NF9 peptide specific cytotoxic T lymphocyte clone cross react to Y453F mutation of SARS-CoV-2 virus spike protein.

The recognition by cytotoxic T cells (CTLs) is essential for the clearance of SARS-CoV-2 virus-infected cells. Several viral proteins have been described to be recognized by CTLs. Among them, the spike (S) protein is one of the immunogenic proteins. The S protein acts as a ligand for its receptors, and several mutants with different affinities for its cognate receptors have been reported, and certain mutations in the S protein, such as L452R and Y453F, have been found to inhibit the HLA-A24-restricted CTL response. In this study, we conducted a screening of candidate peptides derived from the S protein, specifically targeting those carrying the HLA-A24 binding motif. Among these peptides, we discovered that NF9 (NYNYLYRLF) represents an immunogenic epitope. CTL clones specific to the NF9 peptide were successfully established. These CTL clones exhibited the ability to recognize endogenously expressed NF9 peptide. Interestingly, the CTL clone demonstrated cross-reactivity with the Y453F peptide (NYNYLFRLF) but not with the L452R peptide (NYNYRYRLF). The CTL clone was able to identify the endogenously expressed Y453F mutant peptide. These findings imply that the NF9-specific CTL clone possesses the capability to recognize and respond to the Y453F mutant peptide.

Laser-assisted direct roller imprinting of large-area microstructured optical surfaces.

In this study, a high-throughput fabrication method called laser-assisted direct roller imprinting (LADRI) was developed to lower the cost of nanoimprinting large-area polymer films and to address problems associated with nanoimprinting, namely, microstructural damage and precision in flatness of entire film. With LADRI, the laser directly heats the microstructured surface of the roller mold, which heats and melts the surface of a polymethyl methacrylate (PMMA) film to replicate the microstructures on the mold rapidly. In this study, the effects of laser power density, scanning speed, size of the microstructures, and contact pressure on the replication speed were investigated experimentally. The replication speed increased as the power and scanning speed increased. However, because the film required heating until it filled the entire depth of the microstructure, an appropriate replication speed was necessary. This result was supported by simulation of the temperature distribution inside the mold and the PMMA using transient heat conduction analyses. To demonstrate the applications of LADRI, two different optical surfaces were replicated: an antireflection (AR) structure with conical structures sized several hundred nanometers and a light-extraction structure with a microlens array (MLA) comprising 10 µm lenses, for display and illumination, respectively. The replication degree of the MLA was governed by the contact pressure. Polymer flow simulation indicated that the heat conduction and flow speeds of the melted PMMA surface were comparable within several tens of micrometers. In addition, the reflectivity of the AR structure decreased from 4 to 0.5%, and the light intensity of the light-extraction structure increased by a factor of 1.47.

SARS-CoV-2 spike protein-derived immunogenic peptides that are promiscuously presented by several HLA-class II molecules and their potential for inducing acquired immunity.

