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"Kusunoki, Hiroshi"
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Current Status and Significance of Additional Vaccination with COVID-19 Vaccine in Japan—Considerations from Antibody Levels from Hybrid Immunity and Public Perceptions
2024
This report examines the evolving role of coronavirus disease 2019 (COVID-19) vaccination in Japan, especially in light of the reduced public concern following the reclassification of COVID-19 as a Category 5 infectious disease in May 2023. With over half the population estimated to have hybrid immunity from prior infections and vaccinations, this report evaluated the necessity and frequency of additional booster doses. Despite strong recommendations from Japanese medical societies to continue vaccination, public skepticism remains owing to financial burdens, adverse reactions, and the perceived limited benefits of frequent boosters. Studies on antibody responses have revealed that individuals with hybrid immunity maintain robust protection with significantly elevated antibody titers that persist over extended periods. Case studies have indicated durable immunity among individuals who have both been vaccinated and experienced breakthrough infections, raising questions about the need for uniform booster policies. This report also discusses the newly approved replicon-type (self-amplifying) vaccines currently available only in Japan, which have generated public and professional debates regarding their efficacy and safety. A more personalized approach to vaccination that takes into account the antibody titers, prior infection history, and individual choices is recommended. Finally, this report underscores the importance of aligning vaccination policies with scientific evidence and public sentiment to optimize COVID-19 countermeasures in Japan.
Journal Article
Association between oral frailty and cystatin C-related indices—A questionnaire (OFI-8) study in general internal medicine practice
by
Kusunoki, Hiroshi
,
Shimizu, Hideo
,
Ekawa, Kazumi
in
Aged
,
Aged, 80 and over
,
Biology and Life Sciences
2023
Cystatin C-related indices such as the ratio of creatinine to cystatin C (Cr/CysC) and the ratio of estimated glomerular filtration rate by cystatin C (eGFRcys) to creatinine eGFRcre (eGFRcys/eGFRcre) levels have been shown to be associated with muscle mass and strength and can be markers of sarcopenia. Oral frailty is defined as an age-related gradual loss of oral functions, accompanied by a decline in cognitive and physical functions. It results in adverse health-related outcomes in older age, including mortality, physical frailty, functional disability, poor quality of life, and increased hospitalization and falls. Therefore, poor oral health among the elderly is an important health concern due to its association with the pathogenesis of systemic frailty, suggesting it to be a multidimensional geriatric syndrome. The Oral Frailty Index-8 (OFI-8) is a questionnaire that can be used for easy screening of oral frailty. This study aimed to investigate whether cystatin C- related indices are different between patients with low to moderate risk of oral frailty and those at high risk of oral frailty, using the OFI-8 in attending a general internal medicine outpatient clinic.
This is a cross-sectional study that included 251 patients with a mean age of 77.7±6.6 years and a median age of 77 years (128 men: mean age, 77.1±7.3 years; median age, 77 years and 123 women: mean age, 78.4±5.7 years; median age, 78 years) attending general internal medicine outpatient clinics. OFI-8 scores were tabulated by gender to determine whether there were differences between patients at low to moderate risk of oral frailty (OFI-8 score ≤3 points) and those at high risk (OFI-8 score ≥4 points) in Cr/CysC, eGFRcys/eGFRcre levels, height, weight, grip strength, etc. were examined.
The OFI-8 score was higher in women than in men, suggesting that oral frailty is more common in women. Cr/CysC, eGFRcys/eGFRcre and grip strength were significantly lower in both men and women in the high-risk group for oral frailty (OFI-8 score ≥ 4). Height, hemoglobin level, red blood cell count, and serum albumin levels were significantly lower in men with an OFI-8 score ≥4. Receiver operating characteristic curve (ROC) analysis also showed that Cr/CysC and eGFRcys/eGFRcre were significantly associated with an OFI-8 score≥4 in both men and women.
Cr/CysC and eGFRcys/eGFRcre were significantly lower in the high-risk group for oral frailty on the OFI-8in both men and women. A relationship exists among cystatin C-related indices, which can effectively screen systemic frailty. Similarly, the OFI-8 score can be used to effectively screen oral frailty. Thus, a collaboration that incorporates both systemic and oral frailty from medical and dental perspectives is required.
