Miracle-dz/UniFAR-FTUs huggingface dataset:
Disposition of ropinirole in animals and man.

1. The disposition and metabolic fate of ropinirole, a novel compound indicated for the symptomatic treatment of Parkinson's disease, was studied in the mouse, rat, cynomolgus monkey and man, following oral and intravenous administration of ropinirole hydrochloride. 2. In all species, nearly all of the p.o. administered dose (94%) was rapidly absorbed from the gastrointestinal tract following administration of 14C-ropinirole hydrochloride. In rat and monkey, the compound distributed rapidly beyond total body water and was shown to cross the blood-brain barrier. Blood clearance of the compound was high, approximately equal to one-half the hepatic blood flow in the monkey and similar to the hepatic blood flow in rat. Terminal phase elimination half-lives for the compound were relatively short (0.5 and 1.3 h in rat and monkey respectively), although there was evidence of a second elimination phase in the monkey with an elimination half-life of approximately 5-11 h. Plasma concentrations of ropinirole after the intravenous dose were not determined in the mouse and were below the lower limit of quantification in man (0.08 ng/ml) at the doses used in the studies described in this paper. 3. In both animals and man, ropinirole was extensively metabolized. In the rat, the major metabolic pathway was via hydroxylation of the aromatic ring to form 7-hydroxy ropinirole. In mouse, monkey and man, the major pathway was via N-depropylation. The N-despropyl metabolite was metabolized further to form 7-hydroxy and carboxylic acid derivatives. Metabolites formed in all species were generally metabolized further by glucuronidation. 7-Hydroxy ropinirole is the only metabolite of ropinirole previously shown to possess significant dopamine agonist activity in vivo. In all species, the major route of excretion of ropinirole-related material after oral or intravenous administration of the compound was renal (60-90% of dose).
Influence of Postconcussion Sleep Duration on Concussion Recovery in Collegiate Athletes.

OBJECTIVE To determine whether decreased sleep duration postconcussion influences days to asymptomatic and assessment of performance throughout recovery. DESIGN Prospective. SETTING Institutional Clinical Research Laboratory. PATIENTS Four hundred twenty-three collegiate athletes were diagnosed with concussion. INTERVENTIONS Multidimensional concussion assessment battery was conducted at baseline, within 24 to 48 hours, daily [2-4 days postinjury (PI); symptoms only], once asymptomatic, and after return-to-play. The battery included the following: 22-item symptom checklist, Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and computerized neurocognitive test [Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT)]. MAIN OUTCOME MEASURES We subtracted baseline sleep duration from 24 to 48 hours postconcussion sleep duration and categorized athletes into the following groups: shorter sleep (≤-1 hour), no change (>-1 hour, <+1 hour), and longer sleep (≥+1 hour). A 1-way analysis of variance (ANOVA) was conducted to compare days to asymptomatic and separate mixed-model ANOVAs to compare total symptom scores, SAC total scores, BESS total error scores, and ImPACT composite scores between sleep categories across time points (α = 0.05). RESULTS Sleep groups did not differ in days to asymptomatic. The shorter sleep group had greater symptom severity than no sleep change and longer sleep groups at 24 to 48 hours (shorter: 39.1 ± 20.7; no change: 25.1 ± 18.4, P = 0.007; longer: 25.7 ± 21.8, P = 0.004), and at 2 to 4 days PI (shorter: 21.8 ± 21.8; no change: 10.5 ± 10.8, P = 0.013; longer: 11.9 ± 14.2, P = 0.007), but did not differ at other time points (ie, asymptomatic and return-to-play). Participants with shorter sleep exhibited slower ImPACT reaction times at 24 to 48 hours (shorter: 0.68 ± 0.14; no change: 0.61 ± 0.09, P = 0.016; and longer: 0.62 ± 0.12, P = 0.028) and asymptomatic time points (shorter: 0.62 ± 0.11; no change: 0.56 ± 0.05; P = 0.015). CONCLUSION Postinjury sleep declines may be associated with symptom severity and worsened reaction time during initial stages of recovery or may be the result of the concussion itself. Clinicians should be aware of alterations in sleep duration and manage appropriately to mitigate initial symptom burden postconcussion.
BISHOPS IN LATE ANTIQUE ITALY: SOCIAL IMPORTANCE VS. POLITICAL POWER

