COVID-19 transmission in dental and oral/maxillofacial surgical practice during pandemic: questionnaire survey in 51 university hospitals in Japan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a major public health problem. Dental procedures that generate aerosols are considered to impose a high risk of infection; therefore, dental professionals, such as dentists and dental hygienists, may be at high risk of viral transmission. However, few studies have reported COVID-19 clusters in dental care settings. AIM: To investigate whether dental and oral/maxillofacial procedures are associated with the occurrence of COVID-19 clusters and measures taken to prevent nosocomial infection in dental clinics. METHODS: An online questionnaire survey on clinical activities (administrative control), infection control measures (environmental/engineering control, personal protective equipment, etc.), and confirmed or probable COVID-19 cases among patients and clinical staff was administered to the faculties of the dental and oral/maxillofacial surgical departments of university hospitals. FINDINGS: Fifty-one faculty members completed the questionnaire. All members were engaged in the treatment of dental and oral surgical outpatients and actively implemented standard precautions. Fourteen faculty members treated patients with COVID-19, but no infections transmitted from the patients to the medical staff were observed. In seven facilities, patients were found to have the infection after treatment (medical staff came in close contact), but there was no transmission from patients to medical staff. Four facilities had medical staff with infections, but none of them exhibited disease transmission from staff to patients. CONCLUSION: COVID-19 clusters are unlikely to occur in dental and oral surgical care settings if appropriate protective measures are implemented.

Pebbles and sand on asteroid (162173) Ryugu: In situ observation and particles returned to Earth.

The Hayabusa2 spacecraft investigated the C-type (carbonaceous) asteroid (162173) Ryugu. The mission performed two landing operations to collect samples of surface and subsurface material, the latter exposed by an artificial impact. We present images of the second touchdown site, finding that ejecta from the impact crater was present at the sample location. Surface pebbles at both landing sites show morphological variations ranging from rugged to smooth, similar to Ryugu's boulders, and shapes from quasi-spherical to flattened. The samples were returned to Earth on 6 December 2020. We describe the morphology of >5 grams of returned pebbles and sand. Their diverse color, shape, and structure are consistent with the observed materials of Ryugu; we conclude that they are a representative sample of the asteroid.

Reduced rotavirus vaccine efficacy in protein malnourished human-faecal-microbiota-transplanted gnotobiotic pig model is in part attributed to the gut microbiota.

The low efficacy of human rotavirus (HRV) vaccines in low- and middle-income countries (LMIC) remains a major challenge for global health. Protein-calorie malnutrition (kwashiorkor) affects the gut microbiota and compromises immune development, leading to environmental enteropathy, vaccine failures, and increased susceptibility to enteric diseases in young children. Relationship between diet and reduced vaccine efficacy in developing countries is not well established; therefore, we investigated the interconnections between the host-microbiota-nutrition-HRV vaccine using HRV-vaccinated, human infant faecal microbiota (HIFM)-transplanted neonatal gnotobiotic pigs fed with a protein deficient or sufficient diet. The microbiota from faecal, intestinal (duodenum, ileum, jejunum, and colon), and systemic tissue (liver, spleen, and mesenteric lymph node [MLN]) samples was analysed before and after HRV challenge using MiSeq 16S rRNA sequencing. Overall, microbiota from deficient fed HIFM pigs displayed, compared to the sufficient group, significantly higher Shannon index, especially in the faeces and lower intestines; higher level of Proteus and Enterococcus, and lower level of Bifidobacterium, Clostridium, and Streptococcus in the three types of samples collected (P<0.05); and higher unique operational taxonomic units (OTUs), especially in the systemic tissues. Further, the multivariate analysis between microbiota and immunologic data showed that 38 OTUs at the genus level correlated (r2≤0.5 or ≥-0.5; P<0.05) with at least one host immune response parameter (regulatory [Tregs and transforming growth factor-ß], effectors [interferon (IFN)-γ+ CD4+ and CD8+ T cells, IFN-γ and interleukin (IL)-12], and inflammatory [tumour necrosis factor-α, IL-17 and IL-22]) and with opposite trends between diet groups. Differences described above were increased after HRV challenge. We demonstrated that a protein deficient diet affects the composition of the gut microbiota and those changes may further correlate with immune responses induced by HRV and perturbed by the deficient diet. Thus, our findings suggest that the reduced efficacy of HRV vaccine observed in Gn pig model is in part attributed to the altered microbiota composition.

