大村 佳代子

OBJECTIVES: The association between salivary flow rate (SFR) and depressive symptoms have been inconclusive. The present study aimed to investigate the association between SFR and depressive symptoms with and without adjustment for genetic and family environmental factors. MATERIALS AND METHODS: We conducted a cross-sectional study using twins and measured SFR and depressive symptoms as the outcome and explanatory variables, respectively. We also performed three-step regression analyses by first analysing the association between SFR and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed between-within analyses using monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs, and finally using only MZ twin pairs. These between-within analyses estimated the coefficients adjusted for genetic and family environmental factors. Furthermore, differences in the associations between individual-level and between-within suggest confounding by genetic and family environmental factors. RESULTS: We conducted 448 twins aged ≥20 years. In individual-level analyses in males and between-within analyses using MZ and same-sex DZ male twin pairs, SFR associated with depressive symptoms. In between-within analyses using only MZ male twin pairs, SFR did not associate with depressive symptoms. In females, SFR did not associate with depressive symptoms in both individual-level and between-within analyses. CONCLUSIONS: The present study revealed that the association between SFR and depressive symptoms was affected by common genetic factors in males. CLINICAL RELEVANCE: Understanding this association between SFR and depressive symptoms with adjustment for genetic and family environmental factors could lead to an important consideration for the prevention and treatment of hyposalivation.

Brain atrophy is part of the aging process and accelerated by neurodegenerative diseases, so an understanding of the background heritability of brain volume is essential. The purpose of this study was to determine the heritability of brain volume in middle to advanced age East Asian adults, an age group less studied and an ethnicity not previously studied. 3T magnetic resonance images were obtained and volumetric analyses conducted for a total of 74 individuals, 20 monozygotic twin pairs (mean age 61y min 41y max 75y) and 17 dizygotic twin pairs (mean age 64y min 41y max 85y). Total brain volume and a further seven regions were assessed, including lobar volumes, lateral divisions, and separated grey and white matter. Additive genetics and unique environment (AE) models for global brain volumes including total brain (90%), grey matter (91%) and white matter (84%) and many lobar volumes demonstrated high heritability in our study population. Our results present the heritability of brain volume in middle to advanced age as possibly higher in East Asian adults.

BACKGROUND & AIMS: Previous studies have indicated associations between intake of dairy products and better cognitive function and reduced risk of dementia. However, these studies did not adjust for genetic and family environmental factors that may influence food intake, cognitive function, and metabolism of dairy product nutrients. In the present study, we investigated the association between intake of dairy products and short-term memory with and without adjustment for almost all genetic and family environmental factors using a genetically informative sample of twin pairs. METHODS: A cross-sectional study was conducted among twin pairs aged between 20 and 74. Short-term memory was assessed as primary outcome variable, intake of dairy products was analyzed as the predictive variable, and sex, age, education level, marital status, current smoking status, body mass index, dietary alcohol intake, and medical history of hypertension or diabetes were included as possible covariates. Generalized estimating equations (GEE) were performed by treating twins as individuals and regression analyses were used to identify within-pair differences of a twin pair to adjust for genetic and family environmental factors. Data are reported as standardized coefficients and 95% confidence intervals (CI). RESULTS: Analyses were performed on data from 78 men and 278 women. Among men, high intake of dairy products was significantly associated with better short-term memory after adjustment for the possible covariates (standardized coefficients = 0.22; 95% CI, 0.06-0.38) and almost all genetic and family environmental factors (standardized coefficients = 0.38; 95% CI, 0.07-0.69). Among women, no significant associations were found between intake of dairy products and short-term memory. Subsequent sensitivity analyses were adjusted for small samples and showed similar results. CONCLUSIONS: Intake of dairy product may prevent cognitive declines regardless of genetic and family environmental factors in men.