Abstract:A popular view of late antique Italy based on the research framework created by Peter Brown asserts that Italian bishops played important political roles as early as the fifth century due to their social power. I analyse fifth- and sixth-century evidence to show that outside of Rome there was no such “rise to power” and that bishops gained social rather than political importance by carrying out their pastoral duties.
Three-Dimensional Scaffolds as a Model System for Neural and Endothelial ‘In Vitro’ Culture

Biomaterials based on the hydrophobic homopolymer poly(ethyl acrylate), PEA, and its copolymers with hydroxyethyl acrylate, p(EA-co-HEA) and methacrylic acid, p(EA-co-MAAc) were prepared as polymeric scaffolds with interconnected pores of 90 microns and tested in vitro as culture substrates and compared for their impact on the differentiation of neural stem cells (NSC) obtained from the subventricular zone (SVZ) of postnatal rats and human endothelial cells (HUVEC). Immunocytochemical staining assay for specific markers show that p(EA-co-MAAc) scaffolds were suitable substrates to promote cell attachment and differentiation of adult NSC and HUVEC cells.
An Investigation of Relationships Between Internal and External Factors Affecting Technology Integration in Classrooms

Abstract Various factors affecting technology integration have been identified, but little research has examined the relationships between factors, especially internal and external ones, and whether they directly or indirectly influenced each other. To fill this research gap, this study examined the significance and relationships of five factors influencing technology integration. A proposed model was tested using structural equation modeling with self-reported data from 223 K–12 school teachers in the United States. The findings demonstrated that perceived benefits and an appropriate budget directly influenced teachers' technology use in classrooms, and teachers' perceived benefits were affected by their confidence in technology integration and professional development. Results from this study suggest that in order to foster teacher technology integration, educators should develop a systematic approach that holistically addresses different needs for various factors.
Lorentz Force Transient Response at Finite Magnetic Reynolds Numbers

In this paper, we investigate the transient response of Lorentz force at finite magnetic Reynolds numbers Rm on an electrically conducting rectangular bar that is strongly accelerated in the presence of a localized magnetic field. This is done through numerical simulations utilizing a coupled finite-difference boundary element approach. The results show good qualitative agreement with existing experiments with a circular cylinder. The Lorentz force rise time is seen to be a linear function of Rm. The linear dependence of Lorentz force on Rm is found to be valid only for low values of Rm, after which the slope decays leading to an apparent saturation in the Lorentz force at sufficiently large values of Rm. Our results provide important information for the development of Lorentz force flow meters for transient flow applications.
Different Biosynthetic Pathways to Fosfomycin in Pseudomonas syringae and Streptomyces Species

ABSTRACT Fosfomycin is a wide-spectrum antibiotic that is used clinically to treat acute cystitis in the United States. The compound is produced by several strains of streptomycetes and pseudomonads. We sequenced the biosynthetic gene cluster responsible for fosfomycin production in Pseudomonas syringae PB-5123. Surprisingly, the biosynthetic pathway in this organism is very different from that in Streptomyces fradiae and Streptomyces wedmorensis. The pathways share the first and last steps, involving conversion of phosphoenolpyruvate to phosphonopyruvate (PnPy) and 2-hydroxypropylphosphonate (2-HPP) to fosfomycin, respectively, but the enzymes converting PnPy to 2-HPP are different. The genome of P. syringae PB-5123 lacks a gene encoding the PnPy decarboxylase found in the Streptomyces strains. Instead, it contains a gene coding for a citrate synthase-like enzyme, Psf2, homologous to the proteins that add an acetyl group to PnPy in the biosynthesis of FR-900098 and phosphinothricin. Heterologous expression and purification of Psf2 followed by activity assays confirmed the proposed activity of Psf2. Furthermore, heterologous production of fosfomycin in Pseudomonas aeruginosa from a fosmid encoding the fosfomycin biosynthetic cluster from P. syringae PB-5123 confirmed that the gene cluster is functional. Therefore, two different pathways have evolved to produce this highly potent antimicrobial agent.
A temporal estimation of students' on-task mental effort and its effect on students' performance during computer based testing

