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Impact of a Mindfulness Mobile Application on Weight Loss and Eating Behavior in People with Metabolic Syndrome: a Pilot Randomized Controlled Trial.
Matsuhisa, T, Fujie, R, Masukawa, R, Nakamura, N, Mori, N, Ito, K, Yoshikawa, Y, Okazaki, K, Sato, J
International journal of behavioral medicine. 2024;(2):202-214
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Abstract
BACKGROUND Weight-loss approaches involving mindfulness have been reported to reduce overeating behavior. We conducted a preliminary evaluation of the feasibility and effectiveness of a mindfulness mobile application (MMA) combined with a comprehensive lifestyle intervention (CLI) focused on weight loss and eating behaviors for people with metabolic syndrome based on post-intervention follow-up data. METHOD Participants were randomly assigned (1:1) to a CLI group or a CLI + MMA group. Participants received weekly CLI for 13 weeks, followed by telephone counseling for 13 weeks. The CLI + MMA group also had access to the MMA. Feasibility was assessed by the number of people who refused to participate, rate of adherence to the MMA, follow-up rate, and participant satisfaction. The preliminary endpoint was weight change (at 26 weeks). Participants completed the Dutch Eating Behavior Questionnaire (DEBQ). A mixed linear model was used for efficacy analysis. RESULTS Eight of the 40 participants declined to participate. The MMA was used 4.4 ± 1.7 days per week, but the rate of adherence declined over time. The follow-up rate was 100%, and there was no difference in participant satisfaction between the groups. There was no significant group-by-time interaction for weight loss (p = 0.924), but there was a significant interaction for the DEBQ restrained eating score (p = 0.033). CONCLUSIONS This study found that CLI plus MMA was highly feasible and moderately acceptable. There were no significant differences in weight loss between the groups, but the CLI + MMA group showed an increase in restrained eating. Further large-scale studies are needed. TRIAL REGISTRATION Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000042626.
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Expression analysis of zinc-metabolizing enzymes in the saliva as a new method of evaluating zinc content in the body: two case reports and a review of the literature.
Sakata, KI, Hashimoto, A, Kambe, T, Sato, J, Ohga, N, Yamazaki, Y, Koyachi, M, Tatsuki, I, Okada, M, Taro, O, et al
Journal of medical case reports. 2024;(1):198
Abstract
BACKGROUND The activity level of alkaline phosphatase, a zinc-requiring enzyme in the serum, is used to indicate zinc nutritional status; however, it does not correlate with serum zinc levels or subjective symptoms of taste disorder in many cases. Hence, this study focused on the total activity of alkaline phosphatase, a zinc-requiring enzyme. The total alkaline phosphatasa activity level in the saliva was measured before and after zinc supplementation, and the results were compared with serum zinc levels. CASE PRESENTATION This study included patients with hypozincemia, specifically a patient with zinc-deficient taste disorder (patient 1: a 69-year-old Japanese woman) and a patient with glossodynia with zinc deficiency (patient 2: an 82-year-old Japanese woman). Saliva samples were collected, and blood tests were performed before and after zinc supplementation. Subjective symptoms and serum zinc levels were simultaneously evaluated. Zinc supplementation was performed using zinc acetate hydrate or Polaprezinc. CONCLUSIONS Total alkaline phosphatase activity levels were found to be associated with serum zinc levels and subjective symptoms. A further study with a higher number of patients is necessary to confirm whether total alkaline phosphatase activity levels more accurately reflect the amounts of zinc in the body than serum zinc levels.
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Relationship Between SGLT2 Inhibitors and Hemoglobin Levels: A Retrospective Observational Study.
Yoshida, Y, Takahashi, K, Hashimoto, R, Oya, T, Sato, J
In vivo (Athens, Greece). 2023;(5):2327-2333
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Abstract
BACKGROUND/AIM: Diabetes mellitus is a risk for subsequent nephrogenic anemia due to accelerated decline in renal function, and the global diabetic population continues to grow exponentially. In clinical studies, sodium-glucose co-transporter 2 (SGLT2) inhibitors, one of the drugs used to treat diabetes, have recently attracted attention as anemia suppressors, but there is still lack of evidence on this matter. The present study aimed to investigate the effects of SGLT2 inhibitor administration on anemia suppression using hemoglobin (Hb) levels as an indicator. PATIENTS AND METHODS We conducted a longitudinal study to evaluate and compare the changes in Hb levels in diabetes patients treated with SGLT2 inhibitors (n=48) and those treated with DPP-4 inhibitors (n=48). Study participants were stratified into sub-cohorts based on sex, and the Hb level trajectory in the participants was observed for 90 days. RESULTS We evaluated the use of SGLT2 inhibitors as a prophylactic factor for the decline in Hb levels and compared it to that of DPP-4 inhibitors [odds ratio (OR)=3.40, 95% confidence interval (CI)=1.93-6.00]. Administration of SGLT2 inhibitors and DPP-4 inhibitors resulted in decline of 14.4±0.34 and 12.4±0.31 g/dl (p<0.001), respectively, in male Hb levels from baseline to 90 days. Notably, the prophylactic effect of SGLT2 inhibitors on the reduction in Hb levels was independent of renal function and sex. CONCLUSION SGLT2 inhibitors prevent the reduction in Hb levels and exhibit anti-anemic effects.
