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Rat hair-follicle-associated pluripotent (HAP) stem cells can differentiate into atrial or ventricular cardiomyocytes in culture controlled by specific supplementation

by Nanako Takaoka, Michiko Yamane, Ayami Hasegawa, Koya Obara, Kyoumi Shirai, Ryoichi Aki, Hiroyasu Hatakeyama, Yuko Hamada, Nobuko Arakawa, Manabu Tanaka, Robert M. Hoffman, Yasuyuki Amoh

There has been only limited success to differentiate adult stem cells into cardiomyocyte subtypes. In the present study, we have successfully induced beating atrial and ventricular cardiomyocytes from rat hair-follicle-associated pluripotent (HAP) stem cells, which are adult stem cells located in the bulge area. HAP stem cells differentiated into atrial cardiomyocytes in culture with the combination of isoproterenol, activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF), and cyclosporine A (CSA). HAP stem cells differentiated into ventricular cardiomyocytes in culture with the combination of activin A, BMP4, bFGF, inhibitor of Wnt production-4 (IWP4), and vascular endothelial growth factor (VEGF). Differentiated atrial cardiomyocytes were specifically stained for anti-myosin light chain 2a (MLC2a) antibody. Ventricular cardiomyocytes were specially stained for anti-myosin light chain 2v (MLC2v) antibody. Quantitative Polymerase Chain Reaction (qPCR) showed significant expression of MLC2a in atrial cardiomyocytes and MLC2v in ventricular cardiomyocytes. Both differentiated atrial and ventricular cardiomyocytes showed characteristic waveforms in Ca2+ imaging. Differentiated atrial and ventricular cardiomyocytes formed long myocardial fibers and beat as a functional syncytium, having a structure similar to adult cardiomyocytes. The present results demonstrated that it is possible to induce cardiomyocyte subtypes, atrial and ventricular cardiomyocytes, from HAP stem cells.

Relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis

by Mami Tomita, Mizuki Tagami, Norihiko Misawa, Atsushi Sakai, Yusuke Haruna, Shigeru Honda

Purpose

To investigate relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis.

Methods

This retrospective study examined vitreous inflammatory cells (hyperreflective particles) of posterior uveitis on widefield optical coherence tomography (WOCT). We examined the number of hyperreflective particles (possibility of vitreous inflammatory cells) observed on WOCT and the correlations with interleukin-6 (IL-6) levels. The relationship between vitreous IL-6 levels and image findings from WOCT from 37 eyes (34 patients) with posterior uveitis were analyzed. Mean patient age was 63.4±15.7 years. (Mean± standard deviation) IL-6 concentration in vitreous humor was 79.9±7380.9 pg/mL Uveitis was infectious in 9 cases and non-infectious in 28 cases with multiplex polymerase chain reaction system. We measured the number and size of vitreous cells in the posterior vitreous, defined as the space between the upper vitreous and the internal limiting membrane on WOCT at the macular, upper, and lower regions. Image analysis software was also used for cell counting.

Results

A strong correlation was seen between human and software counts. Pearson’s correlation coefficient (PCC) was performed to compare categorial variables (on macular +0.866; upper cavity +0.713; lower cavity +0.568; total vitreous cavity +0.834; P.001 each). IL-6 levels correlated with both vitreous cell counts and cell counts observed on macular WOCT (human-counted group +0.339, P = 0.04; software-counted group +0.349, P = 0.03). Infectious uveitis showed higher IL-6 levels (P = 0.016) and high cell counts compared with non-infectious uveitis (P = 0.04).

Conclusions

Vitreous number of hyperreflective particles (cells) findings on WOCTcorrelated well with human and software cell counts. Vitreous cells findings on WOCT also correlated with IL-6 concentrations on macular.

Naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation: A retrospective, single-center cohort study

by Seiya Nishiyama, Shigehiko Uchino, Yusuke Sasabuchi, Tomoyuki Masuyama, Alan Kawarai Lefor, Masamitsu Sanui

Introduction

There are few reports describing the association of naldemedine with defecation in critically ill patients with opioid-induced constipation. The purpose of this study was to determine whether naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation.

Methods

In this retrospective cohort study, patients admitted to the Intensive Care Unit (ICU) without defecation for 48 hours while receiving opioids were eligible for enrollment. The primary endpoint was the time of the first defecation within 96 hours after inclusion. Secondary endpoints included presence of diarrhea, duration of mechanical ventilation, ICU length of stay, ICU mortality, and in-hospital mortality. The Cox proportional hazard regression analysis with time-dependent covariates was used to evaluate the association naldemedine with earlier defecation.

Results

A total of 875 patients were enrolled and were divided into 63 patients treated with naldemedine and 812 patients not treated. Defecation was observed in 58.7% of the naldemedine group and 48.8% of the no-naldemedine group during the study (p = 0.150). The naldemedine group had statistically significantly prolonged duration of mechanical ventilation (8.7 days vs 5.5 days, p Conclusion

The present study shows that naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation.

