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Abstract Objectives This study explored the changes in bacterial flora composition and total bacterial count in the saliva and tongue coating, along with the change in the tongue coating index (TCI) following an intervention with 0.3% cetylpyridinium chloride (CPC) mouth spray after professional oral care. Materials and Methods Fifty‐two adult volunteers aged 30–60 years were equally divided into CPC spray (n = 26) and control (n = 26) groups. All subjects underwent scaling and polishing. The CPC spray group was administered four puffs of CPC spray to the tongue dorsum four times a day for 3 weeks. The control group performed only routine daily oral care (brushing) and did not use any other spray. Bacteriological evaluation of saliva and tongue coating was performed using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction. The tongue coating was evaluated to calculate the TCI. A per‐protocol analysis was conducted for 44 subjects (CPC spray group, n = 23; control group, n = 21). Results At 1 and 3 weeks after CPC spray use, the flora of the saliva and tongue coating changed; the genus Haemophilus was dominant in the CPC spray group, whereas the genus Saccharibacteria was dominant in the control group. The sampling time differed among individual participants, which may have affected the bacterial counts. There was no significant intragroup change in TCI in either group. Conclusions CPC spray affected the bacterial flora in the saliva and tongue coating, particularly with respect to an increase in the abundance of Haemophilus. However, CPC spray did not change the TCI. These results suggest that it may be optimal to combine CPC spray with a physical cleaning method such as using a tongue brush or scraper. Clinical Trial Registration: University Hospital Medical Information Network UMIN000041140.

Abstract Background The stigmatization against COVID-19 has become a public issue. However, it remains unknown which individual factor contributes to anticipated stigma formation. This study explored socio-psychological factors associated with anticipated stigma toward coronavirus disease 2019 (COVID-19). Methods We obtained cross-sectional data regarding 1,638 middle-aged community residents (mean age, 48.5 years) from a population-based survey in metropolitan Tokyo, Japan during the third wave of the COVID-19 pandemic, when a regional public health emergency had been declared in December 2020 and January 2021. We hypothesized that perceived risk of infection, normative beliefs about preventive behaviors, and past experiences of stigmatization unrelated to COVID-19 would be associated with anticipated stigma. Modified Poisson regression was conducted to examine associations after adjustments for demographic and socioeconomic statuses. Results Higher perceived risk (adjusted prevalence ratio [APR] = 1.17; 95% confidence interval [CI, 1.08–1.27]), past experiences of stigmatization (APR = 1.09; 95% CI [1.00–1.19]), and higher normative beliefs about preventive behaviors (APR = 1.18; 95% CI [1.11–1.26]) were independently associated with anticipated stigma. Conclusions These results suggest that intervention messages to increase risk perception and normative beliefs to enhance protective behaviors may have the unintended effect of increasing anticipated stigma in the context of the COVID-19 pandemic.

Abstract Background Postpartum haemorrhage is a direct cause of maternal death worldwide and usually occurs during the third stage of labour. Most women receive some type of prophylactic management, which may include pharmacological or non-pharmacological interventions. The objective of this study was to summarize systematic reviews that assessed the effects of postpartum haemorrhage prophylactic management during the third stage of labour. Methods We applied the guidelines for conducting an overview of reviews from the Cochrane Handbook for Systematic Reviews of Interventions. We searched MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews to identify all relevant systematic reviews of randomized controlled trials of prophylactic management of postpartum haemorrhage in the third stage of labour compared with no treatment, placebo, or another management technique. Two review authors independently extracted data and assessed methodological quality using a measurement tool to assess reviews and quality of evidence using the Grades of Recommendation, Assessment, Development, and Evaluation for primary outcomes, summarizing results narratively. Results We identified 29 systematic reviews: 18 Cochrane and 11 non-Cochrane. Cochrane systematic reviews were high quality, while the quality of non-Cochrane systematic reviews varied. The following techniques suggested effective, third-stage interventions to reduce the incidence of severe postpartum haemorrhage: active management of the third stage of labour compared to physiological management, active management compared to expectant management, administration of oxytocin compared to placebo, and use of tranexamic acid compared to placebo. The following third-stage management approaches reduced the need for blood transfusion: active management compared to physiological management, active management compared to expectant management, oral misoprostol compared to placebo, and tranexamic acid compared to placebo. Conclusions No effective prophylactic management techniques were identified for maternal mortality. Most methods of effective prophylactic management of postpartum haemorrhage were supported by evidence; however, they were limited to low- or moderate-quality evidence, and high-quality studies are therefore needed. Outcome measures of the included systematic reviews varied. It is recommended that outcome measures in preventive postpartum haemorrhage intervention trials align with the World Health Organization guidelines. Systematic review registration PROSPERO: CRD42016049220.

