Miracle-dz/UniFAR-FTUs huggingface dataset:
Which is the best anticoagulant for whole blood aggregometry platelet function testing? Comparison of six anticoagulants and diverse storage conditions

Major hindrances of impedance aggregometry are caused by limited storage time and the requirement of ex vivo anticoagulation. Data on the influence of different anticoagulants and storage conditions are rare and incomplete. This study has systematically examined the influence of six different anticoagulants (sodium and lithium heparin, 20 µg/mL and 45 µg/mL r-hirudin, benzylsulfonyl-D-Arg-Pro-4-amidinobenzylamide (BAPA), and citrate) on the results of Adenosine 5′-diphosphate (ADP) and arachidonic acid (AA) induced measurements using multiple-electrode impedance aggregometer (MEA). Measurements were carried out in a time frame of 0 min up to 48 h after blood withdrawal. In addition, the influence of storage temperatures of 4°C and 37°C was evaluated. Results of ADP-induced tests significantly varied within the first 30 min in all tested anticoagulants, in citrated blood even within the first 60 min. They remained stable up to 2 h in 20 µg/mL r-hirudin and BAPA, 4 h in citrate, 8 h in 45 µg/mL r-hirudin, and lithium heparin and up to a maximum of 12 h in sodium heparin anticoagulated blood. The analysis of AA-induced tests revealed no significantly different results up to 6 h when BAPA was used, 8 h in lithium heparin, 20 µg/mL r-hirudin and citrate, 12 h in 45 µg/mL r-hirudin, and even 24 h in sodium heparin-anticoagulated samples. A storage temperature of either 4°C or 37°C in contrast to room temperature had a negative influence on the stability of results. In conclusion, sodium heparin and 45 µg/mL r-hirudin as anticoagulants guarantee the longest storage time for impedance aggregometry.
Acceptable alternatives for forced vital capacity in the spirometric diagnosis of bronchial asthma

Background: In patients with advanced obstructive ventilatory disorders, expiration may last for a relatively long time until the end-of-test standards for forced vital capacity (FVC) are satisfied. This may be difficult for both the patient and the technician. The Forced expiratory volume in 3 seconds (FEV3) and Forced expiratory volume in 6 seconds (FEV6) maneuvers are simple, undemanding and easier to perform when compared with FVC; however, their reliability to be used as alternatives for FVC is controversial. Aim: To judge whether FEV3 and FEV6 can be used instead of FVC in detecting airway obstruction in asthmatic patients. Settings and Design: This study was a cross-sectional case–control laboratory-based study. Materials and Methods: The study involved 40 known asthmatic patients and 40 apparently healthy, gender- and age-matched controls. Spirometery was used for assessing pulmonary function according to the American Thoracic Society and European Respiratory Society criteria. Statistical Analysis: A significant difference in the means between the groups was performed using Student's t-test. The receiver operating characteristic (ROC) curves were used to compare efficiency of the studied spirometric measurements on asthma diagnosis. Results: The mean of FEV3 was not significantly different when compared with the mean of FVC (P = 0.352 for asthmatic patients and P = 0.957 for control group). This was also true when the mean of FEV6 was compared with the mean of FVC (P = 0.805 for asthmatic patients and P = 0.957 for control group). The area under the ROC curves of FEV1/FVC%, FEV1/FEV3% and FEV1/FEV6% were also comparable. Conclusion: FEV3 and FEV6 are accurate and reliable alternatives for FVC in assessing airway obstruction of asthmatic patients.
Challenges for computational structure–activity modelling for predicting chemical toxicity: future improvements?

