Association between dietary patterns and subjective and objective measures of physical activity among Japanese adults aged 85 years and older: a cross-sectional study.

A healthy diet and regular physical activity (PA) are delineated as healthy behaviours. Their implementation is associated with better health outcomes and improved quality of life. There is less evidence of a relationship between dietary patterns (DP) and PA, especially in adults aged ≥ 85. Hence, this cross-sectional study investigates the association between DP and PA in people of this age group, using the data from The Kawasaki Aging and Well-Being Project. Brief-type self-administered diet history questionnaire was used to estimate the intake of fifty-eight types of food. After energy adjustment, principal component analysis was performed to identify DP. PA was measured objectively using an accelerometer and subjectively using a questionnaire validated for this age group. Thousand participants (median age: 86·9 years, men: 49·9 %) were included in the analysis. Three major DP (DP1 'various foods', DP2 'red meats and coffee', DP3 'bread and processed meats') were identified. DP1 'various foods' was similar to DP previously named 'healthy' or 'prudent' and showed a positive association with PA time (PAT) as measured by accelerometer (B, 6·25; 95 % CI 0·13, 12·37) and relatively shorter sedentary behaviour (SB) time. DP2 'red meats and coffee' and DP3 'bread and processed meats' were negatively associated with PAT and positively associated with SB time. This study observed the relationship between diet and PA behaviours in adults aged ≥ 85, with healthier and more food-diverse DP associated with longer PAT and relatively unhealthy DP with shorter PAT.

Relationship between dietary patterns and physical performance in the very old population: a cross-sectional study from the Kawasaki Aging and Wellbeing Project.

OBJECTIVES: As the world's population is ageing, improving the physical performance (PP) of the older population is becoming important. Although diets are fundamental to maintaining and improving PP, few studies have addressed the role of these factors in adults aged ≥ 85 years, and none have been conducted in Asia. This study aimed to determine the dietary patterns (DP) and examine their relationship with PP in this population. DESIGN: This cross-sectional study (Kawasaki Aging and Wellbeing Project) estimated food consumption using a brief-type self-administered diet history questionnaire. The results were adjusted for energy after aggregating into thirty-three groups, excluding possible over- or underestimation. Principal component analysis was used to identify DP, and outcomes included hand grip strength (HGS), timed up-and-go test, and usual walking speed. SETTING: This study was set throughout several hospitals in Kawasaki city. PARTICIPANTS: In total, 1026 community-dwelling older adults (85-89 years) were enrolled. RESULTS: Data of 1000 participants (median age: 86·9 years, men: 49·9 %) were included in the analysis. Three major DP (DP1: various foods, DP2: red meats and coffee, DP3: bread and processed meats) were identified. The results of multiple regression analysis showed that the trend of DP2 was negatively associated with HGS (B, 95 % CI -0·35, -0·64, -0·06). CONCLUSIONS: This study suggests a negative association between HGS and DP characterised by red meats and coffee in older adults aged ≥ 85 years in Japan.

Regulation of MEK inhibitor selumetinib sensitivity by AKT phosphorylation in the novel BRAF L525R mutant.

BACKGROUND: Oncogenic mutations in BRAF genes are found in approximately 5-10% of colorectal cancers. The majority of BRAF mutations are located within exons 11-15 of the catalytic kinase domains, with BRAF V600E accounting for more than 80% of the observed BRAF mutations. Sensitivity to BRAF- and mitogen-activated protein kinase (MEK) inhibitors varies depending on BRAF mutations and tumor cell types. Previously, we newly identified, BRAF L525R-mutation, in the activation segment of the kinase in colorectal cancer patient. Here, we characterized the function of the BRAF L525R mutation. METHODS: HEK293 cells harboring a BRAF mutation (V600E or L525R) were first characterized and then treated with cetuximab, dabrafenib, and selumetinib. Cell viability was measured using WST-1 assay and the expression of proteins involved in the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signaling pathways was evaluated using western blot analysis. RESULTS: The MEK inhibitor selumetinib effectively inhibited cell proliferation and ERK phosphorylation in BRAF L525R cells but not in BRAF V600E cells. Further studies revealed that AKT phosphorylation was reduced by selumetinib in BRAF L525R cells but not in BRAF V600E cells or selumetinib-resistant BRAF L525R cells. Moreover, the AKT inhibitor overcame the selumetinib resistance. CONCLUSIONS: We established a model system harboring BRAF L525R using HEK293 cells. BRAF L525R constitutively activated ERK. AKT phosphorylation caused sensitivity and resistance to selumetinib. Our results suggest that a comprehensive network analysis may provide insights to identify effective therapies.

