Aberrant bone marrow-derived microglia in the hypothalamus may dysregulate appetite in diabetes.

Bone marrow derived cells (BMDCs) migrate into the hypothalamus, where those cells give rise to microglia to regulate food intake. Given the fact that diabetes functionally impairs BMDCs, we hypothesized that diabetic microglia would fail to exhibit physiological function, accounting for hyperphagia in diabetes. To examine the role of BMDCs, total bone marrow cells from GFP transgenic mice were transplanted into wild type mice in which diabetes was induced by streptozotocin. We first confirmed that bone marrow transplantation could be utilized to examine BMDCs in the brain parenchyma as GFP positive cells could engraft the brain parenchyma and give rise to microglia even when the BBB was intact in the recipient mice. While diabetic mice manifested hyperphagia, BMDCs were in smaller number in the hypothalamus with less response to fasting in the brain parenchyma compared to nondiabetic mice. This finding was also confirmed by examining nondiabetic chimera mice in which BMDCs were diabetic. Those mice also exhibited less response of BMDCs in response to fasting. In conclusion, diabetic BMDCs had less response of microglia to fasting, perhaps accounting for diabetic hyperphagia.

The pathogenic role of lupus-specific autoantibodies and Interleukin-6 on demyelination of the brainstem and spinal cord in systemic lupus erythematosus.

OBJECTIVES: Demyelinating syndromes that result in brainstem and/or spinal cord lesions similar to those observed in neuromyelitis optica spectrum disorder (NMOSD) as neuropsychiatric syndromes in systemic lupus erythematosus (NPSLE) occasionally develop in patients with SLE. Cerebrospinal fluid (CSF) interleukin (IL)-6 is a known biomarker for NMOSD; however, its application in patients with SLE with brainstem and/or spinal cord lesions is unknown. Additionally, the breakdown of blood-brain barrier (BBB) integrity by autoantibodies is another mechanism of NMOSD; however, it is not elucidated in SLE. Therefore, this study was designed to clarify the use of CSF IL-6 and investigate whether autoantibodies contribute to BBB breaches and the development of brainstem and/or spinal cord lesions. METHODS: Data from patients with NPSLE who had NMOSD-like demyelinating lesions in the central nervous system (CNS), including brainstem and/or spinal cord lesions, were retrospectively analyzed. We retrospectively investigated the interval changes in CSF IL-6 and clinical and serological factors related to BBB permeability using CSF/serum albumin ratio (QAlb). RESULTS: Twelve patients with NPSLE who had demyelinating lesions in the brainstem and/or spinal cord were recruited. Before treatment, CSF IL-6 levels were 29.1 pg/mL and significantly decreased to 3.8 pg/mL by treatment (p = 0.008). Before treatment, CSF IL-6 was significantly correlated with the anti-dsDNA antibody titer (p = 0.027). Furthermore, before treatment, QAlb was significantly correlated with the serum anti-Smith antibody titer. In patients with atypical NMOSD who had specific lesions defined in the NMOSD diagnostic criteria but were negative for antiaquaporin four antibody, a significant correlation was observed between the serum anti-Smith antibody titer and CSF IL-6 (p = 0.025) and QAlb (p = 0.033) values before treatment. CONCLUSION: CSF IL-6 could be a surrogating marker for disease activity, and serum anti-Smith antibody permeabilizes the BBB in patients with NPSLE, supporting the development of NMOSD-like CNS lesions.

Polypharmacy with potentially inappropriate medications as a risk factor of new onset sarcopenia among community-dwelling Japanese older adults: a 9-year Kashiwa cohort study.