Association between physical performance and bone mass in community-dwelling postmenopausal Japanese women: The Unzen study

by Masahiro Suiko, Satoshi Mizukami, Kazuhiko Arima, Hiroki Nakashima, Takayuki Nishimura, Yoshihito Tomita, Yasuyo Abe, Natsumi Tanaka, Yuzo Honda, Michiko Kojima, Tetsuji Okawachi, Maiko Hasegawa, Youko Sou, Ritsu Tsujimoto, Mitsuo Kanagae, Makoto Osaki, Kiyoshi Aoyagi

Background

Low bone mass is an independent risk factor for osteoporotic fractures. We examined the association between physical performance and bone mass using quantitative ultrasound in community-dwelling postmenopausal Japanese women.

Methods

We conducted a cross-sectional study on 524 community-dwelling postmenopausal Japanese women who were not being administered osteoporosis medications. Physical performance was assessed on the basis of grip strength, chair stand time, and functional reach. The stiffness index was measured as a quantitative ultrasound parameter for heel bone mass.

Results

Physical performance, assessed by grip strength, chair stand time, and functional reach, and the stiffness index significantly decreased with age (both p Conclusions

Physical performance was significantly associated with heel bone mass in community-dwelling postmenopausal Japanese women.

Evaluation of photoreceptor features in retinitis pigmentosa with cystoid macular edema by using an adaptive optics fundus camera

by Shohei Kitahata, Kiyoko Gocho, Naohiro Motozawa, Satoshi Yokota, Midori Yamamoto, Akiko Maeda, Yasuhiko Hirami, Yasuo Kurimoto, Kazuaki Kadonosono, Masayo Takahashi

Objective

Cystoid macular edema (CME) in retinitis pigmentosa (RP) is an important complication causing visual dysfunction. We investigated the effect of CME on photoreceptors in RP patients with previous or current CME, using an adaptive optics (AO) fundus camera.

Methods

We retrospectively observed the CME and ellipsoid zone (EZ) length (average of horizontal and vertical sections) by optical coherence tomography. The density and regularity of the arrangement of photoreceptor cells (Voronoi analysis) were examined at four points around 1.5° from superior to inferior and temporal to nasal. We also performed a multivariate analysis using CME duration, central macular thickness and transversal length of CME.

Results

We evaluated 18 patients with previous or current CME (18 eyes; age, 48.7 ± 15.6 years) and 24 patients without previous or current CME (24 eyes; age, 46.0 ± 14.5 years). There were no significant differences in age, logMAR visual acuity, or EZ length. In groups with and without CME, cell density was 11967 ± 3148 and 16239 ± 2935 cells/mm2, and sequence regularity was 85.5 ± 3.4% and 88.5 ± 2.8%, respectively; both parameters were significantly different. The correlation between photoreceptor density and age was more negative in group with CME. The CME group tended toward greater reductions in duration of CME.

Conclusion

Complications of CME in RP patients may lead to a decrease in photoreceptor density and regularity. Additionally, a longer duration of CME may result in a greater reduction in photoreceptor density.

Post-stress changes in the gut microbiome composition in rats with different levels of nervous system excitability

by Alla Shevchenko, Irina Shalaginova, Dmitriy Katserov, Ludmila Matskova, Natalia Shiryaeva, Natalia Dyuzhikova

The gut-brain axis is a critical communication system influencing the interactions between the gastrointestinal tract (GI) and the central nervous system (CNS). The gut microbiota plays a significant role in this axis, affecting the development and function of the nervous system. Stress-induced psychopathologies, such as depression and anxiety, have been linked to the gut microbiota, but underlying mechanisms and genetic susceptibility remain unclear. In this study, we examined stress-induced changes in the gut microbiome composition in two rat strains with different levels of nervous system excitability: high threshold (HT strain) and low threshold (LT strain). Rats were exposed to long-term emotional and painful stress using the Hecht protocol, and fecal samples were collected at multiple time points before and after stress exposure. Using 16S rRNA amplicon sequencing, we assessed the qualitative and quantitative changes in the gut microbiota. Our results revealed distinct microbial diversity between the two rat strains, with the HT strain displaying higher diversity compared to the LT strain. Notably, under prolonged stress, the HT strain showed an increase in relative abundance of microorganisms from the genera Faecalibacterium and Prevotella in fecal samples. Additionally, both strains exhibited a decrease in Lactobacillus abundance following stress exposure. Our findings provide valuable insights into the impact of hereditary nervous system excitability on the gut microbiome composition under stress conditions. Understanding the gut-brain interactions in response to stress may open new avenues for comprehending stress-related psychopathologies and developing potential therapeutic interventions targeted at the gut microbiota. However, further research is needed to elucidate the exact mechanisms underlying these changes and their implications for stress-induced disorders. Overall, this study contributes to the growing body of knowledge on the gut-brain axis and its significance in stress-related neurobiology.

Factors associated with uptake of human papillomavirus vaccination among adolescent girls in Mettu town, southwest Ethiopia: a school-based cross-sectional study

Por: Dawud · A. · Kera · A. M. · Bekele · D. · Hiko · D. · Zewdie · A.
Objective

This study was designed to assess the level of uptake of human papillomavirus (HPV) vaccination and its associated factors among school-age adolescent girls.