The current coronavirus disease 2019 (COVID-19) pandemic that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a significant threat to public health. Although vaccines based on the mRNA of the SARS-CoV-2 spike protein have been developed to induce both cellular and humoral immunity against SARS-CoV-2, there have been some concerns raised about their high cost, particularly in developing countries. In the present study, we aim to identify an immunogenic peptide in the SARS-CoV-2 spike protein to activate cellular immunity, particularly CD4+ helper T lymphocytes (Th cells), which are a commander of immune system. SARS-CoV-2 spike protein-derived peptides Spike448-477 and Spike489-513(N501Y)-specific CD4+ Th cell lines were generated by repetitive stimulation of healthy donor-derived CD4+T-cells with each peptide. Their HLA-restrictions were addressed by using blocking antibodies against HLA and HLA-transfected L-cells. The epitopes of Spike448-477-specific CD4+ Th cell lines were defined using a series of 7-14-mer overlapping truncated peptides and alanine-substituted epitope peptides. To address responsiveness of these CD4+ Th cell lines to several SARS-CoV-2 variants, we stimulated the CD4+ Th cell lines with mutated peptides. We addressed whether these identified peptides were useful for monitoring T-cell-based immune responses in vaccinated donors using the IFN-γ ELISpot assay. The Spike448-477 peptide was found to be a promiscuous peptide presented by HLA- DRB1*08:02, DR53, and DPB1*02:02. Although HLA-DPB1*02:02-restricted CD4+ Th cells did not response to some peptides with the L452R and L452Q mutations, the other CD4+ Th cells were not affected by any mutant peptides. We developed two tetramers to detect HLA-DRB1*08:02/Spike449-463- and Spike449-463(L452R/Y453F)-recognizing CD4+ Th cells. Spike489-513(N501Y) peptide was also a promiscuously presented to HLA-DRB1*09:01 and DRB1*15:02. The T-cell responses specific to both peptides Spike448-477 and Spike489-513 were detected in PBMCs after vaccinations. In addition, we observed that the Spike448-477 peptide activated both CD8+ T-cells and CD4+ Th cells in individuals receiving mRNA vaccines. SARS-CoV-2 spike protein-derived peptides, Spike448-477 and Spike489-513, include several epitopes that are presented by multiple HLA-class II alleles to activate CD4+ Th cells, which are considered useful for monitoring the establishment of acquired immunity after vaccination.

Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy.

The engagement of CD27 on lymphocytes with its ligand, CD70, on tumors is believed to mediate tumor immune evasion and the elevation of serum soluble CD27 (sCD27) levels in patients with CD70-positive malignancies. We previously showed that CD70 is expressed in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), an Epstein-Barr virus (EBV)-related malignancy. However, little is known about serum sCD27 expression and its association with the clinical characteristics of, and the CD27/CD70 interaction in, ENKL. In the present study, we show that serum sCD27 is significantly elevated in the sera of patients with ENKL. The levels of serum sCD27 provided excellent diagnostic accuracy for discriminating patients with ENKL from healthy subjects, correlated positively with the levels of other diagnostic markers (lactate dehydrogenase, soluble interleukin-2 receptor, and EBV-DNA), and decreased significantly following treatment. Elevated serum sCD27 levels also correlated significantly with advanced clinical stage and tended to correspond with shorter survival, in patients with ENKL. Immunohistochemistry indicated that CD27-positive tumor-infiltrating immune cells exist adjacent to CD70-positive lymphoma cells. In addition, serum sCD27 levels in patients with CD70-positive ENKL were significantly higher than those in patients with CD70-negative ENKL, suggesting that the intra-tumoral CD27/CD70 interaction boosts the release of sCD27 in serum. Furthermore, the EBV-encoded oncoprotein latent membrane protein 1 upregulated CD70 expression in ENKL cells. Our results suggest that sCD27 may serve as a novel diagnostic biomarker and also may serve as a tool for evaluating the applicability of CD27/CD70-targeted therapies by predicting intra-tumoral CD70 expression and CD27/CD70 interaction in ENKL.

Celecoxib promotes the efficacy of STING-targeted therapy by increasing antitumor CD8+ T-cell functions via modulating glucose metabolism of CD11b+ Ly6G+ cells.