BACKGROUND: Clinical evidence demonstrating a longitudinal association between prescribed medications and sarcopenia onset is lacking. We investigated the association of polypharmacy (the use of five or more medications) and potentially inappropriate medications (PIMs) with sarcopenia risk in community-dwelling older adults. METHODS: In this longitudinal population-based cohort study, 2,044 older residents with no long-term care needs were randomly selected from a community in Kashiwa, Japan. Baseline data collection was conducted in 2012, with follow-ups in 2013, 2014, 2016, 2018, and 2021. Prescribed medications and PIMs (drugs listed in the Screening Tool for Older Person's Appropriate Prescriptions for the Japanese or potentially muscle-wasting drugs) were identified through interviews. New-onset sarcopenia was identified according to the 2019 criteria of the Asian Working Group for Sarcopenia over a 9-year period and analyzed. We used Cox proportional hazards models to test the longitudinal association of prescribed medications with sarcopenia onset. RESULTS: Of the 1,549 participants without sarcopenia at baseline (mean age, 72.5 ± 5.5 years; 49.1% women; median and interquartile range, 6.0 [4.0-9.0] years), 230 experienced new-onset sarcopenia during the follow-up. After adjusting for confounders, polypharmacy combined with PIM use was strongly associated with new-onset sarcopenia (adjusted hazard ratio, 2.35; 95% confidence interval, 1.58-3.51; P < 0.001). No significant associations were observed for either PIM use or polypharmacy alone. CONCLUSIONS: Polypharmacy combined with PIM use, but not polypharmacy alone, was associated with an increased risk of new-onset sarcopenia over the 9-year follow-up period among community-dwelling older adults. Limiting polypharmacy and imposing the prescription of appropriate medications may facilitate sarcopenia prevention.

Decamethylcyclopentasiloxane affects estradiol production in female rats but not H295R cells.

Sex hormones, such as androgens and estrogens, are predominantly produced in the gonads (ovaries and testes) and adrenal cortex. Endocrine-disrupting chemicals (EDCs) are substances that mimic, block, or interfere with hormones in the endocrine systems of humans and organisms. EDCs mainly act via nuclear receptors and steroidogenesis-related enzymes. In the OECD conceptual framework for testing and assessment of EDCs, several well-known assays are used to identify the potential disruption of nuclear receptors both in vivo and in vitro, whereas the H295R steroidogenesis assay is the only assay that detects the disruption of steroidogenesis. Forskolin and prochloraz are often used as positive controls in the H295R steroidogenesis assay. Decamethylcyclopentasiloxane (D5) was suspected one of EDCs, but the effects of D5 on steroidogenesis remain unclear. To establish a short-term in vivo screening method that detects the disruption of steroidogenesis, rats in the present study were fed a diet containing forskolin, prochloraz, or D5 for 14 days. Forskolin increased plasma levels of 17ß-estradiol (E2) and testosterone as well as the mRNA level of Cyp19 in both the adrenal glands and ovaries. Prochloraz induced the loss of cyclicity in the sexual cycle and decreased plasma levels of E2 and testosterone. D5 increased E2 levels and shortened the estrous cycle in a dose-dependent manner; however, potential endocrine disruption was not detected in the H295R steroidogenesis assay. These results demonstrate the importance of comprehensively assessing the endocrine-disrupting effects of chemicals on steroidogenesis in vivo.

Real-world efficacy of belimumab in achieving remission or low-disease activity in systemic lupus erythematosus: A retrospective study.

OBJECTIVES: We investigated the effect of belimumab (BEL) on achieving low disease activity (LDA) and remission as an additive molecular-targeting agent to standard of care (SoC) in patients with SLE. METHODS: Clinical information was retrospectively collected from patients with SLE who received BEL additive to SoC (BEL+SoC), and from patients treated with SoC alone as a control arm. Disease activity was measured by SLE-disease activity score (SLE-DAS). The proportion of patients in LDA and remission at 12 months was compared after propensity score matching. The factors contributing to LDA and remission achievement was identified by Cox proportional hazard model. RESULTS: BEL+SoC significantly reduced SLE-DAS at 6 months, with a significantly higher proportion of patients achieving LDA and remission at 12 months compared to SoC alone. The presence of arthritis at baseline was significantly associated with achieving LDA and remission. Additionally, both treatment groups experienced a significant reduction in daily glucocorticoid dose. CONCLUSIONS: Adding BEL to SoC was beneficial for patients with arthritis, leading to higher proportion of achieving LDA and remission, while also reducing their glucocorticoid dose. Our results indicate the utility of BEL in a treat-to-target approach for SLE patients in a real-world setting.

Effect of an Oral Frailty Measures Program on Community-Dwelling Elderly People: A Cluster-Randomized Controlled Trial.