Relation between number of teeth, malnutrition, and 3-year mortality in elderly individuals ≥85 years.

OBJECTIVE: The number of teeth has been shown to affect mortality. However, it is unclear why the number of teeth is associated with mortality. We focused on the number of teeth and malnutrition and examined whether these differences affect 3-year all-cause mortality among very elderly individuals. METHODS: This analysis was conducted using data from the Tokyo Oldest Old Survey on Total Health study. Altogether 513 participants ≥85 years were categorized based on remaining teeth (0, 1-7, 8-18, ≥19). All-cause mortality was determined by calculating the cumulative 3-year survival rate according to the remaining number of teeth and the presence/absence of malnutrition. Further, hazard ratios (HRs) were analyzed using Cox regression analyses. RESULTS: No difference was observed according to the number of teeth (p = 0.638), but the presence/absence of malnutrition was significantly associated with mortality (p < 0.001). Malnutrition was independently associated with higher HRs, even after adjusting for confounding factors associated with mortality. (HR: 2.315, 95% CI: 1.431-3.746). Additionally, adjusting for the number of teeth, HR remained significant (HR: 2.365, 95% CI: 1.449-3.853). CONCLUSION: In the very elderly, malnutrition-but not the number of teeth-was independently associated with 3-year all-cause mortality after adjusting for various health issues.

Dietary protein intake and all-cause mortality: results from The Kawasaki Aging and Wellbeing Project.

BACKGROUND: Increased protein intake has been recommended to prevent sarcopenia/frailty, reports on the quantity and quality of protein intake needed and the associated prognosis, particularly in the aging population of Asia, are limited. In this study, we aimed to investigate the relationship between protein intake and mortality in Japanese individuals, aged 85 years and older. METHODS: The data were obtained from The Kawasaki Aging and Wellbeing Project, which is a prospective cohort study of older adults aged between 85 and 89 years with no physical disability at baseline. Of the 1,026 adults in the cohort, 833 were included in the analysis, after excluding those who had not completed a brief, self-administered diet history questionnaire or those who scored less than 24 on the Mini-Mental State Examination. The participants were grouped into quartiles based on protein intake: Q1 (protein < 14.7, %Energy), Q2 (14.7 ≤ protein < 16.7, %Energy), Q3 (16.7 ≤ protein < 19.1, %Energy), and Q4 (≥ 19.1, %Energy). Multivariate Cox proportional hazards models were utilized to evaluate the association between protein intake and all-cause mortality. Kaplan-Meier survival curves were employed to investigate the relationship between protein intake and all-cause mortality. RESULTS: The mean protein intake of our study population was 17.0% of total energy. Animal protein intake, particularly fish intake, increased significantly along with total protein intake. The study had an average observation period of 1,218 days and recorded 89 deaths. After adjusting for age, sex, skeletal muscle mass index, cardiovascular disease, cancer, education, and serum albumin levels, a lower risk of all-cause mortality was observed in the highest protein intake (Q4) group than in the lowest protein intake (Q1) group (hazard ratio: 0.44, 95% confidence interval: 0.22-0.90, p-value: 0.020). CONCLUSION: Protein intake is associated with a reduced risk of all-cause mortality in older adults (aged ≥ 85 years) who engage in independent activities of daily living. This association may impact all-cause mortality independent of muscle mass.

Diagnostic performance of intraoperative cone beam computed tomography compared with postoperative magnetic resonance imaging for detecting hemorrhagic transformation after endovascular treatment following large vessel occlusion.