Relationship between vancomycin-associated nephrotoxicity and the number of combined nephrotoxic agents.

Vancomycin is associated with nephrotoxicity; however, the influence of the number of combined nephrotoxic agents on the incidence of vancomycin nephrotoxicity has not been clarified. We investigated patient backgrounds in 148 inpatients who received vancomycin treatment. The patients were divided into nephrotoxicity (n=35) and non-nephrotoxicity (n=113) groups. A comparison of the patient backgrounds in the two groups revealed significant differences in weight, changes in serum creatinine before vancomycin administration, blood urea nitrogen to serum creatinine ratio, length of vancomycin therapy, vancomycin trough concentration, and number of combined nephrotoxic agents. Multiple logistic regression analysis using these six factors as autonomous variables showed that the highest vancomycin trough concentration (odds ratio, 1.080; 95% confidence interval, 1.030-1.140; p = 0.003) and the number of combined nephrotoxic agents (odds ratio, 1.590; 95% confidence interval, 1.120-2.260; p = 0.010) were significantly related to nephrotoxicity.

Development of an in vitro immunobiotic evaluation system against rotavirus infection in bovine intestinal epitheliocytes.

The bovine intestinal epithelial cell line (BIE cells) expresses the Toll-like receptor (TLR)3 and is able to mount an antiviral immune response after the stimulation with poly(I:C). In the present study, we aimed to further characterise the antiviral defence mechanisms in BIE cells by evaluating the innate immune response triggered by rotavirus (RV) infection. In addition, we attempted to determine whether immunobiotic bifidobacteria are able to confer protection of BIE cells against RV infection by beneficially modulating the antiviral immune response. RV OSU (porcine) and UK (bovine) effectively infected BIE cells, while a significant lower capacity to infect BIE cells was observed for human (Wa) and murine (EW) RV. We observed that viral infection in BIE cells triggered TLR3/RIG-I-mediated immune responses with activation of IRF3 and TRAF3, induction of interferon beta (IFN-ß) and up-regulation of inflammatory cytokines. Our results also demonstrated that preventive treatments with Bifidobacterium infantis MCC12 or Bifidobacterium breve MCC1274 significantly reduced RV titres in infected BIE cells and differentially modulated the innate immune response. Of note, both strains significantly improved the production of the antiviral factor IFN-ß in RV-infected BIE cells. In conclusion, this work provides comprehensive information on the antiviral immune response of BIE cells against RV, that can be further studied for the development of strategies aimed to improve antiviral defences in bovine intestinal epithelial cells. Our results also demonstrate that BIE cells could be used as a newly immunobiotic evaluation system against RV infection for application in the bovine host.

Pituitary adenylate cyclase-activating polypeptide promotes eccrine gland sweat secretion.

