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Background: The evaluation of transition readiness is indispensable for long‐term follow‐ups of adolescent patients with childhood‐onset chronic diseases (CCD). We developed a Japanese version of the TRANSITION‐Q (TRANSITION‐Q‐J) and used it to assess Japanese patients with CCD. Methods: The TRANSITION‐Q‐J was developed through forward and backward translations followed by cognitive interviews with five adolescent patients. The field test was conducted with 125 adolescent patients, and a retest was conducted with 113 adolescent patients. Results: Confirmatory factor analysis supported the two‐factor analysis model including F1 (communication and self‐management) and F2 (examination behavior). Sufficient internal consistency and test‐retest reliability were demonstrated among the total 14 items, F1, and F2 (Cronbach's α > 0.80, intraclass correlation coefficient > 0.85). Convergent and discriminant validity for the 14 items and F1 were acceptable; however, F2 did not correlate significantly with the Rosenberg Self‐Esteem Scale and Independent Consciousness Scale. Regarding known‐groups validity, the older group had a significantly higher mean TRANSITION‐Q‐J score (50.05) than the younger group (43.28; P = 0.04). The same results were found for both F1 and F2. Conclusions: The TRANSITION‐Q‐J for adolescent patients with CCD was developed and its reliability and validity were verified. This scale is easy to administer. In addition to being a tool for transition period support, it could be used to verify effective factors and in program outcome evaluation, including intervention studies. [ABSTRACT FROM AUTHOR]

Aim: Nurses are expected to have a role in the transition of care from pediatric to adult medical practices for adolescents and young adults with childhood‐onset chronic diseases. This study compares the experience, knowledge, and perceptions regarding the ideal care among adult unit and pediatric nurses regarding the transition to adult care for those with childhood‐onset chronic diseases. Methods: A cross‐sectional study using self‐report questionnaires was conducted with nurses in a tertiary hospital in Tokyo. Questions were generated based on a literature review and expert discussion. Data from 1,064 participants were analyzed (adult unit nurses: n = 959, 90.1%; pediatric nurses: n = 105, 9.9%). Results: Among 623 adult unit nurses who had care experience for adult patients with a childhood‐onset chronic disease, 458 nurses (73.6%) were unaware of the concept of transitional care. As the obstructive factors for transition, pediatric nurses recognized problems in healthcare providers' attitudes and lack of transitional care coordinators, while the adult unit nurses emphasized the patients' wishes to continue to receive pediatric healthcare. Most adult unit nurses expected pediatric nurses to function as transitional care coordinators. Conclusion: Adult unit and pediatric nurses had different perceptions of the barriers in transitioning children with chronic diseases to adult care. It is important to have educational programs focusing on transitional care for all nurses, both to enable pediatric nurses to improve transition readiness of children with chronic diseases and to offer adult patients with a childhood‐onset chronic disease continuing support through adult unit nurses. [ABSTRACT FROM AUTHOR]

Inspired by ligand binding-triggered structural transition of biopolymers in living systems, we demonstrated the structural transition of thermoresponsive poly(N-isopropylacrylamide) through specific ligand binding of artificially evolved peptides to the polymer. [ABSTRACT FROM AUTHOR]

A 12-mer peptide with an affinity for the meso diad sequence of poly(N-isopropylacrylamide) (PNIPAM) was identified through affinity-based peptide screening. A model protein (i.e., human serum albumin (HSA)) chemically modified with the peptide was successfully precipitated with PNIPAM above the lower critical solution temperature (LCST) of PNIPAM. [ABSTRACT FROM AUTHOR]

Abstract: TNF plus protein synthesis inhibitor cycloheximide-induced apoptosis in human myelogenous leukemia ML-1a but not in C19, respiration minus mitochondrial DNA-deficient C19 cells, derived from ML-1a. To investigate how mitochondrial DNA depletion inhibits apoptosis, we investigated AKT. Both AKT and its phosphorylated form were observed only in C19, indicating that depletion of mtDNA increased protein and the active form of AKT. Treatment of C19 with LY294002, which inhibits PI-3 kinase and inhibits AKT, significantly increased apoptosis induction by TNF plus cycloheximide and eliminated phosphorylation of AKT. These results indicate that AKT activation was induced by the depletion of mtDNA and inhibited TNF-induced apoptosis. [Copyright &y& Elsevier]