OBJECTIVES: The aim of this study was to investigate the association between subjective memory complaints (SMCs) and depressive symptoms, with and without adjustment for genetic and family environmental factors. METHODS: We conducted a cross-sectional study using twins and measured SMCs and depressive symptoms as outcomes and explanatory variables, respectively. First, we performed regression analyses using generalized estimating equations to investigate the associations between SMCs and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed regression analyses for within-pair differences using monozygotic (MZ) and dizygotic (DZ) twin pairs and MZ twin pairs to investigate these associations with adjustment for genetic and family environmental factors by subtracting the values of one twin from those of co-twin variables (within-pair level analyses). Therefore, differences between the associations at individual- and within-pair level analyses suggested confounding by genetic factors. RESULTS: We included 556 twins aged ≥ 20 years. In the individual-level analyses, SMCs were significantly associated with depressive symptoms in both males and females [standardized coefficients: males, 0.23 (95% CI 0.08-0.38); females, 0.35 (95% CI 0.23-0.46)]. In the within-pair level analyses using MZ and same-sex DZ twin pairs, SMCs were significantly associated with depressive symptoms. In the within-pair level analyses using the MZ twin pairs, SMCs were significantly associated with depressive symptoms [standardized coefficients: males, 0.32 (95% CI 0.08-0.56); females, 0.24 (95% CI 0.13-0.42)]. CONCLUSIONS: This study suggested that SMCs were significantly associated with depressive symptoms after adjustment for genetic and family environmental factors.

OBJECTIVES: The present study aimed to investigate the association between body mass index (BMI) and uric acid (UA) using the twin study methodology to adjust for genetic factors. METHODS: The association between BMI and UA was investigated in a cross-sectional study using data from both monozygotic and dizygotic twins registered at the Osaka University Center for Twin Research and the Osaka University Graduate School of Medicine. From January 2011 to March 2014, 422 individuals participated in the health examination. We measured height, weight, age, BMI, lifestyle habits (Breslow's Health Practice Index), serum UA, and serum creatinine. To investigate the association between UA and BMI with adjustment for the clustering of a twin within a pair, individual-level analyses were performed using generalized linear mixed models (GLMMs). To investigate an association with adjustment for genetic and family environmental factors, twin-pair difference values analyses were performed. RESULTS: In all analysis, BMI was associated with UA in men and women. Using the GLMMs, standardized regression coefficients were 0.194 (95 % confidence interval: 0.016-0.373) in men and 0.186 (95 % confidence interval: 0.071-0.302) in women. Considering twin-pair difference value analyses, standardized regression coefficients were 0.333 (95 % confidence interval: 0.072-0.594) in men and 0.314 (95 % confidence interval: 0.151-0.477) in women. CONCLUSIONS: The present study shows that BMI was significantly associated with UA, after adjusting for both genetic and familial environment factors in both men and women.