Introduction: Structure–activity modelling for predicting toxicology as a discipline is now 50 years old, and great strides have been taken in developing methods for the physicochemical analysis of molecules and their toxicity evaluation, both essential stages in modelling. Computational toxicology also has huge potential for speeding up the screening and prioritisation of chemicals for further testing and for reducing the numbers of expensive and time-consuming conventional tests. Yet, the realisation of this potential has been largely stifled by many problems inherent in developing and validating new structure–activity models of toxicity. Areas covered: Problems of computational toxicology discussed include i) the use of inappropriate molecular descriptors and tools that are not transparent; ii) the undetected existence of chemicals that cause large changes in toxicity with only small differences in molecular structure (causing ‘activity cliffs’ in the structure–activity landscape); iii) spurious correlations between structure and activity; iv) lack of quality control of toxicity data; v) difficulties in determining predictivity for novel chemicals; and vi) an over-reliance on complex mathematics and statistics. Expert opinion: Greater emphasis needs to be placed on i) the selection of training and test sets of chemicals to enable both internal and external validation of models to be undertaken for more accurate assessment of model predictivity and ii) the use of recently developed techniques for characterising structure–activity landscapes.
Two Common Pitfalls in Clinical Audit: Failing to Complete the Audit Cycle and Confusing Audit with Research

This article explores two common pitfalls for occupational therapists in carrying out clinical audit: failing to complete the audit cycle to bring about actual improvements in practice and confusing audit with research. Given the demanding circumstances under which most clinicians work, these problems are neither surprising nor unique to occupational therapy. This article defines clinical audit and summarises good practice in audit. The difficulties with completing the audit cycle are explored and some solutions are suggested. The difference between clinical audit and research is discussed, with strategies for avoiding confusion.
Organotypic systems in drug metabolism and toxicity: challenges and opportunities

Introduction: The frequent failure of high-throughput screening cell-based tools to accurately predict in vivo responses, coupled with limitations of animal models in predicting human safety or drug efficacy, impairs the de-risking process for biotechnology/pharmaceutical companies as they make important decisions to enter human clinical trials. Organotypic systems strive to fill the gap between these screening and in vivo studies and provide a solution. Areas covered: The authors examine the various approaches to recreate physiological response on the bench and trace the evolution of organotypic systems, while discussing intrinsic challenges and opportunities that lie ahead. Furthermore, they cite literature that is the foundation of several biotechnology research companies addressing this issue and discuss major government-funded initiatives to aid the development of these systems in an effort to fill this existing gap. Expert opinion: Decisions from translational systems that bridge basic drug efficacy and toxicity with clinical outcome must be benchmarked against human-relevant endpoints and clinical data for early meaningful pre-clinical decisions. The use of human primary cells coupled with emerging technologies that allow precise control of the culture environment and analysis of meaningful endpoints paves the way for human organotypic systems as a major initiative in de-risking the drug discovery and development process.
Properties of soluble glycoprotein VI, a potential platelet activation biomarker

Abstract Glycoprotein VI (GPVI) plays a critical role in the platelet response to collagen. Clinical studies suggest that the plasma level of soluble GPVI (sGPVI) is a highly specific and useful platelet activation marker. However, many properties of sGPVI have not been fully characterized, such as its sensitivity in detecting platelet activation and its elimination rate from the blood. In this study we established a sandwich enzyme-linked immunosorbent assay for human sGPVI, which cross-reacts to cynomolgus monkey sGPVI, and evaluated the time course of sGPVI production in a cynomolgus monkey model of lipopolysaccharide (LPS)-induced thrombocytopenia. The sGPVI levels in this model were dramatically elevated and returned to baseline by 24 hours after LPS injection, the change was more pronounced than the existing platelet activation biomarker, soluble P-selectin (sP-selectin) levels. The elimination half-life of recombinant human sGPVI was about 2.5 hours following intravenous administration to monkeys. These results suggest that plasma sGPVI closely reflects platelet activation in the bloodstream and has a short half-life. sGPVI would be a useful biomarker for disorders marked by platelet activation and for monitoring anti-platelet therapy.
Vaccination and rheumatic diseases: Is there still a dilemma?

