Miracle-dz/UniFAR-FTUs huggingface dataset:
Analgesics and Osteoarthritis: Are Treatment Guidelines Reflected in Clinical Practice?

Osteoarthritis (OA) treatment is complex and multifactorial, with pharmacological regimens requiring sufficient flexibility to be adapted to individual disease progression, flare ups, and response to treatment. Coexisting conditions are common and can lead to problems regarding polypharmacy. Several guidelines have been published for the management of OA pain. While differences exist, most recommend paracetamol as the initial oral drug for OA, based on its efficacy, tolerability, and cost; in patients who respond inadequately to paracetamol, supplementary or replacement analgesics should be recommended. This article considers the reality of analgesic use for OA in clinical practice and the extent to which guidelines are followed both in primary and secondary care. An international survey of rheumatologists (n = 610) found that paracetamol was recommended as first-choice analgesic for OA by 82% of those surveyed. Similarly, in a survey of French GPs, 90% of those surveyed recommended paracetamol first line; NSAIDs were recommended more frequently for stronger pain relief but were also recommended alongside paracetamol as a first-line treatment of mild to moderate pain by 43% of GPs. Finally, a UK patient survey, conducted at a London hospital (n = 200), found that 64% of patients were taking more than 1 drug for treatment of painful OA of the knee or hip; 76% were taking paracetamol and 40% were taking an NSAID. A further 39% had used an NSAID in the past but switched treatment, primarily due to side effects. These findings reinforce the case for the simple analgesic paracetamol to be seen as the cornerstone of pharmacological OA treatment, both as a first-line analgesic and as a foundation to which additional treatment modalities, including NSAIDs, can be added if and when necessary.
Stages of Polymyxin B Interaction with theEscherichia coli Cell Envelope

ABSTRACT The effects of polymyxin B (PMB) on the Escherichia coli outer (OM) and cytoplasmic membrane (CM) permeabilities were studied by monitoring the fluxes of tetraphenylphosphonium, phenyldicarbaundecaborane, and K+ and H+ions. At concentrations between 2 and 20 μg/ml, PMB increased the OM permeability to lipophilic compounds and induced a leakage of K+ from the cytosol and an accumulation of lipophilic anions in the cellular membranes but did not cause the depolarization of the CM. At higher concentrations, PMB depolarized the CM, forming ion-permeable pores in the cell envelope. The permeability characteristics of PMB-induced pores mimic those of bacteriophage- and/or bacteriocin-induced channels. However, the bactericidal effect of PMB took place at concentrations below 20 μg/ml, indicating that this effect is not caused by pore formation. Under conditions of increased ionic strength, PMB made the OM permeable to lipophilic compounds and decreased the K+gradient but was not able to depolarize the cells. The OM-permeabilizing effect of PMB can be diminished by increasing the concentration of Mg2+. The major new findings of this work are as follows: (i) the OM-permeabilizing action of PMB was dissected from its depolarizing effect on the CM, (ii) the PMB-induced ion-permeable pores in bacterial envelope were registered, and (iii) the pore formation and depolarization of the CM are not obligatory for the bactericidal action of PMB and dissipation of the K+gradient on the CM.
Occam's Inversion and the North American Central Plains Electrical Anomaly

iterations excess structure was removed to reveal three discrete conductive zones of resistivity less than 1 Ωm at depths of 8–22 km in a relatively resistive background layer of 100–1000 Ωm. The inversion algorithm was modified to take advantage of the 1D structure of the shorter periods, which were inverted to obtain a model representative of surface sediments which extend to a depth of about 2 km. This surface structure was included in the long-period inversion by imposing a second penalty term in the regularized inversion, and the resulting model featured a broader, more complex conductive anomaly and a pronounced, westward-dipping fabric in the mid-to lower-crustal rocks. Graphitic rocks can account for the highly conductive parts of the models. In this paper we present the results of two-dimensional (2D), smooth inversions of the COPROD2 magnetotelluric (MT) data set (Jones and Savage, 1986; Jones, 1988) using the Occam’s inversion algorithm of Constable, Parker and Constable (1987), modified for 2D MT by deGrootHedlin and Constable (1990). The MT data were obtained over the North American Central Plains (NACP) and Thompson Belt electromagnetic anomalies in order to obtain a quantitative model of features previously identified in numerous geomagnetic depth sounding (GDS) surveys (see the summary by Jones and Craven, 1990). The GDS surveys indicated that the NACP anomaly is a large scale, linear feature extending from southeastern Wyoming northward to the exposed Canadian Shield in northern Saskatchewan, and from there extending eastward along the regional geological strike into the Hudson’s Bay basin. The alignment of zones of intense shearing and folding in the exposed Precambrian crust with both the northern and southern ends of the NACP anomaly led Camfield and Gough (1977) to suggest that the anomaly is associated with a Proterozoic plate boundary. Our aim here is to develop methods of interpretation of approximately 2D MT data sets using smooth inversion methods and to apply these techniques to determine the conductivity structure of the NACP anomaly. Although three-dimensionality is evident along the length of the conductivity anomaly in the GDS data (Alabi et al., 1975), as well as in MT observations recorded in two profiles to the north of the COPROD2 line (Jones and Craven, 1990), the NACP
The effects of seizures on the brain

