Syntheses and in vitro antimicrobial activities of thiazolo-[3,2-a]benzimidazol-3(2H)-ones

Taking advantage of the nucleophilic reactivity of the 2-methylene carbon atom in thiazolo[3,2-a]-benzimidazol-3(2H)-one, a number of 2-isatinylidene and 2-arylazo derivatives have been prepared. The novel compounds were subjected to antimicrobial testing.     

Automated sphygmomanometer in spinal cord injured patients during head-up tilt: an evaluation

Fifteen patients with spinal cord injury above T6 who were complete or had sensory sparing only were monitored during head-up tilt to evaluate the clinical application of an indirect blood pressure monitoring device, Vital Signs Measurement System. Comparisons of the machine's auscultatory and oscillometric modes were made to simultaneously auscultated blood pressures obtained by a physician. Mean differences and standard deviations were calculated. The comparison between automatic auscultatory and manual pressures yielded a mean difference and standard deviation of 1.8 mmHg and 4.2 mmHg for systolic, and -0.8 mmHg and 4.9 mmHg for diastolic pressures. The comparison between automatic oscillometric and manual pressures yielded a mean difference and standard deviation of 2.2 mmHg and 7.1 mmHg for systolic, and -12.7 mmHg and 7.5 mmHg for diastolic. All automatically obtained values except oscillometric diastolic pressure indicate machine accuracy suitable for clinical testing when compared to standards set by the Association for the Advancement of Medical Instrumentation for ideal test conditions. Uncontrolled patient or tubing movement, room noise, and the small subject population may have contributed to the less favorable values. This study suggests that the automatic sphygmomanometer tested is capable of clinically acceptable accuracy in a very dynamic setting.     

Therapeutic potential of medicinal plants for the management of scabies

Sarcoptes scabiei (S. scabiei), a parasite mite which causes scabies disease resulting in serious public health concern. The long‐term scabies disease can lead to complications such as septicemia, acute post‐streptococcal glomerulonephritis, heart disease, and secondary infections. Timely treatment to the affected patients is required to control the disease and get rid of the causative agent. Delayed diagnosis and inappropriate treatment can lead to serious consequences. The most common treatment strategy is the use of allopathic medicines which can immediately relieve the patient but have the drawback of side effects. The safe and cost‐effective alternative treatment strategy is the use of medicinal plants which have beneficial therapeutic potential against variety of diseases due to the presence of many bioactive phytoconstituents with no or minimal side effects. For the present review, the published articles describing scabies disease and its phytotherapeutic modalities were searched through different data bases including Google Scholar, PubMed, Medline, and ScienceDirect using the keywords like S. scabiei, prevalence of scabies disease, and phytotherapy of scabies. A large number of medicinal plants, such as Melaleuca alternifolia, Curcuma longa, Azadirachta indica, Rosmarinus officinalis, Capsicum annuum, Cinnamomum camphor, Solanum nigrum, and Eupatorium perfoliatum, have been reviewed for the promising future treatments of scabies. All the studied plants have many bioactive compounds with potential therapeutic effects against scabies and can be utilized for therapeutic purposes for this disease. This literature study has limitations because of the lack of sufficient data due to limited pre‐clinical trials in this particular area. This review provides a baseline to explore the therapeutic potential of these medicinal plants against skin diseases. However, extensive studies are required to identify, authenticate, and characterize the bioactive compounds present in these plants which may lead to value addition in pharmaceutical industries providing the cost‐effective way of treatment with minimal side effects.     

Benefits of lower neonatal platelet transfusion thresholds

• Degree of thrombocytopenia is not a predictor of bleeding risk in neonates, yet most platelet transfusions are given prophylactically in non-bleeding premature infants.
• Recent data support a lower platelet transfusion threshold of 25 × 10⁹/L in non-bleeding premature neonates and indicate that higher transfusion thresholds may be associated with harm including increased risk of death and bleeding.
• The mechanism of increased adverse events with higher platelet transfusion threshold is unknown, but considerations include adult platelets disrupting the neonatal hemostatic balance of hypoactive platelets in a hypercoagulable and fragile environment and having a pro-inflammatory effect.

     

Optimal vaccine trial design when estimating vaccine efficacy for susceptibility and infectiousness from multiple populations

Vaccination can have important indirect effects on the spread of an infectious agent by reducing the level of infectiousness of vaccinees who become infected. To estimate the effect of vaccination on infectiousness, one typically requires data on the contacts between susceptible and infected vaccinated and unvaccinated people. As an alternative, we propose a trial design that involves multiple independent and interchangeable populations. By varying the fraction of susceptible people vaccinated across populations, we obtain an estimate of the reduction in infectiousness that depends only on incidence data from the vaccine and control groups of the multiple populations. One can also obtain from these data an estimate of the reduction of susceptibility to infection. We propose a vaccination strategy that is a trade-off between optimal estimation of vaccine efficacy for susceptibility and of vaccine efficacy for infectiousness. We show that the optimal choice depends on the anticipated efficacy of the vaccine as well as the basic reproduction number of the underlying infectious disease process. Smaller vaccination fractions appear desirable when vaccine efficacy is likely high and the basic reproduction number is not large. This strategy avoids the potential for too few infections to occur to estimate vaccine efficacy parameters reliably. © 1998 John Wiley & Sons, Ltd.     

