Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of sildenafil and tadalafil on intraocular pressure in sheep: implications for aqueous humor dynamics.

PURPOSE To determine the effects of vasodilators on intraocular pressure (IOP) and the protein content of sheep aqueous humor (AH), because the vasodilators may increase fluid leakage from the fenestrated capillaries of the ciliary body to the extracellular tissue and directly to the anterior chamber (AC) via the iris, and some senior patients (older than 70) treated with sildenafil have exhibited elevated IOP. METHODS Experiments were performed on domestic sheep residing on a ranch in Argentina. These docile and compliant animals readily swallowed tablets of sildenafil (50 and 100 mg) and tadalafil (20 mg). IOP was monitored by Perkins applanation tonometry in 21 normal sheep receiving orally administered drugs. In addition, paracentesis was performed on six sheep to quantify changes in AH protein levels. RESULTS Ingestion of both sildenafil and tadalafil increased sheep IOP from normal levels of approximately 9 to 11 mm Hg within 1 hour. The IOP elevation was approximately 1.6-fold with both doses of sildenafil. IOP returned to control values within 4 hours. With the longer-lasting vasodilator tadalafil, IOP remained 1.6- to 1.9-fold higher than normal for at least 48 hours and returned to control levels within 4 days. The AH protein content was approximately 39% higher in sheep given 100 mg sildenafil. CONCLUSIONS These data are consistent with a vasodilator-evoked increase in plasma-like fluid in the AC, which likely accounts for the IOP elevation. The results are discussed with a model for AH dynamics that may be of importance to senior individuals treated for vascular diseases with these compounds.
Dimensions of Operational Stress and Forms of Unacceptable Risk-Taking With Small Arms

This research studied the association between dimensions of operational stress, forms of risk-taking with small arms, and possible mediators. Operational threat and negative affect were predictors, unauthorized preparedness and risky games were dependent variables, and safety climate and personality profile from the Eysenck Personality Questionnaire—Revised Short Form were mediators. The participants were 461 compulsory service soldiers in 31 companies. The results revealed that operational threat is related to unauthorized preparedness, and positive–negative affect is related to risky games. Safety climate mediated risky games only. Unauthorized preparedness and risky games were influenced by the interaction of Psychoticism and the Lie scale from the Eysenck Personality Questionnaire—Revised Short Form.
Molecular Analysis of Bacterial Species Associated with Childhood Caries

ABSTRACT Although substantial epidemiologic evidence links Streptococcusmutans to caries, the pathobiology of caries may involve more complex communities of bacterial species. Molecular methods for bacterial identification and enumeration now make it possible to more precisely study the microbiota associated with dental caries. The purpose of this study was to compare the bacteria found in early childhood caries (ECC) to those found in caries-free children by using molecular identification methods. Cloning and sequencing of bacterial 16S ribosomal DNAs from a healthy subject and a subject with ECC were used for identification of novel species or uncultivated phylotypes and species not previously associated with dental caries. Ten novel phylotypes were identified. A number of species or phylotypes that may play a role in health or disease were identified and warrant further investigation. In addition, quantitative measurements for 23 previously known bacterial species or species groups were obtained by a reverse capture checkerboard assay for 30 subjects with caries and 30 healthy controls. Significant differences were observed for nine species: S. sanguinis was associated with health and, in order of decreasing cell numbers, Actinomycesgerencseriae, Bifidobacterium, S. mutans, Veillonella, S. salivarius, S. constellatus, S. parasanguinis, and Lactobacillusfermentum were associated with caries. These data suggest that A. gerencseriae and other Actinomyces species may play an important role in caries initiation and that a novel Bifidobacterium may be a major pathogen in deep caries. Further investigation could lead to the identification of targets for biological interventions in the caries process and thereby contribute to improved prevention of and treatment for this significant public health problem.
Evaluation of the toxic activity of anorectic diethylpropion in Chinese hamster ovary cells

Diethylpropion has been available in the market for treating obesity for over 50 years. Refined studies are lacking to fully elucidate its action spectrum. The aim of our study was to evaluate possible toxic effects of anorectic diethylpropion in Chinese hamster ovary (CHO) cells. Comet assay (detects breaks in the DNA strand), micronucleus test (detects clastogenic/aneugenic damage), and cell survival test (detects cytotoxic damage) were used to evaluate the toxic effects. In comet assay, we found that the damage scores with diethylpropion treatments at the concentrations of 20 and 40 μg/mL were more significant ( p < 0.05) than that of the negative control. When assessing the possible aneugenic and/or clastogenic damage caused by the drug in CHO cells, we found no difference ( p > 0.05) in the values of micronucleated cells when comparing different diethylpropion treatments and the negative control. Regarding the cell viability, for all the diethylpropion concentrations tested, higher values ( p < 0.05) of apoptosis were found compared with those of the negative control. In relation to the number of necrotic cells, no difference ( p > 0.05) was noted between the means of the three concentrations of diethylpropion evaluated and the negative control. In the experimental conditions, we conclude that diethylpropion has weak genotoxic and cytotoxic activities.
Acidosis Potentiates the Host Proinflammatory Interleukin-1β Response to Pseudomonas aeruginosa Infection