Journal Article
Fourteen babies born after round spermatid injection into human oocytes
2015
During the human in vitro fertilization procedure in the assisted reproductive technology, intracytoplasmic sperm injection is routinely used to inject a spermatozoon or a less mature elongating spermatid into the oocyte. In some infertile men, round spermatids (haploid male germ cells that have completed meiosis) are the most mature cells visible during testicular biopsy. The microsurgical injection of a round spermatid into an oocyte as a substitute is commonly referred to as round spermatid injection (ROSI). Currently, human ROSI is considered a very inefficient procedure and of no clinical value. Herein, we report the birth and development of 14 children born to 12 women following ROSI of 734 oocytes previously activated by an electric current. The round spermatids came from men who had been diagnosed as not having spermatozoa or elongated spermatids by andrologists at other hospitals after a first Micro-TESE. A key to our success was our ability to identify round spermatids accurately before oocyte injection. As of today, all children born after ROSI in our clinic are without any unusual physical, mental, or epigenetic problems. Thus, for men whose germ cells are unable to develop beyond the round spermatid stage, ROSI can, as a last resort, enable them to have their own genetic offspring.
Journal Article
Physical frailty predicts the development of social frailty: a prospective cohort study
2020
Background
It has not been clarified whether physical frailty symptoms predict social.
frailty. The purpose of this study was to elucidate the effect of physical frailty on social frailty, and to determine which domains of physical frailty predict the development of social frailty.
Methods
We employed a two-year prospective cohort study. A total of 342 socially robust community-dwelling older adults were recruited. We used a modified social frailty screening index consisting of four social domains including financial difficulties, living alone, social activity, and contact with neighbors. Physical frailty status was also assessed at baseline. At the two-year follow-up, we assessed the development of social frailty. Social status was assessed using four social subdomains for the primary analysis. Social status was assessed using the two social subdomains of social activity and contact with neighbors, which would be affected by the physical frailty component, for the secondary analysis. The risk ratios (RR) of physical frailty for the development of social frailty were estimated.
Results
Although physical frailty symptoms were not a significant risk factor for future development of social frailty as assessed by four social subdomains (adjusted RR 1.39, 95% CI 0.95–2.15), it became significant when development of social frailty was assessed by the two social subdomains (adjusted RR 1.78, 95% CI 1.10–2.88). An analysis using the physical frailty subdomain showed that slow gait speed (adjusted RR 3.41, 95% CI 1.10–10.53) and weakness (adjusted RR 1.06, 95% CI 1.01–1.12) were independent risk factors for development of social frailty as assessed by two social subdomains.
Conclusions
Physical frailty symptoms predict the development of social frailty. Among physical frailty subdomains, gait speed and muscle strength are critical independent risk factors for future decline in the social aspect. The prevention of physical frailty, especially by maintaining gait ability and muscle strength, may be effective for avoiding social frailty.
Journal Article
Relationships between cystatin C- and creatinine-based eGFR in Japanese rural community- dwelling older adults with sarcopenia
by
Kusukawa Tomoyuki
,
Maeda Hatsuo
,
Sugita Hideyuki
in
Creatinine
,
Cystatin C
,
Epidermal growth factor receptors
2021
BackgroundSarcopenia is prevalent in patients with chronic kidney disease (CKD). The indices of physical function, such as grip power and gait speed, decreased according to the decline in the estimated glomerular filtration rate (eGFR).MethodsWe examined the relationships between cystatin C-based GFR (eGFRcys), creatinine-based GFR (eGFRcre), their ratio (eGFRcys/eGFRcre) and sarcopenia in community-dwelling older adults in Japan. This cross-sectional study included 302 men aged 73.9 ± 6.2 years and 647 women aged 72.9 ± 5.8 years from a rural area in Hyogo Prefecture, Japan. eGFRcys and eGFRcre were simultaneously measured, and sarcopenia based on the Asia Working Group for Sarcopenia (AWGS) 2019 criteria was evaluated.ResultseGFRcys and the eGFRcys/eGFRcre ratio were significantly correlated with grip power and gait speed (p < 0.001). The eGFRcys/eGFRcre ratio was also correlated with skeletal muscle mass index (SMI) (p < 0.01). Univariate logistic regression analysis showed eGFRcys and eGFRcys/eGFRcre ratio but not eGFRcre were associated with sarcopenia (p < 0.01). The presence of low eGFRcys (CKDcys) and low eGFRcys/eGFRcre ratio (< 1.0) but not that of low eGFRcre (CKDcre) were associated with sarcopenia (p < 0.01). In the multivariate logistic regression analysis, when the eGFRcys/eGFRcre ratio was added as a covariate to the basic model, it was significantly associated with sarcopenia in women (p < 0.05). Moreover, low eGFRcys/eGFRcre ratio (< 1.0) was associated with a higher risk of sarcopenia in men (p < 0.01).ConclusionIn conclusion, CKDcys but not CKDcre is associated with sarcopenia. A lower eGFRcys/eGFRcre ratio may be a practical screening marker of sarcopenia in community-dwelling older adults.
