Cellular senescence and wound healing in aged and diabetic skin

Cellular senescence is a biological mechanism that prevents abnormal cell proliferation during tissue repair, and it is often accompanied by the secretion of various factors, such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). SASP-mediated cell-to-cell communication promotes tissue repair, regeneration, and development. However, senescent cells can accumulate abnormally at injury sites, leading to excessive inflammation, tissue dysfunction, and intractable wounds. The effects of cellular senescence on skin wound healing can be both beneficial and detrimental, depending on the condition. Here, we reviewed the functional differences in cellular senescence that emerge during wound healing, chronic inflammation, and skin aging. We also review the latest mechanisms of wound healing in the epidermis, dermis, and subcutaneous fat, with a focus on cellular senescence, chronic inflammation, and tissue regeneration. Finally, we discuss the potential clinical applications of promoting and inhibiting cellular senescence to maximize benefits and minimize detrimental effects

Autonomic function measurements for evaluating fatigue and quality of life in patients with breast cancer undergoing radiation therapy: a prospective longitudinal study

Background: Fatigue during radiation therapy in women with breast cancer can decrease quality of life (QOL), yet it is often underestimated and needs to be evaluated objectively. This longitudinal study aimed to evaluate fatigue and QOL of women with breast cancer undergoing radiotherapy with a simple autonomic function measurement. Methods: Women with breast cancer who underwent postoperative radiotherapy in eight cancer care hospitals in Chubu and Kinki regions in Japan were recruited between October 2021 and June 2022. The women underwent a self-administered questionnaire that included the Cancer Fatigue Scale (CFS) and the Short Form-8 Health Survey (SF-8) and an autonomic nervous function measurement using a simple, non-invasive device before (T0, baseline), mid (T1), and at the end (T2) of treatment. Results: The 57 women showed similar trends, with CFS scores and log LF/HF ratio being the highest at T0 and significantly decreasing at T1 (both p < 0.05). The log LF/HF trends differed between those with high and low baseline log LF/HF values. Women with mental component summary (MCS) score improvement (T0 to T2) had the highest log LF/HF ratio at T0 and had significantly lower log LF/HF values at T1 and T2 than at T0 (p < 0.01 and p < 0.05, respectively). The change of (⊿) MCS from T0 to T1 was negatively correlated with ⊿log LF/HF from T0 to T1 (r = − 0.36, p < 0.01). Conclusions: Measurement of autonomic nerve function with a simple device is useful for objective fatigue assessment during radiotherapy. Psychological support is important as improvement in mental health helps improve autonomic nerve function and, in turn, fatigue.Aoki M., Kuratsune H., Yamamoto S., et al. Autonomic function measurements for evaluating fatigue and quality of life in patients with breast cancer undergoing radiation therapy: a prospective longitudinal study. Radiation Oncology 18, 171 (2023); https://doi.org/10.1186/S13014-023-02362-W

ANÁLISE DO PERFIL DA VIOLÊNCIA INFANTIL NO MUNICÍPIO DE GOIÂNIA-GOIÁS

Child violence is considered a serious public health problem, and with this several efforts are made to solve this situation. This study aimed to characterize the sociodemographic aspects related to child violence in the city of Goiânia-GO and to verify the spatial distribution and temporal tendency in relation to the differences in the number of notifications of child violence. This is a descriptive-analytical study, based on the notifications of violence available in the Notifiable Diseases Information System (SINAN NET), against children aged 0 to 11 years, 11 months and 29 days, which occurred in the municipality of Goiânia/Goiás, from 2010 to 2021. The results pointed to the higher prevalence of reports of violence by negligence. In relations with the violence studied, children aged 1 to 3 years, the most affected, female, the main place of occurrence is the victim's residence and the peripheral regions of the municipality of Goiânia-GO were more sensitive to child violence. In view of the findings, children are exposed to violence in various ways, and the period of growth and development is threatened by the event of violence.A violência infantil é considerada um grave problema de saúde pública, e com isso diversos esforços são realizados na tentativa de solucionar esta situação. O presente estudo objetivou caracterizar os aspectos sociodemográficos relacionados a violência infantil no município de Goiânia-GO e verificar a distribuição espacial e tendência temporal em relação às diferenças do número de notificações de violência infantil. Trata-se de um estudo descritivoanalítico, baseado nas notificações de violência disponíveis no Sistema de Informação de Agravos de Notificação (SINAN NET), contra crianças na faixa etária entre 0 e 11 anos, 11 meses e 29 dias, ocorridas no município de Goiânia/Goiás, no período de 2010 a 2021. Os resultados apontaram para a maior prevalência de notificações da violência por negligência. Em relações as violências estudadas, as crianças de a 1 a 3 anos as mais acometidas, do sexo feminino, o principal local de ocorrência é a residência da vítima e as regiões periféricas do município de Goiânia-GO foram mais sensíveis a violência infantil. Diante dos achados as crianças estão expostas a violências de diversas formas, tendo o período de crescimento e desenvolvimento ameaçados pelo evento de violência

