Fatal cytokine release syndrome by an aberrant FLIP/STAT3 axis

Inflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune responses can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, a protein that controls caspase-8 death pathways, was highly expressed in myeloid cells of COVID-19 lungs. FLIP controlled CRS by fueling a STAT3-dependent inflammatory program. Indeed, constitutive expression of a viral FLIP homolog in myeloid cells triggered a STAT3-linked, progressive, and fatal inflammatory syndrome in mice, characterized by elevated cytokine output, lymphopenia, lung injury, and multiple organ dysfunctions that mimicked human CRS. As STAT3-targeting approaches relieved inflammation, immune disorders, and organ failures in these mice, targeted intervention towards this pathway could suppress the lethal CRS inflammatory state

Compliance: Encoded information and behavior in a team of cooperative object handling robots

The role of compliant elements in a team of distributed object handling robots is discussed from the information, robot behavior, and cooperation protocol points of view. Also main benefits and some limitations on implementing compliant units in a group of distributed cooperative object handling robots are shown. It is proved that, any error in position of the stiff robots executing the Constrain-Move strategy [1] to transport an object will cause a movement lock in the system. Also, difficulties in stabilizing the robot-object contact in a team of distributed mobile object handling robots with stiff arms are discussed. It is verified that, specially designed compliant arms can be used to simplify the robot-object stabilization task and to remove the movement lock. Doing so, the system would be less sensor dependent and the robot control system is simplified. In addition, a distributed method is developed to help the compliant robots to solve the lock problem when there is a limitation on possible softness of the arms. Based on the discussions, a novel compliant arm is introduced and its main features are reviewed. Moreover, the role of this compliant mechanism in simplifying the distributed cooperation and coordination protocols, the robot information system, and the robot controller for executing th

Cost-benefit Analysis of IUI and IVF based on willingness to pay approach; case study: Iran

Assisted reproductive technologies (ARTs) are often considered luxury services by policymakers and the general population, which are always susceptible of removal from public funding of health care. The analysis of the economic aspects of this scope seems essential due to the high prevalence of infertility in Iran and the high costs of infertility treatments. This study aimed to investigate the value put on IUI and IVF treatments by communities in Iran and the affordability of services based on community preferences. A cost-benefit analysis (CBA) was performed based on the WTP approach, and the contingent valuation method (CVM) was used to estimate WTP for IUI and IVF using a researcher-made survey in two cities of Kerman and Isfahan, Iran, in 2016�17. The sample size was 604, and the study sample frame to estimate WTP included two groups of couples who were/were not aware of their fertility statuses. The costs of one cycle of IUI and IVF were calculated according to the treatment protocols, tariffs of 2016�17, and medical information records of patients. The mean direct and indirect medical costs of one cycle of IUI and IVF were equivalent to 19561140 and 60897610 IRR, respectively. Also, the mean WTP for IUI and IVF treatments were obtained of 15941061 and 28870833 IRR, respectively. The demand for IUI and IVF treatments was elastic and the community was sensitive to price changes of these treatment methods. IUI and IVF treatments brought no positive net benefits, and economic variables had the highest impact on the WTP and community preferences, indicating the significant role of financial constraints in the community�s valuation for advanced infertility treatments in Iran. © 2020 Darvishi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Association of pesticide exposure with human congenital abnormalities

Human pesticide exposure can occur both occupationally and environmentally during manufacture and after the application of indoor and outdoor pesticides, as well as through consumption via residues in food and water. There is evidence from experimental studies that numerous pesticides, either in isolation or in combination, act as endocrine disruptors, neurodevelopmental toxicants, immunotoxicants, and carcinogens. We reviewed the international literature on this subject for the years between 1990 and 2017. The studies were considered in this review through MEDLINE and WHO resources. Out of the n = 1817 studies identified, n = 94 were reviewed because they fulfilled criteria of validity and addressed associations of interest. Epidemiological studies have provided limited evidence linking pre- and post-natal exposure to pesticides with cancers in childhood, neurological deficits, fetal death, intrauterine growth restriction, preterm birth, and congenital abnormalities (CAs). In this review, the potential association between pesticide exposure and the appearance of some human CAs (including among others musculoskeletal abnormalities; neural tube defects; urogenital and cardiovascular abnormalities) was investigated. A trend towards a positive association between environmental or occupational exposure to some pesticides and some CAs was detected, but this association remains to be substantiated. Main limitations of the review include inadequate exposure assessment and limited sample size. Adequately powered studies with precise exposure assessments such as biomonitoring, are warranted to clarify with certainty the potential association between pesticide exposure and human CAs. © 2018 Elsevier Inc