The prognostic significance of glandular differentiation in urothelial carcinoma (UC) is controversial, and thus far there is no established treatment strategy against metastasis of glandular component. We describe here a case of metastatic UC with glandular differentiation that had histological disappearance of adenocarcinoma components at autopsy after sequential chemotherapy with S-1 and cisplatin (CDDP) and with mFOLFOX6 (fluorouracil, oxaliplatin, and leucovorin) plus bevacizumab (mFOLFOX6+Bev). A 62-year-old Asian male was diagnosed with invasive UC with glandular differentiation (T2N0M0) by radical cystectomy and ileal conduit, and careful follow-up observation was made. Eight years after radical operation, peritoneal metastases occurred, and a biopsy specimen using colon fiber revealed high-grade adenocarcinomas with an immunohistochemical profile that included positivity for cytokeratin 7 (CK7) and negativity for cytokeratin 20 (CK20) and uroplakin, which was identical to the radical cystectomy specimen. Thus, he received combination chemotherapy consisting of S-1 and CDDP; however, the peritoneal metastasis worsened after 2 cycles. Therefore, second-line mFOLFOX6+Bev chemotherapy was performed for a total of 5 courses. In spite of this, the patient died, and the final diagnosis by autopsy was multiple metastases of infiltrating pure UC to the lung, bone, and peritoneum. Interestingly, there were no pathological findings of adenocarcinoma, and the immunohistochemical profile of the metastatic lesions was identical to that of the previous specimens from the bladder and colon. This suggests that sequential chemotherapy of S-1 and CDDP and second-line mFOLFOX6+Bev might be a feasible option in metastatic UC with glandular differentiation.

BACKGROUND Hypertension is a major cause of heart failure. Excessive sympathoexcitation in patients with heart failure leads to poor prognosis. Since carotid body denervation (CBD) has been shown to reduce sympathetic nerve activity in animal models of hypertension and heart failure, we examined if bilateral CBD attenuates the progression of hypertensive heart failure and improves survival. METHODS We randomly allocated Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age into CBD (n = 31) and sham-operation (SHAM; n = 50) groups, and conducted CBD or SHAM at 7 weeks of age. We examined the time course of 24-hour urinary norepinephrine (uNE) excretion, blood pressure (BP) and the percent fractional shortening assessed by echocardiography, and estimated the pressure-natriuresis relationship at 14 weeks of age. Finally, we assessed hemodynamics, histological findings, and survival at 16 weeks of age. RESULTS Compared to SHAM, CBD significantly reduced 24-hour uNE at 12, 14, and 16 weeks of age, shifted the pressure-natriuresis relationship leftward without changing its slope, and attenuated the increase in BP. CBD preserved percent fractional shortening (34.2 ± 1.2 vs. 29.1 ± 1.3%, P < 0.01) and lowered left ventricular end-diastolic pressure (5.0 ± 0.9 vs. 9.0 ± 1.4 mm Hg, P ‹ 0.05). Furthermore, CBD significantly attenuated myocardial hypertrophy (P < 0.01) and fibrosis (P < 0.01). Consequently, CBD markedly improved survival (relative risk reduction: 64.8%). CONCLUSIONS CBD attenuated the progression of hypertension and worsening of heart failure possibly through sympathoinhibition, and markedly improved survival in a rat model of hypertensive heart failure. [ABSTRACT FROM AUTHOR]

In constant light, where Drosophila rhythms are normally disrupted, temperature cycles induce circadian rhythms at both the molecular and behavioral level. The authors investigated the process by which the thermoperiod induces the rhythms using temperature steps. A 10 °C temperature step-up induced a single locomotor activity peak ca 9 h after the temperature transition, whereas a 10 °C step-down induced a strong activity peak ca 24 h after the transition, and the peak recurred for several cycles, suggesting that the underlying clock is reset. Arrhythmic per01, tim01, dClkJrk, and cyc01 mutant flies failed to show the rhythm after the step-down, suggesting that per, tim, dClk, and cyc are necessary for the step-down-induced rhythm. After the step-up, per01 flies exhibited an activity peak similar to that of wild-type flies, suggesting that the peak can be induced by the step-up in absence of PER. mRNA levels of per, tim, dClk, vri, and Pdp1ε were changed in response to the temperature steps, but the changes differed depending on the direction of temperature steps, suggesting that steps-up and steps-down have different roles in the initiation of the oscillation. Probably, alternating 12-h temperature steps-up and steps-down will induce opposite changes in mRNA levels of clock genes, eventually producing stable molecular oscillations. Although TIM shows responses to temperature consistent with the changes of its mRNA, this is not the case for PER, consistent with posttranscriptional regulation. Changes of the mRNA levels were significantly altered but still observed in per01 flies but not observed in dClkJrk flies, except for per mRNA. This suggests that dCLK is involved in the temperature-induced changes in the levels of most clock gene mRNA but that per is regulated via a different mechanism. [ABSTRACT FROM AUTHOR]