Objectives. We investigated the influence of cytokines on the expression of RANK ligand (RANKL) in fibroblast-like synoviocytes from RA patients (RA-FLS). Methods. RA-FLS were stimulated by IL-6, ...TNF-α, IL-17 and IL-1β with or without soluble IL-6 receptor (sIL-6R) for 24 h. The expression of RANKL was measured by real-time PCR, western blotting and immunostaining. In proliferation assay, RA-FLS were cultured with cytokines for 3 days. RA-FLS were co-cultured with RAW cell in the presence of IL-6/sIL-6R for 3 days and then NFATc1 mRNA expression in RAW cells was examined. RA-FLS was cultured with parthenolide PAR, signal transducer and activator of transcription (STAT) inhibitor or PD98059 (PD, mitogen-activated protein kinase inhibitor) in the presence of IL-6/sIL-6R and then the influence of these drugs on phosphorylation of STAT3 and ERK1/2, and RANKL expression was examined. Results. RANKL expression was induced by IL-6/sIL-6R (but not IL-6 alone) and by IL-1β. On the other hand, TNF-α and IL-17 did not induce RANKL expression, although TNF-α, IL-17 or IL-1β stimulated cell growth and IL-6 production. However, in the presence of sIL-6R, TNF-α or IL-17 induced RANKL expression. By the co-culture of RA-FLS, NFATc1 mRNA expression was induced in RAW cells. Finally, IL-6/sIL-6R induced phosphorylation of STAT3 and ERK1/2 in RA-FLS, and was completely inhibited by PAR and PD, respectively. PAR completely inhibited IL-6/sIL-6R-induced RANKL expression, but PD did not. Conclusions. IL-6/sIL-6R directly induced RANKL expression in RA-FLS and it is essential for RANKL induction by TNF-α and IL-17. Moreover, RANKL induction by IL-6/sIL-6R is mediated by the janus kinase/STAT signalling pathway.
The aim of this study was the development of an innovative biocompatible sealant composed of Alaska pollock-derived gelatin partially modified with a dodecyl group (C12-ApGltn) and a poly(ethylene ...glycol)-based crosslinker, pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate. The burst strength of the developed sealants was measured using porcine aorta and rat lungs. The maximum burst strength of a C12-ApGltn-based sealant against the porcine aorta was 4-fold higher than that of an original ApGltn (Org-ApGltn)-based sealant. No significant increase in the burst strength was observed between C12-ApGltn-based sealants with 4.2 and 8.9 mol% modification ratios. From histological observation after burst strength measurement, tissue tearing was observed when a C12-ApGltn-based sealant was applied. In contrast, the Org-ApGltn-based sealant was peeled away from the aorta surface due to cohesion failure. Similar to the porcine aorta, the burst strength of C12-ApGltn-based sealants applied on a rat lung defect was 3-fold higher than that of an Org-ApGltn-based sealant. The curing time of the C12-ApGltn-based sealant measured by a simple mixing method was shorter (2.6 ± 0.1 s) than that of the Org-ApGltn-based sealant (4.1 ± 0.3 s). The swelling ratio of the C12-ApGltn-based sealant (23.7 ± 3.1) was significantly lower than that of the Org-ApGltn-based sealant (32.3 ± 1.1). The C12-ApGltn-based sealant was completely degraded within 28 days after implantation in the backs of rats without a severe inflammation reaction. However, the Org-ApGltn-based sealant disappeared within 14 days. These results indicated that hydrophobically-modified ApGltn has an effective sealing effect on moist tissues and biocompatibility in vivo.
In Japan, several studies have reported no excess all-cause deaths (the difference between the observed and expected number of deaths) during the coronavirus disease 2019 (COVID-19) pandemic in 2020. ...This study aimed to estimate the weekly excess deaths in Japan's 47 prefectures for 2021 until June 27.
Vital statistical data on deaths were obtained from the Ministry of Health, Labour and Welfare of Japan. For this analysis, we used data from January 2012 to June 2021.
A quasi-Poisson regression was used to estimate the expected weekly number of deaths. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the one-sided prediction interval.