The development of rheumatic diseases after immunization has been reported in the medical literature but a causal relationship has not been established. Infections remain an important cause of morbidity and mortality in patients with rheumatic diseases who may be immunodepressed for immunological dysfunctions or immunosuppressed due to the pharmacologic therapy. Although vaccines against infectious diseases are considered the standard way in preventive medicine, it is still a controversial issue among rheumatologists whether or not patients with rheumatic disorders should undergo vaccination. In recent decades increased numbers of studies on influenza and pneumococcal vaccines administered to patients with systemic lupus erythematosus have proven their safety. These vaccinations, generally immunogenic (i.e. able to induce a protective level of specific antibodies), may not induce an adequate response in patients receiving immunosuppressive therapy. The safety and the immunogenity of Tetanus toxoid, and HBV vaccinations in SLE patients are not completely defined so far. Considering the few available studies, influenza, pneumococcal, and HBV vaccines seem to be safe and immunogenic in patients with rheumatoid arthritis. The effect of TNFα blocking therapies on human immune responses to vaccination is discussed. We also review existing knowledge on vaccination in patients with Sjogrens syndrome and in children with rheumatic disorders, discussing risks and benefits.
Pharmacokinetic evaluation of topical calcineurin inhibitors for treatment of allergic conjunctivitis

Introduction: Topical calcineurin (Cn) inhibitors delivered via ophthalmic drop is emerging as a potential treatment for severe, immune-mediated forms of allergic conjunctivitis, such as vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis. Areas covered: This article is based on a comprehensive literature search, with information taken from meta-analyses, systematic reviews, treatment guidelines and clinical studies in children and adults. The articles that have been selected evaluate the use of topical Cn inhibitors and their role in the treatment of allergic conjunctivitis. Expert opinion: Ophthalmic topical Cn inhibitors have been shown to be safe for short-term use, with minimal systemic absorption and toxicity. For patients with severe, refractory forms of allergic conjunctivitis, topical Cn inhibitors offer a promising treatment option and an alternative to steroidal therapies. The safety profile and efficacy data for topical cyclosporine are more robust compared to that of tacrolimus and pimecrolimus, although larger trials will be needed for all three agents. With more randomized controlled trials involving larger sample sizes and long-term follow-up to establish both efficacy and safety, ophthalmic Cn inhibitors offer exciting treatment possibilities for the prevention of morbidity associated with refractory allergic conjunctivitis.
Do genetic polymorphisms alter patient response to inhaled bronchodilators?

Introduction: Short- and long-acting β agonists (SABA and LABA) are bronchodilators for treating asthma. Bronchodilator response (BDR) is quantified by measuring air expired in the first second during a forced expiratory maneuver, prior to and following inhalation of SABA. BDR has been associated with a significant degree of heterogeneity, in part attributable to genetic variation. Heritability, the proportion of phenotypic variability accounted for by genetic variation is estimated to account for 50% of pulmonary function and 28.5% for BDR. Areas covered: A MEDLINE search for English articles published from January 1990 to June 2014 was completed using the terms: bronchodilator, bronchodilator response, short-acting bronchodilator, long-acting bronchodilator, β2 adrenergic receptor gene (ADRB2), asthma and pharmacogenomics. The effects of ADRB2 variants on BDR and the safety of SABA and LABA + inhaled corticosteroids have been studied with equivocal results. Single and candidate gene studies have identified variants in other genes that alter response to bronchodilators. Associations were recently observed between hospital admission rates and two rare ADRB2 polymorphisms: Thr164Ile and a 25 base pair insertion-deletion at nucleotide -376. This was the first report of life-threatening events associated with LABA being linked to rare ADRB2 variants. Expert opinion: Pharmacogenomic studies over the last two decades clearly demonstrate that polymorphisms alter patient response to bronchodilators in patients with asthma.
Dead enzymes in the aldehyde dehydrogenase gene family: role in drug metabolism and toxicology