BACKGROUND: Sweat secretion is the major function of eccrine sweat glands; when this process is disturbed (paridrosis), serious skin problems can arise. To elucidate the causes of paridrosis, an improved understanding of the regulation, mechanisms and factors underlying sweat production is required. Pituitary adenylate cyclase-activating polypeptide (PACAP) exhibits pleiotropic functions that are mediated via its receptors [PACAP-specific receptor (PAC1R), vasoactive intestinal peptide (VIP) receptor type 1 (VPAC1R) and VPAC2R]. Although some studies have suggested a role for PACAP in the skin and several exocrine glands, the effects of PACAP on the process of eccrine sweat secretion have not been examined. OBJECTIVES: To investigate the effect of PACAP on eccrine sweat secretion. METHODS: Reverse transcriptase-polymerase chain reaction and immunostaining were used to determine the expression and localization of PACAP and its receptors in mouse and human eccrine sweat glands. We injected PACAP subcutaneously into the footpads of mice and used the starch-iodine test to visualize sweat-secreting glands. RESULTS: Immunostaining showed PACAP and PAC1R expression by secretory cells from mouse and human sweat glands. PACAP immunoreactivity was also localized in nerve fibres around eccrine sweat glands. PACAP significantly promoted sweat secretion at the injection site, and this could be blocked by the PAC1R-antagonist PACAP6-38. VIP, an agonist of VPAC1R and VPAC2R, failed to induce sweat secretion. CONCLUSIONS: This is the first report demonstrating that PACAP may play a crucial role in sweat secretion via its action on PAC1R located in eccrine sweat glands. The mechanisms underlying the role of PACAP in sweat secretion may provide new therapeutic options to combat sweating disorders.

Molecular mechanism mediating cytotoxic activity of axitinib in sunitinib-resistant human renal cell carcinoma cells

Purpose: This study aimed to clarify the molecular mechanism mediating the cytotoxicity of axitinib, a selective inhibitor of the vascular endothelial growth factor receptor (VEGFR), in sunitinib-resistant renal cell carcinoma (RCC). Methods: In our previous study (Sakai et al. in BJU Int 112:E211-E220, 2013), a human RCC cell line, ACHN, resistant to sunitinib (ACHN/R), was developed from a parental cell line (ACHN/P). Differences in molecular phenotypes following treatment with sunitinib or axitinib between these two cell lines were compared. Results: ACHN/R showed an approximately fivefold higher IC50 of sunitinib than ACHN/P; however, there was no significant difference in the sensitivity to axitinib between these two cell lines. In ACHN/R, despite the lack of a difference in the phosphorylated (p)-Akt or STAT-3 expression between treatment with sunitinib and axitinib, the expression of p-p44/42 mitogen-activated protein kinase (MAPK) and p-VEGFR-2 after treatment with axitinib was markedly down-regulated compared with those after treatment with sunitinib. Furthermore, additional treatment of ACHN/R with an inhibitor of MAPK kinase significantly enhanced the cytotoxic activity of sunitinib, but not that of axitinib. In vivo growth of ACHN/R in nude mice after treatment with axitinib was significantly inhibited compared with that following treatment with sunitinib, accompanying the marked inhibition of angiogenesis. Conclusions Antitumor activity of axitinib in RCC cells even after the acquisition of resistance to sunitinib could be explained, at least in part, by the inactivation of p44/42 MAPK and VEGFR-2, which were persistently phosphorylated in sunitinib-resistant RCC cells under treatment with sunitinib (AU)

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Molecular mechanism mediating cytotoxic activity of axitinib in sunitinib-resistant human renal cell carcinoma cells.

PURPOSE: This study aimed to clarify the molecular mechanism mediating the cytotoxicity of axitinib, a selective inhibitor of the vascular endothelial growth factor receptor (VEGFR), in sunitinib-resistant renal cell carcinoma (RCC). METHODS: In our previous study (Sakai et al. in BJU Int 112:E211-E220, 2013), a human RCC cell line, ACHN, resistant to sunitinib (ACHN/R), was developed from a parental cell line (ACHN/P). Differences in molecular phenotypes following treatment with sunitinib or axitinib between these two cell lines were compared. RESULTS: ACHN/R showed an approximately fivefold higher IC50 of sunitinib than ACHN/P; however, there was no significant difference in the sensitivity to axitinib between these two cell lines. In ACHN/R, despite the lack of a difference in the phosphorylated (p)-Akt or STAT-3 expression between treatment with sunitinib and axitinib, the expression of p-p44/42 mitogen-activated protein kinase (MAPK) and p-VEGFR-2 after treatment with axitinib was markedly down-regulated compared with those after treatment with sunitinib. Furthermore, additional treatment of ACHN/R with an inhibitor of MAPK kinase significantly enhanced the cytotoxic activity of sunitinib, but not that of axitinib. In vivo growth of ACHN/R in nude mice after treatment with axitinib was significantly inhibited compared with that following treatment with sunitinib, accompanying the marked inhibition of angiogenesis. CONCLUSIONS: Antitumor activity of axitinib in RCC cells even after the acquisition of resistance to sunitinib could be explained, at least in part, by the inactivation of p44/42 MAPK and VEGFR-2, which were persistently phosphorylated in sunitinib-resistant RCC cells under treatment with sunitinib.