Students' on-task mental effort is an important factor of their achievement behavior. Most studies in literature adopt self-reported methods for effort estimation. In this paper we present and evaluate a method for estimating students' on-task mental effort during testing, based ontemporal, user-generated trace data. Our goal is to construct a metric that unobtrusively and seamlessly measures students' on-task mental effort. Additionally, we use this metric in order to investigate the effect of effort expenditure on students' performance during low-stakes computer based testing procedures. For that reason, we examined on-task mental effort - as defined here - with Temporal Learning Analytics. We present the results from an evaluation case study with 259 undergraduate participant students for the Computers II course. The results are encouraging, since the proposed factor significantly improves the general prediction of students' performance.
Hide and “sick”: Self-concealment, shame and distress in the setting of psycho-oncology

ABSTRACT Objective: Both trait and contextual self-concealment, as well as shame- and guilt-proneness, have previously been found to be associated with psychological distress. However, findings regarding the associations between these variables among patients with cancer and among the spouses of patients with cancer are limited. The aim of the current study was therefore to investigate the relationship between shame-proneness and psychological distress (anxiety and depression) by examining the mediating role of both trait and contextual self-concealment among patients with cancer and among the spouses of patients with cancer. Method: The current study was part of a large-scale cross-sectional study on self-concealment among patients with cancer and spouses of patients with cancer. It was based on two independent subsamples: patients with cancer and spouses of patients with cancer, who were not dyads. A total of 80 patients with cancer and 80 spouses of (other) patients with cancer completed questionnaires assessing shame- and guilt-proneness, trait and contextual self-concealment, anxiety, and depression. Results: Results indicate that spouses reported both greater shame-proneness and anxiety than did patients (main effect of role). Female participants reported greater shame-proneness, higher levels of contextual self-concealment, and greater depression and anxiety than did male participants (main effect of gender). No group differences (role/gender) were found for guilt-proneness and trait self-concealment. Trait and contextual self-concealment partially mediated the relationship between shame-proneness and distress, pointing out the need to further examine additional mediators. Significance of results: Findings suggest that contextual self-concealment and shame-proneness are important variables to consider when assessing distress in the setting of psycho-oncology. Study results may have significant clinical implications regarding the need to identify patients and spouses who are more prone to shame and self-concealment behavior in order to better tailor interventions for them.
Effect of Propranolol as Antiadhesive Therapy in Sickle Cell Disease

Sickle red blood cells (SSRBCs) adhere to both endothelial cells (ECs) and the extracellular matrix. Epinephrine elevates cyclic adenosine monophosphate in SSRBCs and increases adhesion of SSRBCs to ECs in a β‐adrenergic receptor and protein kinase A‐dependent manner. Studies in vitro as well as in vivo have suggested that adrenergic stimuli like epinephrine may contribute to vaso‐occlusion associated with physiologic stress. We conducted both animal studies and a Phase I dose‐escalation study in sickle cell disease (SCD) patients to investigate whether systemically administered propranolol inhibits SSRBC adhesion and to document the safety of propranolol in SCD. Systemically administered propranolol prevented SSRBC adhesion and associated vaso‐occlusion in a mouse model. In patients receiving a single oral dose of 10, 20, or 40 mg propranolol, SSRBC adhesion to ECs was studied before and after propranolol, with and without stimulation with epinephrine. Propranolol administration significantly reduced epinephrine‐stimulated SSRBC adhesion in a dose dependent manner (p = 0.03), with maximum inhibition achieved at 40 mg. Adverse events were not severe, did not show dose dependence, and were likely unrelated to drug. No significant heart rate changes occurred. These results imply that β‐blockers may have a role as antiadhesive therapy for SCD. Clin Trans Sci 2012; Volume 5: 437–444
Fluoxetine – do the benefits outweigh the risks in adolescent major depression?