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Efficacy and safety of bone management agents administered at 12 weeks vs. 4 weeks in patients with bone metastases: A systematic review.
Sato, J, Kodaira, M, Harada, H, Iguchi, H, Yoshida, T, Shibata, H, ,
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2023;:10781552231203720
Abstract
BACKGROUND Bone modifying agents (BMAs) have been used to prevent skeletal-related events (SRE) in cancer patients with bone metastases. In this meta-analysis, efficacy and adverse events (AEs) were studied based on a de-escalation strategy in which the BMA dosing interval was prolonged from 4 to 12 weeks. METHODS PubMed, Cochrane, ICHUSHI, and CINAHL were searched for articles on BMA dosing intervals from outcomes measured were the incidence of SRE and related various AEs. A quantitative meta-analysis was performed using a random-effects model to calculate relative risk ratios (RRs) and 95% confidence intervals (CIs). RESULT The meta-analysis included three randomized controlled studies (RCTs) of Zoledronic acid hydrate (ZA) (n = 2663) and six RCTs (n = 141) on BMA other than ZA. There was no difference in the incidence of SREs when comparing the dosing frequency of 12 versus 4 weeks for BMA (RR = 1.21, 95% CI [0.82-1.78], p = 0.33). Further, AEs related to treatment discontinuation were significantly less frequent with ZA given every 12 weeks than when given every 4 weeks (RR = 0.51 [0.30-0.89], p = 0.02). In particular, renal dysfunction leading to grade ≥3 or discontinuation of treatment with ZA occurred significantly less frequently with every 12-week dosing (RR = 0.33 [0.12-0.91], p = 0.33). CONCLUSION This meta-analysis showed no influence of BMA de-escalation on the incidence of SRE; nevertheless, AEs appeared to reduce with the de-escalated usage of ZA.
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Phase Ib/II Study of a Liposomal Formulation of Eribulin (E7389-LF) plus Nivolumab in Patients with Advanced Solid Tumors: Results from Phase Ib.
Ida, H, Shimizu, T, Nishino, M, Nakamura, Y, Yazaki, S, Katsuya, Y, Sato, J, Koyama, T, Iwasa, S, Sudo, K, et al
Cancer research communications. 2023;(7):1189-1199
Abstract
PURPOSE To determine a recommended dose of liposomal eribulin (E7389-LF) in combination with nivolumab in patients with advanced solid tumors, and to evaluate the safety, efficacy, pharmacokinetics, and biomarker impact of this regimen. EXPERIMENTAL DESIGN Japanese patients with advanced, nonresectable, or recurrent solid tumors and no existing alternative standard/effective therapy (except nivolumab monotherapy) were assigned to either E7389-LF 1.7 mg/m2 plus nivolumab 360 mg every 3 weeks, E7389-LF 2.1 mg/m2 plus nivolumab 360 mg every 3 weeks, E7389-LF 1.1 mg/m2 plus nivolumab 240 mg every 2 weeks, or E7389-LF 1.4 mg/m2 plus nivolumab 240 mg every 2 weeks. Primary objectives were to evaluate the safety/tolerability of each dose cohort and to determine the recommended phase II dose (RP2D). Secondary/exploratory objectives, including safety [dose-limiting toxicities (DLT) and adverse events (AE)], pharmacokinetics, efficacy [including objective response rate (ORR)], and biomarker results were used in determining the RP2D. RESULTS Twenty-five patients were enrolled to treatment [E7389-LF 1.7 mg/mg2 every 3 weeks (n = 6), E7389-LF 2.1 mg/m2 every 3 weeks (n = 6), E7389-LF 1.1 mg/m2 every 2 weeks (n = 7), E7389-LF 1.4 mg/m2 every 2 weeks (n = 6)]. Twenty-four patients were evaluated for DLTs, of whom 3 had DLTs (1 at E7389-LF 1.7 mg/m2 every 3 weeks, 1 at 1.1 mg/m2 every 2 weeks, and 1 at 1.4 mg/m2 every 2 weeks). All patients had ≥1 treatment-related treatment-emergent AE (TEAE); 68.0% had ≥1 grade 3-4 treatment-related TEAE. Changes in vasculature and IFN-related biomarkers were seen in each cohort. The overall ORR was 16%. CONCLUSIONS E7389-LF plus nivolumab was tolerable overall; the recommended dose for future study was 2.1 mg/m2 plus nivolumab 360 mg every 3 weeks. SIGNIFICANCE This phase Ib part of a phase Ib/II study assessed the tolerability and activity of a liposomal formulation of eribulin (E7389-LF) plus nivolumab in 25 patients with advanced solid tumors. The combination was tolerable overall; 4 patients had a partial response. Vasculature and immune-related biomarker levels increased, suggesting vascular remodeling.