Abstract The effect of fibroblast growth factor-2 (FGF-2) on synapse formation was investigated using rat cultured hippocampal neurons. Treatment with FGF-2 (0.4–10 ng/mL) for 6 days enhanced synaptogenesis on these neurons by ∼50%, as determined by counting puncta immunostained for presynaptic- or postsynaptic-specific proteins. This enhancement was statistically significant, and was abolished by a specific inhibitor of mitogen-activated protein kinase (MAPK). The majority of neurons expressed FGF receptors (types 1–3) abundantly on the membrane of somata, dendrites, and growth cones, and in these regions phosphorylation of MAPK was enhanced after FGF-2 application. Furthermore, our experiments showed that the majority of synapses formed in cultures containing FGF-2 were positive both for presynaptic proteins and postsynaptic excitatory synapse-specific proteins, and that these synapses had a similar capacity to recycle the fluorescent styryl dye FM4-64 as those in the control culture. These results indicate that: (i) FGF-2 increases excitatory synapses on hippocampal neurons by activating MAPK activity through FGF receptors; and (ii) synapses formed in FGF-2-treated culture are capable of cycling vesicles. [ABSTRACT FROM AUTHOR]

It has been suggested that fibroblast growth factor (FGF)-I serves as a physiological satiety factor in the hypothalamus, although the molecular mechanism underlying such a function is poorly understood. To gain additional insight into this issue, we used a Sendai virus (SeV) gene expression system in rats to explore genes differentially expressed subsequent to expression of FGF-1. Using cDNA arrays, we determined that infusion of FGF-1/SeV into one lateral ventricle induced selective expression of heat shock protein (HSP) 27 in the hypothalamus. Whereas FGF-1 expression was restricted to the ependymal cell layer of the cerebral ventricles, HSP27 was more widely expressed in astrocytes residing in the surrounding periventricular region. Similarly, infusion of FGF-1 polypeptide into a lateral ventricle induced dose-dependent HSP27 expression in periventricular astrocytes surrounding the third ventricle, with maximum mRNA levels being attained 6 h after infusion. This induction of HSP27 was accompanied by a significant suppression of feeding behaviour. Interestingly, suppression of feeding caused by intracerebro-ventricular infusion of ciliary neurotrophic factor was also accompanied by induction of HSP27 in periventricular astrocytes, but suppression of feeding caused by infusion of leptin was not. It therefore appears that suppression of feeding by FGF-1 is accompanied by selective induction of HSP27 expression in hypothalamic astrocytes surrounding the third ventricle, and that this response may be a key component of the mechanism by which appetite is regulated by FGF-1. [ABSTRACT FROM AUTHOR]

N:-(4-Hydroxyphenyl)retinamide (4HPR) is currently used in cancer prevention and therapy trials. It is thought that its effects result from induction of apoptosis. 4HPR-induced apoptosis in human cervical carcinoma C33A cells involves enhanced generation of reactive oxygen species (ROS). In this study we explored the mechanism by which 4HPR increases ROS and induces apoptosis in these cells. 4HPR induced cytochrome c release from mitochondria to cytoplasm, activated caspase-3, and caused a membrane permeability transition (MPT). All these 4HPR's effects, as well as the induction of apoptosis, were inhibited by antioxidants, which decrease ROS. Thenoyltrifluoroacetone, a mitochondrial respiratory chain (MRC) complex II inhibitor, and carbonylcyanide m-chlorophenyl hydrazone, which uncouples electron transfer and ATP synthesis and inhibits ROS generation by MRC, inhibited 4HPR-induced ROS generation very effectively. Rotenone, an MRC complex I inhibitor was less effective and azide, an MRC complex IV inhibitor, exhibited a marginal effect. In contrast, antimycin A, an MRC complex III inhibitor, enhanced 4HPR-induced ROS generation. These findings suggest that 4HPR enhances ROS generation by affecting a target between complex II and complex III, presumably coenzyme Q. This effect is followed by release of cytochrome c, increased caspase-3 activity, induction of MPT and eventual DNA fragmentation and cell death. [ABSTRACT FROM AUTHOR]

Determines whether the levels of reactive oxygen species increase in cells undergoing apoptosis after exposure to N-(4-hydroxyphenyl)-retinamide (4HPR). Inhibitory effect of 4HPR on tumorigenesis and tumor growth; Quantitative assay for DNA fragmentation; Assay of generation of reactive oxygen species.

