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The effects of systemic diseases, genetic disorders and lifestyle on keloids

Abstract

Keloid are a fibroproliferative disorder caused by abnormal healing of skin, specifically reticular dermis, when subjected to pathological or inflammatory scars demonstrating redness, elevation above the skin surface, extension beyond the original wound margins and resulting in an unappealing cosmetic appearance. The severity of keloids and risk of developing keloids scars are subjected to elevation by other contributing factors such as systemic diseases, general health conditions, genetic disorders, lifestyle and natural environment. In particular, recently, daily physical work interpreted into mechanical force as well as the interplay between mechanical factors such as stress, strain and stiffness have been reported to strongly modulate the cellular behaviour of keloid formation, affect their location and shape in keloids. Herein, we review the extensive literature on the effects of these factors on keloids and the contributing predisposing mechanisms. Early understanding of these participating factors and their effects in developing keloids may raise the patient awareness in preventing keloids incidence and controlling its severity. Moreover, further studies into their association with keloids as well as considering strategies to control such factors may help clinicians to prevent keloids and widen the therapeutic options.

High frequency of germline recombination in Nestin-Cre transgenic mice crossed with Glucagon-like peptide 1 receptor floxed mice

by Yusuke Kajitani, Takashi Miyazawa, Tomoaki Inoue, Nao Kajitani, Masamichi Fujita, Yukina Takeichi, Yasutaka Miyachi, Ryuichi Sakamoto, Yoshihiro Ogawa

The Cre-loxP strategy for tissue-specific gene inactivation has become a widely employed tool in several research studies. Conversely, inadequate breeding and genotyping without considering the potential for non-specific Cre-recombinase expression may lead to misinterpretations of results. Nestin-Cre transgenic mice, widely used for the selective deletion of genes in neurons, have been observed to have an incidence of Cre-line germline recombination. In this study, we attempted to generate neuron-specific Glucagon-like peptide 1 receptor (Glp1r) knock-out mice by crossing mice harboring the Nestin-Cre transgene with mice harboring the Glp1r gene modified with loxP insertion, in order to elucidate the role of Glp1r signaling in the nervous system. Surprisingly, during this breeding process, we discovered that the null allele emerged in the offspring irrespective of the presence or absence of the Nestin-Cre transgene, with a high probability of occurrence (93.6%). To elucidate the cause of this null allele, we conducted breeding experiments between mice carrying the heterozygous Glp1r null allele but lacking the Nestin-Cre transgene. We confirmed that the null allele was inherited by the offspring independently of the Nestin-Cre transgene. Furthermore, we assessed the gene expression, protein expression, and phenotype of mice carrying the homozygous Glp1r null allele generated from the aforementioned breeding, thereby confirming that the null allele indeed caused a global knock-out of Glp1r. These findings suggest that the null allele in the NestinCre-Glp1r floxed breeding arose due to germline recombination. Moreover, we demonstrated the possibility that germline recombination may occur not only during the spermatogenesis at testis but also during epididymal sperm maturation. The striking frequency of germline recombination in the Nestin-Cre driver underscores the necessity for caution when implementing precise breeding strategies and employing suitable genotyping methods.

Prevalence of psychological distress and associated factors among patients undergoing comprehensive genomic profiling testing: protocol for a multicentre, prospective, observational study

Por: Matsuoka · A. · Fujimori · M. · Koyama · T. · Sato · A. · Mori · K. · Hirata · M. · Tanabe · N. · Nakachi · K. · Kato · S. · Okamoto · H. · Ogawa · K. · Komatsu · H. · Iwasaku · M. · Miyaji · T. · Uchitomi · Y.
Introduction

Since May 2019, comprehensive genomic profiling (CGP) has been covered by Japan’s health insurance system for patients with solid tumours that have progressed on standard chemotherapy, rare tumours or tumours of unknown primary origin. Although CGP has the potential to identify actionable mutations that can guide the selection of genomically matched therapies for patients with advanced cancer and limited treatment options, less than 10% of patients benefit from CGP testing, which may have a negative impact on patients’ mental status. The aim of this study is to investigate the prevalence of psychological distress and associated factors among patients with advanced cancer who are undergoing CGP testing across Japan.

Methods and analysis

This multicentre, prospective cohort study will enrol a total of 700 patients with advanced cancer undergoing CGP testing. Participants will be asked to complete questionnaires at three timepoints: at the time of consenting to CGP testing (T1), at the time of receiving the CGP results (T2; 2–3 months after T1) and 4–5 months after T2 (T3). Primary outcome is the prevalence of depression as measured by the Patient Health Questionnaire-9 at the three timepoints. Secondary outcomes are the prevalence of anxiety and Quality of Life Score. Associated factors with psychological distress will also be examined, including knowledge about CGP, attitudes, values and preferences towards CGP, satisfaction with oncologists’ communication and patient characteristics as well as medical information including CGP test results and genomically matched therapies if provided. The prevalence of depression and anxiety will be estimated using the unadjusted raw rates observed in the total sample. Longitudinal changes in measures will be explored by calculating differences between the timepoints. Multivariate associations between variables will be examined using multiple or logistic regression analysis depending on the outcomes to adjust for confounders and to identify outcome predictors.

Ethics and dissemination

This study was approved by the Institutional Review Board of the National Cancer Center Japan on 5 January 2023 (ID: 2022-228). Study findings will be disseminated through peer-reviewed journals and conference presentations.

Trial status

The study is currently recruiting participants and the enrolment period will end on 31 March 2025, with an expected follow-up date of 31 March 2026.

Trial registration number

UMIN000049964.

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.

The incidence of intraoperatively acquired pressure injuries in the park‐bench position was reduced by applying soft silicone multilayer foam dressings

Abstract

The Park-Bench Position (PBP) is associated with a high incidence rate of intraoperatively acquired pressure injuries (IAPIs). Preventive measures must be established to prevent the development of IAPIs. We investigated the risk factors for PBP by applying a soft silicone multilayered foam dressing (SMD) under core temperature management to prevent IAPIs. We conducted a prospective, single-centre, open-label observational study of patients undergoing elective neurosurgery operations using PBP in a university hospital in Japan. The incidence rate of IAPIs in this study was compared with that in our two previous studies, in which a film dressing was applied and core temperature management was not performed. IAPIs developed in 90 patients (6.7%); in the lateral thoracic region in five patients and the iliac crest region in one patient. The operative time (every 1 h: p = 0.0001, OR: odds ratio 3.62, 95% CI: confidence interval 1.73–11.42) was significantly associated with the incidence of IAPIs. In our two previous studies, the incidence rate of IAPIs was 11.0% and 24.1%, respectively, when film dressing was used. SMD may weaken the involvement of risk factors in IAPIs.

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