INTRODUCTION: Oral frailty describes a trivial decline in the oral function and is considered to be related to frailty. Thus, effective management of oral frailty could prevent or ameliorate physical frailty and the need for care. However, there is a lack of consensus regarding specific interventions for oral frailty. In this cluster-randomized controlled trial, we investigated the effects of a newly developed oral frailty measures program mentored by dentists and dental hygienists for elderly people in a clinical setting. METHODS: Of 3,296 participants included in a field survey, 219 who regularly visited dental clinics and met at least 3 of the following 6 criteria for oral frailty were considered eligible: <20 natural teeth, decreased chewing ability, decreased articulatory oral-motor skills, decreased tongue pressure, and substantial subjective difficulties in eating and swallowing. After applying the inclusion and exclusion criteria, we studied 51 patients in the intervention group (14 men and 37 women; mean age, 78.6 years) and 32 patients in the control group (7 men and 25 women; mean age, 78.0 years). We implemented a 12-week oral frailty measures program only for the intervention group. The program included preparatory oral exercises, mouth-opening training, tongue pressure training, prosodic training, and masticatory training. Primary outcome measures were the chewing ability score, articulatory oral motor skill for /ta/, tongue pressure, subjective difficulty in eating tough foods, and subjective difficulty in swallowing. We compared baseline characteristics using the Mann-Whitney U and χ2 tests for continuous and categorical variables, respectively. A repeated-measures two-way ANOVA was used to determine the efficacy of independent intervention variables, following the Wilcoxon signed-rank test. The groups (intervention/control) and time (baseline/week 12) were the independent variables. Oral frailty measures were the dependent variables. RESULTS: Baseline characteristics and assessment results were similar between groups. We observed significant improvements in the intervention group in terms of articulatory oral motor skill for /ta/ and tongue pressure (p < 0.001). No improvements were observed in the control group. DISCUSSION/CONCLUSION: Our results suggest that our oral frailty measures program effectively alleviates oral frailty. Future studies are needed to clarify the impact on preventing physical frailty and improving the nutritional status.

Distribution analysis of hydrogel spacer and evaluation of rectal dose reduction in Japanese prostate cancer patients undergoing stereotactic body radiation therapy.

BACKGROUND: To report on our primary experience with the placement of a hydrogel spacer following stereotactic body radiation therapy (SBRT) in low- and intermediate-risk prostate cancer patients and assess its impact on dosimetry as well as acute toxicity. METHODS: A total of 70 patients treated with SBRT (total dose of 36.25 Gy) in 5 fractions were included. Hydrogel spacers were inserted in 53 patients along with gold fiducial markers. For dosimetry, we trisected the rectum on the sagittal image of magnetic resonance imaging and defined it as the upper rectum (UR), middle rectum (MR), and lower rectum (LR). We compared the dose to each part of the rectum with and without hydrogel spacer using dose volume histograms. Genitourinary (GU) and gastrointestinal (GI) toxicity assessments were conducted until 6 months of follow-up visits. RESULTS: The median volume of the hydrogel spacer was 12.3 mL. Overall, the hydrogel spacer could significantly reduce the rectal dose in the middle-to-high-dose region (V20-V35). The rectum doses at the UR and MR were significantly lower in the spacer group in the middle to high dose region (V20-V35); the dose at the LR was significantly lower in the spacer group in the high-dose region (V30-V35). There was no grade ≥ 3 toxicity observed, but grade 2 toxicity of GU and GI occurred in 17.1% and 1.4% of the patients, respectively. CONCLUSION: Hydrogel spacers could contribute to rectal dose reduction, especially in high dose regions, by creating a prostate-rectum distance.

Niclosamide suppresses macrophage-induced inflammation in endometriosis†.