ABSTRACT Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are increased pro-IL-1β induction and increased caspase-1 activity, the latter being dependent upon a functional type III secretion system of the bacteria and the NLRC4 inflammasome of the host. Using an in vivo peritonitis model, we have validated that the IL-1β inflammatory response is increased in mice in response to P. aeruginosa infection within an acidic microenvironment. These data reveal novel insights into the regulation and exacerbation of inflammatory responses to P. aeruginosa.
Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis.

RATIONALE Gastroesophageal reflux (GER) is highly prevalent in patients with idiopathic pulmonary fibrosis (IPF). Chronic microaspiration secondary to GER may play a role in the pathogenesis and natural history of IPF. OBJECTIVES To investigate the relationship between GER-related variables and survival time in patients with IPF. METHODS Regression analysis was used to investigate the relationship between GER-related variables and survival time in a retrospectively identified cohort of patients with well-characterized IPF from two academic medical centers. MEASUREMENTS AND MAIN RESULTS Two hundred four patients were identified for inclusion. GER-related variables were common in this cohort: reported symptoms of GER (34%), a history of GER disease (45%), reported use of GER medications (47%), and Nissen fundoplication (5%). These GER-related variables were significantly associated with longer survival time on unadjusted analysis. After adjustment, the use of GER medications was an independent predictor of longer survival time. In addition, the use of gastroesophageal reflux medications was associated with a lower radiologic fibrosis score. These findings were present regardless of center. CONCLUSIONS The reported use of GER medications is associated with decreased radiologic fibrosis and is an independent predictor of longer survival time in patients with IPF. These findings further support the hypothesis that GER and chronic microaspiration may play important roles in the pathobiology of IPF.
A lifting approach to models of opinion dynamics with antagonisms

Different recent works have studied polarized versions of models of opinion dynamics, in which an agent opinion can be attracted by the opinions of some agents and by the opinions opposite to those of some others, representing a form of antagonism. We show that these systems correspond to the projection of specific trajectories of classical opinion dynamics systems involving twice as many agents, to which a large number of existing results apply. We take advantage of this to prove several convergence results for models with antagonisms, extending those previously available. Our approach can be applied in both discrete and continuous time.
Molecular markers in Paget disease of the breast

Molecular markers are increasingly being analyzed in tumor specimens because of their relevance to both prognosis and choice of therapy. Paget disease of the breast is an uncommon form of breast cancer, in which molecular markers have not been well characterized. The objective of this study was to investigate the expression of c‐erbB‐2, p53, Ki‐67, Cyclin D1, Bcl‐2, estrogen receptors (ER), and progesterone receptors (PR) in mammary Paget disease.
Psychological Models of Suicide

Suicidal behavior is highly complex and multifaceted. Consequent to the pioneering work of Durkheim and Freud, theoreticians have attempted to explain the biological, social, and psychological nature of suicide. The present work presents an overview and critical discussion of the most influential theoretical models of the psychological mechanisms underlying the development of suicidal behavior. All have been tested to varying degrees and have important implications for the development of therapeutic and preventive interventions. Broader and more in-depth approaches are still needed to further our understanding of suicidal phenomena.
Modification by Acetylcholine of the Response of Rat Mesenteric Arteries to Sympathetic Stimulation

The aim of this study was to determine the effect of varying concentrations of acetylcholine on the vasoconstriction of the perfused mesenteric arteries of the rat caused by stimulation of their sympathetic postganglionic nerves. Perfusion was carried out with a peristaltic pump, and the constriction caused by stimulation was measured by the rise of pressure in the cannula tied in the artery. Two effects were found. At rates of stimulation between 2 and 8/sec, acetylcholine added to the perfusion fluid in very low concentrations (50 pg/ml) caused an increase in the vasoconstriction. An increase was also caused by adding a concentration of 2 ng/ml for 15 seconds. If, however, this or a greater concentration was added for a longer time, it had the opposite effect and the vasoconstriction was greatly reduced or blocked. This reduction or block was not due in the main to a reduction or block of the vasoconstrictor action of norepinephrine. Block of response to stimulation was also produced by guanethidine. The block produced by acetylcholine resembled the block produced by guanethidine in two respects. The block was removed by raising the calcium concentration, and it was also removed by adding d-amphetamine to the perfusion fluid. The block produced by a given concentration of acetylcholine was abolished by a much higher concentration of atropine or hyoscine.
Call Path Profiling of Monotonic Program Resources in UNIX