Lymphatic abnormalities in the normal contralateral arms of subjects with breast cancer-related lymphedema as assessed by near-infrared fluorescent imaging

Current treatment of unilateral breast cancer-related lymphedema (BCRL) is only directed to the afflicted arm. Near-infrared fluorescent imaging (NIRF) of arm lymphatic vessel architecture and function in BCRL and control subjects revealed a trend of increased lymphatic abnormalities in both the afflicted and unafflicted arms with increasing time after lymphedema onset. These pilot results show that BCRL may progress to affect the clinically “normal” arm, and suggest that cancer-related lymphedema may become a systemic, rather than local, malady. These findings support further study to understand the etiology of cancer-related lymphedema and lead to better diagnostics and therapeutics directed to the systemic lymphatic system

ジュツゴ ソウキ ノ フジンカ ガン サバイバー ノ シエン ニーズ ノ ジッタイ

本研究の目的は、術後早期の婦人科がんサバイバーの支援ニーズの実態を明らかにすることである。病期や術式を問わず婦人科がんと診断されて手術療法を受けた70名に、情報と医療・身体機能・心理・社会・人生観の5領域の支援ニーズについて尋ねる自記式質問紙を配布し、退院1か月後に郵送で回収した。分析は記述統計を用いた。55名（78.6%）より回答を得た。支援を「やや必要としている～非常に必要としている」と答えた者の割合において、「情報と医療」の領域における婦人科がんに関する情報の支援ニーズは約6～7割、「心理」の領域における再発不安に関する支援ニーズは5割以上、「身体機能」の領域における症状マネジメントに関する支援ニーズは5割未満であった。術後早期から婦人科がんサバイバーが自分らしい生活を送ることができるように、婦人科がんそのものの影響を考慮しつつ、多角的に支援ニーズの内容を検討することの重要性が示された。This study aimed to describe the supportive care needs of gynecologic cancer survivors during the early postoperative period. Participants comprised 70 patients with gynecologic cancer who had undergone surgery, regardless of disease stage and surgery type. A self-administered questionnaire evaluating the supportive care needs was distributed and collected by mail one month after the patients had left the hospital. In the questionnaire, we have defined the supportive care needs as the five areas: information and medical, physical, psychological, social, and life perspectives. The data were subjected to descriptive statistics. A total of 55 patients (78.6%) responded to the questionnaire. The findings revealed the percentage of respondents who answered that they “somewhat to very much need” support. About 60–70% of the respondents needed support for information on gynecological cancer in the area of “information and medical care” whereas more than 50% needed support for anxiety about recurrence in the area of “psychological aspects” and less than 50% needed support for symptom management in the area of “physical functions.” This indicates the importance of considering supportive care needs from various perspectives while taking into account the impact of gynecological cancer itself so that gynecological cancer survivors can lead independent lives from the early postoperative period.原著論文Original Article

Overexpression of Myocilin in the Drosophila Eye Activates the Unfolded Protein Response: Implications for Glaucoma

Glaucoma is the world's second leading cause of bilateral blindness with progressive loss of vision due to retinal ganglion cell death. Myocilin has been associated with congenital glaucoma and 2-4% of primary open angle glaucoma (POAG) cases, but the pathogenic mechanisms remain largely unknown. Among several hypotheses, activation of the unfolded protein response (UPR) has emerged as a possible disease mechanism.We used a transgenic Drosophila model to analyze whole-genome transcriptional profiles in flies that express human wild-type or mutant MYOC in their eyes. The transgenic flies display ocular fluid discharge, reflecting ocular hypertension, and a progressive decline in their behavioral responses to light. Transcriptional analysis shows that genes associated with the UPR, ubiquitination, and proteolysis, as well as metabolism of reactive oxygen species and photoreceptor activity undergo altered transcriptional regulation. Following up on the results from these transcriptional analyses, we used immunoblots to demonstrate the formation of MYOC aggregates and showed that the formation of such aggregates leads to induction of the UPR, as evident from activation of the fluorescent UPR marker, xbp1-EGFP. CONCLUSIONS / SIGNIFICANCE: Our results show that aggregation of MYOC in the endoplasmic reticulum activates the UPR, an evolutionarily conserved stress pathway that culminates in apoptosis. We infer from the Drosophila model that MYOC-associated ocular hypertension in the human eye may result from aggregation of MYOC and induction of the UPR in trabecular meshwork cells. This process could occur at a late age with wild-type MYOC, but might be accelerated by MYOC mutants to account for juvenile onset glaucoma