OBJECTIVES: Early detection of hemorrhagic transformation (HT) in patients with large vessel occlusion (LVO) after endovascular treatment is important for postoperative patient management. We investigated the diagnostic performance of intraoperative cone beam computed tomography (CBCT) with reference standard magnetic resonance imaging (MRI) for detecting HT. MATERIALS AND METHODS: Consecutive patients with LVO treated by endovascular treatment who underwent intraoperative CBCT and postoperative MRI were included. Two observers evaluated all images for the presence of HT. Sensitivity and specificity for detecting HT were calculated with MRI as reference standard. The observers classified HT according to the European Cooperative Acute Stroke Study (ECASS). Inter-method and inter-rater agreement for the detection of HT and for the ECASS classification were assessed using kappa or weighted Brennan-Prediger (wBP) statistics. RESULTS: Images of 106 procedures (94 for anterior circulation) were analyzed. The sensitivity and specificity for detecting HT on CBCT were 0.77 and 0.83, respectively, for all procedures and 0.83 and 0.8, respectively, for anterior circulation. The inter-method agreement for HT detection (κ = 0.63 overall, κ = 0.69 anterior circulation) and ECASS classification (wBP = 0.67 overall, wBP = 0.77 anterior circulation) were substantial. The inter-rater agreement for HT detection (κ = 0.87 overall, κ = 0.85 anterior circulation) and for ECASS classification (wBP = 0.95 overall, wBP = 0.92 anterior circulation) were almost perfect. CONCLUSIONS: The diagnostic performance of CBCT for the detection of HT in stroke patients treated for LVO was acceptable with excellent inter-rater agreement. Intraoperative CBCT may be useful to trigger early interventions if HT is detected, although detailed classifications of HT may be difficult.

[Identification of dietary patterns and their relationship with physical performance in adults of 85 years of age and older -A cross sectional study from The Tokyo Oldest Old survey on Total Health study].

AIM: While the proportion of people of ≥85 years of age is expected to increase, there is limited research on the dietary patterns and physical performance of this population in Japan. The purpose of this study was to identify the dietary patterns of people of ≥85 years of age who live in Tokyo and to examine the relationship with their physical performance. METHODS: Using data from the baseline survey (conducted in 2008-2009) of The Tokyo Oldest Old survey on Total Health study, the estimated 58 food intake items were aggregated into 33 items after energy adjustment, and a principal component analysis was performed. For physical performance, the results of grip strength, chair standing test, and 3 m timed up and go test conducted at normal walking speed were used. A multiple regression analysis was used to adjust for confounders and to examine the relationship between each dietary pattern and physical performance. RESULTS: The subjects of the analysis were 87.3 (86.2-88.8) years of age (median [25-75th percentile] ). From the principal component analysis, three dietary patterns were identified: "various vegetable foods", "fish and mushrooms", and "cooked rice and miso soup". A higher propensity for the "fish and mushrooms" dietary pattern was significantly associated with grip strength (partial regression coefficient, B (95% confidence interval): 0.48 (0.13-0.83) ). CONCLUSIONS: In a population of people of ≥85 years of age in Tokyo, a positive association was observed between hand grip strength and a dietary pattern characterized by fish and mushroom intake.

Behavioral changes and hygiene practices of older adults in Japan during the first wave of COVID-19 emergency.