Digital enzyme‐linked immunosorbent assay (ELISA) is a single molecule counting technology and is one of the most sensitive immunoassay methods. The key aspect of this technology is to concentrate enzyme reaction products from a single target molecule in femtoliter droplets. On the other hand, we have developed a novel Digital ELISA that does not require droplets; instead, enzyme reaction products are concentrated using a tyramide signal amplification system. In this study, we present a method that enables the multiplex detection of proteins based on Droplet‐free Digital ELISA. First, two types of paramagnetic beads immobilized with antibodies specific to different target proteins were incubated with a sample solution, and target proteins were captured on their specific beads. Then, these beads were labeled with horseradish peroxidase (HRP), and tyramide substrate reacted with HRP on beads, resulting in products of this reaction deposited on those beads. This signal amplification on beads makes it possible to count the number of labeled beads digitally. We used this approach to simultaneously detect IL‐6 and HBs Ag with single molecule resolution. The obtained limit of detections were 0.1 pg/mL and 0.013 IU/mL, respectively. Our method has potential applications in simple in vitro diagnostic systems for simultaneous and high‐sensitive detection of protein biomarkers. [ABSTRACT FROM AUTHOR]

Background: The number of adult patients with childhood-onset chronic diseases is increasing. However, the process of transitioning these patients from child- to adult-centered medical services faces many difficulties. Despite the key role that doctors in the pediatric field are considered to play in transition, few fact-finding surveys about transition have been conducted among these doctors. Objective: The aim of this study was to demonstrate the current status and challenges in the transition of patients with childhood-onset chronic diseases by a fact-finding survey of pediatricians and pediatric surgeons at a university hospital. Methods: A cross-sectional survey was performed using an anonymous self-administered questionnaire. Seventy-six doctors of pediatrics and pediatric surgery (excluding junior residents) in a university hospital were asked to answer an anonymous self-report questionnaire. A multidisciplinary research team selected items related to the transitional process. Results: Sixty (79%) doctors participated, of whom 52 (87%) showed awareness of transition. No doctor answered that "Transition is conducted smoothly." Doctors with shorter pediatric department experience had lower awareness and poorer experience with transition. In contrast to pediatric surgeons, pediatricians explained "job-seeking activities" and "contraceptive methods" to the patient, and reported a higher patient age at which to initiate explanation of transition to the patient and his/her family. Among factors inhibiting transition, 39 (65%) respondents selected "The patient's family members do not desire transition" and 34 (57%) selected "Although a relevant adult healthcare department is available, it will not accept the patient." The medical providers most frequently considered to have responsibility for playing a central role in the transition process were "pediatrician/pediatric surgeon," "medical social worker," and "regional medical liaison office." Discussion: To promote transition, pediatric and adult healthcare departments should share concerns about and cooperate in the establishment of more effective methods of transition, and provide multidisciplinary collaboration to support patients and their families. [ABSTRACT FROM AUTHOR]

Background: Families raising children with disabilities assume risks to their health and lives. Therefore, it is necessary to support these families to improve family empowerment, which is the ability of these families to control their own lives and to promote the collaborative raising of children with disabilities. This is the first online intervention program focusing on the empowerment of families raising children with disabilities who live at home in Japan. Method: The program consists of four online peer-based group sessions. Moreover, the families engage in several activities in stages wherein they discover their own issues, find measures to resolve them, and take action, while visualizing interfamily relationships, including social resources, and the status of their family life, with facilitators and other peer members. This study is a non-randomized, waitlist-controlled trial. It compares the results of the intervention group (early group) and the waitlist-controlled group (delayed group). The participants are allocated to the early or delayed group in the order of their applications. The main outcome is family empowerment. Other outcomes are the caregiver burden, self-reported capability to use social resources, self-compassion, and the quality of life (QOL) of primary caregivers. The timeline of the online outcome evaluation is as follows: the initial evaluation (Time 1 [T1]) is conducted before the start of the first early group program, and post-intervention evaluation (Time 2 [T2]) is conducted immediately (within 1 week) after the early group completes all four sessions (4 weeks) of the program. Follow-up evaluation (Time 3 [T3]) is conducted 4 weeks after the post-intervention evaluation. This timing is the same in the delayed group, but the delayed group will attend the program after a 4-week waiting period, compared to the early group. Discussion: The intention is to evaluate whether the provision of the program developed in this study and the evaluation test design are feasible and to verify the efficacy of this program. Trial registration: The UMIN Clinical Trials Registry (UMIN000044172), registration date: May 19, 2021. [ABSTRACT FROM AUTHOR]