Major depressive disorder probably occurs in ∼ 5% of adolescents. In these adolescents, selective serotonin re-uptake inhibitors (SSRIs), other than fluoxetine, have shown limited benefit and may increase the risk of suicide. In the Treatment for Adolescents with Depression Study, treatment with fluoxetine of adolescents diagnosed with major depressive disorder, or with the combination of fluoxetine and cognitive behavioural therapy, was superior to placebo. Cognitive behavioural therapy alone was not shown to be superior to placebo. Of the patients in the study, 27% had at least minimal suicidal ideation at baseline, and this reduced to 9% at the end of the treatment period, with the reduction being similar in each of the treatment groups. There were more suicide-related adverse events in the patients treated with fluoxetine (15 of 216) than in patients not treated with fluoxetine (9 of 223). There were no actual suicides. Although further investigation of any association between fluoxetine and suicidal tendencies is clearly required, at present, fluoxetine is the only SSRI for which benefit has been clearly shown, and the benefits seem to outweigh the risks. Thus, fluoxetine should generally be the first choice drug of clinicians if they decide that antidepressant drug treatment is indicated in adolescents with major depressive disorder.
Outcomes following excision of Morton's interdigital neuroma: a prospective study.

AIMS This is the first prospective study to report the pre- and post-operative patient reported outcomes and satisfaction scores following excision of interdigital Morton's neuroma. PATIENTS AND METHODS Between May 2006 and April 2013, we prospectively studied 99 consecutive patients (111 feet) who were to undergo excision of a Morton's neuroma. There were 78 women and 21 men with a mean age at the time of surgery of 56 years (22 to 78). Patients completed the Manchester-Oxford Foot Questionnaire (MOXFQ), Short Form-12 (SF-12) and a supplementary patient satisfaction survey three months pre-operatively and six months post-operatively. RESULTS Statistically significant differences were found between the mean pre- and post-operative MOXFQ and the physical component of the SF-12 scores (p = 0.00081 and p = 0.00092 respectively). Most patients reported their overall satisfaction as excellent (n = 49, 49.5%) or good (n = 29, 29.3%), but ten patients were dissatisfied, reporting poor (n = 8, 8.1%) or very poor (n = 2, 2.0%) results. Only 63 patients (63%) were pain-free at follow-up: in eight patients (8.1%), the MOXFQ score worsened. There was no statistically significant difference in outcome between surgery on single or multiple sites. However, the MOXFQ scores were significantly worse after revision surgery (p = 0.004). CONCLUSIONS The patient-reported outcomes after resection of a symptomatic Morton's neuroma are acceptable but may not be as good as earlier studies suggest. Surgery at several sites can be undertaken safely but caution should be exercised when considering revision surgery. Cite this article: Bone Joint J 2016;98-B:1376-81.
Dose‐finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A randomized, double‐blind, placebo‐controlled trial

Liver cirrhosis represents the end stage of any chronic liver disease, and it is associated with hepatic edema such as ascites. Many patients with ascites do not respond to diuretic therapy or require administration of diuretics at high doses that can cause adverse events. This 7‐day, multicenter, double‐blind trial of tolvaptan was designed to determine the optimal dose of tolvaptan for producing the intended pharmacological effect in hepatic edema.
Frequency of class B carbapenemases (MbetaL) in enterobacteriacae.

OBJECTIVE To determine the frequency of Metallo- -lactamase producing Enteriobacteriaceae species. METHOD The descriptive cross-sectional study was carried out from January to December 2011 in the Department of Microbiology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. A total of 500 specimens were initially collected. The culture positive samples were analysed for further identification, and antimicrobial sensitivity was done according to Clinical and Laboratory Standards Institute guidelines 2009. The Carbapenemases Producing Enterobacteriaceae strains were screened by the Modified Hodge Test, and Metallo-beta-Lactamase production was confirmed by the EDTA combined disc test. RESULT From amongst 402 organisms detected, 200 (49.75%) were Enterobacteriaceae, while Escherichia coli was the leading pathogen (65%). Only 6% were identified as Carbapenemases Producing Enterobacteriaceae and 9 (75%) of them were Metallo-beta-Lactamase producing strains, while 3 (25%) contained other enzymes. CONCLUSION Metallo-beta-Lactamase producing Enterobacteriaceae species are causing problems in tertiary care hospitals.
Mutations that define the promoter of ompF, a gene specifying a major outer membrane porin protein

