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Somatic mutations are the most common oncogenic variants in lung cancer and are associated with poor prognosis. Using a-induced lung cancer mouse model, CC-LR, we previously showed a role for inflammation in lung tumorigenesis through activation of the NF-κB pathway, along with induction of interleukin 6 (IL6) and an IL17-producing CD4 T-helper cell response. IL22 is an effector molecule secreted by CD4 and γδ T cells that we previously found to be expressed in CC-LR mice. IL22 mostly signals through the STAT3 pathway and is thought to act exclusively on nonhematopoietic cells with basal IL22 receptor (IL22R) expression on epithelial cells. Here, we found that higher expression of in patients with-mutant lung adenocarcinoma was an independent indicator of poor recurrence-free survival. We then showed that genetic ablation of in CC-LR mice (CC-LR/IL22KO mice) caused a significant reduction in tumor number and size. This was accompanied by significantly lower tumor cell proliferation, angiogenesis, and STAT3 activation. ablation was also associated with significant reduction in lung-infiltrating inflammatory cells and expression of protumor inflammatory cytokines. Conversely, this was accompanied with increased antitumor Th1 and cytotoxic CD8 T-cell responses, while suppressing the protumor immunosuppressive T regulatory cell response. In CC-LR/IL22KO mice, we found significantly reduced expression of core stemness genes and the number of prototypical SPCCCSP stem cells. Thus, we conclude that IL22 promotes -mutant lung tumorigenesis by driving a protumor inflammatory microenvironment with proliferative, angiogenic, and stemness contextual cues in epithelial/tumor cells..

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BACKGROUND Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin–blocking antibody and those that received an isotype control antibody. CONCLUSION P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin–blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.

This study showed that overall retinal electrophysiologic function in patients with vitiligo or psoriasis is significantly impaired compared with normal population, independent of age and sex.

This retrospective study aimed to address whether or to what extent spatial and non-spatial factors with a focus on a healthcare delivery system would influence successful tuberculosis (TB) treatment outcomes in Urmia, Iran. In this cross-sectional study, data of 452 new TB cases were extracted from Urmia TB Management Center during a 5-year period. Using the Geographical Information System (GIS), health centers and study subjects' locations were geocoded on digital maps. To identify the statistically significant geographical clusters, Average Nearest Neighbor (ANN) index was used. Logistic regression analysis was employed to determine the association of spatial and non-spatial variables on the occurrence of adverse treatment outcomes. The spatial clusters of TB cases were concentrated in older, impoverished and outskirts areas. Although there was a tendency toward higher odds of adverse treatment outcomes among urban TB cases, this finding after adjusting for distance from a given TB healthcare center did not reach statistically significant. This article highlights effects of spatial and non-spatial determinants on the TB adverse treatment outcomes, particularly in what way the policies of healthcare services are made. Accordingly, non-spatial determinants in terms of low socio-economic factors need more attention by public health policy makers, and then more focus should be placed on the health delivery system, in particular men's health.

With more than 150,000 deaths per year in the US alone, lung cancer has the highest number of deaths for any cancer. These poor outcomes reflect a lack of treatment for the most common form of lung cancer, non-small cell lung carcinoma (NSCLC). Lung adenocarcinoma (ADC) is the most prevalent subtype of NSCLC, with the main oncogenic drivers being KRAS and epidermal growth factor receptor (EGFR). Whereas EGFR blockade has led to some success in lung ADC, effective KRAS inhibition is lacking. KRAS-mutant ADCs are characterized by high levels of gel-forming mucin expression, with the highest mucin levels corresponding to worse prognoses. Despite these well-recognized associations, little is known about roles for individual gel-forming mucins in ADC development causatively. We hypothesized that MUC5AC/Muc5ac, a mucin gene known to be commonly expressed in NSCLC, is crucial in KRAS/Kras-driven lung ADC. We found that MUC5AC was a significant determinant of poor prognosis, especially in patients with KRAS-mutant tumors. In addition, by using mice with lung ADC induced chemically with urethane or transgenically by mutant-Kras expression, we observed significantly reduced tumor development in animals lacking Muc5ac compared with controls. Collectively, these results provide strong support for MUC5AC as a potential therapeutic target for lung ADC, a disease with few effective treatments.

Abstract. Crimean-Congo hemorrhagic fever is a tick-borne viral zoonosis with the potential of human-to-human transmission with case fatality rates from 3% to 50%. The incubation period depends on host, route of infection, and viral dose. Herein, we report a nosocomial spread of the disease in a hospital at Mashhad, northeastern Iran, with a very short incubation period for one of the secondary cases. The patient was a medical student who had a negligible contact with a Crimean-Congo hemorrhagic fever patient during his admission to the hospital. The time interval between the contact and the onset of symptoms was merely 20 hours. Unfortunately, he died within 1 week of exposure.