

Background. Hepatocellular carcinoma frequently is associated with chronic hepatitis C virus (HCV) infection. The presence of HCV in hepatocellular carcinoma has been detected by reverse‐transcription polymerase chain reaction of antigenomic HCV RNA, a tissue‐specific replicative form of the virus. Now, however, this method of detecting the presence of HCV has been invalidated by reports of antigenomic RNA in the blood or in peripheral blood mononuclear cells.