Clotting and fibrinolytic activity change during the 1 h after a submaximal run

PURPOSE: To determine the changes in clotting and fibrinolytic activity during the 1-h period after an acute submaximal exercise at a specific relative exercise intensity to ascertain whether during this time there is a greater risk for developing a clot formation or thrombus. METHODS: Ten healthy men reported between 0700 and 1000 h and ran at 70-75% VO2max or walked at 1.2 mph for 30 min in a random counter-balanced order. Venous blood was obtained at rest, immediately after, and every 20 min during the 1-h recovery. RESULTS: There were no differences in the resting parameters for each treatment. Walking did not alter the activity of any of the measures analyzed compared with rest. Clotting indicators activated partial thromboplastin time (APTT) was significantly decreased by approximately 2 s and remained at this level during the 1-h recovery, and factor VIII activity was elevated 66% immediately after the run and remained elevated at this level during the 1-h recovery period. Fibrinolytic indicators, t-PA, and D-dimers were significantly increased immediately after the run. However, t-PA demonstrated a quadratic negative slope during the 1-h recovery time. D-dimers remained elevated during the 1-h recovery time. CONCLUSIONS: These results suggest that running at 70-75% VO2max resulted in elevated clotting and fibrinolytic activity. However, the clotting activity was sustained during a time when fibrinolytic activity declined, which suggests a more favorable situation for clot formation during this time after exercise.     

Intraventricular tuberculous abscess: a case report

Ventricles can be involved in different ways in neurotuberculosis, however, the occurrence of intraventricular abscess has been rarely reported. We report a young woman who had intraventricular tubercular abscess. Cranial computed tomographic scan showed hypodense ring enhancing lesion in the right lateral ventricle with unilateral hydrocephalus. She underwent parasagittal craniotomy with total excision of the lesion. The pus obtained from the lesion was teeming with acid fast bacilli.     

Antimuscarinics for the treatment of overactive bladder: current options and emerging therapies

Antimuscarinic drugs have been the mainstay in the treatment of overactive bladder (OAB) for over two decades. An ideal antimuscarinic medicine is one that can normalize bladder function without interfering with parasympathetic regulation of other organs. Currently, extended-release formulations of tolterodine (tolterodine-ER) and oxybutynin (oxybutynin-ER and oxybutynin-TDS) serve as the cornerstone in the pharmacotherapy of OAB. Although these products represent a significant improvement over older agents, especially with respect to convenience of dosing schedule, their tolerability concerns and modest efficacy make them less than ideal therapies. Advances in our understanding of muscarinic receptor pharmacology have raised optimism in our ability to widen the therapeutic index and increase the efficacy of antimuscarinics by selectively targeting one or more of the five muscarinic subtypes. A structurally diverse group of molecules, having varying receptor-selectivity profiles (non-selective, M3 selective, M2 selective, M2 sparing and M5 sparing), are in development for OAB. Results of clinical trials with these drugs must be awaited before their therapeutic value can be accurately judged.     

The use of databases,data mining and immunoinformatics in vaccinology: where are we?

Introduction: Vaccinology has evolved from a sub-discipline focussed on simplistic vaccine development based on antibody-mediated protection to a separate discipline involving epidemiology, host and pathogen biology, immunology, genomics, proteomics, structure biology, protein engineering, chemical biology, and delivery systems. Data mining in combination with bioinformatics has provided a scaffold linking all these disciplines to the design of vaccines and vaccine adjuvants.

Areas covered: This review provides background knowledge on immunological aspects which have been exploited with informatics for the in silico analysis of immune responses and the design of vaccine antigens. Furthermore, the article presents various databases and bioinformatics tools, and discusses B and T cell epitope predictions, antigen design, adjuvant research and systems immunology, highlighting some important examples, and challenges for the future.

Expert opinion: Informatics and data mining have not only reduced the time required for experimental immunology, but also contributed to the identification and design of novel vaccine candidates and the determination of biomarkers and pathways of vaccine response. However, more experimental data is required for benchmarking immunoinformatic tools. Nevertheless, developments in immunoinformatics and reverse vaccinology, which are nascent fields, are likely to hasten vaccine discovery, although the path to regulatory approval is likely to remain a necessary impediment.     