Endometriosis is a common gynecological disease, which causes chronic pelvic pain and infertility in women of reproductive age. Due to limited efficacy of current treatment options, a critical need exists to develop new and effective treatments for endometriosis. Niclosamide is an efficacious and FDA-approved drug for the treatment of helminthosis in humans that has been used for decades. We have reported that niclosamide reduces growth and progression of endometriosis-like lesions via targeting STAT3 and NFĸB signaling in a mouse model of endometriosis. To examine the effects of niclosamide on macrophage-induced inflammation in endometriosis, a total of 29 stage III-IV endometrioma samples were used to isolate human endometriotic stromal cells (hESCs). M1 or M2 macrophages were isolated and differentiated from fresh human peripheral blood samples. Then, hESCs were cultured in conditioned media (CM) from macrophages with/without niclosamide. Niclosamide dose dependently reduced cell viability and the activity of STAT3 and NFκB signaling in hESCs. While macrophage CM stimulated cell viability in hESCs, niclosamide inhibited this stimulation. Macrophage CM stimulated the secretion of proinflammatory cytokines and chemokines from hESCs. Most of these secreted factors were inhibited by niclosamide. These results indicate that niclosamide is able to reduce macrophage-induced cell viability and cytokine/chemokine secretion in hESCs by inhibiting inflammatory mechanisms via STAT3 and/or NFκB signaling.

Mdm2-p53-SF1 pathway in ovarian granulosa cells directs ovulation and fertilization by conditioning oocyte quality.

Functions of tumor suppressor p53 and its negative regulator mouse double minute 2 homolog (Mdm2) in ovarian granulosa cells remain to be elucidated, and the current study aims at clarifying this issue. Mice with Mdm2 deficiency in ovarian granulosa cells [ Mdm2-loxP/ progesterone receptor ( Pgr)-Cre mice] were infertile as a result of impairment of oocyte maturation, ovulation, and fertilization, and those with Mdm2/p53 double deletion in granulosa cells ( Mdm2-loxP/ p53-loxP/ Pgr-Cre mice) showed normal fertility, suggesting that p53 induction in the ovarian granulosa cells is detrimental to ovarian function by disturbing oocyte quality. Another model of Mdm2 deletion in ovarian granulosa cells ( Mdm2-loxP/ anti-Mullerian hormone type 2 receptor-Cre mice) also showed subfertility as a result of the failure of ovulation and fertilization, indicating critical roles of ovarian Mdm2 in ovulation and fertilization. Mdm2-p53 pathway in cumulus granulosa cells transcriptionally controlled an orphan nuclear receptor steroidogenic factor 1 (SF1), a key regulator of ovarian function. Importantly, MDM2 and SF1 levels in human cumulus granulosa cells were positively associated with the outcome of oocyte maturation and fertilization in patients undergoing infertility treatment. These findings suggest that the Mdm2-p53-SF1 axis in ovarian cumulus granulosa cells directs ovarian function by affecting their neighboring oocyte quality.-Haraguchi, H., Hirota, Y., Saito-Fujita, T., Tanaka, T., Shimizu-Hirota, R., Harada, M., Akaeda, S., Hiraoka, T., Matsuo, M., Matsumoto, L., Hirata, T., Koga, K., Wada-Hiraike, O., Fujii, T., Osuga, Y. Mdm2-p53-SF1 pathway in ovarian granulosa cells directs ovulation and fertilization by conditioning oocyte quality.

Species-specific nitrogen resorption proficiency in legumes and nonlegumes.

Nitrogen (N) resorption from senescing leaves enables plants to reuse N, thereby making them less dependent on current N uptake from the environment. Therefore, N resorption is important for survival and fitness, particularly for plants growing under low N supply. We studied N resorption from senescing leaves of 25 legumes and 25 nonlegumes in a temperate region of Japan to test the hypothesis that high N resorption has not evolved in legumes that fix atmospheric N2. The extent of N resorption was quantified by N resorption proficiency that is measured as the level to which leaf N concentration was reduced during senescence, i.e., the lower the senesced leaf N concentration, the lower the N loss through leaf fall and higher the N resorption proficiency. In support of the hypothesis, senesced leaf N concentration was higher in legumes than in nonlegumes, but there was considerable overlap between the groups. The higher senesced leaf N concentration of legumes was associated with a lower proportion of leaf N resorbed during senescence, particularly in species with higher leaf N concentrations. According to a hierarchical partitioning analysis, there was a large contribution of species to the total variance in the senesced leaf N concentration as opposed to a minor contribution of functional group (legume/nonlegume). This study reveals that legumes are not proficient at resorbing N from senescing leaves but that N2-fixation might not be the single most important determinant of N resorption.

Gestational psittacosis: A case report and literature review.