Recent studies have shown that activation of the cGAS-STING pathway is a key process in antitumor immune responses and various kinds of STING agonists have been developed for cancer immunotherapy. Despite promising preclinical studies, preliminary clinical results have shown only a modest effect of STING agonists. There is therefore a need to develop more effective treatment strategies. Based on previous observations that COX-2 is frequently overexpressed not only in a variety of cancers but also in tumor myeloid cells and that it suppresses antitumor immunity and promotes tumor survival by producing PGE2, we investigated the antitumor effects of combination therapy with a STING agonist cGAMP and the selective COX-2 inhibitor celecoxib in mouse models. Combination treatment with cGAMP and celecoxib inhibited tumor growth compared with either monotherapy, and the combination therapy induced both local and systemic antitumor immunity. cGAMP treatment decreased PD-1 expression on tumor-infiltrating T-cells and enhanced T-cell activation in tumor-draining lymph nodes regardless of the presence of celecoxib. Meanwhile, although celecoxib treatment did not alter the frequency of CD4+ CD25+ Foxp3+ regulatory T-cells, it enhanced the expression of costimulatory molecules and glycolysis-associated genes in tumor-infiltrating CD11b+ Ly6G+ cells. Moreover, we also found that celecoxib decreased lactate efflux and increased the frequency of IFN-γ- and TNF-α-producing CD8+ T-cells in the tumor microenvironment. Taken together, our findings suggest that combined treatment with celecoxib may be an effective strategy to improve the antitumor efficacy of STING agonists.

A tumor metastasis-associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity.

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen-derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor-specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1140-162 , which effectively activated TWIST1-specific CD4+ T-cells. In a short-term culture system, we detected more TWIST1-specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1-reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.

CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes.

Activation of STING signaling plays an important role in anti-tumor immunity, and we previously reported the anti-tumor effects of STING through accumulation of M1-like macrophages in tumor tissue treated with a STING agonist. However, myeloid cells express SIRPα, an inhibitory receptor for phagocytosis, and its receptor, CD47, is overexpressed in various cancer types. Based on our findings that breast cancer patients with highly expressed CD47 have poor survival, we evaluated the therapeutic efficacy and underlying mechanisms of combination therapy with the STING ligand cGAMP and an antagonistic anti-CD47 mAb using E0771 mouse breast cancer cells. Anti-CD47 mAb monotherapy did not suppress tumor growth in our setting, whereas cGAMP and anti-CD47 mAb combination therapy inhibited tumor growth. The combination therapy enhanced phagocytosis of tumor cells and induced systemic anti-tumor immune responses, which rely on STING and type I IFN signaling. Taken together, our findings indicate that coadministration of cGAMP and an antagonistic anti-CD47 mAb may be promising for effective cancer immunotherapy.

Resilience and related factors as predictors of relapse risk in patients with substance use disorder: a cross-sectional study.

BACKGROUND: Resilience, referring to the inherent ability to naturally recover in the face of adverse conditions, is an essential concept in discussions of substance use disorder (SUD) recovery. This study's objective was to shed light on resilience and related factors that affect relapse risk in patients with SUDs. METHOD: Fifty-two patients with SUDs were given a self-administrated questionnaire from February to April 2015 consisting of question items for sociodemographic characteristics, relapse risk (Stimulant Relapse Risk Scale), and resilience (Bidimensional Resilience Scale). Scale scores were tested for associations with subject attributes, after which resilience's effects on relapse risk were analyzed using correlation and multiple regression (forced-entry) analyses. RESULTS: Stimulants were the most common substance related to SUD (n = 26, 21.7%; multiple answers). Bivariate correlation showed that higher acquired resilience was significantly associated with a lower relapse risk (r = - 0.314, P < 0.01). Reduced relapse risk was significantly associated with current employment (Std. ß = - 0.446, P < 0.05). CONCLUSION: Our findings demonstrate the necessity of recovery support to enhance acquired resistance in patients with SUDs to prevent relapses. Reinforcing employment support services and encouraging patients to continue treatment were suggested as potentially effective measures to enhance resilience in individuals with SUDs on their road to recovery.

A stealth antigen SPESP1, which is epigenetically silenced in tumors, is a suitable target for cancer immunotherapy.