Conclusion: It was proved that cyclin D1-positive status in surgical margins was an independent prognostic indicator of local recurrence. The expression of cyclin D1 in tumor-free surgical margins may better predict local recurrence in patients with head and neck squamous cell carcinoma (HNSCC) after surgical treatment with curative intent. Objective: This retrospective study aimed to determine the prognostic indicators for local recurrence in HNSCC. Methods: A total of 116 HNSCC patients who underwent surgical treatment with curative intent and had histopathologically tumor-free margins were eligible for this study. The expression of p53 and cyclin D1 was assessed by immunohistochemical staining in surgical margins as well as in tumor specimens. Results: In all, 63 patients (54.3%) had p53-positive tumor specimens and 34 patients (29.3%) had p53-positive margins. Seventy-six patients (65.6%) had cyclin D1-positive tumor specimens and 54 patients (46.6%) had cyclin D1-positive margins. A significant difference in local control rates was observed between patients with cyclin D1-positive and -negative margins (77.2% vs 91.5%, log rank test, p = 0.0139). Multivariate Cox proportional hazards testing indicated that the hazard ratio of cyclin D1-positive margins for local recurrence was 4.58 (95% confidence interval 1.14-21.69, p = 0.0304). [ABSTRACT FROM AUTHOR]

We used immunoblot analysis to investigate the phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)-receptor glutamate receptor-1 (GluR1) and related protein kinases in rat hippocampus on postnatal days (PND) 1-28. Total GluR1 expression increased up to PND 9, and stayed high thereafter. The proportions of the forms of GluR1 phosphorylated at serines (S) 845 and S831, which were both high at birth, decreased at different rates: phosphorylated S831 decreased rapidly after PND 7, and was almost zero after PND 21, while phosphorylated S845 decreased slowly, and after PND 14 stayed at one third of its PND 1 level. The expression patterns of cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC), but not that of calcium/calmodulin-dependent protein kinase II, were similar to those of the forms of GluR1 phosphorylated at S845 and S831, respectively. Thus, the status of GluR1 phosphorylation, through PKA and PKC modulation, may contribute to the development of hippocampal synaptic plasticity. [Copyright &y& Elsevier]

Background: The prevalence of oropharyngeal carcinoma is rising in western Europe and the United States, where there appears to be a strong association between human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma (OPSCC). However, such a correlation has not yet been fully evaluated in Japan. Methods: We performed a retrospective analysis of the association between tumour HPV status and the demographic and clinicopathological parameters of 71 patients with OPSCC at Hokkaido University Hospital, Japan, between 1998 and 2009. The parameters included age, gender, survival, tumour subsite, tumour-node-metastasis (TNM) stage, smoking history, second primary tumour status, recurrence/residual disease at the primary site, and overall survival. HPV status was established by multiplex polymerase chain reaction (PCR) analysis. Results: Of the 71 oropharyngeal cancers, 20 were positive for HPV-16, two for HPV-18, and one for HPV-58. Kaplan-Meier survival analysis showed improved overall survival rates in patients with HPV-positive tumours ( p = 0.0038) compared with HPV-negative tumours. Of the 45 patients who received chemoradiotherapy, HPV-positive patients experienced better overall survival than HPV-negative patients ( p = 0.0032). In a multivariate analysis, the survival benefit of HPV-positive patients was independent of age and T and N classification. Conclusions: HPV status is a significantly favourable prognostic factor in oropharyngeal cancer and could be used as a marker to optimize the treatment of patients with this type of cancer in Japan. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Although three-weekly high-dose (100mg/m2) cisplatin (three cycles) chemoradiotherapy has been considered a standard regimen for patients with advanced head and neck squamous cell carcinomas (HNSCC), this protocol is associated with significant acute and late toxicities. Therefore, weekly cisplatin at a dose of 40mg/m2 has been used at our institution since 2006. This retrospective study was aimed at assessing the oncologic efficacy of weekly cisplatin chemoradiotherapy for the control of nodal metastasis. Methods: We analyzed 28 patients with node-positive HNSCC treated with weekly cisplatin and concurrent radiotherapy. Computed tomography was performed 4–8 weeks after the completion of chemoradiotherapy to evaluate nodal response. If residual neck disease was apparent or suspected, we performed early salvage neck dissection (ND). In cases with a complete response (CR), we took a “wait and see” approach. When no viable tumor cells were observed in the surgical specimens obtained by ND, nodal metastasis was defined as controlled by weekly cisplatin chemoradiotherapy alone. Results: Nodal metastasis was evaluated as having a CR in 20 patients (71%). Eight patients (29%) underwent early salvage ND. Recurrent primary tumors were observed in the other four patients (14%). Salvage primary resection and associated ND were performed for these four patients. In 7 of 12 patients undergoing ND, no viable tumor cells were observed. In 23of 28 patients, neck diseases were controlled by chemoradiotherapy alone (not including salvage by ND). In 27 of 28 patients, neck diseases were controlled by the overall treatment (including salvage by ND). The rate of nodal control by chemoradiotherapy alone and by the overall treatment was found to be 82.0% and 96.3%, respectively, using the Kaplan–Meier method. The three-year overall and disease free survival rates were 86.8% and 80.8%, respectively. Conclusion: Concomitant weekly cisplatin at a dose of 40mg/m2 chemoradiotherapy showed a good control rate of not only primary lesions but also neck diseases. [Copyright &y& Elsevier]