Gestational psittacosis is a rare disease that is associated with significant maternal and fetal morbidity and mortality. Currently, there is no examination method which allows for a quick diagnosis. We report a case of gestational psittacosis that could not be diagnosed as psittacosis during treatment and resulted in maternal and fetal death despite intensive treatment. We also reviewed 23 cases of gestational psittacosis. Fetal and maternal mortality was 82.6% (19/23) and 8.7% (2/23), respectively. In pregnant women with high fever and flu-like symptoms, we should suspect Chlamydia psittaci infection if at least one of the following is present; contact with sheep, parrots, parakeets or goats; normal or moderately decreased leucocyte count, thrombocytopenia and hepatic and/or renal dysfunction; cough and/or lobe consolidation or infiltration on chest X-ray. Antibiotic therapy with macrolide prenatally, macrolide or tetracycline postnatally and termination of pregnancy should be considered.

Relationship between radiation doses and erectile function deterioration in patients with localized prostate cancer treated with permanent prostate brachytherapy.

OBJECTIVES: To investigate the relationship between radiation doses in prostate brachytherapy and deterioration of erectile function in patients with localized prostate cancer. METHODS: A longitudinal survey study was carried out among 261 prostate cancer patients who received prostate brachytherapy. A total of 48 patients were potent at baseline and they did not receive any supplemental therapy preoperatively. Dosimetry parameters of the whole prostate gland, prostate apex, urethra and rectum were collected using the VariSeed 8.0 treatment planning system (Varian Medical Systems, Palo Alto, CA, USA). We carried out a logistic regression analysis to clarify the relationship between radiation doses and erectile function deterioration, which was assessed using the International Index of Erectile Function-15 questionnaire. RESULTS: The median patient age was 66 years (range 53-70 years) with a median follow-up time of 44 months (36-71 months). The mean total International Index of Erectile Function-15 score decreased from 49.9 at baseline to 34.7 after 12 months (P < 0.001), but gradually plateaued within 36 months. Erectile function deterioration was noted in 32 (66.7%) patients 36 months after prostate brachytherapy. In an analysis of risk factors for erectile function deterioration after prostate brachytherapy, age ≥70 years (P = 0.029), prostate V100 ≥95% (P = 0.024), apex V100 ≥95% (P = 0.024), apex V150 ≥70% (P = 0.009) and apex D90 ≥150 Gy (P = 0.011) correlated with erectile function deterioration. A multivariate analysis identified an age of ≥70 years (odds ratio 7.91, P = 0.024) and apex V150 ≥70% (odds ratio 7.75, P = 0.007) as independent risk factors for erectile function deterioration after prostate brachytherapy. CONCLUSIONS: An excessive radiation dose, particularly to the prostate apex area, and an advanced age might have a negative impact on the preservation of potency after prostate brachytherapy.

Development of a simple method to measure masseter muscle mass.

OBJECTIVE: To develop a simple method to estimate masseter muscle mass. BACKGROUND: The masseter muscle is important for optimal oral function. A decrease in the masseter muscle mass may affect the oral and physical function of the whole body; therefore, it is an important entity to measure. However, to date, no easy measurement method has been developed for the same. Herein, we devised a simple method to estimate masseter muscle mass. In addition, we compared our method with magnetic resonance imaging (MRI) and skeletal muscle mass (SMM) to verify its validity. MATERIALS AND METHODS: We recorded the age, sex, masseter muscle mass (by MRI), number of retained natural teeth, number of functional teeth, length and thickness of masseter muscle, and skeletal muscle mass in 53 community-dwelling elderly people (21 men and 32 women, average age 72.9 ± 4.5 years). The estimated masseter muscle mass was calculated by multiplying the length, width and thickness of the muscle. RESULTS: The correlation coefficient between masseter muscle mass and estimated masseter muscle mass was r = .903; thus, a strong correlation was recognised. The correlation coefficient between the estimated masseter muscle mass and SMM was r = .279, considering age and sex. CONCLUSION: We obtained substantial results using our method for estimating the masseter muscle mass and verified its validity by comparing it with masseter muscle mass measured by MRI and SMM. We believe that our proposed technique is simple and useful for estimating masseter muscle mass.

[Oral frailty is associated with food satisfaction in community-dwelling older adults].