BACKGROUND: On April 7, 2020, Japan declared a state of emergency due to the first wave of coronavirus disease 2019 (COVID-19) with the associated social distancing likely to have had a great impact on older adults' lifestyle and health. This study aimed to explore the behavioral changes and personal hygiene practices in relation with background psychosocial and health characteristics of older adults during the COVID-19 emergency. METHODS: A cross-sectional telephonic survey was conducted with the participants of the Kawasaki Aging and Wellbeing Project (KAWP), an on-going longitudinal cohort study of older adults aged 85 or older. The interviews were conducted using a structured questionnaire consisting of 11 closed questions regarding behavioral changes and personal hygiene practices during the state of emergency. Sociodemographic and health data were obtained from the KAWP baseline survey conducted 2.2 years before the telephonic survey. RESULTS: Overall, 487 participants from the KAWP responded to the telephonic survey (response rate: 89.2%). 94.5% of the respondents reported no changes in basic lifestyle habits, such as eating, sleeping, smoking, and drinking, whereas 28.1% reported a decrease in physical activity, and 54.6% reported going out less frequently. One-third of the respondents reported a decrease in the number of people to converse with, as well as the amount of time to converse. For personal hygiene practices, 93.8% reported wearing a mask when they went out, and 50.3% reported an increased frequency of handwashing. Multiple logistic regression analysis revealed that engagement in physical activity at baseline (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.23-3.08), smartphone ownership (OR = 2.15, 95% CI = 1.33-3.47), and visual impairment (OR = 1.79; 95% CI = 1.10-2.91) were independently associated with decreased physical activity during the COVID-19 emergency. Female respondents and smartphone ownership were significantly associated with more frequent handwashing. CONCLUSIONS: The study revealed that older adults in an urban setting responded to the COVID-19 emergency with behavioral changes. The findings of this study have implications for the design of preventive strategies to maintain the health and wellbeing of at-risk older adults.

The effects of single and a combination of determinants of anaemia in the very old: results from the TULIPS consortium.

BACKGROUND AND OBJECTIVES: Nutritional deficiencies, renal impairment and chronic inflammation are commonly mentioned determinants of anaemia. The aim of this study was to investigate the effects of these determinants, singly and in combination, on anaemia in the very old. METHOD: The TULIPS Consortium consists of four population-based studies in oldest-old individuals: Leiden 85-plus Study, LiLACS NZ, Newcastle 85+ study, and TOOTH. Five selected determinants (iron, vitamin B12, and folate deficiency; low estimated glomerular filtration rate (eGFR); and high C-reactive protein (CRP)) were summed. This sum score was used to investigate the association with the presence and onset of anaemia (WHO definition). The individual study results were pooled using random-effects models. RESULTS: In the 2216 participants (59% female, 30% anaemia) at baseline, iron deficiency, low eGFR and high CRP were individually associated with the presence of anaemia. Low eGFR and high CRP were individually associated with the onset of anaemia. In the cross-sectional analyses, an increase per additional determinant (adjusted OR 2.10 (95% CI 1.85-2.38)) and a combination of ≥2 determinants (OR 3.44 (95% CI 2.70-4.38)) were associated with the presence of anaemia. In the prospective analyses, an increase per additional determinant (adjusted HR 1.46 (95% CI 1.24-1.71)) and the presence of ≥2 determinants (HR 1.95 (95% CI 1.40-2.71)) were associated with the onset of anaemia. CONCLUSION: Very old adults with a combination of determinants of anaemia have a higher risk of having, and of developing, anaemia. Further research is recommended to explore causality and clinical relevance.

Associations of poor oral health with frailty and physical functioning in the oldest old: results from two studies in England and Japan.

BACKGROUND: Very few studies have examined the relationship of oral health with physical functioning and frailty in the oldest old (> 85 years). We examined the association of poor oral health with markers of disability, physical function and frailty in studies of oldest old in England and Japan. METHODS: The Newcastle 85+ Study in England (n = 853) and the Tokyo Oldest Old Survey on Total Health (TOOTH; n = 542) comprise random samples of people aged > 85 years. Oral health markers included tooth loss, dryness of mouth, difficulty swallowing and difficulty eating due to dental problems. Physical functioning was based on grip strength and gait speed; disability was assessed as mobility limitations. Frailty was ascertained using the Fried frailty phenotype. Cross-sectional analyses were undertaken using logistic regression. RESULTS: In the Newcastle 85+ Study, dry mouth symptoms, difficulty swallowing, difficulty eating, and tooth loss were associated with increased risks of mobility limitations after adjustment for sex, socioeconomic position, behavioural factors and co-morbidities [odds ratios (95%CIs) were 1.76 (1.26-2.46); 2.52 (1.56-4.08); 2.89 (1.52-5.50); 2.59 (1.44-4.65) respectively]. Similar results were observed for slow gait speed. Difficulty eating was associated with weak grip strength and frailty on full adjustment. In the TOOTH Study, difficulty eating was associated with increased risks of frailty, mobility limitations and slow gait speed; and complete tooth loss was associated with increased risk of frailty. CONCLUSION: Different markers of poor oral health are independently associated with worse physical functioning and frailty in the oldest old age groups. Research to understand the underlying pathways is needed.

