Risk Prediction Method for Anticholinergic Action Using Auto-quantitative Structure-Activity Relationship and Docking Study with Molecular Operating Environment.

Lower urinary tract symptoms (LUTS) induced by anticholinergic drug action impair the QOL of patients and are associated with a poor prognosis. Therefore, it is expedient to develop methods of predicting the anticholinergic side effects of drugs, which we aimed to achieve in this study using a quantitative structure-activity relationship (QSAR) and docking study with molecular operations environment (MOE; Molecular Simulation Informatics Systems [MOLSIS], Inc.) In the QSAR simulation, the QSAR model built using the partial least squares regression (PLS) and genetic algorithm-multiple linear regression (GA-MLR) methods showed remarkable coefficient of determination (R2) and XR2 values. In the docking study, a specific relationship was identified between the adjusted docking score (-S) and bioactivity (pKi) values. In conclusion, the methods developed could be useful for in silico risk assessment of LUTS, and plans are potentially applicable to numerous drugs with anticholinergic activity that induce serious side effects, limiting their use.

The creation and dissemination of downloadable information on dementia and driving from a social health perspective.

BACKGROUND: Driving cessation is a likely consequence of progressive dementia. Patients and families can benefit from support through this transition, both to safeguard the patient and public and to help preserve healthy social activity of the patient. METHODS: To provide appropriate supportive information, we developed a 35-page manual ('Supporting family caregivers of older drivers with dementia') available as a free download from our department website. We then informed municipal governments of its availability, tracked website access metrics, and followed up 7 months later with a postal survey to the heads of each municipal government's department of welfare for older citizens. RESULTS: From February to September 2010, the manual was accessed 33 494 times. Of the 1750 municipalities sent surveys, we received 1067 responses (61%). The responses showed that 943 professionals (94.6%) were able to obtain information they needed from the manual, 247 (23%) had used the manual to help residents during the 7 months, and 89% of those who used the manual used it to provide relevant advice to family caregivers. The responses also showed that significantly more use occurred in towns and villages as opposed to cities, consistent with the limited public transportation options in smaller municipalities (P = 0.002). CONCLUSIONS: We anticipate that use of this manual will raise general awareness of this social health issue and facilitate collaborations to provide more social support for those with dementia and their family members.

Self-assessed driving behaviors associated with age among middle-aged and older adults in Japan.

With the increasing number of older drivers, road traffic safety is an urgent public health issue. It is not easy for older drivers or their relatives to detect early signs of dangerous driving behaviors. We examine the types of driving behavior that increase in frequency with age. We surveyed people aged 40 and over among the general public in Japan using a self-administered questionnaire on sociodemographic factors, driving status, frequency of driving, 12-items on physical symptoms possibly related to driving performance, and 28-items on driving behaviors. Multiple logistic regression models were used to estimate the odds ratios (OR) of occurrence of each of the 28 driving behaviors for a 5-year increase in age. Significant associations with a 5-year increase in age after adjusting for confounding factors were found for the following directly unsafe driving behaviors: (1) little or no sign of attempts to avoid dangerous situations (OR for a 5-year increase in age=1.38, 95% CI: 1.18-1.63); (2) lack of attention to other people and cars (1.33, 1.12-1.60); (3) improper maneuvering around curves (1.33, 1.09-1.65); and (4) improper or no turn signals (1.33, 1.06-1.69). Information about these driving behaviors should be given to drivers and their stakeholders and used to caution participants when implementing educational programs for older drivers. Self-assessment of driving ability in older drivers provides useful information to raise awareness of their driving performance.

Depression among family caregivers of community-dwelling older people who used services under the Long Term Care Insurance program: a large-scale population-based study in Japan.

OBJECTIVE: To identify predictors for depression among family caregivers of community-dwelling older people under the Long Term Care Insurance (LTCI) program in Japan through a large-scale population-based survey. METHOD: All 5938 older people with disabilities, using domiciliary services under the LTCI in the city of Toyama, and their family caregivers participated in this study. Caregiver depression was defined as scores of ≥16 on the Center for Epidemiological Studies Depression Scale (CES-D). Other caregiver measures included age, sex, hours spent caregiving, relationship to the care recipient, income adequacy, living arrangement, self-rated health, and work status. Care recipient measures included age, sex, level of functional disability, and severity of dementia. The data from 4128 pairs of the care recipients and their family caregivers were eligible for further analyses. A multiple logistic regression analysis was used to examine the predictors associated with being at risk of clinical depression (CES-D of ≥16). RESULTS: Overall, 34.2% of caregivers scored ≥16 on the CES-D. The independent predictors for depression by logistic regression analysis were six caregiver characteristics (female, income inadequacy, longer hours spent caregiving, worse subjective health, and co-residence with the care recipient) and one care-recipient characteristic (moderate dementia). CONCLUSION: This is one of the first population-based examinations of caregivers of older people who are enrolled in a national service system that provides affordable access to services. The results highlighted the importance of monitoring caregivers who manifest the identified predictors to attenuate caregiver depression at the population level under the LTCI.

A natural variant of NAL1, selected in high-yield rice breeding programs, pleiotropically increases photosynthesis rate.