Practical performance improvement of a complex program must be guided by empirical measurements of its resource usage. Essentially, the programmer wants to know where in the source code the program is inefficient and why this is so. The process interface of UNIX System V (proc(4)) provides access to the raw data (e.g. time, faults, traps, and system calls) necessary to answering the why question, but gives no guidance in answering the where question. This paper describes a novel approach to the latter, Call Path Profiling, which is both more informative and more closely tied to the process of program optimization than either trace-based or prof/gprof-like approaches. In addition, by viewing consumption of a resource as the ticking of a clock, we generalize the interval-based sampling approach of time profilers to arbitrary monotonic resources. The approach is embodied in several prototypes, including CPPROF which operates under System V.
SPRR1 gene induction and barrier formation occur as coordinated moving fronts in terminally differentiating epithelia.

Stratified, terminally differentiated epithelia, such as epidermis and oral epithelia, provide protective barriers against the environment. We recently developed wholemount assays that demonstrate epidermal barrier function during late gestation and showed that epidermal barrier forms at specific sites (epidermal initiation sites), and then spreads around the body as apparent moving fronts. We now ask if this is a fundamental and widespread mode of epithelial developmental change. If so, then the pattern should be apparent when assaying for developmental change other than barrier institution (e.g., gene induction) and similar types of patterned change should be apparent in other types of epithelia. In this study we demonstrate patterned barrier function in a range of additional stratified epithelia from the oral cavity and show that the gene induction pattern of a stratum corneum precursor small proline-rich region protein 1 (SPRR1) precedes barrier function and occurs in the barrier pattern, i.e., gene induction occurs first at initiation sites and propagates across epithelia as apparent moving fronts. These results demonstrate that late gestational developmental change in multiple terminally differentiating epithelia occurs via initiation sites and moving fronts. The pattern precedes barrier formation and results in a developmental gradient that influences gene induction.
Medical treatments in the short term management of reflux oesophagitis.

BACKGROUND Oesophagitis arises when reflux of acid from the stomach into the oesophagus causes mucosal inflammation. It is a common problem and a systematic review on the optimum treatment would be useful. OBJECTIVES To assess the effectiveness of proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), prokinetic therapy, sucralfate and placebo in healing oesophagitis or curing reflux symptoms or both. To compare adverse effects with the different treatments. SEARCH STRATEGY We searched MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and the National Research Register until December 2004 and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA Randomised controlled trials assessing the healing of oesophagitis or reflux symptoms or both. Treatment involving PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo for 2 and 12 weeks. DATA COLLECTION AND ANALYSIS Two reviews independently assessed trial quality and extracted data. MAIN RESULTS We included 134 trials involving 35,978 oesophagitis participants. Five RCTs evaluated standard dose of PPI versus placebo in 965 participants. There was a statistically significant benefit of taking standard dose PPI therapy compared to placebo in healing of oesophagitis (RR = 0.22; 95% CI 0.15 to 0.31). Ten RCTs reported on the outcome for H2RA versus placebo evaluating 1241 participants. There was statistically significant benefit of taking H2RA compared to placebo in healing of oesophagitis (RR 0.74,95% CI = 0.66 to 0.84). Three RCTs evaluated prokinetic therapy versus placebo in 198 participants. There was no statistically significant benefit of taking prokinetic therapy compared to placebo in healing of oesophagitis (RR 0.71, 95% CI 0.46 to 1.10). Twenty six RCTs reported the outcome for PPI versus H2RA or H2RA plus prokinetics, evaluating 4032 participants. There was statistically significant benefit of taking PPI therapy compared to H2RA or H2RA plus prokinetics in healing of oesophagitis (RR 0.51, 95% CI 0.44 to 0.59). AUTHORS' CONCLUSIONS PPI therapy is the most effective therapy in oesophagitis but H2RA therapy is also superior to placebo. There is a paucity of evidence on prokinetic therapy but no evidence that it is superior to placebo.
Relationship between the Qt and the Wais

Quick Test IQs (combination form) correlated highly with WAIS Full Scale IQ for 43 neuropsychiatric inpatients. A significantly higher relationship was found between WAIS Verbal IQ and QT scores than between WAIS Performance IQ and QT scores. The results were interpreted as supporting the position that the QT is a good estimate of intelligence which is highly resistant to the reduction in performance on some intelligence test tasks often associated with psychopathology.
Age-differences in cognitive flexibility when overcoming a preexisting bias through feedback