Reduced home cage and social activity in Pou3f2⊿ mice.

Pou3f2/Brn2 is a transcription factor that helps to determine the cellular identity of neocortical or hypothalamic neurons. Mammalian Pou3f2 contains three homopolymeric amino acids that are not present in amphibian Pou3f2. These amino acids contribute to monoamine function, which may play specific roles in mammalian development and behavior. Previous work has indicated that Pou3f2⊿ mice, which lack the homopolymeric amino acids, exhibited declined maternal activity and impaired object and spatial recognition. The current study, analyzed weight gain, brain development, home cage activity, social interaction, and response to novel objects in Pou3f2⊿ mice to determine which aspects of behavior were affected by monoamine dysregulation. Compared to their wild type counterparts, Pou3f2⊿ mice showed decreased social interaction and reduced home cage activity during their active phase. However, they showed normal weight gain, brain development, and responses to novelty. These results indicate that monoamine dysregulation in Pou3f2⊿ mice may specifically affect basal activity and social development, without altering non-social motivation.

Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction.

Although both conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) are present in the gut-associated lymphoid tissues (GALT), the roles of pDCs in the gut remain largely unknown. Here we show a critical role for pDCs in T cell-independent (TI) IgA production by B cells in the GALT. When pDCs of the mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) (which are representative GALT) were cultured with naive B cells to induce TI IgA class switch recombination (CSR), IgA production was substantially higher than in cocultures of these cells with cDCs. IgA production was dependent on APRIL and BAFF production by pDCs. Importantly, pDC expression of APRIL and BAFF was dependent on stromal cell-derived type I IFN signaling under steady-state conditions. Our findings provide insight into the molecular basis of pDC conditioning to induce mucosal TI IgA production, which may lead to improvements in vaccination strategies and treatment for mucosal-related disorders.

4D Digital Subtraction Angiography for the Temporal Flow Visualization of Intracranial Aneurysms and Vascular Malformations.

PURPOSE: To assess the benefit and radiation dose of four-dimensional (4D) digital subtraction angiography (DSA) - a time resolved three-dimensional (3D) DSA application - to evaluate the flow and architecture of aneurysms and vascular malformations. METHODS: All patients with cerebrovascular disease were considered who underwent 4D-DSA at our institution between January 2015 and February 2016. For the aneurysm patients, we evaluated the image quality in terms of the visualization of contrast flow in the aneurysm on a 3-point scale (excellent, fair and poor). Interrater agreement between two raters was estimated using Cohen's Kappa statistics. For the shunt disease patients, the additional information obtained from the 4D-DSA was described for each disease. The median radiation dose and volume of contrast medium required for the acquisitions were estimated. RESULTS: A total of 173 patients underwent 4D-DSA; 126 intracranial aneurysms, 10 arteriovenous malformations (AVM), 15 dural arteriovenous fistula (dAVF) and 22 other diseases. For aneurysm patients, excellent and fair visualization of the intra-aneurysmal flow was observed in 27.7%, 72.3%, and excellent (κ = 0.9) agreement between the raters was found. For AVM and dAVF patients, 4D-DSA clarified the complex vasculature by viewing the discrete time phase of contrast filling. Median radiation dose for intracranial lesions was 79.6 mGy for 6s 4D-DSA, and 175 mGy for 12s 4D-DSA. The median amount of contrast medium used was 18.0 ml for 6s 4D-DSA and 21.0 ml for 12s 4D-DSA. CONCLUSIONS: 4D-DSA provided additional information regarding intra-aneurysmal flow and contributed to detect different component of nidus or shunt points.