SmartSIM ‐ a virtual reality simulator for laparoscopy training using a generic physics engine

Virtual reality (VR) training simulators have started playing a vital role in enhancing surgical skills, such as hand–eye coordination in laparoscopy, and practicing surgical scenarios that cannot be easily created using physical models. We describe a new VR simulator for basic training in laparoscopy, i.e. SmartSIM, which has been developed using a generic open‐source physics engine called the simulation open framework architecture (SOFA). This paper describes the systems perspective of SmartSIM including design details of both hardware and software components, while highlighting the critical design decisions. Some of the distinguishing features of SmartSIM include: (i) an easy‐to‐fabricate custom‐built hardware interface; (ii) use of a generic physics engine to facilitate wider accessibility of our work and flexibility in terms of using various graphical modelling algorithms and their implementations; and (iii) an intelligent and smart evaluation mechanism that facilitates unsupervised and independent learning.     

How we approach transfusions in a patient with high risk of alloimmunization from McLeod phenotype

McLeod phenotype—caused by the missing Xk protein—is a very rare red cell phenotype, one characteristic of McLeod syndrome, and sometimes associated with X-linked chronic granulomatous disease (CGD). Diagnosis of McLeod phenotype is important for appropriate transfusion management, because red blood cells from all healthy donors will have the Xk protein with its Kx antigen and can lead to red cell antibody formation without the ability to find compatible McLeod phenotype blood for transfusion. We offer a review and approach to diagnosis of the McLeod phenotype and special transfusion considerations.     

Anti‐tuberculosis effect of isoniazid scales accurately from zebrafish to humans

Background and PurposeThere is a clear need for innovation in anti‐tuberculosis drug development. The zebrafish larva is an attractive disease model in tuberculosis research. To translate pharmacological findings to higher vertebrates, including humans, the internal exposure of drugs needs to be quantified and linked to observed response.Experimental ApproachIn zebrafish studies, drugs are usually dissolved in the external water, posing a challenge to quantify internal exposure. We developed experimental methods to quantify internal exposure, including nanoscale blood sampling, and to quantify the bacterial burden, using automated fluorescence imaging analysis, with isoniazid as the test compound. We used pharmacokinetic–pharmacodynamic modelling to quantify the exposure–response relationship responsible for the antibiotic response. To translate isoniazid response to humans, quantitative exposure–response relationships in zebrafish were linked to simulated concentration–time profiles in humans, and two quantitative translational factors on sensitivity to isoniazid and stage of infection were included.Key ResultsBlood concentration was only 20% of the external drug concentration. The bacterial burden increased exponentially, and an isoniazid dose corresponding to 15 mg·L⁻¹ internal concentration (minimum inhibitory concentration) leads to bacteriostasis of the mycobacterial infection in the zebrafish. The concentration–effect relationship was quantified, and based on that relationship and the translational factors, the isoniazid response was translated to humans, which correlated well with observed data.Conclusions and ImplicationsThis proof of concept study confirmed the potential of zebrafish larvae as tuberculosis disease models in translational pharmacology and contributes to innovative anti‐tuberculosis drug development, which is very clearly needed.     

Fibrinolysis parameters in Sudanese women with severe preeclampsia

Background: Although preeclampsia remains a major cause of maternal and fetal morbidity and mortality, its pathogenesis is not fully understood. Coagulation and fibrinolysis changes were suggested to have a role in the pathogenesis of preeclampsia. Objectives: A case-control study was conducted in Medani Hospital, Sudan, to investigate thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen-activated inhibitor (PAI) in women with severe preeclampsia. Obstetrics and medical history was gathered using questionnaire. TAFI, PAI-1, and PAI-2 levels were measured using ELISA. Results: In comparison with the controls, women with severe preeclampsia had significantly higher levels [mean (SD)] of TAFI [3.4 (1.1) vs. 3.0(0.7) ng/ml, P = 0.019], PAI-1 [3.2 (1.3) vs. 2.5(1.0), IU/ml, P = 0.001], and significantly lower PAI-2 level [4.2(1.3) vs. 5.8(2.6) ng/ml, P < 0.001]. In linear regression, severe preeclampsia was significantly associated with TAFI (0.408 ng/ml, P = 0.038), PAI-1 (0.722, IU/ml P = 0.003), and PAI-2 (?1.745, ng/ml, P < 0.001). Conclusion: The current study revealed a significant increase level of TAFI and PAI-1, coupled with a decrease in PAI-2 in women with severe preeclampsia in comparison with the control group.