AIM: The fact that accumulated reductions in the oral function with aging (i.e. oral frailty) lead to physical frailty has recently received considerable attention, and countermeasures are being promoted, mainly in the field of dentistry. We assessed the relationship between oral frailty and subjective food satisfaction under the hypothesis that oral frailty is also related to psychological problems. METHODS: Participants were attendees of the fourth wave of the Kashiwa cohort study in 2016. We excluded individuals with cognitive impairment and those who had missing values in the main variables. Regarding food satisfaction, "tastiness," "enjoyment," and "amount of food" were evaluated with self-administered questionnaires. Oral conditions were evaluated based on the number of remaining teeth and oral frailty. RESULTS: Of the 940 participants (mean age 76.3±5.1 years; 53% men), 71% responded that their food was "tasty," 96% said it was "enjoyable," 23% said that the amount of food was "large," and 63% said that the amount was "normal." While the number of teeth (20.8±8.5) was not significantly associated with food satisfaction, compared to those without oral frailty, those who had oral frailty were less likely to feel satisfaction with their meals ( "tasty," adjusted odds ratio [95% confidence interval] = 0.49 [0.29-0.83]; "large," 0.36 [0.15-0.84]; "normal," 0.44 [0.22-0.85]). CONCLUSIONS: Our results indicated negative associations between oral frailty and food satisfaction. In addition, the absence of a significant association with the number of teeth suggests that it is necessary to maintain not only the number of teeth but also the comprehensive oral function to support older people's enriched diets.

[The associations of frailty with regular participation in physical, cultural, and community social activities among independent elders in Japan].

Objective　The goal of the study was to assess the relationships of the frequency (more than one time per week) of various activities to frailty among independent elderly people in Japan.Methods　Survey data were collected from 73,341 community-dwelling elders who were not certified as Needing Long-Term Care. Basic checklist survey items developed by the Ministry of Health, Labour and Welfare were used along with exhaustive items on the weekly physical, cultural, community, and volunteer activities of the respondents. The effects of the frequencies of each activity with and without frailty were estimated. The relationship between frailty and pre-frailty was analyzed in a multinomial logistic regression model regarding involvement in activities and controlling for the effects of gender, age, and with non-frailty as a reference category.Results　Data on 49,238 individuals in the study area not certified as Needing Long-Term Care (24,632 males and 24,606 females), corresponding to 67% of all elderly (aged 65 or more years) Japanese people were analyzed. About 65.9% of the respondents reported that they engaged in physical activities, 78.8% reported cultural activities, and 14.9% reported community social activities. The percentages classified as frail and pre-frail were 12.8% and 22.7%, respectively. All of the activities significantly related to frailty. The adjusted odds ratio (95% CI) of frailty among the respondents that engaged in all the types of activity was: 2.19 (1.71, 2.80) among those that reported no physical activities, 1.48 (0.91, 2.43) among those with no cultural activities, and 2.09 (1.80, 2.44) among those with no community social activities. The adjusted odds ratio on frailty for the three groups reporting one type of activity ranged from 5.40 to 6.42, which was statistically significant, and the adjusted odds ratio on the group reporting no activities was 16.41 (14.02, 19.21). These results indicate that the extent of frailty increased as the number of activities decreased.Conclusions　This cross-sectional study found that frailty among elders in Japan was separately associated with participation in cultural activities, social community activities, and physical activities. Frailty was more severe among those with less participation. This result suggests that, for elders who find it difficult to participate in physical activities, engaging in cultural or community social activities might help to prevent or delay frailty.

Complete genome sequence of Paraburkholderia terrae strain KU-46, a 2,4-dinitrophenol-degrading bacterium.

Paraburkholderia terrae strain KU-46 has been studied for its capability to degrade 2,4-dinitrophenol. Here, we present the complete 10,833,180bp genome of this microorganism, comprising five circular chromosomes housing 9,797 protein-coding sequences. The genes responsible for 2,4-dinitrophenol and 4-nitrophenol degradation are located on chromosome 2.

Medical care priorities of community-dwelling older adults according to three dimensions of quality of life: Quality of daily living, satisfaction and happiness from birth to death, and human vitality.