Development and preclinical testing of HNVAC,a cell culture-based H1N1 pandemic influenza vaccine from India

Several limitations of the use of embryonated eggs and the threat of pandemics have highlighted the need for other platforms for the production of influenza vaccines. We report the indigenous development and pre-clinical testing of an MDCK-based H1N1 pandemic influenza vaccine HNVAC from India. The cell bank and virus seed were characterized extensively. The cells were characterized by PCR, electron microscopy, and karyotyping, and found to be of female canine epithelial origin. The virus was confirmed by neutralization, haemagglutination inhibition, neuraminidase inhibition, and PCR and nucleotide sequencing. Adventitious agent testing was performed by both in vitro and in vivo studies. The in vitro studies included culturing, haemadsorption, haemagglutination, PCR and RT-PCR, whereas in vivo studies included passage in embryonated eggs and in laboratory animals. Both cell bank and virus seed were free of adventitious agents. MDCK cell lysates as well as cellular DNA did not produce tumours in newborn or adult laboratory animals. The bioprocess parameters were standardized to recover antigen with minimal levels of process-related impurities. The vaccine bulk was tested for the presence of specific antigen, and quantified by single radial immunodiffusion. Finally, non-adjuvanted and aluminium hydroxide adjuvanted vaccine formulations were found to be safe in preclinical toxicity studies in mice, rats, guinea pigs and rabbits, and immunogenic in mice and rabbits. This is the first and only cell culture-based influenza vaccine platform developed in any developing country.     

Feasibility of integrating a clinical decision support tool into an existing computerized physician order entry system to increase seasonal influenza vaccination in the emergency department

While emergency department (ED) seasonal influenza vaccination programs are feasible, reported implementation barriers include added staffing requirements to identify eligible patients and getting busy ED personnel to order and provide vaccination. We present a prospective, observational trial of integrating a clinical decision support tool into an existing ED computerized physician order entry (CPOE) system to increase ED seasonal influenza vaccination without added staffing resources, the operational barriers identified to program implementation, the revenue generated and data on opportunities for future quality improvement. Compared to the comparable pre-protocol period, ED influenza vaccination rose by 17.5% with a resultant profit margin of 34.5%.     

Effect of training, education, professional experience, and need for cognition on accuracy of exposure assessment decision-making

Results are presented from a study that investigated the effect of characteristics of occupational hygienists relating to educational and professional experience and task-specific experience on the accuracy of occupational exposure judgments. A total of 49 occupational hygienists from six companies participated in the study and 22 tasks were evaluated. Participating companies provided monitoring data on specific tasks. Information on nine educational and professional experience determinants (e.g. educational background, years of occupational hygiene and exposure assessment experience, professional certifications, statistical training and experience, and the 'need for cognition (NFC)', which is a measure of an individual's motivation for thinking) and four task-specific determinants was also collected from each occupational hygienist. Hygienists had a wide range of educational and professional backgrounds for tasks across a range of industries with different workplace and task characteristics. The American Industrial Hygiene Association exposure assessment strategy was used to make exposure judgments on the probability of the 95th percentile of the underlying exposure distribution being located in one of four exposure categories relative to the occupational exposure limit. After reviewing all available job/task/chemical information, hygienists were asked to provide their judgment in probabilistic terms. Both qualitative (judgments without monitoring data) and quantitative judgments (judgments with monitoring data) were recorded. Ninety-three qualitative judgments and 2142 quantitative judgments were obtained. Data interpretation training, with simple rules of thumb for estimating the 95th percentiles of lognormal distributions, was provided to all hygienists. A data interpretation test (DIT) was also administered and judgments were elicited before and after training. General linear models and cumulative logit models were used to analyze the relationship between accuracy of judgments and the various characteristics describing the participants. Data interpretation training (P < 0.0001), the company that the hygienist worked for (P < 0.0001), the total number of years hygienists had experience doing exposure assessments (P < 0.0001), and professional certifications (P < 0.0001) held by hygienists were found to be significant determinants of accurately predicting the correct exposure category for DITs as well as for task-specific judgment accuracy. Years of experience with a particular task (P < 0.0001), task evaluated, and the number of datapoints used for making judgments were found to be significant predictors of task-specific judgment accuracy. The NFC score was a predictor of the improvement in task judgment accuracy after training. The NFC score was itself predicted by determinants, such as company, years on current job, years of exposure assessment experience, and professional certifications. The results of this study are relevant not only for the case of industrial hygienists making exposure judgments prospectively but also possibly for those hygienists engaged in retrospective exposure assessments for epidemiological studies.     