Recent studies have revealed that tumor cells decrease their immunogenicity by epigenetically repressing the expression of highly immunogenic antigens to survive in immunocompetent hosts. We hypothesized that these epigenetically hidden "stealth" antigens should be favorable targets for cancer immunotherapy due to their high immunogenicity. To identify these stealth antigens, we treated human lung cell line A549 with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5Aza) and its prodrug guadecitabine for 3 d in vitro and screened it using cDNA microarray analysis. We found that the gene encoding sperm equatorial segment protein 1 (SPESP1) was re-expressed in cell lines including solid tumors and leukemias treated with 5Aza, although SPESP1 was not detected in untreated tumor cell lines. Using normal human tissue cDNA panels, we demonstrated that SPESP1 was not detected in normal human tissue except for testis and placenta. Moreover, we found using immunohistochemistry SPESP1 re-expression in xenografts in BALB/c-nu/nu mice that received 5Aza treatment. To assess the antigenicity of SPESP1, we stimulated human CD4+ T-cells with a SPESP1-derived peptide designed using a computer algorithm. After repetitive stimulation, SPESP1-specific helper T-cells were obtained; these cells produced interferon-γ against HLA-matched tumor cell lines treated with 5Aza. We also detected SPESP1 expression in freshly collected tumor cells derived from patients with acute myeloid leukemia or lung cancer. In conclusion, SPESP1 can be classified as a stealth antigen, a molecule encoded by a gene that is epigenetically silenced in tumor cells but serves as a highly immunogenic antigen suitable for cancer immunotherapy.

A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment.

Stimulator of interferon genes (STING) contributes to anti-tumor immunity by activating antigen-presenting cells and inducing mobilization of tumor-specific T cells. A role for tumor-migrating neutrophils in the anti-tumor effect of STING-activating therapy has not been defined. We used mouse tumor transplantation models for assessing neutrophil migration into the tumor triggered by intratumoral treatment with STING agonist, 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Intratumoral STING activation with cGAMP enhanced neutrophil migration into the tumor in an NF-κB/CXCL1/2-dependent manner. Blocking the neutrophil migration by anti-CXCR2 monoclonal antibody impaired T cell activation in tumor-draining lymph nodes (dLNs) and efficacy of intratumoral cGAMP treatment. Moreover, the intratumoral cGAMP treatment did not show any anti-tumor effect in type I interferon (IFN) signal-impaired mice in spite of enhanced neutrophil accumulation in the tumor. These results suggest that both neutrophil migration and type I interferon (IFN) induction by intratumoral cGAMP treatment were critical for T-cell activation of dLNs and the anti-tumor effect. In addition, we also performed in vitro analysis showing enhanced cytotoxicity of neutrophils by IFN-ß1. Extrinsic STING activation triggers anti-tumor immune responses by recruiting and activating neutrophils in the tumor via two signaling pathways, CXCL1/2 and type I IFNs.

Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer.

Colorectal cancer (CRC) patients with metastatic lesions have low 5-year survival rates. During metastasis, cancer cells often obtain unique characteristics such as epithelial-mesenchymal transition (EMT). Vimentin a biomarker contributes to EMT by changing cell shape and motility. Since abnormal phosphorylation is a hallmark of malignancy, targeting phosphorylated vimentin is a feasible approach for the treatment of metastatic tumors while sparing non-tumor cells. Recent evidence has revealed that both CD8 cytotoxic T lymphocytes (CTLs) and also CD4 helper T lymphocytes (HTLs) can distinguish post-translationally modified antigens from normal antigens. Here, we showed that the expression of phosphorylated vimentin was upregulated in metastatic sites of CRC. We also showed that a chemotherapeutic reagent augmented the expression of phosphorylated vimentin. The novel phosphorylated helper peptide epitopes from vimentin could elicit a sufficient T cell response. Notably, precursor lymphocytes that specifically reacted to these phosphorylated vimentin-derived peptides were detected in CRC patients. These results suggest that immunotherapy targeting phosphorylated vimentin could be promising for metastatic CRC patients.

Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma.