Since the time of Sommer's review of hippocampal pathology and Gower's tenet that 'seizures beget seizures' there has been interest in changes in brain structure and function that may be associated with epilepsy. From recent experimental studies and clinical observations, there is increasing evidence that epilepsy is not only associated with structural and functional alterations in the nervous system, but also that seizures induce a diverse variety of molecular, cellular, and functional alterations in the brain.
RELATIONSHIP BETWEEN SOME BODY MEASUREMENTS AND FERTILITY IN MALES OF TWO LOCAL STRAINS OF CHICKEN .

A total number of 100 pedigreed cocks from two strains of chickens, El-Salam and Mandarah (50 cocks each strain) at 8 weeks of age according to their sire families were used in this experiment to study the relationship between fertility with some body measurements such as body weight, lengths of shank and keel and secondary sexual characters (comb and wattle lengths and widths) in both strains. The cocks were classified at 40 weeks of age into three groups according to comb size. The 1st group: males with a large comb (LC), the 2nd group: males with a control comb (CC) and the 3rd group: males with a small comb (SC). The following results were obtained: Semen ejaculate volume, sperm concentration, percentage of live sperm and sperm motility were significantly (P≤0.05) higher at 50 wks than those at 40 and 30 wks of age for both strains, in overall mean of Mandarah than El-Salam cocks at different ages and in heavy body weight cocks than control or light in both strains at 40 wk of age. Body weight, lengths of shank and keel and secondary sexual characters (length and width of both comb and wattle) increased linearly with increasing age in both strains. Cocks with (LC) had ejaculated volume, sperm concentration, percentage of live sperm, sperm motility and percentage of fertility higher than either (CC) or (SC) cocks in both strains at 40 weeks of age. Heritability estimates for ejaculate volume, semen pH and sperm motility were high and moderate of both strains at all ages studied. Phenotypic correlation in both strains was positive and moderate to high values between ejaculate volume and each sperm concentration, percentage of live sperm and sperm motility, between sperm concentration and percentage of live sperm and between body weight at 8 wk and each ejaculate volume, sperm concentration and percentage of live sperm in both strains. In Mandarah strain lengths of shank, keel and comb were highly positively correlated with ejaculate volume, sperm concentration and percentage of live sperm compared with El-Salam strain. Genetic correlation was positive and moderate to high between ejaculate volume and each percentage of live sperm, sperm concentration, and percentage of abnormal sperm and between percentage of live sperm and sperm motility in both strains. Genetic correlation was positive and moderate to high between body weight and each ejaculate volume, sperm concentration and percentages of live and abnormal sperm, and between wattle length and percentage of abnormal sperm in both strains. Results provide evidence that phenotypic traits can be used as useful indicators to predict male's fertility in local strains, indicators for high semen physical quality traits, used in selection programs to improve local strain in early age and get rid of subfertile males for reducing production cost. Key Word: Body Measurements, Fertility, Local Strains.
Unaltered insulin sensitivity after resistance exercise bout by postmenopausal women.

PURPOSE The major aims of this study were to determine whether a single session of resistance exercise would alter insulin sensitivity, glucose effectiveness, and C-peptide response to glucose challenge in a group of previously sedentary, postmenopausal women. METHODS Ten postmenopausal women (aged 57.5 +/- 1.6 yr) were studied. Each participant underwent two frequently sampled intravenous glucose tolerance tests (FSIVGTT): without prior exercise (no exercise), and postexercise (15 h after a session of resistance exercise: three sets of 10 repetitions performed at 50%, 75%, and 100% of 10-repetition maximum for 7 exercises). Insulin sensitivity and glucose effectiveness were determined according to Bergman's minimal model procedure. In addition, C-peptide concentration and glucose disappearance were measured. RESULTS There was no significant difference between trials for insulin sensitivity, glucose effectiveness, glucose disappearance, or area under the curve (AUC) for glucose or insulin during the glucose challenge. AUC for C-peptide tended (P = 0.059) to be 10% higher in the postexercise versus no exercise trial, and C-peptide values were significantly (P < or = 0.02) higher at several time points (60, 70, 140, and 180 min) during the postexercise compared with no exercise trial. CONCLUSIONS In contrast to previously reported results with young men and women after a single bout of endurance exercise, insulin sensitivity was unaltered by a single session of resistance exercise in postmenopausal women. Higher plasma C-peptide values concomitant with unchanged insulin values provide evidence that resistance exercise may have induced a slightly higher insulin secretion and a proportional increase in insulin clearance.
Flow cytometric analysis of isolated liver mitochondria to detect changes relevant to cell death