Conclusion: We conclude that intra-arterially injected cisplatin passed via lymph flow into sentinel nodes (SNs) as the platinum concentration in the SNs was higher than that in the non-sentinel nodes (NSNs). It is possible that preoperative intra-arterial chemotherapy targeting primary cancer also has a therapeutic effect on subclinical metastatic SNs. Objectives: Intra-arterial chemoradiotherapy has been reported to be effective against not only primary tumors but also nodal metastases. We considered the hypothesis that intra-arterially injected cisplatin passed via lymph flow into regional nodes. This study aimed to investigate intra-arterially injected cisplatin distribution to regional nodes by comparing platinum concentrations in SNs and NSNs. Methods: Five patients with T1-2 N0 tongue cancer were treated with preoperative intra-arterial chemotherapy (cisplatin, 100 mg/m2) targeting primary cancer. Partial glossectomy together with SN biopsy and elective neck dissection were performed 2 weeks after intra-arterial chemotherapy. Platinum concentrations in the lymph nodes were measured using a Zeeman atomic absorption spectrometer. Results: Thirteen SNs were harvested together with eight NSNs from the areas adjacent to the SNs. Platinum concentrations were then measured, revealing a significant difference in platinum concentration between the SNs and the NSNs (mean ± SD, 0.682 ± 0.246 µg/g vs 0.506 ± 0.274 µg/g; p = 0.049). [ABSTRACT FROM AUTHOR]

This retrospective study aimed to assess the role of salvage surgery for local recurrence in hypopharyngeal cancer (HPC) patients who had received radiotherapy (RT) or concomitant chemoradiotherapy (CRT) as an initial treatment. The local recurrence rate, salvage rate after local recurrence and overall survival rate were investigated in 104 HPC patients who received treatment between 1991 and 2005. Local recurrence in the primary site was observed in 41 patients (rate, 39.4%) of whom only 12 could undergo further salvage surgery. Disease control was achieved in seven of these patients (successful salvage rate, 17.1%). The 5-year overall survival rate was 40.6% in the RT/CRT patient group and successful salvage rates for T1, T2, T3 and T4 primary disease were 33.3% (1/3), 20.0% (4/20), 16.7% (2/12) and 0% (0/6), respectively. Severe postoperative complications such as pharyngo-cutaneous fistula were seen in six patients (50.0%). Prognosis of patients with locally recurring HPC after RT/CRT is poor at any primary T-stage and the incidence of postoperative complication is relatively high. This should be taken into consideration when the initial treatment plan is decided and the choice of salvage surgery for such recurrent cases should be carefully determined. [ABSTRACT FROM AUTHOR]

It has been reported that the gene for murine fibroblast growth factor-5 (Fgf-5) is expressed in the rat hair follicle and that this expression may be associated with catagen induction (Hébert et al. 1994). In this study, we analyzed the Fgf-5 gene product in skin because the gene generates two mRNA that translate into the FGF-5 protein and a short form of the FGF-5 protein (FGF-5S) as a result of an alternative splicing (Hattori et al. 1996; Ozawa et al. 1996). Indeed, we detected both types of FGF-5 mRNA in rat skin samples. Two monoclonal anti-FGF-5 antibodies, one (E723) being specific for FGF-5 long-form protein and the other (B2B6) being reactive with both FGF-5 and FGF-5S proteins, were used to locate these proteins by immunohistochemistry. Staining of the rat skin revealed that only the B2B6 antibody reacted with hair follicles and that both antibodies reacted with macrophage-like round cells, suggesting that the product of the Fgf-5 gene in the hair follicle is FGF-5S. The immunoreactivity of the FGF-5S protein increased during early anagen VI and decreased rapidly during catagen. The density of FGF-5-positive macrophage-like cells in the dermis increased during anagen and decreased during catagen and telogen, whereas the density of these cells in the panniculus adiposus did not change during anagen and increased during catagen and telogen. There was no apparent association between the density of FGF-5positive macrophage-like cells and that of FGF-5-negative, dendritic macrophage-like cells. Thus, the results suggest the possible involvement of FGF-5S in the hair follicle in anagen VI and catagen development and that the density of FGF-5-positive macrophage-like cells may also be associated with the hair growth cycle. [ABSTRACT FROM AUTHOR]