AIM: Although the maintenance and improvement of quality of life (QoL) through holistic care are important in geriatric medical care, care priorities might differ depending on three essential aspects of QoL: the quality of daily living, satisfaction and happiness from birth to death, and human vitality, which are "Seikatsu," "Jinsei," "Seimei" in Japanese, respectively. We aimed to clarify these priorities in terms of medical care and examined how the definitions of QoL affected these priorities' rankings. METHODS: This cross-sectional study involved community-dwelling older adults aged ≥65 years living in Kashiwa City, Chiba Prefecture, Japan. The number of participants was 1550 (mean age, 76.1 ± 5.8 years; 699 women [45.1%]). A self-administered questionnaire distributed in advance was used to rank 12 items sought in medical care. Participants were randomly assigned to one of three groups and sent the corresponding questionnaire, which differed only in the definition of QoL. RESULTS: The top priorities for medical care were "effective treatment of illness," "improvement of physical function," and "maintaining a high level of activity." When QoL was defined as "the quality of daily living, satisfaction and happiness from birth to death, and human vitality," participants were significantly more likely to rank QoL improvement as one of the top three items (adjusted odds ratio, 1.46; 95% confidence interval, 1.03-2.05). CONCLUSIONS: As a medical care priority, older adults desire improvement of multidimensional elements of life, including human vitality. Health care providers should consider this when making medical care decisions. Geriatr Gerontol Int 2024; 24: 493-498.

Integrated effects of nutrition-related, physical, and social factors on frailty among community-dwelling older adults: A 7-year follow-up from the Kashiwa cohort study.

AIM: To investigate the impact of nutrition-related, physical, and social factors as well as their transitions on frailty over a 7-year follow-up period among community-dwelling older adults. METHODS: Participants were 868 non-frail older adults. Frailty was assessed using the Cardiovascular Health Study index. Nutrition-related, physical, and social factors have been defined in our previous study. Cox regression analysis was conducted to investigate the association between the three factors at baseline and new-onset frailty during a 7-year follow-up period. Furthermore, transitions in the three factors over two/three consecutive years and their association with frailty were investigated using lagged generalized estimating equations. RESULTS: The mean age was 73.8 ± 4.8 years (women, 47.0%), and the incidence of frailty was 12.5% during the 7-year follow-up period. Compared with participants who met the three factors' criteria at baseline, those who met two, one, and none showed associations with greater adjusted hazard ratios of new-onset frailty (1.73, 95% confidence interval 0.87-3.42; 2.04 [1.01-4.12]; and 5.69 [2.82-11.47]). Generalized estimating equation analysis showed that, compared with older adults who maintained all the three criteria met, those who improved the quantity of criteria met, who maintained the less than three criteria met, and who decreased the quantity of criteria met showed (marginally) significant associations with greater adjusted odds ratios of frailty (2.86 [0.88-9.31], 3.70 [1.10-12.45], and 4.75 [1.42-15.85]). CONCLUSIONS: Practicing and maintaining all three factors in daily life are crucial for frailty prevention. Future research should explore strategies to motivate behavioral modifications in these factors at the population level. Geriatr Gerontol Int 2024; 24: 162-169.

Precise microbiome engineering using natural and synthetic bacteriophages targeting an artificial bacterial consortium.

In natural microbiomes, microorganisms interact with each other and exhibit diverse functions. Microbiome engineering, which enables bacterial knockdown, is a promising method to elucidate the functions of targeted bacteria in microbiomes. However, few methods to selectively kill target microorganisms in the microbiome without affecting the growth of nontarget microorganisms are available. In this study, we focused on the host-specific lytic ability of virulent phages and validated their potency for precise microbiome engineering. In an artificial microbiome consisting of Escherichia coli, Pseudomonas putida, Bacillus subtilis, and Lactiplantibacillus plantarum, the addition of bacteriophages infecting their respective host strains specifically reduced the number of these bacteria more than 102 orders. Remarkably, the reduction in target bacteria did not affect the growth of nontarget bacteria, indicating that bacteriophages were effective tools for precise microbiome engineering. Moreover, a virulent derivative of the λ phage was synthesized from prophage DNA in the genome of λ lysogen by in vivo DNA assembly and phage-rebooting techniques, and E. coli-targeted microbiome engineering was achieved. These results propose a novel approach for precise microbiome engineering using bacteriophages, in which virulent phages are synthesized from prophage DNA in lysogenic strains without isolating phages from environmental samples.