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Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men.
Igarashi, M, Nakagawa-Nagahama, Y, Miura, M, Kashiwabara, K, Yaku, K, Sawada, M, Sekine, R, Fukamizu, Y, Sato, T, Sakurai, T, et al
npj aging. 2022;(1):5
Abstract
Preclinical studies have revealed that the elevation of nicotinamide adenine dinucleotide (NAD + ) upon the administration of nicotinamide mononucleotide (NMN), an NAD + precursor, can mitigate aging-related disorders; however, human data on this are limited. We investigated whether the chronic oral supplementation of NMN can elevate blood NAD + levels and alter physiological dysfunctions in healthy older participants. We administered 250 mg NMN per day to aged men for 6 or 12 weeks in a placebo-controlled, randomized, double-blind, parallel-group trial. Chronic NMN supplementation was well tolerated and caused no significant deleterious effect. Metabolomic analysis of whole blood samples demonstrated that oral NMN supplementation significantly increased the NAD + and NAD + metabolite concentrations. There were nominally significant improvements in gait speed and performance in the left grip test, which should be validated in larger studies; however, NMN exerted no significant effect on body composition. Therefore, chronic oral NMN supplementation can be an efficient NAD + booster for preventing aging-related muscle dysfunctions in humans.
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Intake of mother's milk by very-low-birth-weight infants and variation in DNA methylation of genes involved in neurodevelopment at 5.5 years of age.
Xu, J, Shin, J, McGee, M, Unger, S, Bando, N, Sato, J, Vandewouw, M, Patel, Y, Branson, HM, Paus, T, et al
The American journal of clinical nutrition. 2022;(4):1038-1048
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BACKGROUND Mechanisms responsible for associations between intake of mother's milk in very-low-birth-weight (VLBW, <1500 g) infants and later neurodevelopment are poorly understood. It is proposed that early nutrition may affect neurodevelopmental pathways by altering gene expression through epigenetic modification. Variation in DNA methylation (DNAm) at cytosine-guanine dinucleotides (CpGs) is a commonly studied epigenetic modification. OBJECTIVES We aimed to assess whether early mother's milk intake by VLBW infants is associated with variations in DNAm at 5.5 y, and whether these variations correlate with neurodevelopmental phenotypes. METHODS This cohort study was a 5.5-y follow-up (2016-2018) of VLBW infants born in Ontario, Canada who participated in the Donor Milk for Improved Neurodevelopmental Outcomes trial. We performed an epigenome-wide association study (EWAS) to test whether percentage mother's milk (not including supplemental donor milk) during hospitalization was associated with DNAm in buccal cells during early childhood (n = 143; mean ± SD age: 5.7 ± 0.2 y; birth weight: 1008 ± 517 g). DNAm was assessed with the Illumina Infinium MethylationEPIC array at 814,583 CpGs. In secondary analyses, we tested associations between top-ranked CpGs and measures of early childhood neurodevelopment, e.g., total surface area of the cerebral cortex (n = 41, MRI) and Full-Scale IQ (n = 133, Wechsler Preschool and Primary Scale of Intelligence-IV). RESULTS EWAS analysis demonstrated percentage mother's milk intake by VLBW infants during hospitalization was associated with DNAm at 2 CpGs, cg03744440 [myosin XVB (MYO15B)] and cg00851389 [metallothionein 1A (MT1A)], at 5.5 y (P < 9E-08). Gene set enrichment analysis indicated that top-ranked CpGs (P < 0.001) were annotated to genes enriched in neurodevelopmental biological processes. Corroborating these findings, DNAm at several top identified CpGs from the EWAS was associated with cortical surface area and IQ at 5.5 y (P < 0.05). CONCLUSIONS In-hospital percentage mother's milk intake by VLBW infants was associated with variations in DNAm of neurodevelopmental genes at 5.5 y; some of these DNAm variations are associated with brain structure and IQ.This trial was registered at isrctn.com as ISRCTN35317141 and at clinicaltrials.gov as NCT02759809.