Histopathological and immunohistochemical features of atypical epithelial tumours of the gland of the third eyelid in seven dogs.

This report documents the histopathological and immunohistochemical features of atypical epithelial tumours of the gland of the third eyelid (GTE) in seven dogs. Cases 1 and 2 were diagnosed as myoepithelioma, comprising of compressive proliferations of interlacing bundles of neoplastic spindle cells expressing cytokeratin 14, p63, calponin and α-smooth muscle actin. Cases 3, 4 and 5 were diagnosed as complex carcinomas comprising of atypical glandular cells expressing cytokeratin 8/18, together with spindle-shaped or round neoplastic cells expressing cytokeratin 14, p63, calponin and α-smooth muscle actin. Cases 6 and 7 were diagnosed as basal cell adenocarcinomas (BCACs) comprising of a mixed proliferation of glandular and basal-type cells expressing cytokeratin 14 and p63. Therefore, in addition to glandular components, these tumours may include neoplastic cells with a myoepithelial or basal cell phenotype. Hence, there is diversity in the features of epithelial neoplasia of the GTE in dogs, similar to tumours in human salivary and lacrimal glands.

Cytotoxic Effects of Hydrogen Peroxide on Human Gingival Fibroblasts In Vitro.

In-office bleaching is a popular treatment in modern esthetic dentistry. However, bleaching agents sometimes accidentally adhere to the gingiva and peripheral tissues, even when applied by well-trained dentists. This can lead to transient pain and whitish changes in the gingiva. Although these symptoms disappear within several hours, the effects of bleaching agents on gingiva have not been well described in the literature. The present study aimed to elucidate the cytotoxic effects of a bleaching agent on cultured human gingival fibroblasts (HGFs). We performed a comprehensive analysis of the toxic effects of in-office bleaching agents on gingiva using cultured HGFs and DNA microarray. Survival rates of HGFs decreased with increases in the concentration of hydrogen peroxide, which became significant at concentrations of 1.5 × 10(-3)% or higher at every time point. Concentrations lower than 1.5 × 10(-3)% did not affect survival rates of HGFs. Cytotoxicity of hydrogen peroxide was significantly weakened by the addition of vitamin E. Stimulation by in-office bleaching agents triggered the proinflammatory cytokine tumor necrosis factor (TNF)-α cascade in gingival fibroblasts. As the TNF-α cascade can be inhibited by vitamin E additives, treatment with vitamin E may protect gingival fibroblasts against the toxic effects of an in-office bleaching agent. The present results suggest that local administration of vitamin E to gingiva before in-office bleaching may be useful for preventing gingival irritation due to accidental adhesion of a bleaching agent.

Experimental teschovirus encephalomyelitis in gnotobiotic pigs.

A central nervous system (CNS) disorder characterized by non-suppurative encephalomyelitis with neurological signs was induced experimentally in gnotobiotic pigs by intravenous and oral or intranasal inoculation of the porcine teschovirus (PTV) Toyama 2002 strain isolated from breeding pigs in Japan. Lesions consisting of perivascular cuffing of mononuclear cells, focal gliosis, neuronal necrosis and neuronophagia were observed in the brainstem, cerebellum and spinal cord. Non-suppurative ganglionitis in the spinal ganglion and neuritis in the spinal root were also observed. Regardless of the route of inoculation, all pigs infected experimentally with PTV showed a similar distribution of CNS lesions. Histological lesions in the CNS caused by oral or intranasal inoculation of the virus were mild compared with those induced by intravenous infection. Immunohistochemically, the distribution of PTV antigens corresponded closely with the distribution of brain lesions. PTV particles were detected via electron microscopy in the cytoplasm of nerve cells and the endothelial cells of blood vessels in the spinal cord of inoculated pigs. Polymerase chain reaction analysis demonstrated the presence of PTV RNA in the CNS, tonsils and large intestines of 21 of the 22 pigs inoculated. Direct CNS invasion via the blood vessels appears to be a major route of infection for PTV. The gnotobiotic pig provides a useful model for further study of PTV pathogenesis.

