Community Trial on Heat Related-Illness Prevention Behaviors and Knowledge for the Elderly

This study aims to explore whether broadcasting heat health warnings (HHWs), to every household and whether the additional home delivery of bottled water labeled with messages will be effective in improving the behaviors and knowledge of elderly people to prevent heat-related illness. A community trial on heat-related-illness-prevention behaviors and knowledge for people aged between 65 and 84 years was conducted in Nagasaki, Japan. Five hundred eight subjects were selected randomly from three groups: heat health warning (HHW), HHW and water delivery (HHW+W), and control groups. Baseline and follow-up questionnaires were conducted in June and September 2012, respectively. Of the 1524 selected subjects, the 1072 that completed both questionnaires were analyzed. The HHW+W group showed improvements in nighttime AC use (p = 0.047), water intake (p = 0.003), cooling body (p = 0.002) and reduced activities in heat (p = 0.047) compared with the control, while the HHW group improved hat or parasol use (p = 0.008). An additional effect of household water delivery was observed in water intake (p = 0.067) and cooling body (p = 0.095) behaviors. HHW and household bottled water delivery improved heat-related-illness-prevention behaviors. The results indicate that home water delivery in addition to a HHW may be needed to raise awareness of the elderly

Genetic screening for malignant hyperthermia and comparison of clinical symptoms in Japan

Malignant hyperthermia (MH) is an anaesthetic complication that causes an abnormal hypermetabolic state. RYR1 encoding ryanodine receptors of the sarcoplasmic reticulum and CACNA1S encoding α subunits of dihydropyridine receptors are known to be associated with MH pathogenicity. We performed genetic screening using next-generation sequencing to evaluate the prevalence of genes associated with MH pathogenicity and clinical symptoms. This was a retrospective cohort study wherein next-generation sequencing data of 77 families diagnosed with MH predisposition by calcium-induced calcium release (CICR) tests from 1995 to 2019 was used to search for RYR1 and CACNA1S variants. Furthermore, the clinical symptoms and predisposition tests in participants with RYR1 and CACNA1S variants were compared. In the 77 families, 44.2%, 7.8%, and 48.1% individuals had RYR1, CACNA1S, and neither RYR1 nor CACNA1S variants, respectively. Clinically significant differences were found in the maximum body temperature, maximum elevated body temperature for 15 min, creatinine kinase level, and CICR rate between the RYR1 and CACNA1S groups. The prevalence of pathogenic CACNA1S variants appears to be prominent in Japan. The severity of clinical symptoms and the CICR rate were greater in individuals with RYR1 variants than in those with CACNA1S variants, likely due to more direct regulation of calcium levels by ryanodine receptors than by dihydropyridine receptors. Genetic analysis of MH in future studies may help identify other genes associated with MH, which will further clarify the relationship between genotypes and MH symptoms and contribute to safer anaesthesia practice.This study was supported by a Grant-in-Aid for Young Scientists (grant number: 17K16733 to Y.N. and 20K17783 to R.K.) from the Japan Society for the Promotion of Science and by the Takeda Science Foundation (H.K.)

Study on the Development of a New Device with Dual Cameras for Evaluating Expiratory Nasal Flow

[Background] Use of the Glatzel mirror for measuring expiratory nasal flow in preschool children has the disadvantage of vagueness, and the mirror may induce fear and inhibition of interest in those children. In response to these limitations, we developed a new device with dual cameras for measuring expiratory nasal flow in 2 to 6 year old children. The aim of this study is to compare the Glatzel mirror and the new device, in terms of accurate assessment of expiratory nasal flow, children’s feelings, and correlation to each child’s profile. [Methods] This study evaluated 20 cleft lip and palate patients and 21 healthy children aged between 2 and 6 (under 7) years. After consent was granted, a 4-week screening period was undertaken followed by inspection at weeks 8, 16, 24, and 32. Each inspection was conducted while the children were asked to pronounce various sounds and comprised three stages: i) use of the Glatzel mirror, ii) subjective visual assessment using the new device, and iii) image recording by dual cameras of the new device. Questionnaires for the new device were administered at the initial and final inspections. To contrast the results between the Glatzel mirror and the new device, the numbers that indicated values of subjective visual assessment and camera assessment greater than the assessment values of the Glatzel mirror were compared. For measuring the children’s responses to the new device compared with those to the Glatzel mirror, the answers to the questionnaires were compared. For the comparison of the children’s profiles (age and sex) and feelings, the numbers of subjects who could use the new device were measured. [Results] The camera assessment of the new device indicated significantly greater values than that of the Glatzel mirror (P < 0.05). The feelings of the subjects to the new device mostly improved as the study progressed. Subjects aged 3 years and older were generally able to use the new device from the initial inspection. For both sexes, as the inspection progressed, the number occasions of successful use increased. [Conclusion] This study demonstrated the superiority of the new device with dual cameras to the Glatzel mirror in terms of functionality and attitude of children