Placenta-specific 1 (PLAC1) is expressed primarily in placental trophoblasts but not in normal tissues and is a targetable candidate for cancer immunotherapy because it is a cancer testis antigen known to be up-regulated in various tumors. Although peptide epitopes capable of stimulating CD8 T cells have been previously described, there have been no reports of PLAC1 CD4 helper T lymphocyte (HTL) epitopes and the expression of this antigen in head and neck squamous cell carcinoma (HNSCC). Here, we show that PLAC1 is highly expressed in 74.5% of oropharyngeal and 51.9% of oral cavity tumors from HNSCC patients and in several HNSCC established cell lines. We also identified an HTL peptide epitope (PLAC131-50) capable of eliciting effective antigen-specific and tumor-reactive T cell responses. Notably, this peptide behaves as a promiscuous epitope capable of stimulating T cells in the context of more than one human leukocyte antigen (HLA)-DR allele and induces PLAC1-specific CD4 T cells that kill PLAC1-positive HNSCC cell lines in an HLA-DR-restricted manner. Furthermore, T-cells reactive to PLAC131-50 peptide were detected in the peripheral blood of HNSCC patients. These findings suggest that PLAC1 represents a potential target antigen for HTL based immunotherapy in HNSCC.

Intratumoral STING activations overcome negative impact of cisplatin on antitumor immunity by inflaming tumor microenvironment in squamous cell carcinoma.

Although cisplatin (CDDP) has been used as a major chemotherapeutic drug for head and neck squamous cell carcinoma (HNSCC), its impact on T-cell functions is controversial. Therefore, we investigated the immunologic effects of CDDP and antitumor effects by combination therapy of CDDP with a ligand for stimulator of interferon genes, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Direct impacts of CDDP on T-cell functions were addressed by comparing T-cell functions between human subjects treated and untreated with CDDP. The immune responses and the efficacy of combination therapy using CDDP and cGAMP were assessed using BALB/c mice inoculated with mouse squamous cell carcinoma (SCC) cell lines. CDDP inhibited T-cell proliferation in a dose-dependent manner. T-cell functions of CDDP-treated HNSCC patients were comparable to those of healthy donors and CDDP-untreated HNSCC patients. In the mice bearing SCC cell lines, combination therapy using CDDP and cGAMP enhanced the gene expressions of CXCL9 and CXCL10 in the tumor tissues and inhibited tumor growth. The antitumor effect was cancelled by anti-CXCR3 monoclonal antibody. These findings suggest that the combination therapy using CDDP and an immunomodulating drug like cGAMP would be a rational cancer immunotherapy for patients with HNSCC.

Laser-Assisted Thermal Imprinting of Microlens Arrays-Effects of Pressing Pressure and Pattern Size.

Polymer films with nano- or microstructured surfaces have been widely applied to optical devices, bioplates, and printed electronics. Laser-assisted thermal imprinting (LATI), in which a laser directly heats the surfaces of a mold and a thermoplastic polymer, is one of the high-throughput methods of replicating nano- or microstructures on polymer films. Only the surfaces of the mold and polymer film are heated and cooled rapidly, therefore it is possible to replicate nano- or microstructures on polymer films more rapidly than by using conventional thermal nanoimprinting. In this study, microlens arrays (MLAs) were replicated on polymethylmethacrylate (PMMA) films using LATI, and the effects of the pressing pressure (10-50 MPa) and the pattern size (33- and 5-µm pitch) of the MLA on the filling ratio were investigated by analyzing a microlens replicated using different laser-irradiation times (0.1-2 ms). The filling ratio increased with increasing pressing pressure and laser-irradiation time in the replication of MLAs with varying sizes, while the flow of the PMMA varied with the pressing pressure and laser-irradiation time. It was found that during filling, the shape of the polymer cross-sectional surface demonstrated a double and single peak in the 33- and 5-µm-pitch patterns, respectively. This was because the depth of the heated area in the 33-µm-pitch pattern was smaller than the pattern size, whereas that of the 5-µm-pitch pattern was comparable to (or larger) than the pattern size.

The alkalizer citrate reduces serum uric Acid levels and improves renal function in hyperuricemic patients treated with the xanthine oxidase inhibitor allopurinol.