Introduction: Dead enzymes are gene products (proteins) that lack key residues required for catalytic activity. In the pre-genome era, dead enzymes were thought to occur only rarely. However, they now have been shown to represent upwards of 10% of the total enzyme population in many families. The aldehyde dehydrogenase (ALDH) gene family encodes proteins that, depending on the isozyme, may be either catalytically-active or -inactive. Importantly, several ALDHs exhibit biological activities independent of their catalytic activity. For many of these, the physiological and pathophysiological functions remain to be established. Areas covered: This article reviews the non-enzymatic functions of the ALDH superfamily. In addition, a search for additional non-catalytic ALDH records is undertaken. Our computational analyses reveal that there are currently 182 protein records (divided into 19 groups) that meet the criteria for dead enzymes. Expert Opinion: Dead enzymes have the potential to exert biological actions through protein-protein interaction and allosteric modulation of the activity of an active enzyme. In addition, a dead enzyme may also influence availability of substrate for other active enzymes by sequestering substrate, and/or anchoring the substrate to a particular subcellular space. A large number of putatively non-catalytic ALDH proteins exist that warrant further study.
Imaging in endometriosis

Laparoscopy is the gold standard for diagnosis and staging of endometriosis.Characteristically, endometriomas have a uniform low-echo content on ultrasound but appearances can be very diverse.The ability of MRI to characterize the products of haemorrhage make it the test of choice for problem solving and for the identification of extra-ovarian deposits.MRI is the most reliable non-invasive tool for evaluation of disease distribution and complications prior to surgery but endocavitary ultrasound plays a complementary role.MRI is able to identify malignant change in endometriosis. In this article, we present the imaging features of endometriosis on ultrasound and magnetic resonance imaging (MRI). We give particular emphasis to the manifestations of different sites of pelvic involvement on MRI. Complications such as renal tract obstruction and associated malignancy are also illustrated.
Sagittal pubic osteotomy in the investigation and treatment of intrapelvic neoplasia in the dog

Sagittal pubic osteotomy was used as the surgical approach in 24 cases of intrapelvic neoplasia in the dog. Thirteen cases involved the urethra, seven cases the colorectum, one case the prostate and three cases the iliac periosteum. Surgical excision was performed in 10 cases of urethral neoplasia, four cases of rectal neoplasia, two cases of periosteal fibrosarcoma and one case of chondrosarcoma. The remaining cases were assessed as inoperable due to the extent of disease and euthanasia was carried out. Access to intrapelvic structures via a caudal midline laparotomy, perineal or dorsal routes or via an episiotomy is severely limited. The structures within the pelvic canal most likely to require surgical attention are the urethra, rectum and prostate. Procedures which require wide excision, accurate anastomotic techniques or relocation of intrapelvic organs necessitate an approach that allows generous exposure. A simple method of pubic osteotomy has been employed which has allowed resection of intrapelvic neoplasms.
Quantification of health effects of breastfeeding -Review of the literature and model simulation

Breastfeeding has positive health effects, with the largest health gain realized through policy that focuses on encouraging all mothers to start breastfeeding. A literature review shows that breastfeeding has beneficial health effects in both the short and the longer term. There is convincing evidence that the incidence of gastrointestinal infections, inflammation of middle ear, obesity and high blood pressure is reduced in breastfed children. Probably breastfed children suffer less from asthma, wheezing, eczema and among them intellectual and motor development is probably enhanced. Breastfeeding is possibly related to a reduction of incidence in Crohn's disease, atopy, diabetes mellitus type I, and leukaemia. Regarding the mother, there is convincing evidence for a protective effect of breastfeeding on rheumatoid arthritis. The incidence of pre-menopausal breast and ovarian cancer is probably lower among mothers who breastfed their infants longer. The health effects of several intervention scenarios are simulated and compared to the present situation. The largest public health gain can be achieved when all newborns get breastfeeding for at least 6 months. Greater public health gain can be achieved by introducing breastfeeding to all newborns than through a policy only focussing on extending the lactation of women already breastfeeding beyond three months.
Improvement of cardiac efficacy and safety models in drug discovery by the use of stem cell-derived cardiomyocytes