A Role of Aromatase in Sjögren Syndrome

Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is a converting enzyme from androgens to estrogens. In the present study, we used female aromatase gene knockout (ArKO) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory lesions in the lacrimal and salivary glands of ArKO mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArKO mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 (MCP-1) increased in white adipose tissue (WAT) of ArKO mice and was significantly higher than that in wild-type mice. Moreover, an increased number of inflammatory M-1 macrophage was observed in WAT of ArKO mice. A significantly increased MCP-1 mRNA expression of the salivary gland tissue in ArKO was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sjögren’s syndrome (SS) were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play in a key role in the pathogenesis of SS-like lesions by controlling the target organ and adipose tissue-associated macrophage

Cross-talk between autoimmunity and tumor immunity

Both autoimmunity and tumor immunity are immune responses against self-tissues or cells. However, the precise similarity or difference between them remains unclear. In this study, to understand a novel mechanism of tumor immunity, we performed transplantation experiments with a murine autoimmune model, C57BL/6J (B6)/lpr mice. A melanoma cell line, B16F10 cells, or granulocyte macrophage colony-stimulating factor- overexpressing B16F10 (B16F10/mGM) cells were transplanted into B6 or B6/lpr mice. Tumor growth by transplanted B16F10/mGM cells was significantly accelerated in B6/lpr mice compared with that in B6 mice. The accumulation of M1 macrophages in the tumor tissues of B6/lpr recipient mice was significantly lower compared with that in the control mice. In vitro co-culture experiment showed that impaired differentiation into M1 macrophages was observed in B6/lpr mice. The number of tumor vessels and vascular endothelial growth factor (VEGF) expression were also significantly enhanced in the tumor tissues of B6/lpr mice compared with those in the B6 mice. Moreover, VEGF expression was correlated with the increased expression of hypoxia-inducible factor-1α in the tumor tissues of B6/lpr mice. These results suggest that dysfunctional tumor immunity and enhanced angiogenesis in autoimmunity influence tumor growth

Fas-Independent T-Cell Apoptosis by Dendritic Cells Controls Autoimmune Arthritis in MRL/lpr Mice

Background: Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF)-kB ligand (RANKL)-activated dendritic cells (DCs) play a key role in the pathogenesis of rheumatoid arthritis (RA) in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity. Methods and Finding: Cellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4+ T, B, and CD4‾CD8‾ double negative (DN) T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) on T cells and TRAIL on Fas-deficient DCs in MRL/lpr mice. Conclusion: These results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice

Odontogenic stem cells

Epithelial cell rests of Malassez (ERM) are quiescent epithelial remnants of the Hertwig’s epithelial root sheath (HERS) that are involved in the formation of tooth roots. ERM cells are unique epithelial cells that remain in periodontal tissues throughout adult life. They have a functional role in the repair/regeneration of cement or enamel. Here, we isolated odontogenic epithelial cells from ERM in the periodontal ligament, and the cells were spontaneously immortalized. Immortalized odontogenic epithelial (iOdE) cells had the ability to form spheroids and expressed stem cell-related genes. Interestingly, iOdE cells underwent osteogenic differentiation, as demonstrated by the mineralization activity in vitro in mineralization-inducing media and formation of calcification foci in iOdE cells transplanted into immunocompromised mice. These findings suggest that a cell population with features similar to stem cells exists in ERM and that this cell population has a differentiation capacity for producing calcifications in a particular microenvironment. In summary, iOdE cells will provide a convenient cell source for tissue engineering and experimental models to investigate tooth growth, differentiation, and tumorigenesis