Effect of training on exposure judgment accuracy of industrial hygienists

Results are presented from a study that investigated the effect of data interpretation training on exposure judgment accuracy of industrial hygienists across several companies in different industry sectors. Participating companies provided monitoring information on specific exposure tasks. Forty-nine hygienists from six companies participated in the study, and 22 industrial tasks were evaluated. The number of monitoring data points for individual tasks varied between 5 and 24. After reviewing all available basic characterization information for the job, task, and chemical, hygienists were asked to provide their judgment on the probability of the 95th percentile of the underlying exposure distribution being located in one of four exposure categories relative to the occupational exposure limit as outlined in the AIHA exposure assessment strategy. Ninety-three qualitative judgments (i.e., without reviewing monitoring data) and 2142 quantitative judgments (i.e., those made after reviewing monitoring data) were obtained. Data interpretation training, with simple rules of thumb for estimating 95th percentiles, was provided to all hygienists. A data interpretation test was administered before and after training. All exposure task judgments were collected before and after training. Data interpretation test accuracy for the hygienists increased from 48% to 67% after training (p < 0.001) and a significant underestimation bias was removed. Hygienist quantitative task judgment accuracy improved from 46% to 69% (p < 0.001) post-training. Accuracy results showed good improvement in industrial hygienists' quantitative judgments as a result of training. Hence, the use of statistical tools is promoted to improve judgments based on monitoring data and provide feedback and calibration to improve qualitative judgments. It may be worthwhile to develop standard training programs to improve exposure judgments.     

Effects of the antioxidant properties of millet species on oxidative stress and glycemic status in alloxan-induced rats

Reactive oxygen species play a significant role in accelerating the complications of diabetes mellitus, and antioxidants alleviate these effects. Finger millet (FM; Eleusine coracana) and kodo millet (KM; Paspalum scrobiculatum) are rich sources of phenolics, tannins, and phytates, which can act as antioxidants. Hence, the beneficial role of a millet-based diet in protecting against oxidative stress and maintaining glucose levels in vivo in type II diabetes was investigated. Whole grain flour of finger millet and KM was incorporated at 55% by weight in the basal diet fed to alloxan-induced diabetic rats over a period of 28 days. Blood glucose, cholesterol, enzymatic and nonenzymatic antioxidants, lipid peroxides in blood plasma, and glycation of tail tendon collagen were measured. The rats fed the KM-enriched diet showed a greater reduction in blood glucose (42%) and cholesterol (27%) than those fed the finger millet (36% and 13%). The levels of enzymatic (glutathione, vitamins E and C) and nonenzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and lipid peroxides were significantly reduced in diabetic animals and restored to normal levels in the millet-fed groups. Glycation of tail tendon collagen was only 40% in the finger millet–fed rats and 47% in the KM-fed rats compared to the controls. Diets containing whole grain millet meal flour can protect against hyperglycemic and alloxan-induced oxidative stress in Wistar rats.     

Evaluation of Viewpoints of Health Care Professionals on the Role of Ethics Committees and Hospitals in the Resolution of Clinical Ethical Dilemmas Based on Practice Environment

We sought to evaluate whether health care professionals’ viewpoints differed on the role of ethics committees and hospitals in the resolution of clinical ethical dilemmas based on practice location. We conducted a survey study from December 21, 2013 to March 15, 2014 of health care professionals at six hospitals (one tertiary care academic medical center, three large community hospitals and two small community hospitals). The survey consisted of eight clinical ethics cases followed by statements on whether there was a role for the ethics committee or hospital in their resolution, what that role might be and case specific queries. Respondents used a 5-point Likert scale to express their degree of agreement with the premises posed. We used the ANOVA test to evaluate whether respondent views significantly varied based on practice location. 240 health care professionals (108—tertiary care center, 92—large community hospitals, 40—small community hospitals) completed the survey (response rate: 63.6 %). Only three individual queries of 32 showed any significant response variations across practice locations. Overall, viewpoints did not vary across practice locations within question categories on whether the ethics committee or hospital had a role in case resolution, what that role might be and case specific queries. In this multicenter survey study, the viewpoints of health care professionals on the role of ethics committees or hospitals in the resolution of clinical ethics cases varied little based on practice location.