Since January 2021, excess deaths were observed for the first time in the week corresponding to April 12–18 and have continued through mid-June, with the highest excess percentage occurring in the week corresponding to May 31–June 6 (excess deaths: 1431–2587; excess percentage: 5.95–10.77%). Similarly, excess deaths were observed in consecutive weeks from April to June 2021 in 18 of 47 prefectures.
For the first time since February 2020, when the first COVID-19 death was reported in Japan, excess deaths possibly related to COVID-19 were observed in April 2021 in Japan, during the fourth wave. This may reflect the deaths of non-infected people owing to the disruption that the pandemic has caused.
Background
Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying ...mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here.
Methods
Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography–mass spectrometry.
Results
In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α‐diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces).
Conclusion
LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α‐diversity that may contribute to the metabolic changes.
Antecedentes
La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA).
Métodos
Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida‐espectrometría de masas.
Resultados
En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0‐61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7‐95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46‐11,35)) antes de la operación (10,26 log10 células/g heces (9,44‐10,91)) y después de la misma (10,42 log10 células/g heces (9,57‐10,96)).
Conclusión
LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.
Obesity is the most common metabolic disease, with an increasing trend worldwide. Bariatric surgery has been proven to be the best line of treatment for morbid obesity. Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. To clarify the mechanisms underlying the efficacy of LSG, this study examined the effect of LSG on the gut microbiota and bile acids (BAs) in patients with morbid obesity. The findings indicated an increase in α‐diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, which was strongly associated with reduced faecal BA levels. These changes were closely associated with excess weight loss and metabolic alterations. However, the total number of bacteria in patients before and after surgery was lower than that in healthy subjects. Quantitative abnormalities in major gut bacteria in patients with morbid obesity were not restored after operation. These findings indicate that LSG alone has limited effects on obesity‐related dysbiosis in the gut microbiota. %EWL, percentage excess weight loss; BW, bodyweight; HbA1c, haemoglobin A1c; HOMA‐R, homeostasis model assessment ratio; HOMA‐β, homeostasis model assessment of β‐cell function; CPI, C peptide immunoreactivity index; CPR, C peptide immunoreactivity; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TG, triglyceride; HDL, high‐density lipoprotein; PD, phylogenetic diversity; F/B, Firmicutes/Bacteroidetes.
Insights into the altered microenvironment
Although multiple combinations of weather factors may contribute to an increased incidence of Mycoplasma pneumoniae pneumonia, few studies have investigated the association between weather factors ...and cases of M pneumoniae pneumonia.
Data on cases of M pneumoniae pneumonia and weather factors in Fukuoka, Japan from 1999 to 2007 were obtained and time-series analysis was used to assess the effects of weather variables on M pneumoniae pneumonia cases, adjusting for confounding factors. A total of 13 056 M pneumoniae pneumonia cases were reported during the 9-year study period, of which 12 234 (93.7%) were under 15 years of age.
The weekly number of M pneumoniae pneumonia cases increased by 16.9% (95% CI 11.3% to 22.8%) for every 1 degrees C increase in the average temperature and by 4.1% (95% CI 2.7% to 5.5%) for every 1% increase in relative humidity.
From 1999 to 2007, cases of M pneumoniae pneumonia increased significantly with increased average temperature and relative humidity in Fukuoka, Japan.
The increasing international interest in the potential health effects of climate change has emphasized the importance of investigations into the relationship between weather variability and ...infectious diseases. However, few studies have examined the impact of weather variability on mumps in children, despite the fact that children are considered particularly vulnerable to climate change. We acquired data about cases of mumps in children aged <15 years and weather variability in Fukuoka, Japan from 2000 to 2008, and then used time-series analyses to assess how weather variability affected mumps cases, adjusting for seasonal variations, inter-annual variations, and temporal variations of two large epidemics in 2001 and 2004–2005. The weekly number of mumps cases increased by 7·5% (95% CI 4·0–11·1) for every 1°C increase in average temperature and by 1·4% (95% CI 0·5–2·4) for every 1% increase in relative humidity. The percentage increase was greatest in the 0–4 years age group and tended to decrease with increasing age. The number of mumps cases in children increased significantly with increased average temperature and relative humidity.