OBJECTIVE: Hyperuricemia, an integral component of metabolic syndrome, is a major health problem causing gout and renal damage. Urine alkalizers such as citrate preparations facilitate renal excretion of the uric acid, but its supportive effect on xanthine oxidase inhibitors has not been tested yet. We performed a randomized, prospective study of the effect of a combination of allopurinol and a citrate preparation on renal function in patients with hyperuricemia, employing 70 patients who had hyperuricemia with serum uric acid levels ≥7.0 mg/dL, or those diagnosed as having hyperuricemia in the past. METHODS: They were randomly enrolled into two study groups: the allopurinol monotherapy (MT) group or combination treatment (CT) group with allopurinol and a citrate preparation. Allopurinol (100-200 mg/day) in the absence or presence of a citrate preparation (3 g/day) was administered for 12 weeks and levels of serum uric acid, its urinary clearance (Cua), and the renal glomerular filtration rates assessed with the creatinine clearance (Ccr) were evaluated before and after the treatment. RESULTS: Serum levels of uric acid decreased significantly in both groups, whereas the change observed was much greater in CT group. Cua was significantly increased in CT group but not in MT group. Ccr was not altered in both groups in general, whereas it was significantly increased in a fraction of CT group with decreased renal function. CONCLUSIONS: These results indicate that an additional use of citrate preparations with xanthine oxidase inhibitors is beneficial for patients with hyperuricemia, reducing circulating uric acid and improving their glomerular filtration rates.

Long-term clinical course of IgG4-related systemic disease accompanied by hypophysitis.

A 70-year old man with a 14 year history of Sjögren syndrome, interstitial pneumonia, and autoimmune hepatitis (AIH) was admitted to our hospital due to hyponatremia with a one month history of fatigue, thirst, and nausea. Laboratory tests on admission revealed that this patient had a central adrenal insufficiency. Pituitary magnetic resonance imaging (MRI) further showed swelling of the stalk and posterior lobe of his pituitary, suggesting infundibulo-hypophysitis. Based on his past history of autoimmune disease, his serum IgG4 levels were measured and found to be remarkably high (924 mg/ dL). Previous biopsy specimens from his liver, lung, and parotid gland were immunostained for IgG4, which revealed a marked infiltration of IgG4-positive plasma cells. As a result of our tests, we made a diagnosis of IgG4-related systemic disease. Interestingly, a subsequent MRI scan at three weeks after the patient commenced glucocorticoid replacement therapy for adrenal insufficiency showed that the swelling of his pituitary stalk was reduced. This finding suggested that IgG4-related hypophysitis may improve either as a result of a supplemental dose of glucocorticoid or possibly spontaneously. Although six cases of IgG4-related hypophysitis have been reported in the scientific literature published in English, our current case is the first in which IgG4-related hypophysitis likely occurred as a result of a long-term history of IgG4-related systemic disease. We report this case herein and review the relevant literature.

Social support, self-efficacy and psychological stress responses among outpatients with diabetes in Yogyakarta, Indonesia.

We attempted to study whether social support promotes self-efficacy and reduces stress responses of patients with diabetes in Yogyakarta, Indonesia. Diabetic outpatients at Dr. Sardjito Hospital voluntarily participated in a questionnaire survey. Data from 125 patients were subjected to analysis. The questionnaires included the scales and subscales of social support, self-efficacy, psychological stress response, and demographic measure. Data were analyzed by Spearman's rank correlation test to examine the relationships between parameters, Mann-Whitney U-test and Kruskal-Wallis test to compare the scales by characteristics, and structural equation modeling to explore the best-fit model. This study was performed in September 2003. It was found that augmentation of emotional support to patients significantly increased the 'active coping for the disease' and 'controllability of health', and that 'helplessness' was reduced significantly. Behavioral support affected only 'controllably of health'. Self-efficacy reduced stress response of the patients. It was also found that subjects who received support from their children significantly scored higher in perceived availability of social support than those without support from their children. To know their behavioral support better as well as emotional support may be one area to focus on in improving the health status of people with diabetes in Yogyakarta.