Mitochondria are key players in many forms of cell death, and mitochondrial production of reactive oxygen species (ROS), membrane depolarization, permeability changes, and release of apoptogenic proteins are involved in these processes. Flow cytometric analysis of isolated mitochondria enables parallel analysis of mitochondrial structure and function in individual mitochondria, and small mitochondrial samples are sufficient for analysis. This article describes a well‐characterized protocol for flow cytometric analysis of isolated liver mitochondria that can be used to detect mitochondrial alterations relevant to cell death.
DETERMINANTS OF THE EFFECTIVENESS OF THE AUDITOR GENERAL IN KENYA IN PUBLIC FINANCIAL MANAGEMENT OVERSIGHT

Audit is an integral part of the financial management of public sector. Over the years, the precise role of audit has shifted from mere detection oriented procedures to prevention and advocacy oriented performance evaluation approach. The purpose of this study was to explore the factors that influence the effectiveness of the auditor general’s oversight role in the Kenya public financial management. The specific objectives of the study were to establish the effect of statutory position, institutional management, resources availability and audit processes on the effectiveness of the Auditor General’s oversight role. The target population for this study was the entire staff establishment in the Office of the Auditor General who were 1226 in number and spread in 70 branches across the country. Stratified random sampling was used to select a sample of 302. Questionnaires were used to collect data and analysis was through descriptive and inferential statistics. The results indicated that statutory position of the OAG, institutional management of the OAG, resources availability and audit processes were significant in influencing effectiveness of OAG in providing oversight into public financial management in Kenya. Key words : Audit, Effectiveness, Oversight, Public sector, Resources, Statutory position.
CHIEF EXECUTIVE OFFICER’S GENDER AND FIRM PERFORMANCE IN THE JSE SRI FIRMS

There is a growing campaign for the corporate to accommodate more women on the corporate top echelon. Gender equality in the workplace encourages equality between men and women and should be considered from the lower level right to the top level of the organisation. There is, therefore, a growing advocacy for hiring and supporting women to the CEO level as part of the strategies to enhance sustainable development (Bear et al., 2010). Whilst there is a global campaign of gender equality, corporate across the world are still hesitant to consider women in the CEOs’ positions unless there is probable evidence that such transition will benefit the organisation. Contemporary research has proven that women representation on the top-level management can affect the corporate social responsibility ratings, which influence corporate reputation, and which also impacts on corporate performance. Aspects such as financial performance, institutional investment and share price can be affected by the positive reputation of the company. This is because investment decisions made by the board of directors are influenced among others by environmental, social and corporate governance factors (Bear et al., 2010). Previous literature such as Smith and Villa (2010) has indicated that participation of women CEOs may have a significant effect on corporate performance. Some recent studies have shown that gender equality has an impact on the firm's turnover (Faccio et al. 2015; Mkhize et al., 2011). For instance, it has been recognised that female directors make acquisition decisions that influence shareholder value leading to macroeconomic implications that affect the long-term economic growth of the company (Faccio et al., 2015). Women are reported to contribute to the implementation of unique skills to the corporates that affect the net profit of the organisation (Mkhize et al., 2011). Since Abstract
Readability Assessment of Online Patient Resources for Breast Augmentation Surgery

Background: Patients increasingly rely on Internet resources for medical information. Well-informed patients are more likely to be active participants in their health care, contributing to higher satisfaction and better overall outcomes. Access to online patient material, however, can be limited by inadequate functional health literacy. The National Institutes of Health and the American Medical Association recommend that educational content be written at a sixth-grade reading level. This study aims to assess the readability of online patient resources for breast augmentation surgery. Methods: A Web search for “breast implant surgery” was performed using the largest public search engine. After sponsored results were excluded, the 12 most accessed sites were identified. Patient-directed information from all relevant articles immediately linked from the main site was downloaded and formatted into plain text. The readability of 110 articles was evaluated using 10 established analyses, both overall and by Web site. Results: The overall average readability of the 12 most popular Internet resources for breast augmentation was at a thirteenth-grade reading level (Coleman-Liau, 13.4; Flesch-Kincaid, 12.7; FORCAST, 11.3; Fry, 13; New Dale-Chall, 12.9; New Gunning Fog, 13.8; Raygor Estimate, 15; and Simple Mesaure of Gobbledygook Formula, 14.3). The Flesch Reading Ease index was 41, which falls into a “difficult” reading category. No individual article or Web site was at the recommended sixth-grade level. Conclusions: Online resources for breast augmentation are above recommended reading levels. This may potentially serve as a barrier to patients seeking this type of surgery. Plastic surgeons should be aware of potential gaps in understanding and direct patients toward more appropriate resources.
A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder.