Concentration and particle size distribution of polycyclic aromatic hydrocarbons formed by thermal cooking.

The concentration and particle size distribution of 19 major polycyclic aromatic hydrocarbons (PAHs) emitted by thermal cooking were investigated. Corn, trout, beef, prawns, and pork were selected for grilling. The PAHs in the oil mist emitted when the food was grilled were collected according to particle size range and analysed by GC/MS. Much higher concentrations of PAHs were detected in the oil mist emitted by grilled pork, trout, and beef samples, which were rich in fat. The main components of the cooking exhaust were 3- and 4-ring PAHs, regardless of food type. The particle size distribution showed that almost all the PAHs were concentrated in particles with diameters of <0.43 µm. For pork, the toxic equivalent of benzo[a]pyrene accounted for 50% of the PAHs in particles with diameters of <0.43 µm. From these results, we estimated that >90% of the PAHs would reach the alveolar region of the lungs.

Successful treatment for Cronkhite-Canada syndrome with endoscopic mucosal resection and salazosulfapyridine.

A 79-year-old woman was referred to our hospital because numerous polyps were found in her stomach and large intestine at an ambulatory clinic. Although there were no characteristic symptoms or signs of Cronkhite-Canada syndrome (CCS), endoscopic and pathological findings indicated CCS. Moreover, colonoscopy showed two polypoid lesions (Is type), which appeared neoplastic by magnifying observation with image-enhanced endoscopy (IEE), in the ascending colon. Histologically, the resected specimens revealed tubular adenomas arising in the CCS inflammatory polyps. Remarkable remission of the polyps and edematous mucosa in the stomach and colon was seen after 8 months of administration of salazosulfapyridine (SASP) (3 g/day). Another adenoma was detected and removed endoscopically in the sigmoid colon. This is the first report to describe an asymptomatic case of CCS probably detected in the early phase of the disease, by magnifying IEE which enabled detection and treatment for associated colonic adenomas. SASP was effective in eradication of the inflammatory polyposis, and an additional adenoma was successfully found and removed by surveillance colonoscopy thereafter.

Distribution of indium, thallium and bismuth in the environmental water of Japan.

Indium, thallium and bismuth are toxic and it is important to know the distribution of these elements in environmental water. The concentrations of these elements were measured in 50 sampling points in Japan and the reasons of high concentrations in several samples were discussed. The average concentrations (ng/L) of dissolved and particulate indium in river, lake and coastal seawater were 1.4-3.0 and 2.4-9.1, respectively. Those for thallium were 7.2-11.3 and 3.5-36.0. Those for bismuth were 12.7-24.0 and 12.1-52.7.

Direct observation of the hyperfine transition of ground-state positronium.

We report the first direct measurement of the hyperfine transition of the ground state positronium. The hyperfine structure between ortho-positronium and para-positronium is about 203 GHz. We develop a new optical system to accumulate about 10 kW power using a gyrotron, a mode converter, and a Fabry-Pérot cavity. The hyperfine transition has been observed with a significance of 5.4 standard deviations. The transition probability is measured to be A = 3.1(-1.2)(+1.6) × 10(-8) s(-1) for the first time, which is in good agreement with the theoretical value of 3.37 × 10(-8) s(-1).

Identification of Hic-5 as a novel regulatory factor for integrin αIIbß3 activation and platelet aggregation in mice.