Journal Article
Usefulness of a newly developed ultrasonic system to estimate skeletal muscle mass and muscle strength in community-dwelling older adults
by
Kusunoki, Hiroshi
,
Nagai, Koutatsu
,
Nagasawa, Yasuyuki
in
692/308
,
692/699
,
Absorptiometry, Photon
2025
Measuring skeletal muscle mass index using bioelectrical impedance analysis or dual-energy X-ray absorptiometry is challenging for home care patients and those with implanted devices. Contrastingly, ultrasound measurement of skeletal muscle mass is a simple and non-invasive method. We aimed to investigate quadriceps muscle cross-sectional area measured using a newly developed ultrasonic muscle imaging system to serve as a diagnostic tool for sarcopenia. The cross-sectional study including 510 independent adults aged 65 years and older (180 men; median age, 75 years) was performed between October 2021 and December 2022. Quadriceps muscle cross-sectional area of the dominant leg was measured, and the average value was analyzed for correlation with body composition indices measured using the bioelectrical impedance analysis method, muscle strength and physical performance tests. Quadriceps muscle cross-sectional area showed a good correlation with skeletal muscle mass index (R = 0.78,
P
< 0.001), handgrip strength (R = 0.70,
P
< 0.001), and knee extension strength (R = 0.68,
P
< 0.001). This study demonstrated that quadriceps muscle cross-sectional area using a newly developed ultrasonic system shows a strong correlation with skeletal muscle mass index and muscle strength. These findings suggest that this system could be an alternative to bioelectrical impedance analysis for the diagnosis of sarcopenia.
Journal Article
Predicting cognitive function changes from oral health status: a longitudinal cohort study
2024
Recent studies indicate a potential link between oral health and cognitive function; however, long-term associations remain unclear. This study aimed to identify oral health factors that predict changes in cognitive function among older adults over time. The study included 583 independent older adults (201 male, 382 female) with a mean age of 72.7 years. Cognitive function was assessed using Mini-Mental State Examination (MMSE) at baseline and follow-up over two years, with relative change in MMSE (rMMSE) calculated. Baseline oral health variables included number of remaining teeth, masticatory performance, occlusal force, oral diadochokinesis and tongue pressure. Physical performance and confounding factors were also considered. The relationship between rMMSE and the variables was analyzed using Pearson’s correlation, Mann-Whitney U test, and multiple linear regression analysis. Cognitive function declined in 196 subjects, with rMMSE significantly correlated with oral diadochokinesis. Regression analysis revealed significant associations between cognitive changes and oral diadochokinesis (
p
= 0.020) and knee extension strength as a physical performance (
p
= 0.047). Our findings suggest that cognitive decline may be indicated by declines in both physical and oral motor performance. Incorporating oral diadochokinesis testing into health screenings could aid early detection of cognitive decline, improving outcomes and reducing healthcare burdens.
Journal Article
Association between Physical Frailty Subdomains and Oral Frailty in Community-Dwelling Older Adults
by
Okuda, Kazuki
,
Nagai, Koutatsu
,
Kusunoki, Hiroshi
in
Aged
,
Body mass index
,
Cognitive ability
2021
This cross-sectional study aimed to demonstrate the association between physical frailty subdomains and oral frailty. This study involved community-dwelling older adults (aged ≥65 years). Physical frailty was assessed with the Japanese version of the Cardiovascular Health Study criteria. Oral frailty was defined as limitations in at least three of six domains. Logistic regression analysis was used to analyze the association between physical frailty risk and oral frailty. In addition, we examined the association between physical frailty subdomains (gait speed, grip strength, exhaustion, low physical activity, and weight loss) and oral frailty. A total of 380 participants were recruited for this study. Overall, 18% and 14% of the participants were at risk of physical frailty and had oral frailty, respectively. Physical frailty risk (odds ratio (OR) = 2.40, 95% confidence interval (CI): 1.22–4.75, p = 0.012) was associated with oral frailty in multivariate analysis. In secondary analysis, among physical frailty subdomains, gait speed (OR = 0.85, 95% CI: 0.73–0.97, p = 0.019) was associated with oral frailty. The present findings suggest that physical frailty is closely related to oral frailty. Among physical frailty subdomains, decreased gait speed in particular is an important indicator related to the development of oral frailty.