OBJECTIVE To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique anti-obsessional properties, is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride. DESIGN Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10-week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine. SETTING Outpatient clinic. PATIENTS A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study. MEASURES Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale, and the Clinical Global Impressions Scale. RESULTS Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P < .05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity. CONCLUSION Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.
MUCOSOLVAN IN THE TREATMENT OF PATIENTS WITH PRIMARY SJÖGREN'S SYNDROME

Thirty‐six patients with primary Sjögren's syndrome were randomized to Mucosolvan (60 mg × 2 daily) or placebo, in a double‐blind cross‐over study. Each period of treatment was 3 weeks with 1 week wash‐out in between. None of the objective ophthalmological tests (Schirmer‐1—test, break‐up time, van Bijsterveld score, cornea sensitivity, appearance of nuclear chromatin in conjunctival epithelial cells, tear lysozyme) improved during the investigation period.
Substrate and Inhibitor-induced Dimerization and Cooperativity in Caspase-1 but Not Caspase-3*

Background: The inflammatory caspase-1 shows positive cooperativity not seen for the apoptotic caspase-3. Results: Substrate binding increases the dimerization affinity and activity of caspase-1 but not for caspase-3. Conclusion: Caspase-1 is regulated by concentration with substrates, whereas caspase-3 is not. Significance: Subcellular co-localization of caspase-1 with substrates in inflammosomes may explain its more restricted family of substrates observed. Caspases are intracellular cysteine-class proteases with aspartate specificity that is critical for driving processes as diverse as the innate immune response and apoptosis, exemplified by caspase-1 and caspase-3, respectively. Interestingly, caspase-1 cleaves far fewer cellular substrates than caspase-3 and also shows strong positive cooperativity between the two active sites of the homodimer, unlike caspase-3. Biophysical and kinetic studies here present a molecular basis for this difference. Analytical ultracentrifugation experiments show that mature caspase-1 exists predominantly as a monomer under physiological concentrations that undergoes dimerization in the presence of substrate; specifically, substrate binding shifts the KD for dimerization by 20-fold. We have created a hemi-active site-labeled dimer of caspase-1, where one site is blocked with the covalent active site inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. This hemi-labeled enzyme is about 9-fold more active than the apo-dimer of caspase-1. These studies suggest that substrate not only drives dimerization but also, once bound to one site in the dimer, promotes an active conformation in the other monomer. Steady-state kinetic analysis and modeling independently support this model, where binding of one substrate molecule not only increases substrate binding in preformed dimers but also drives the formation of heterodimers. Thus, the cooperativity in caspase-1 is driven both by substrate-induced dimerization as well as substrate-induced activation. Substrate-induced dimerization and activation seen in caspase-1 and not in caspase-3 may reflect their biological roles. Whereas caspase-1 cleaves a dramatically smaller number of cellular substrates that need to be concentrated near inflammasomes, caspase-3 is a constitutively active dimer that cleaves many more substrates located diffusely throughout the cell.
Definition, reporting, and interpretation of composite outcomes in clinical trials: systematic review

Objective To study how composite outcomes, which have combined several components into a single measure, are defined, reported, and interpreted. Design Systematic review of parallel group randomised clinical trials published in 2008 reporting a binary composite outcome. Two independent observers extracted the data using a standardised data sheet, and two other observers, blinded to the results, selected the most important component. Results Of 40 included trials, 29 (73%) were about cardiovascular topics and 24 (60%) were entirely or partly industry funded. Composite outcomes had a median of three components (range 2–9). Death or cardiovascular death was the most important component in 33 trials (83%). Only one trial provided a good rationale for the choice of components. We judged that the components were not of similar importance in 28 trials (70%); in 20 of these, death was combined with hospital admission. Other major problems were change in the definition of the composite outcome between the abstract, methods, and results sections (13 trials); missing, ambiguous, or uninterpretable data (9 trials); and post hoc construction of composite outcomes (4 trials). Only 24 trials (60%) provided reliable estimates for both the composite and its components, and only six trials (15%) had components of similar, or possibly similar, clinical importance and provided reliable estimates. In 11 of 16 trials with a statistically significant composite, the abstract conclusion falsely implied that the effect applied also to the most important component. Conclusions The use of composite outcomes in trials is problematic. Components are often unreasonably combined, inconsistently defined, and inadequately reported. These problems will leave many readers confused, often with an exaggerated perception of how well interventions work.