Background: The pharmaceutical industry suffers from high attrition rates during late phases of drug development. Improved models for early evaluation of drug efficacy and safety are needed to address this problem. Recent developments have illustrated that human stem cell-derived cardiomyocytes are attractive for using as a model system for different cardiac diseases and as a model for screening, safety pharmacology and toxicology. Objective: In this review, we discuss contemporary drug discovery models and their characteristics for cardiac efficacy testing and safety assessment. Additionally, we evaluate various sources of stem cells and how these cells could potentially improve early screening and safety models. Conclusion: We conclude that human stem cells offer a source of physiologically relevant cells that show great potential as a future tool in cardiac drug discovery. However, some technical challenges related to cell differentiation and production and also to validation of improved platforms remain and must be overcome before successful application can become a reality.
Cell based in vitro and ex vivo models in metabolic disease drug discovery: nice to have or critical path?

Background: The use of cellular models as tools in drug discovery is almost universal. However, in disease areas such as metabolic diseases, are they relevant to the process and do they add value? Objective: In this article, we explore the variety of cellular models now used in drug discovery in metabolic diseases as revealed by publication. We have tried to make some connections between drug phenotypes in these models with clinical parallels. We also ask the question as to whether such models add value in the drug discovery process. This overview is not about recombinant cell systems used in target-based screening; rather, we focus on in vitro, including ex vivo, models as physiological systems in drug discovery in obesity and diabetes. Conclusion: In terms of building target confidence, in vitro models are often the only mechanistic link to human systems early in a projects life. Many of the current targets in metabolic diseases in the early discovery phase are not yet clinically supported, let alone validated. In this respect, therefore, in vitro models warrant a place in the critical path in early discovery. In terms of any predictive role for decision-making today, this is much more difficult and is more likely pushed to a supporting role as part of a wider package. However, there is a rapid rate of advancement in this field and future developments hold much promise.
AAAE Members' Computer Technology Assessment

The purpose was to identify AAAE members’ computer anxiety levels, attitudes toward computers and perceptions of Web-based survey methods. A total of 389 AAAE members participated in this experimental study. Respondents were assigned randomly to Web- and paperbased data collection method subgroups. AAAE members perceived that they did not suffer from computer anxiety, held positive attitudes toward computers and perceived that Web-based survey methods provide valid, reliable, and secure methods of collecting data. Significant differences showed that Web-based respondents held significantly more positive attitudes for “computers eliminating tedious work and improving higher order thinking skills” and significantly stronger perceptions that Web-based surveys “are as reliable as paper surveys and researchers could feel confident in reporting data obtained in Web-based surveys. ” Females held significantly different attitudes toward computers (less favorable) and perceptions of Web-based survey methods (more favorable) than did males. Full professors had significantly higher computer anxiety levels, less favorable attitudes toward computers, and a more limited view of the usefulness of Web-based survey methods than did all other respondents. AAAE members are encouraged to used Webbased survey methods to collect research data and participate in computer workshops offered by their universities’ faculty development programs.
Wheat germ cell-free technology for accelerating the malaria vaccine research

Background: Malaria causes about 300 million illnesses and 1 million deaths annually. The likeliest scenario is the aggravation of this disease due to the re-emergence of drug-resistant parasites and insecticide-resistant mosquitoes. One of the promising solutions to this disease are vaccines. However, until now, not even a single licensed malaria vaccine has been developed despite intensive efforts. Even the efficacy of RTS,S, the most advanced vaccine candidate in the pipeline of malaria vaccine development, is only around 50%. Objective: Against this backdrop, there is an urgency to rapidly enrich the pipeline of vaccine development with novel vaccine candidates that can be discovered by synthesizing and screening a multitude of malaria proteins. Methods: However, to achieve this objective, we require optimal technologies for high-throughput synthesis of quality malaria proteins. Among the various protein synthesis systems, the wheat germ cell-free protein synthesis system is advantageous and successful to this end. Results/conclusion: The wheat germ cell-free protein synthesis system is optimal for accelerating the decoding of malaria genome and hence characterization of malaria proteins and discovery of malaria vaccine candidates.