Journal Article
Is Oral Function Associated with the Development of Sarcopenic Obesity and Sarcopenia in Older Adults? A Prospective Cohort Study
2025
Background: Sarcopenic obesity, defined as the concurrent loss of muscle mass and adipose tissue accumulation, is associated with reduced physical function and poor health status in older adults. Although oral function can impact the overall health of older adults, its role in the development of sarcopenic obesity remains unclear. Herein, we aimed to examine the association between oral function and the incidence of sarcopenic obesity. Methods: This longitudinal cohort study included 597 independent older adults (aged ≥65 years) from Tamba-Sasayama, a rural region of Japan, who participated in academic studies between June 2016 and December 2023. Participants underwent surveys at least twice, with a minimum two-year interval. The participants were divided into four groups (robust, obese, sarcopenic, and sarcopenic obese) according to their health condition. Sarcopenic obesity was diagnosed based on the guidelines of the Japanese Working Group on Sarcopenic Obesity. The oral function was evaluated by assessing the number of remaining teeth, tongue pressure, occlusal force, masticatory performance, and oral diadochokinesis. Cox proportional hazards regression analysis evaluated the association between oral function and the incidence of sarcopenic obesity after adjusting for relevant confounders. Results: The sarcopenic obesity group was older, had lower skeletal muscle mass, and inferior physical function. This cohort also had the highest prevalence of hypertension and significantly fewer remaining teeth. The proportion of individuals with sarcopenic obesity was 1.7% of the total population, with 2.8% in the obesity group at baseline, and 8.0% of those were diagnosed with sarcopenia progressing to sarcopenic obesity. The Cox regression model revealed that reduced tongue pressure was significantly associated with an increased risk of sarcopenic obesity, with a hazard ratio of 0.906 (95% confidence interval: 0.829–0.990; p = 0.028), independent of other variables related to sarcopenia and obesity. Conclusions: Our findings suggest that oral function is associated with the incidence of sarcopenic obesity but not with that of sarcopenia or obesity alone.
Journal Article
Effect of deterioration of swallowing functions on the frailty status in older adults: a longitudinal cohort study
2025
Background
Deterioration of swallowing function (DSF) is common among aging adults and can lead to negative health outcomes such as increased risk of malnutrition. However, the longitudinal relationship between the DSF and frailty status remains unclear. This study aimed to investigate whether declining swallowing function is linked to frailty progression in independent older adults.
Methods
This study included 795 community-dwelling Japanese individuals aged ≥ 65 years who participated in two surveys: one at baseline and one after two years. Swallowing function was evaluated using the repetitive saliva swallowing test, tongue pressure test, and questionnaire. DSF was identified by meeting more than one of three criteria: Repeated Saliva Swallow Test below 3, tongue pressure under 27.4 kPa for men and 26.5 kPa for women, and a “yes” response to the questionnaire. Frailty status was assessed using the Kihon Checklist, with participants showing a decline categorized into the “aggravation group.” Oral function (number of teeth, occlusal force, masticatory performance, and oral dryness) and physical function (body mass index, gait speed, grip strength, and skeletal muscle mass index) were evaluated. Comparisons between the two groups were made using the Student’s t-test or the χ2 test. Differences among the three groups were assessed using the one-way analysis of variance or the χ2 test. Significant differences in continuous variables were analyzed using the Least Significant Difference method, with
P
-values adjusted using the Bonferroni correction.
Results
Initially, 87 (10.9%) participants were frail. By follow-up, 149 participants (37.9%) had progressed to frailty, 83 of whom (55.7%) exhibited impaired swallowing function at baseline. At baseline, frailty was significantly associated with age, gait speed, decreased swallowing function, number of functional teeth, occlusal force, and masticatory performance. None of the three swallowing function assessment methods were significantly associated with the progression of frailty. In contrast, logistic regression analysis of frailty progression showed that impaired swallowing function was a significant explanatory variable (OR, 1.53; 95% CI: 1.04–2.21).
Conclusion
This study found a significant association between frailty and multiple factors, particularly oral function. Specifically, diminished swallowing function has emerged as a notable independent predictor of frailty progression.
Journal Article