The COVID-19 pandemic placed an enormous strain on healthcare systems and raised concerns for delays in the management of patients with acute cerebrovascular events. In this study, we investigated ...cerebrovascular excess deaths in Japan.
Vital mortality statistics from January 2012 to May 2022 were obtained from the Japanese Ministry of Health, Labour and Welfare.
Using quasi-Poisson regression models, we estimated the expected weekly number of cerebrovascular deaths in Japan from January 2020 through May 2022 by place of death. Estimates were calculated for deaths in all locations, as well as for deaths in hospitals, in geriatric health service facilities, and at home. The age subgroups of ≥75 and <75 years were also considered. Weeks with a statistically significant excess of cerebrovascular deaths were determined when the weekly number of observed deaths exceeded the upper bound of 97.5% prediction interval.
Excess deaths were noted in June 2021 and became more pronounced from February 2022 onward. The trend was notable among those aged ≥75 years and for those who died in hospitals. With respect to the location of deaths, the excess was significant in geriatric health services facilities from April 2020 to June 2021, whereas no evidence of excess hospital deaths was observed during the same period.
Beginning in the late 2021, excess cerebrovascular deaths coincided with the spread of the Omicron variant and may be associated with increased healthcare burden. In 2020, COVID-19 altered the geography of cerebrovascular deaths, with fewer people dying in hospitals and more dying in geriatric health service facilities and at home.
Summary Objective We previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) aggravated cartilage degeneration and that hyaluronate (HA) reversed the cartilage destruction accelerated ...by NSAIDs in a rabbit osteoarthritis (OA) model. In the present study, we analyzed the mechanisms of these effects of NSAIDs and HA. Method An experimental rabbit model of OA was induced by partial meniscectomy and treated with NSAIDs, HA and the combination of NSAIDs and HA over 2 weeks. After sacrifice, cartilage degeneration and the levels of matrix metalloproteases (MMP)-1, MMP-3 and MMP-13 in synovial lavage fluid were measured. In an in vitro study, human articular chondrocytes were cultured with NSAIDs and HA in the presence of interleukin (IL)-1β or IL-6 + sIL-6 for 24 h. After culture, the production of MMPs, IL-1β, and IL-6 was measured. Results The levels of MMP-1, MMP-3 and MMP-13 in synovial fluid from the NSAID-treated group were significantly higher than in controls. The increased production of MMPs induced by NSAIDs was counteracted by the concomitant administration of HA. In vitro studies showed that NSAIDs augmented IL-1β- and IL-6-induced production of MMPs from human chondrocytes, while completely inhibiting the IL-1β- and IL-6/sIL-6R-induced production of prostaglandin E2 (PGE2 ). The addition of PGE2 did not reduce the augmentation of MMP production. HA inhibited the promotion of cytokine-induced MMP and cytokine production by NSAIDs. Conclusions Our data clearly showed that HA inhibited NSAID-accelerated MMP production which was followed by inflammatory cytokine production from cytokine-activated chondrocytes. The results warrant further evaluation of the potential chondroprotective effects of co-administration of HA with NSAIDs.
Highlights • Network activity (NA) was induced by kainate in mouse ACC using submerged slice. • NA was more robust in the superficial layer than in the deep layer. • TTX, blockers of glutamate or ...GABAA receptors and gap junction greatly diminished NA.
Although multiple combinations of weather variability may contribute to an increased incidence of infectious gastrointestinal disease, few studies have investigated the association between weather ...variability and cases of infectious gastroenteritis. We acquired data for infectious gastroenteritis cases and weather variability in Fukuoka, Japan, from 1999 to 2007 and used time-series analysis to assess the effects of weather variability on infectious gastroenteritis cases, adjusting for confounding factors. In total, 422 176 infectious gastroenteritis cases were reported during the 9-year study period. The weekly number of infectious gastroenteritis cases increased by 7·7% (95% CI 4·6–10·8) for every 1°C increase in the average temperature and by 2·3% (95% CI 1·4–3·1) for every 1% decrease in relative humidity. From 1999 to 2007, infectious gastroenteritis cases increased significantly with increased average temperature and decreased relative humidity in Fukuoka, Japan.
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