ABSTRACT Introduction: Older adults are often worse than younger adults at adapting to changing situational demands, and this difference is commonly attributed to an age-related decline in acquiring and updating information. Previous research on aging and cognitive flexibility has used measures that require adapting to novel associations learned during a laboratory task (e.g., choice X led to positive outcomes but now leads to negative outcomes). However, in everyday life people must frequently overcome associations based on preexisting beliefs and biases (e.g., you like to eat cake, but your doctor said to limit your sugar intake). The goal of the present study was to examine possible age-differences in overcoming a preexisting bias and determine whether age-related changes in the acquisition and updating of information influence this form of flexibility. Method: Older (n = 20) and younger (n = 20) adults completed a novel task in which repeated choices were made between a sure option (gain or loss) and one of two risky options that were initially ambiguous. Optimal performance required overcoming a framing bias toward being risk seeking to avoid a sure loss and risk averse when offered a sure gain. Probe questions assessed knowledge of choice outcomes, while skin conductance assessed physiological reactions to choices and choice outcomes. Results: Both older and younger adults demonstrated flexibility by reducing the impact of bias over trials, but younger adults had better performance overall. Age-differences were associated with distinct aspects of processing. Young adults had more precise knowledge of choice outcomes and developed skin conductance responses in anticipation of bad choices that were not apparent in older adults. Conclusions: Older adults showed significant improvement over trials in their ability to decrease bias-driven choices, but younger showed greater flexibility. Age-differences in task performance were based on differences in learning and corresponding representations of task-relevant information.
Personal and social influences on loneliness: the mediating effect of social provisions

Building on several recent investigations, we propose a theoretical model in which the effects on loneliness of an individual's personality characteristics and features of his or her social network are mediated by the availability of specific social provisions. More than 500 college students completed questionnaires assessing personality variables, social network characteristics, structural features of the social environment, and three kinds of loneliness (global, social, and emotional). In keeping with the model, personality and social network features were related significantly and substantially to the availability of social provisions; provisions, in turn, were associated substantially with all three kinds of loneliness. Moreover, the direct effects of personality and network features on loneliness were explained largely by social provisions
KRAS mutations affect prognosis of non-small-cell lung cancer patients treated with first-line platinum containing chemotherapy

KRAS mutations seem to indicate a poor outcome in Non-Small-Cell Lung Cancer (NSCLC) but such evidence is still debated. The aim of this planned ancillary study within the TAILOR trial was to assess the prognostic value of KRAS mutations in advanced NSCLC patients treated with platinum-based first-line chemotherapy. Patients (N = 540), enrolled in the study in 52 Italian hospitals, were centrally genotyped twice in two independent laboratories for EGFR and KRAS mutational status. Of these, 247 patients were eligible and included in the present study. The primary endpoint was overall survival (OS) according to KRAS mutational status in patients harboring EGFR wild-type. Sixty (24.3%) out of 247 patients harbored KRAS mutations. Median OS was 14.3 months and 10.6 months in wild-type and mutated KRAS patients, respectively (unadjusted Hazard Ratio [HR]=1.41, 95%Confidence Interval [CI]: 1.03-1.94 P = 0.032; adjusted HR=1.39, 95%CI: 1.00-1.94 P = 0.050). This study, with all consecutive patients genotyped, indicates that the presence of KRAS mutations has a mild negative impact on OS in advanced NSCLC patient treated with a first-line platinum-containing regimen. Trial Registration: clinicaltrials.gov identifier NCT00637910
Dose effects and comparative effectiveness of extended release dexmethylphenidate and mixed amphetamine salts.

OBJECTIVE To compare the dose effects of long-acting extended-release dexmethylphenidate (ER d-MPH) and ER mixed amphetamine salts (ER MAS) on attention-deficit/hyperactivity disorder (ADHD) symptom dimensions, global and specific impairments, and common adverse events associated with stimulants. METHODS Fifty-six children and adolescents with ADHD participated in an 8-week, double-blind, crossover study comparing ER d-MPH (10, 20, 25-30 mg) and ER MAS (10, 20, 25-30) with a week of randomized placebo within each drug period. Efficacy was assessed with the ADHD Rating Scale-IV (ADHD-RS-IV), whereas global and specific domains of impairment were assessed with the Clinical Global Impressions Severity and Improvement Scales and the parent-completed Weiss Functional Impairment Scale, respectively. Insomnia and decreased appetite, common stimulant-related adverse events, were measured with the parent-completed Stimulant Side Effects Rating Scale. RESULTS Both ER d-MPH and ER MAS were associated with significant reductions in ADHD symptoms. Improvement in Total ADHD and Hyperactivity/Impulsivity symptoms were strongly associated with increasing dose, whereas improvements in Inattentive symptoms were only moderately associated with dose. About 80% demonstrated reliable change on ADHD-RS-IV at the highest dose level of ER MAS compared with 79% when receiving ER d-MPH. Decreased appetite and insomnia were more common at higher dose levels for both stimulants. Approximately 43% of the responders were preferential responders to only one of the stimulant formulations. CONCLUSIONS Dose level, rather than stimulant class, was strongly related to medication response.