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Rationale: OX40-OX40 ligand (OX40L) interactions have been proposed to support induction of allergic airway inflammation, which may be attributable to OX40 signaling in CD4(+) helper T cells for adaptive immune responses. However, a possible involvement of natural killer T (NKT) cells in the pathogenesis suggests that the underlying mechanisms are not yet fully elucidated. Objectives: We aimed to characterize the OX40-modulated cellular contribution to allergic airway inflammation in a mouse model of house dust mite (HDM) allergen exposure. Methods: Mice were sensitized to HDM and, 3 weeks later, challenged with HDM on three consecutive days through the airways. Two days after the last exposure, bronchoalveolar lavage fluids and blood samples and lung tissues were evaluated for the airway inflammation. Measurements and Main Results: The development of HDM-induced eosinophilic airway inflammation was dependent on OX40 of both CD4(+) T cells and NKT cells; OX40 engagement on CD4(+) T cells in the sensitization led to pulmonary OX40L augmentation after the allergen challenge, which stimulated pulmonary NKT cells through OX40 to provide the pathogenic cytokine milieu. This was ablated by OX40L blockade by inhalation of the neutralizing antibody during the challenge, suggesting the therapeutic potential of targeting pulmonary OX40-OX40L interactions. Moreover, OX40 expression in CD4(+) T cells, but not in NKT cells, was reciprocally regulated by the helper T cell type 1-skewing transcription factor Runx3. Conclusions: OX40 on not only CD4(+) T cells but also NKT cells is involved in allergic airway inflammation. Notably, pulmonary blockade of OX40 ligation on NKT cells has therapeutic implications. [ABSTRACT FROM AUTHOR]

Afatinib is an epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI). In a randomized phase III study(Lux- Lung 3 study)employing patients harboring EGFR mutations, patients administered afatinib show a significantly longer progression free survival time(PFS)than those administeredcombination chemotherapy comprising cisplatin andpemetrexed . However, most of the patients(95.2%)treatedwith afatinib experiencedd iarrhea. In the present report, 16 patients with EGFR mutations were treatedby afatinib at our institution from May 2014 to December 2014. Twelve patients were administered a diarrhea prevention herbal medicine, Hange-shashin-to. Seven of 12 patients(58%)had no diarrhea during the 28 days of therapy. All 4 of the patients who did not receive Hange-shashin-to experienced diarrhea above Grade 1 within 6 days of starting therapy. The rate of diarrhea differed significantly between the patients receiving and not receiving Hangeshashin- to. In conclusion, preventive administration of Hange-shashin-to may reduce the occurrence of diarrhea during afatinib treatment.

The megathrust earthquake and the towering tsunami hit the east coast of Japan on March 11th of 2011 after intervals of 1,142 years. About 90 % of nearly 20,000 victims were drowned in devastating waves, while every town and city along the coast turned out to be a ruin. Over 400,000 people were forced to move to the evacuation centers where the evacuees slept on the floor without electricity, running water or heating systems at freezing nights. Emergency medicine, therefore, was more required during the evacuation phase than during the acute phase of the tsunami disaster. Here discussed is the phenomenon that the events happened mostly to the elderly evacuees especially in the swept area by silty polluted seawater.

Background: On 11 March 2011, the Tohoku earthquake and tsunami struck off the coast of northeastern Japan. Within 3 weeks, an increased number of pneumonia admissions and deaths occurred in local hospitals., Methods: A multicentre survey was conducted at three hospitals in Kesennuma City (population 74 000), northern Miyagi Prefecture. All adults aged ≥18 years hospitalised between March 2010 and June 2011 with community-acquired pneumonia were identified using hospital databases and medical records. Segmented regression analyses were used to quantify changes in the incidence of pneumonia., Results: A total of 550 pneumonia hospitalisations were identified, including 325 during the pre-disaster period and 225 cases during the post-disaster period. The majority (90%) of the post-disaster pneumonia patients were aged ≥65 years, and only eight cases (3.6%) were associated with near-drowning in the tsunami waters. The clinical pattern and causative pathogens were almost identical among the pre-disaster and post-disaster pneumonia patients. A marked increase in the incidence of pneumonia was observed during the 3-month period following the disaster; the weekly incidence rates of pneumonia hospitalisations and pneumonia-associated deaths increased by 5.7 times (95% CI 3.9 to 8.4) and 8.9 times (95% CI 4.4 to 17.8), respectively. The increases were largest among residents in nursing homes followed by those in evacuation shelters., Conclusions: A substantial increase in the pneumonia burden was observed among adults after the Tohoku earthquake and tsunami. Although the exact cause remains unresolved, multiple factors including population aging and stressful living conditions likely contributed to this pneumonia outbreak.

Marrow stromal cells (MSCs) isolated from mesenchymal tissues can propagate in vitro to some extent and differentiate into various tissue lineages to be used for cell-based therapies. Cellular senescence, which occurs readily in continual MSC culture, leads to loss of these characteristic properties, representing one of the major limitations to achieving the potential of MSCs. In this study, we investigated the effect of lysophosphatidic acid (LPA), a ubiquitous metabolite in membrane phospholipid synthesis, on the senescence program of human MSCs. We show that MSCs preferentially express the LPA receptor subtype 1, and an abrogation of the receptor engagement with the antagonistic compound Ki16425 attenuates senescence induction in continually propagated human MSCs. This anti-aging effect of Ki16425 results in extended rounds of cellular proliferation, increased clonogenic potential, and retained plasticity for osteogenic and adipogenic differentiation. Expressions of p16(Ink4a), Rb, p53, and p21(Cip1), which have been associated with cellular senescence, were all reduced in human MSCs by the pharmacological inhibition of LPA signaling. Disruption of this signaling pathway was accompanied by morphological changes such as cell thinning and elongation as well as actin filament deformation through decreased phosphorylation of focal adhesion kinase. Prevention of LPA receptor engagement also promoted ubiquitination-mediated c-Myc elimination in MSCs, and consequently the entry into a quiescent state, G(0) phase, of the cell cycle. Collectively, these results highlight the potential of pharmacological intervention against LPA signaling for blunting senescence-associated loss of function characteristic of human MSCs.