Expression of the major porin structural genes, ompF and ompC, is influenced by medium osmotic strength and requires the products of two regulatory genes, ompR and envZ. To help define the sites required for the expression of both porin genes, we have used a novel selection to identify mutations that decrease ompF transcription. From our assignment of the mRNA start site by the primer extension method, these mutations appear to delineate poorly conserved -10 and -35 consensus promoter regions. In addition, one mutation provides the first genetic evidence that an A residue at position -45 may be important for RNA polymerase recognition.
Identification of Proteins Modulated in the Date Palm Stem Infested with Red Palm Weevil (Rhynchophorus ferrugineus Oliv.) Using Two Dimensional Differential Gel Electrophoresis and Mass Spectrometry

A state of the art proteomic methodology using Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI TOF) has been employed to characterize peptides modulated in the date palm stem subsequent to infestation with red palm weevil (RPW). Our analyses revealed 32 differentially expressed peptides associated with RPW infestation in date palm stem. To identify RPW infestation associated peptides (I), artificially wounded plants (W) were used as additional control beside uninfested plants, a conventional control (C). A constant unique pattern of differential expression in infested (I), wounded (W) stem samples compared to control (C) was observed. The upregulated proteins showed relative fold intensity in order of I > W and downregulated spots trend as W > I, a quite interesting pattern. This study also reveals that artificially wounding of date palm stem affects almost the same proteins as infestation; however, relative intensity is quite lower than in infested samples both in up and downregulated spots. All 32 differentially expressed spots were subjected to MALDI-TOF analysis for their identification and we were able to match 21 proteins in the already existing databases. Relatively significant modulated expression pattern of a number of peptides in infested plants predicts the possibility of developing a quick and reliable molecular methodology for detecting plants infested with date palm.
The Instant Obsolescence Problem With Price-Dependent Demand

Abstract This paper develops ordering policies for a retailer confronted with a product subject to instant obsolescence, as a result of the imminent end to its economic lifetime, usually for technological, economic or change-in-fashion reasons. The retailer’s objective function exhibits a profit maximizing rather tlian a cost minimising optimization objectiva to better reflect the profit-generating role of the retailer’s merchandise. There is also a price-induced demand function to provide the retailer an additional profitability tool to handle the sudden loss of the product’s income generating potential. Due to the highly complex nature of the model needed to solve the instant obsolescence problem, three heuristic solutions are proposed. The first exhibits orders of equal size. Such a feature is highly coveted in practice, but produces optimal solutions only under rather restrictive assumptions about the probability distribution of the product’s economic lifetime. The second yields approximated solutions, valid for any probability distribution, regardless of whether an optimal solution can be derived. The third includes both features. A numerical example highlights the nature of the various heuristic solutions. This example also brings forward an important supply-chain characteristic, namely without any price incentive when purchasing the item in question, a profit-maximizing retailer may find it rational to discourage sales of the item or even to refuse to stock it at all.
A Tyrosine-Hydroxylase Characterization of Dopaminergic Neurons in the Honey Bee Brain

Dopamine (DA) plays a fundamental role in insect behavior as it acts both as a general modulator of behavior and as a value system in associative learning where it mediates the reinforcing properties of unconditioned stimuli (US). Here we aimed at characterizing the dopaminergic neurons in the central nervous system of the honey bee, an insect that serves as an established model for the study of learning and memory. We used tyrosine hydroxylase (TH) immunoreactivity (ir) to ensure that the neurons detected synthesize DA endogenously. We found three main dopaminergic clusters, C1–C3, which had been previously described; the C1 cluster is located in a small region adjacent to the esophagus (ES) and the antennal lobe (AL); the C2 cluster is situated above the C1 cluster, between the AL and the vertical lobe (VL) of the mushroom body (MB); the C3 cluster is located below the calyces (CA) of the MB. In addition, we found a novel dopaminergic cluster, C4, located above the dorsomedial border of the lobula, which innervates the visual neuropils of the bee brain. Additional smaller processes and clusters were found and are described. The profuse dopaminergic innervation of the entire bee brain and the specific connectivity of DA neurons, with visual, olfactory and gustatory circuits, provide a foundation for a deeper understanding of how these sensory modules are modulated by DA, and the DA-dependent value-based associations that occur during associative learning.