The multiplex bead array approach to identifying serum biomarkers associated with breast cancer

Introduction Breast cancer is the most common type of cancer seen in women in western countries. Thus, diagnostic modalities sensitive to early-stage breast cancer are needed. Antibody-based array platforms of a data-driven type, which are expected to facilitate more rapid and sensitive detection of novel biomarkers, have emerged as a direct, rapid means for profiling cancer-specific signatures using small samples. In line with this concept, our group constructed an antibody bead array panel for 35 analytes that were selected during the discovery step. This study was aimed at testing the performance of this 35-plex array panel in profiling signatures specific for primary non-metastatic breast cancer and validating its diagnostic utility in this independent population. Methods Thirty-five analytes were selected from more than 50 markers through screening steps using a serum bank consisting of 4,500 samples from various types of cancer. An antibody-bead array of 35 markers was constructed using the Luminex (TM) bead array platform. A study population consisting of 98 breast cancer patients and 96 normal subjects was analysed using this panel. Multivariate classification algorithms were used to find discriminating biomarkers and validated with another independent population of 90 breast cancer and 79 healthy controls. Results Serum concentrations of epidermal growth factor, soluble CD40-ligand and proapolipoprotein A1 were increased in breast cancer patients. High-molecular-weight-kininogen, apolipoprotein A1, soluble vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, vitamin-D binding protein and vitronectin were decreased in the cancer group. Multivariate classification algorithms distinguished breast cancer patients from the normal population with high accuracy (91.8% with random forest, 91.5% with support vector machine, 87.6% with linear discriminant analysis). Combinatorial markers also detected breast cancer at an early stage with greater sensitivity. Conclusions The current study demonstrated the usefulness of the antibody-bead array approach in finding signatures specific for primary non-metastatic breast cancer and illustrated the potential for early, high sensitivity detection of breast cancer. 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Systematic review and meta-analysis of therapeutic hypothermia in animal models of spinal cord injury

Therapeutic hypothermia is a clinically useful neuroprotective therapy for cardiac arrest and neonatal hypoxic ischemic encephalopathy and may potentially be useful for the treatment of other neurological conditions including traumatic spinal cord injury (SCI). The pre-clinical studies evaluating the effectiveness of hypothermia in acute SCI broadly utilise either systemic hypothermia or cooling regional to the site of injury. The literature has not been uniformly positive with conflicting studies of varying quality, some performed decades previously.In this study, we systematically review and meta-analyse the literature to determine the efficacy of systemic and regional hypothermia in traumatic SCI, the experimental conditions influencing this efficacy, and the influence of study quality on outcome. Three databases were utilised; PubMed, ISI Web of Science and Embase. Our inclusion criteria consisted of the (i) reporting of efficacy of hypothermia on functional outcome (ii) number of animals and (iii) mean outcome and variance in each group.Systemic hypothermia improved behavioural outcomes by 24.5% (95% CI 10.2 to 38.8) and a similar magnitude of improvement was seen across a number of high quality studies. The overall behavioural improvement with regional hypothermia was 26.2%, but the variance was wide (95% CI -3.77 to 56.2). This result may reflect a preponderance of positive low quality data, although a preferential effect of hypothermia in ischaemic models of injury may explain some of the disparate data. Sufficient heterogeneity was present between studies of regional hypothermia to reveal a number of factors potentially influencing efficacy, including depth and duration of hypothermia, animal species, and neurobehavioural assessment. However, these factors could reflect the influence of earlier lower quality literature.Systemic hypothermia appears to be a promising potential method of treating acute SCI on the basis of meta-analysis of the pre-clinical literature and the results of high quality animal studies