BACKGROUND: Integrin αIIbß3 plays key roles in platelet aggregation and subsequent thrombus formation. Hydrogen peroxide-inducible clone-5 (Hic-5), a member of the paxillin family, serves as a focal adhesion adaptor protein associated with αIIbß3 at its cytoplasmic strand. OBJECTIVES: Hic-5 function in αIIbß3 activation and subsequent platelet aggregation remains unknown. To address this question, platelets from Hic-5(-/-) mice were analyzed. METHODS AND RESULTS: Hic-5(-/-) mice displayed a significant hemostatic defect and resistance to thromboembolism, which were explained in part by weaker thrombin-induced aggregation in Hic-5(-/-) platelets. Mechanistically, Hic-5(-/-) platelets showed limited activation of αIIbß3 upon thrombin treatment. Morphological alteration in Hic-5(-/-) platelets after thrombin stimulation on fibrinogen plates was also limited. As a direct consequence, the quantity of actin co-immunoprecipitating with the activated αIIbß3 was smaller in Hic-5(-/-) platelets than in wild-type platelets. CONCLUSION: We identified Hic-5 as a novel and specific regulatory factor for thrombin-induced αIIbß3 activation and subsequent platelet aggregation in mice.

Endoscopic full-thickness resection of a lateral spreading rectal tumor after unplanned injection of dilute hyaluronic acid into the subserosal layer (with video).

A 74-year-old woman underwent colonoscopy for investigation of a liver tumor. A lateral spreading tumor of the non-granular type (LST-NG), 25 mm in diameter, was detected at the rectosigmoid junction. As magnifying image-enhanced colonoscopy suggested a tubulovillous adenoma, endoscopic mucosal resection (EMR) was chosen for removal of the LST-NG. The lesion was effectively and evenly lifted after injection of 0.4% hyaluronic acid diluted with glycerol in the ratio of 1:1. A small amount of indigo-carmine dye was also added for coloration of the plane of resection. The lesion was completely removed en bloc. Although a blue-colored layer was identified in the resection defect, a small amount of a whitish layer was detected above the blue layer. The muscle layer was clearly located on the underside of the resected polyp. A total of 14 endoclips were used to close the defect completely. The patient was successfully treated conservatively without surgery. Histology of the resected specimen showed that it contained a tubulovillous adenoma with the submucosal layer and both layers of the muscularis propria. The surgical margin was free of neoplastic change horizontally and vertically. To the best of our knowledge, this is the first case report of full-thickness resection associated with EMR after unplanned injection of dilute hyaluronic acid into the subserosal layer rather than the intended submucosal layer. We describe how to promptly recognize this complication during colonoscopy, in order to achieve immediate closure of the defect, with the identification of a "mirror target sign" on the colonic wall.

Clinical efficacy of two forms of intravenous iron--saccharated ferric oxide and cideferron--for iron deficiency anemia.

Over 90% of iron deficiency anemia cases are due to iron deficiency associated with depletion of stored iron or inadequate intake. Parenteral iron supplementation is an important part of the management of anemia, and some kinds of intravenous iron are used. However, few studies have evaluated the clinical efficacy of these drugs. The purpose of this study was to compare and assess the clinical efficacy of two types of intravenous iron injection, saccharated ferric oxide (SFO) and cideferron (CF). Medical records were obtained for 91 unrelated Japanese anemia patients treated with SFO (n = 37) or CF (n = 54) from May 2005 to May 2010 at Gunma University Hospital. Patients treated with blood transfusion, erythropoietin or oral iron were excluded. Hemoglobin (Hb) values measured on day 0, 7 and 14 were used to assess the efficacy of intravenous irons. A significant increase was observed in the mean Hb value by day 14 of administration in both the CF group and SFO group, and the mean Hb increase due to administration of CF for 7 days was comparable to that of SFO for 14 days. Age and sex did not affect improvement of Hb value. CF is fast acting and highly effective compared with SFO for the treatment of iron deficiency anemia. The use of CF may shorten a therapeutic period for iron deficiency anemia, and CF may be feasible for reducing the hospitalization period.