The effects of caregiving resources on the incidence of depression over one year in family caregivers of disabled elderly.

The purpose of the study was to investigate the over-time effects of physical, psychological and social resources on the incidence of depression in family caregivers of the disabled elderly. Data were collected twice at a one-year interval from 1,141 primary caregivers of a disabled older person in an urban area of Japan using a self-reported questionnaire survey. The questionnaire included physical health as an indicator of physical resources, caregiving satisfaction and intention to care as indicators of psychological resources, and instrumental and emotional support network and formal home care service utilization as indicators of social resources. The mental health outcome measure was the General Health Questionnaire 12-item version (GHQ-12). Complete data on 235 non-depressed female caregivers were separated into 3 groups according to the relationship type (wife, daughter and daughter-in-law) and analyzed separately. Multivariate logistic regression models controlling for duration of caregiving, care-recipient's gender, ADL dependency and behavioral problems demonstrated that significant predictors of depression were caregiving satisfaction and intention to care in wives, caregiving satisfaction in daughters, and physical health and emotional support network in daughters-in-law. Noteworthy, intention to care increased the risk of depression in wives, while decreasing the risk of depression in daughters-in-law. The findings indicate that the effects of caregivers' resources on mental health may differ by relationship type.

Construct validity of the Frenchay Activities Index for community-dwelling elderly in Japan.

Many researchers have developed various measures to evaluate the functional status of community-dwelling elderly. The Frenchay Activities Index (FAI) was developed to measure instrumental activities of daily living in stroke populations. The FAI has undergone the most intensive evaluation, but its factor structure has not been examined in Japan. The primary purpose of this study was to investigate the construct validity of the FAI for non-stroke community-dwelling elderly in Japan. The study subjects were 1,323 randomly selected community older residents in Hojo city, Ehime prefecture, the southern part of Japan. In order to investigate the construct validation, we performed factor analyses, i.e., exploratory factor analysis and confirmatory factor analysis. Furthermore, we examined the influences of age and gender on the FAI constructs. In the results, the FAI had a two-factor structure consisting of domestic chores, including washing clothes and preparing meals, and work and leisure, including gardening, driving and outings. Younger age was significantly related to increased performance on both factors. In addition, relative to females, males had a lower performance on the domestic chores and a greater performance on the work and leisure. These results suggest that the FAI satisfies the construct validity in the Japanese community-dwelling elderly. The FAI and its two factors provide important and clinically valuable information for understanding the patterns of functional status in the Japanese community-dwelling elderly.

Validity and utility of the Craig Hospital Inventory of Environmental Factors for Korean community-dwelling elderly with or without stroke.

The social environmental barriers are considered to be important because the "social participation" of people with impairments would be facilitated by the prevention and reduction of environmental barriers. The Craig Hospital Inventory of Environmental Factors (CHIEF) is one of the few scales to assess the environmental barriers. In this study, we developed the Korean version of CHIEF and evaluated its construct validity and utility in a sample of Korean community-dwelling elderly with or without stroke. We evaluated the construct validity of the CHIEF by testing the original five-factor structure using a confirmatory factor analysis in 400 elderly in Seoul, Korea. The utility of the CHIEF was then assessed by examining the relationships between individual characteristics, Barthel Index and perceived environmental barriers, measured by the CHIEF, using a structural equation modeling approach. The confirmatory factor analysis result demonstrated the validity of a second-order factor model of the CHIEF comprising the five factors as first-order factors. The perceived environmental barrier was a second-order factor when provided acceptable fit indices after two modifications. The structural equation modeling indicates that perceived environmental barriers are significantly related to activities of daily life but not age, gender, and the episode of stroke. The CHIEF is useful in measuring environmental factors for Korean older adults with or without stroke.