Improvement of leaf photosynthesis is an important strategy for greater crop productivity. Here we show that the quantitative trait locus GPS (GREEN FOR PHOTOSYNTHESIS) in rice (Oryza sativa L.) controls photosynthesis rate by regulating carboxylation efficiency. Map-based cloning revealed that GPS is identical to NAL1 (NARROW LEAF1), a gene previously reported to control lateral leaf growth. The high-photosynthesis allele of GPS was found to be a partial loss-of-function allele of NAL1. This allele increased mesophyll cell number between vascular bundles, which led to thickened leaves, and it pleiotropically enhanced photosynthesis rate without the detrimental side effects observed in previously identified nal1 mutants, such as dwarf plant stature. Furthermore, pedigree analysis suggested that rice breeders have repeatedly selected the high-photosynthesis allele in high-yield breeding programs. The identification and utilization of NAL1 (GPS) can enhance future high-yield breeding and provides a new strategy for increasing rice productivity.

Factors influencing caregivers' burden among family caregivers and institutionalization of in-home elderly people cared for by family caregivers.

OBJECTIVES: The purpose of this study was to determine the factors related to changes in the burden of caregivers who look after the elderly at home, as well as factors related to the institutionalization of the elderly who require care. The types of care services associated with reducing caregivers' burden and continuing in-home care were also studied. METHODS: The study subjects were adults aged ≥65 years who used the services of in-home care management centres located in Osaka Prefecture, Japan, and their caregivers. This 2-year longitudinal study began in October 2007, with a total of three surveys undertaken once a year. The survey methods included self-administered questionnaires and the review of clinical records. RESULTS: Dementia and its accompanying behavioural disturbances were found to be significantly related to the increased burden of caregivers and the institutionalization of those requiring care. A significantly higher proportion of caregivers with an increasing burden or those who maintained a high level of burden used day care services compared to those in the other groups. CONCLUSION: Preventive intervention against dementia and its accompanying behavioural disturbances should be considered in the day care service to reduce caregivers' burden and to decrease institutionalization.

Exploring strategies to alleviate caregiver burden: effects of the National Long-Term Care insurance scheme in Japan.

The ever-increasing population of older people with disabilities, including dementia, has been accompanied by a corresponding growth in the number of family caregivers, who are themselves at risk of developing mental and physical health problems. As a result, the need for practical and effective approaches for alleviating caregiver burden has become a major public health concern. One approach involves the development of public policy initiatives to allow the caregiver burden to be borne partly by society as a whole, rather than falling solely on individuals. In 2000, Japan introduced a National Long-Term Care (LTC) insurance scheme that requires adults over the age of 40 years to pay compulsory monthly premiums, with one aim of the program being to reduce caregiver burden. The present paper reviews the effects of this scheme on caregivers' and the general public's perception of caregiver burden and assesses what other measures are needed to further reduce and/or prevent burden. Drawing on recent studies, four questions are addressed: (i) have caregivers' attitudes towards caregiving changed since the implementation of the scheme; (ii) do services provided under the scheme alleviate caregiver burden; (iii) what are the general public's attitudes to and understanding of family caregiving; and (iv) what is the general public's level of understanding of dementia? Results from recent studies suggest that the LTC insurance scheme in Japan appears to be an effective measure for alleviating the burden of caregiving among current family caregivers, but larger studies are needed to determine overall effectiveness.

Differences in perceptions regarding driving between young and old drivers and non-drivers in Japan.

OBJECTIVE: The issue of driving cessation for dementia patients is one of the urgent public health priorities in Japan and is often complicated, with family or social barriers yet to be sufficiently addressed. Because the possibility of dementia or family caregiving can befall anyone, we focused on the disparity in people's perceptions of driving as possible barriers. The present study aimed to assess perceptions of driving among the general public and examine differences in perceptions based on age and driving status. METHODS: A survey was conducted in a sample of the general public aged 40 and over in Japan. Respondents were 1010 people who received a self-administered questionnaire that included questions regarding perceptions about driving and sociodemographic factors. RESULTS: The drivers that participated in this study tended to highly agree that 'driving is a "right" which we all deserve', compared with the non-drivers. The most common reason for reluctance to stop driving among drivers was the possible loss of personal mobility. Apart from transportation, older drivers were more likely than younger drivers to value the qualitative aspects of driving, for example, driving was viewed as 'a motivating factor in my life'. CONCLUSIONS: These disparities in the general public's perceptions about driving may be possible family or social barriers to driving cessation in the case of drivers with dementia. Our findings also suggest that when addressing the need for driving retirement, not only mobility but also the qualitative aspects of driving be paid more attention.

[The transition of amino acids drug development for 50 years in Japan (part 2)--ethical drugs containing amino acids (except alpha-amino acid parenteral fluid)].

There are approximately 1300 kinds of ethical drugs currently approved for use in Japan, excluding high molecular weight drugs and Chinese medicines. Among them, 81 contain alpha-amino acids, though some consist of a-amino acid parenteral fluid and peptide-type drugs, which include ACE inhibitors. Of these, 30 kinds of drugs are made from both natural and non-natural amino acids, and 51 kinds of drugs are prepared from amino acid derivatives. All of these drugs were developed in the last 50 years. Amino acids moieties such as D-phenylglycine and D-phydroxyphenylglycine have contributed to enhancing the stability, absorbability, and effectiveness of many drugs, particularly antibiotics, such as certain types of penicillin and cephalosporin. In recent years, radioactive and antiviral agents containing amino acid skeletons have also been developed for use as anti-AIDS medications.