Design

School-based cross-sectional study.

Setting

High schools in Mettu town, southwest Ethiopia, from 5 February to 10 March 2022.

Participants

Data were collected using a pretested and structured questionnaire through face-to-face interviews with 667 adolescent girls selected via multistage random sampling. Data were entered into EpiData V.3.1 and exported to SPSS V.26 for analysis. Simple binary logistic regression was done, and variables with a p value less than 0.25 were entered into a multivariable logistic regression model; variables with a p value

Results

About half (48.6%) of adolescent girls aged 14–18 years had received the HPV vaccine. Being in the 16–18 years age group (adjusted OR 2.7, 95% CI 1.50 to 4.80), having good knowledge (2.14, 95% CI 1.29 to 3.52), having a positive attitude (5.86, 95% CI 3.51 to 9.76), and getting encouragement from healthcare workers (3.04, 95% CI 1.36 to 6.79), teachers (2.14, 95% CI 1.05 to 4.34) and parents (2.39, 95% CI 1.02 to 5.64) were significantly associated with vaccine uptake.

Conclusion

The uptake of HPV vaccination was low. Having good knowledge and positive attitude as well as encouragement from parents, healthcare workers and teachers were identified as factors associated with HPV vaccine uptake. Improving knowledge about HPV and involving teachers and parents in the immunisation campaign might help promote HPV vaccine uptake.

Frailty and social isolation before and during the coronavirus disease 2019 pandemic among older adults: A path analysis

Abstract

Aim

To explore the prevalence of social isolation among Japanese community-dwelling older adults before and during the COVID-19 pandemic as well as determine how family and friend connections before and during the pandemic affected frail older adults during the pandemic.

Design

A cross-sectional study.

Methods

A total of 852 community-dwelling older adults in Hokkaido and Tokyo, Japan were surveyed conducted between April and November 2021 using convenience sampling. The Lubben social network scale-6, frailty screening index, and geriatric depression scale were used to assess social isolation, frailty and depression, respectively. A path analysis was conducted to evaluate the effect of social isolation on frailty.

Results

Participants had a mean age of 76.8 ± 6.6 years. Overall, 46% and 59% of participants were socially isolated before and during the COVID-19 pandemic, respectively. Frailty was found in 19% of participants during the pandemic. Friends and family connectedness before the pandemic had no direct relationship with frailty; only friend connectedness affected frailty indirectly via depression. Family connectedness during the pandemic had a significant, negative and direct relationship with frailty.

Conclusion

The findings show that connectedness with family and friends is critical for older people's physical and mental health.

Impact

Nurses in the community should consider these findings to reduce mental health problems and physical decline among older adults. It is important to identify older adults who are socially isolated from their families or friends and provide resources to help them build relationships within their communities.

Patient or Public Contribution

Community centre staff and community volunteers assisted in data collection. The public was not involved in data analysis, interpretation or manuscript preparation.

Impact of home‐visit nursing service use on costs in the last 3 months of life among older adults: A retrospective cohort study

Abstract

Introduction

Considering Japan's aging society, the number of older individuals who die at home is expected to increase. In Japan, there are challenges in utilizing and promoting home-visit nursing services at the end of life for community-dwelling older adults. We examined the use of home-visit nursing services at the end of patients' lives and the recommended use patterns of this service (utilization, timing of initiation, and continuity) that contribute to reducing the medical care and long-term care costs (total costs) in the last 3 months of life.

Design

This was a retrospective cohort study.

Methods

We examined 33 municipalities in Japan, including depopulated areas. The analysis included 22,927 people aged 75 or older who died between September 2016 and September 2018. We used monthly medical care and long-term care insurance claims data. Participants were classified into five groups based on their history of home-visit nursing service use: (1) early initiation/continuous use, (2) early initiation/discontinued or fragment use, (3) not-early initiation/continuous use, (4) not-early initiation/fragment use, and (5) no use. Univariate and multivariate linear regression analyses were performed to examine the association between total costs in the last 3 months of life and patterns of home-visit nursing service use.

Results

Overall, the median age was 85, and 12,217 participants were men (53.3%). In the last half year before death, 5424 (23.7%) older adults used home-visit nursing services. Multivariable linear regression analysis of the log10-transformed value of total costs revealed that compared with the no use group, the early initiation/continuous use group was estimated to have 0.88 times (95% confidence interval: 0.84, 0.93) the total costs in the last 3 months of life (p < 0.001).

Conclusion

Early initiation use of home-visit nursing services may contribute to reducing total costs in the last 3 months of life for Japanese people aged 75 years or older living at home as they approach the end of life.

Clinical relevance

When approaching the end of life, many older adults require daily life care and palliative care. Policymakers are strengthening end-of-life care for community-dwelling older adults in Japan. Although the current results do not demonstrate the effectiveness of home-visit nursing services, they provide a perspective from which to assess the use of home-visit nursing services and its impact on older adults. The findings can be helpful in considering how to provide nursing care in home-care settings for older adults who prefer to spend their final days at home.

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