Birth of a marmoset following injection of elongated spermatid from a prepubertal male.

The common marmoset is a small nonhuman primate in which the application of transgenesis and genetic knockout techniques allows the generation of gene-modified models of human diseases. However, its longer generation time than that of rodents is a major obstacle to the widespread use of gene-modified marmosets for biomedical research. In this study, we examined the feasibility of shortening the generation time by using prepubertal marmoset males as gamete donors. We collected late round stage spermatids (Steps 5-7), elongated spermatids, and testicular spermatozoa from the testis of a prepubertal 11-month-old male marmoset and injected them into in vitro-matured oocytes. After 7 days in culture, two embryos from elongated spermatid injection and two embryos from sperm injection were transferred into two separate recipient females. The recipient female that received elongated spermatid injection-derived embryos became pregnant and gave birth to one female infant. This is the first demonstration that a spermatid from a prepubertal male primate can support full-term development. Using this method, we can expect to obtain offspring of gene-modified males 6 months to a year earlier than with natural mating.

The adduct formation between the thioguanine-polyamine ligands and DNA with the AP site under UVA irradiated and non-irradiated conditions.

The AP sites are representative of DNA damage and known as an intermediate in the base excision repair (BER) pathway which is involved in the repair of damaged nucleobases by reactive oxygen species, UVA irradiation, and DNA alkylating agents. Therefore, it is expected that the inhibition or modulation of the AP site repair pathway may be a new type of anticancer drug. In this study, we investigated the effects of the thioguanine-polyamine ligands (SG-ligands) on the affinity and the reactivity for the AP site under UVA irradiated and non-irradiated conditions. The SG-ligands have a photo-reactivity with the A-F-C sequence where F represents a tetrahydrofuran AP site analogue. Interestingly, the SG-ligands promoted the ß-elimination of the AP site followed by the formation of a covalent bond with the ß-eliminated fragment without UVA irradiation.

Relative validity of brief-type self-administered diet history questionnaire among very old Japanese aged 80 years or older.

OBJECTIVE: Dietary questionnaires for assessing dietary intakes among populations of individuals aged 80 years or older (the very old) are very limited. We examined the relative validity of forty-three nutrients and twenty-seven food groups estimated by a brief-type self-administered diet history questionnaire (BDHQ) targeting very old Japanese, using semi-weighed dietary records (DR) as a reference. DESIGN: Between June and August 2012 and between June 2015 and February 2016, a three-day non-consecutive DR (at two-week intervals) and a BDHQ were completed. SETTING: Tokyo, the capital prefecture of Japan. SUBJECTS: Eighty very old Japanese (thirty-six men and forty-four women) aged 82-94 years. RESULTS: The median intakes of 40-70 % of the crude and energy-adjusted nutrients estimated by the BDHQ were significantly different from those estimated by the DR. The median Spearman's correlation coefficient of nutrient intakes between the BDHQ and the DR was 0·39-0·46. About half (48-56 %) of the food groups were significantly different in terms of the median intakes estimated by the BDHQ and the DR in crude and energy-adjusted values. The median Spearman's correlation coefficient between the BDHQ and the DR was 0·45-0·48. CONCLUSIONS: Acceptable Spearman's correlations (≥0·3) were obtained for many dietary intakes among the very old Japanese population. The BDHQ is a good candidate for epidemiological studies among very old Japanese, although, for some nutrients and food groups, the difficulty of estimating accurate median intakes is one of the limitations for the tool. Further efforts to enhance the validity of the BDHQ for very old populations are needed.

Angelica keiskei (Ashitaba) powder and its functional compound xanthoangelol prevent heat stress-induced impairment in sperm density and quality in mouse testes.

