by Makiko Sasaki, Mamoru Tanaka, Akihiro Nomoto, Ryusei Yamasaki, Tomokazu Yoshimura, Shigenobu Yano, Yasunari Sasaki, Yuki Kojima, Taketo Suzuki, Hirotada Nishie, Keiji Ozeki, Takaya Shimura, Eiji Kubota, Hiromi Kataoka
Photodynamic therapy (PDT) is an anti-cancer therapy that employs a photosensitizer (PS) and an optimal wavelength of light, causing a photochemical reaction that releases reactive oxygen species, thereby inducing cancer cell death via oxidative stress. Because light irradiation is limited to the tumor site, PDT has minimal adverse effects. The cancer cell selectivity of the PS is important for reducing damage to the normal mucosa caused by scattered light. Antibody-drug conjugates (ADC) are novel anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a drug bonded through chemical linkers. ADCs enable the targeted delivery of a variety of drugs to cancer cells while minimizing their delivery to healthy tissues. One such tumor surface receptor is the human epidermal growth factor receptor 2 (HER2), which is of interest in the treatment of many cancers, including gastrointestinal cancer. To improve tumor selectivity and minimize damage to the mucosa surrounding the tumor in PDT, we established a novel PS glucose-linked chlorin e6-conjugated trastuzumab (G-Ce6-trastuzumab) that is conjugated to existing PS glucose-linked chlorin e6 (G-Ce6) and evaluated its anti-cancer effect compared to G-Ce6. The effect of PDT was evaluated using HER2-high-expression cells NCI-N87 and HER2-low-expression cells MKN-45. G-Ce6-trastuzumab is internalized by the intracellular organelles in cancer cells. Evaluation of cell death using the WST-8 assay also demonstrated a significantly higher cytotoxic effect of G-Ce6-trastuzumab in HER2-high-expression cells compared with conventional PS G-Ce6. Thereby, G-Ce6-trastuzumab may be an excellent novel PS for PDT because of its strong selectivity for HER2-high-expression cells.The global need for developing comprehensive mental healthcare systems for children and adolescents has been increasingly evident. The system-of-care (SOC) model in the USA is among the most studied cases for such a system, which demonstrates how integrated services, encompassing psychiatric care, can effectively support children and adolescents with severe emotional disturbance. Over the past decades, the SOC framework has been widely expanded, with nearly every state in the USA receiving federal funding to implement or expand the SOC initiatives. The number of studies investigating the efficacy of the SOC is increasing, but no systematic review of the instruments for the evaluation of the implementation of the SOC exists today. This protocol paper documents the plan of a systematic review, which aims to identify and synthesise the existing instruments, which are designed and used to evaluate the implementation of the SOC.
This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Protocol guidelines. To identify relevant studies, we will perform a comprehensive search in five databases: PubMed, PsycINFO, ERIC, Social Work Abstracts and Web of Science. The title and abstracts of all searched articles will be screened independently by two reviewers according to the eligible criteria. Full-text screening of potentially relevant articles will be performed by at least two independent reviewers. A summary of included articles will describe the availability, progress and cultural adaptability of instruments.
The current systematic review will be solely based on previously reported data and will not involve new data collection. There are no concerns that require ethical vetting. Findings of the review will be disseminated through conference presentations and publication in a peer-reviewed journal.
1065693.
To investigate the association between occupation and Parkinson’s disease (PD) risk and whether patients with PD change occupation after onset.
A matched case–control study using secondary analysis of the Inpatient Clinico-Occupational Survey of the Rosai Hospital Group in Japan.
A nationwide multicentre inpatient dataset in Japan from 2005 to 2021.
The PD group comprised 2205 inpatients diagnosed with PD (International Statistical Classification of Diseases and Related Health Problems, 10th Revision code G20) and 10 436 matched controls without PD, matched for age, sex, year of admission and hospital.
Associations between the longest-held occupation—classified by industry (blue-collar, service, white-collar) and occupational class (blue-collar workers, service workers, professionals, managers)—and PD risk.
Occupations and industries with increased PD risk; occupational changes before and after diagnosis among participants aged
After adjustment for smoking and alcohol, professionals in the service (OR=2.01, 95% CI 1.24 to 3.25) and white-collar (OR=1.33, 95% CI 1.10 to 1.61) industries had higher PD risk than service workers. Doctors, dentists, veterinarians and pharmacists showed elevated risk. Among 160 PD patients, 47% were unemployed, 20% left voluntarily and 30% continued working after diagnosis. Chemical handling was not associated with PD risk after adjustment of multiple comparisons. Former or current smokers among blue-collar and service workers in blue-collar industry had a decreased risk of PD.
Professionals in the service and white-collar industries, particularly those in healthcare occupations, had a higher risk of PD. Approximately 20% became unemployed after diagnosis.
by Azusa Kubota, Kentaro Kojima, Shinnosuke Koketsu, Takayuki Kannon, Takehiro Sato, Kazuyoshi Hosomichi, Yoshiaki Shinohara, Atsushi Tajima
Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein–protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2–Grin2b–Cdkl5–Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell–cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.Commentary on: Perrella A, Geen, O, Ahuja, M, et al. Exploring the Impact of Age, Frailty, and Multimorbidity on the Effect of ICU Interventions: A Systematic Review of Randomized Controlled Trials. Critical Care Med. 2024 September. doi: 10.1097/CCM.0000000000006315
Implications for practice and research More information on how age, frailty, and multimorbidity affect responses to interventions in critically ill older adults would be important and beneficial for shared decision-making. Future studies should focus more on these understudied populations of older patients with frailty or multimorbidity and examine how they respond to intensive care unit interventions.
Recent data show that there has been an increase in the older populations admitted to intensive care unit (ICU).