To investigate the effect of genetic and environmental influences on cerebral motor function, we determined similarities and differences of movement-related cortical fields (MRCFs) in middle-aged and elderly monozygotic (MZ) twins. MRCFs were measured using a 160-channel magnetoencephalogram system when MZ twins were instructed to repeat lifting of the right index finger. We compared latency, amplitude, dipole location, and dipole intensity of movement-evoked field 1 (MEF1) between 16 MZ twins and 16 pairs of genetically unrelated pairs. Differences in latency and dipole location between MZ twins were significantly less than those between unrelated age-matched pairs. However, amplitude and dipole intensity were not significantly different. These results suggest that the latency and dipole location of MEF1 are determined early in life by genetic and early common environmental factors, whereas amplitude and dipole intensity are influenced by long-term environmental factors. Improved understanding of genetic and environmental factors that influence cerebral motor function may contribute to evaluation and improvement for individual motor function.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to describe and synthesize the experiences and perspectives of illness for patients living with both hemophilia and human immunodeficiency virus (HIV). BACKGROUND: Hemophilia is an inherited bleeding disorder caused by low concentrations of specific coagulation factors. There are two major types of this condition characterized by deficiencies of factor VIII (hemophilia A) and factor IX (hemophilia B). Bleeding occurs in hemophilia owing to failure of secondary hemostasis. The bleeding tendency is related to the measured concentration of the factor and is classified as mild, moderate, or severe. Severe hemophilia A and B is classified as repeated (as often as weekly) bleeds into joints and muscles. The main treatment is to arrest spontaneous and traumatic bleeds by prophylactic injection of factor concentrates or to prevent injury by restriction of exercise. Most people with severe hemophilia are on therapy at home with intravenous infusion of the relevant missing factor. Joint bleeds are painful, and the build up of blood is irritating to the synovial lining and damages joint tissue, so that adherence to hemophilia therapy is important.Global research in 18 countries reported that compliance with therapy by patients with hemophilia was low with self-injection adherence under 75% with as few as 53-65% of adults complying with therapy. Some of the most frequently cited factors affecting patients' compliance to therapy are as follows; inability to understand potential benefits (75%); denial (67%); interference with life style (62%); and lack of time (42%).The self-injection method of administering coagulation products became popular in the 1970s. In the early 1980s, 1,432 patients with hemophilia in Japan were infected with HIV (human immunodeficiency virus) because of the use of untreated blood products contaminated with the HIV virus. In addition commercial factor concentrates, which are prepared from pools of 2 to 6000 liters of plasma obtained by plasmapheresis from paid donors, carries a much higher risk of transmission of hepatitis B or C or HIV. Acquired autoimmune disease or AIDS, which is caused by HIV was once an incurable and fatal disease. However the anti-retro virus therapy, from the commencement of protease inhibitor based therapy in 1996, has increased the life expectancy of HIV patients. Nevertheless, adherence to highly active anti-retroviral therapy (HAART) medication by patients with hemophilia (66%-84%) is lower than that of patients with only HIV (98%) in Japan.Although the causes of low adherence of hemophilia therapy or HAART medication are considered to be associated with patient values, qualitative evidence of previous studies have not been synthesized We searched previous reviews and review protocols in the Cochrane Library, Joanna Briggs Institute Library (JBI), MEDLINE, CINAHL, PsycINFO, JBI COnNECT+ protocols. Regarding hemophilia or HIV, there were 11 systematic reviews, 7 protocols, and 128 other reviews. We excluded the reviews that were randomized controlled trials (RCTs) of treatment effects or therapies, and quantitative research of quality of life (QOL). We also excluded children as they are supervised by their parents to maintain high adherence. After the title and abstract review, 15 reviews remained and upon reading the full articles, one protocol and nine narrative reviews were identified.The systematic review protocol of Shaibu et al. investigated HIV positive adult patients on HAART focusing on the experience of HIV positive patients with patients' lifestyles and beliefs about HIV/AIDS and HAART effectiveness, and the role these play in adherence. However, the review differs from this one in terms of classification of HIV positive adults by the route of infection such as iatrogenic and sexually transmitted infection. Taking the deferent rate of adherence of HAART in Japan into consideration, we will focus on the experience of hemophilic patients with HIV.There were also narrative reviews that were concerned with management and treatment of hemophilia; recommendations for assessment and follow-up for patients and caregivers and for health providers, co-morbidity and QOL in the aging patient, and psychosocial issues of hemophilic patients. However, these reviews did not describe the methods in detail such as search engines, inclusion and exclusion criteria, and number of studies included. Furthermore, there was a lack of patients' voice as evidence that composed each category. Strictly speaking, these were not systematic reviews but a narrative review or study related to sociology of knowledge.The systematic review of Cassis et al. is the most similar to our proposed systematic review. They identified studies evaluating psychological stressors in hemophilic patients to address psychological needs and to improve QOL. They mainly evaluated methodologies. The psychosocial stressors synthesized findings from 22 quantitative studies as well as 2 qualitative ones. However, the review differs from this one as they excluded studies related to the HIV epidemic. Additionally, the review was limited as only one search engine, PubMed, was used.The illness which patients with hemophilia and HIV experience has changed from incurable disease to a manageable one by the progress of medicine. A similar scenario might exist for young patients with other incurable diseases at this time. Therefore, synthesizing the patients' experiences of living with both hemophilia and HIV will help not only this patient group but also young patients with other incurable diseases. Furthermore, there are few studies of hemophilia patients as hemophilia is a rare disease. Thus, synthesis of qualitative evidence is critical to understand patient values.