Recently, gradual decline in human sperm production has become a serious worldwide concern because it leads to increased rates of infertility. Endocrine disrupters, lifestyle changes, and varicocele, all of which elevate testicular temperature, are thought to be the main causes of this decline. The present study aimed to determine whether the dietary phytochemicals Angelica keiskei (Ashitaba) powder (57.5 mg/kg) and its functional component, xanthoangelol (3 mg/kg), can prevent heat stress-induced impairment in sperm density and quality in mice. Sperm parameters were analyzed 28 days after mice exposure to heat. Supplementation with Ashitaba powder completely prevented heat-induced impairment in sperm parameters, including densities of motile sperms and progressive sperms (> 25 µm/sec), and amplitude of lateral head displacement. Xanthoangelol did not exert a complete protective effect; nevertheless, it significantly prevented heat stress-induced reduction in most parameters. Both Ashitaba powder and xanthoangelol elevated the expression of the widely expressed heat shock proteins (HSPs) Hspa1a and Hsp40 and the antioxidant enzyme glutathione synthase in non-stressed testes. Ashitaba powder significantly prevented heat stress-induced reduction in the expression of Hspa1l and Hspa2, which are highly expressed in the testes and critical for fertility. Our results showed that Ashitaba powder and xanthoangelol protected testicular cells from heat stress, probably by elevating the levels of antioxidant enzymes and HSPs. Supplementation with dietary functional phytochemicals may help prevent heat stress-induced male infertility.

[Effects of polypharmacy and anticholinergic/sedative drugs on the physical/cognitive/mental related outcomes of community-dwelling elderly people: The Kawasaki Wellbeing Project].

AIM: To assess the burdens of polypharmacy and the drug burden index in community-dwelling elder people. METHODS: The survey was conducted on 396 participants who participated in The Kawasaki Wellbeing Project from March to December 2017. We investigated the associations between the drug burden and the physical/cognitive/mental outcomes. The drug burden was determined by calculating the number of medications and the drug burden index (DBI) based on the use of anticholinergic and sedative drugs. A multivariate regression analysis was conducted for the outcome measures ADL, IADL, MMSE, J-CHS, and EQ5D5L after adjusting for the sex, age, number of diseases, education level, smoking history, and alcohol history. RESULTS: A total of 389 subjects were analyzed, the mean age of the population was 86 years old, and 187 people (48%) were male. Polypharmacy was reported in 243 people (62%), and DBI exposure was reported for 142 people (36.5%). We found that this population was physically healthy, with a median ADL of 100, and had high quality of life, with a median EQ5D5L of 0.895. Polypharmacy was found to be related to the J-CHS (ß: 0.04) and EQ5D5L (-0.01). The DBI was also related to the EQ5D5L (-0.04). CONCLUSION: These results showed that even though this population was healthier than the general Japanese elderly population, the drug burden of polypharmacy and high dosages of anticholinergic/sedative drugs exerted significant negative effects on frailty and the quality of life. Additional research should be conducted to investigate the long-term effects of polypharmacy and anticholinergic/sedative drugs on elderly people.

Oocyte-activating capacity of fresh and frozen-thawed spermatids in the common marmoset (Callithrix jacchus).

The common marmoset (Callithrix jacchus) represents a promising nonhuman primate model for the study of human diseases because of its small size, ease of handling, and availability of gene-modified animals. Here, we aimed to devise reproductive technology for marmoset spermatid injection using immature males for a possible rapid generational turnover. Spermatids at each step could be identified easily by their morphology under differential interference microscopy: thus, early round spermatids had a round nucleus with a few nucleolus-like structures and abundant cytoplasm, as in other mammals. The spermatids acquired oocyte-activating capacity at the late round spermatid stage, as confirmed by the resumption of meiosis and Ca2+ oscillations upon injection into mouse oocytes. The spermatids could be cryopreserved efficiently with a simple medium containing glycerol and CELL BANKER®. Late round or elongated spermatids first appeared at 10-12 months of age, 6-8 months before sexual maturation. Marmoset oocytes microinjected with frozen-thawed late round or elongated spermatids retrieved from a 12-month-old male marmoset developed to the 8-cell stage without the need for artificial oocyte activation stimulation. Thus, it might be possible to shorten the intergeneration time by spermatid injection, from 2 years (by natural mating) to 13-15 months including gestation.