Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

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We present a search-based method for the generation of a terrainadaptive optimal gait of a six-legged walking machine. In this, several heuristic rules have been proposed to reduce the search effort. We identify the useful support states of the machine and form a table to indicate for each of these states the list of other states to which a transition can be made. This helps in converging to and maintaining a periodic gait through a limited search while retaining adequate options to deviate from such a gait as and when needed. The criterion for optimization is coded into a function that evaluates the promise of a node in the search graph. We have shown how this function may be designed to generate the common periodic gaits like the wave gait, the equal phase gait, and the follow-the-leader gait. The purpose is to demonstrate that the proposed method is sufficiently general and can cater to a wide range of optimizing requirements. KEY WORDS—walking machine, graph search, heuristic search, periodic gait, free gait 1

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Levamisole induces interleukin-18 and shifts type 1/type 2 cytokine balance

Immune responses can be classified, according to the predominant cytokines involved, into type 1 (featuring interferon-γ, IFN-γ) and type 2 (featuring interleukin-4, IL-4); imbalance between type 1 and type 2 cytokine compartments has been implicated in many human diseases. Levamisole is a drug with an unknown mode of action that has been used to boost immunity in infectious diseases including leprosy, and in some cancers. To test the hypothesis that levamisole acts by inducing a shift to a type 1 immune response, we used Brown Norway (BN) rats, which are markedly biased to type 2 responses. BN rats treated with levamisole showed a dose-dependent rise in serum IFN-γ and fall in serum immunoglobulin E (IgE) level. Detailed analysis of cytokine gene expression showed upregulation of IFN-γ and downregulation of IL-4 messenger RNA. This coincided with marked upregulation of IL-18, a recently characterized cytokine with potent activity in stimulating IFN-γ production. IL-12 was not induced. Further, the type 2 response induced in BN rats by mercuric chloride was markedly attenuated when rats were pretreated with levamisole: there was a 2-log reduction in maximum serum IgE level and marked attenuation of IL-4 gene upregulation. These data indicate that levamisole acts by resetting the immune balance towards a type 1 response via induction of IL-18. Our findings provide a direction for development of more specific immunomodulating therapy

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, there were 27.08 million (95% uncertainty interval [UI] 24.30-30.30 million) new cases of TBI and 0.93 million (0.78-1.16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55.50 million (53.40-57.62 million) and of SCI was 27.04 million (24 .98-30 .15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8.4% (95% UI 7.7 to 9.2), whereas that of SCI did not change significantly (-0.2% [-2.1 to 2.7]). Age-standardised incidence rates increased by 3.6% (1.8 to 5.5) for TBI, but did not change significantly for SCI (-3.6% [-7.4 to 4.0]). TBI caused 8.1 million (95% UI 6. 0-10. 4 million) YLDs and SCI caused 9.5 million (6.7-12.4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe

Insights into Insect Resistance in Pulse Crops: Problems and Preventions

Globally, insect pests cause considerable damage to pulse crops. Hence developing broad-spectrum resistance against insect pests has been a major challenge to pulse growers and scientists. Traditionally, cultural practices and synthetic insecticides are being utilized for effective control of insect pests since ages. Apart from these, other strategies such as host plant resistance, insect-resistant transgenic crops, and IPM are also being used to manage the infestation in pulse crops. Though screening of genetic resources for insect resistance has been promising in some pulse crops, fertility barriers and linkage drag minimize the effective utilization of identified resistance in commercially viable crop breeding programs. In parallel, insect-resistant transgenic plants have been developed using various insecticidal proteins from various sources including Bacillus thuringiensis endotoxin, plant protease inhibitors, chitinases, alpha-amylase inhibitors, secondary metabolites, and vegetative insecticidal proteins (VIPs). Deploying transgenic plants with high levels of toxin expression by gene pyramiding is another practical option to delay the resistance development in insects. Nevertheless, the success achieved so far in managing insect pests is limited mainly due to the complex mechanisms underlying the defense strategies together with the lack of precision in screening techniques. Here, we discuss the recent progress and current status of studies toward developing resistance to the most common insect pests of pulses. This chapter points the lack of detailed molecular studies exploring the insect resistance that can advance our knowledge on plant resistance mechanisms and the genes involved. Therefore, a step forward now will be on exploiting natural variations with novel technologies in combination of eco-safe management practices to develop durable insect-resistant pulse crops. Despite technical and regulatory difficulties, developing insect resistance should be the major priority area for future breeding and genetic engineering studies aiming at pulse crop improvement