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Dose Escalation Data from the Phase 1 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Japanese Patients with Advanced Solid Tumors.
Sato, J, Shimizu, T, Koyama, T, Iwasa, S, Shimomura, A, Kondo, S, Kitano, S, Yonemori, K, Fujiwara, Y, Tamura, K, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2022;(9):1783-1791
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PURPOSE We report the dose-escalation part of a phase I study of liposomal eribulin (E7389-LF) in Japanese patients with advanced solid tumors and no alternative standard therapy. PATIENTS AND METHODS Patients ≥20 years old were enrolled. E7389-LF doses of 1.0 to 1.5 mg/m2 once every two weeks (Q2W) or 1.0 to 2.5 mg/m2 once every three weeks (Q3W) were planned. The primary objective was to determine the MTD by evaluating dose-limiting toxicities (DLT). Secondary objectives included safety/tolerability assessments, objective response rate (ORR), and progression-free survival; serum biomarker assessment was an exploratory objective. RESULTS Twenty-one patients were enrolled and treated; 12 in the Q3W group (1.0 mg/m2, n = 3; 1.5 mg/m2, n = 3; 2.0 mg/m2, n = 6) and 9 in the Q2W group (1.0 mg/m2, n=3; 1.5 mg/m2, n = 6). The Q3W and Q2W MTDs were 2.0 mg/m2 and 1.5 mg/m2, respectively. One patient receiving 2.0 mg/m2 Q3W had a DLT of grade 3 febrile neutropenia. The most common grade 3 treatment-emergent adverse events were neutropenia (66.7% in Q3W and Q2W) and leukopenia (Q3W, 58.3%; Q2W, 33.3%). One patient in the Q3W group (2.0 mg/m2) and 3 in the Q2W group (1.0 mg/m2, n = 1; 1.5 mg/m2, n = 2) achieved a partial response [overall ORR, 19.0%; 95% confidence interval (CI), 5.4-41.9]. Endothelial [TEK receptor tyrosine kinase (TEK), intercellular adhesion molecule 1 (ICAM1), vascular endothelial growth factor receptor 3 (VEGFR3), platelet/endothelial cell adhesion molecule 1 (PECAM1)], vasculature (collagen IV), and immune-related [interferon gamma (IFNγ), C-X-C motif chemokine ligand 11 (CXCL11), C-X-C motif chemokine ligand 10 (CXCL10)] biomarker levels were increased. CONCLUSIONS E7389-LF was well tolerated at 2.0 mg/m2 Q3W and 1.5 mg/m2 Q2W. Considering the toxicity profile of both regimens, the recommended dose was 2.0 mg/m2 Q3W. Expansion cohorts are ongoing.
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Social-emotional functioning and dietary intake among children born with a very low birth weight.
Walton, K, McGee, M, Sato, J, Law, N, Hopperton, KE, Bando, N, Kiss, A, Unger, SL, O'Connor, DL
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2022;(7):737-748
Abstract
Very low birth weight (VLBW, <1500 g) infants are at an elevated risk of neurodevelopmental disorders, later obesity and cardiometabolic disease; if and how neurodevelopmental disorders impact chronic disease risk is poorly understood. The most common neurodevelopmental disorders experienced by VLBW children are those of social-emotional functioning. We compared dietary patterns and body composition between VLBW children with poor vs. typical social-emotional functioning using linear mixed models adjusted for sex, gestational age, cognitive impairment, parental education, and body mass index (BMI). VLBW children (n=158) attending the Donor Milk for Improved Neurodevelopmental Outcomes trial with 5.5-year follow-up participated. Poor social-emotional functioning was based on standardized parent-rated questionnaires and/or parent-reported physician diagnosis of autism spectrum or attention-deficit/hyperactivity disorders. Most children had diets categorized as "needs improvement" (67%) or "poor" (27%) and 29% of children exhibited poor social-emotional functioning. Poor social-emotional functioning was positively associated with 100% fruit juice (β=0.3 cup equivalents/day; 95% CI 0.1, 0.5) and energy intake (β=118.1 kcal/day; 95% CI 0.9, 235.2). Children with poor social-emotional functioning were more likely to have a limited food repertoire (p=0.02), but less likely to exceed dietary fat recommendations (p=0.04). No differences in overall diet quality or body composition were observed. Diet counselling and research are essential to improving the nutrition of VLBW children to mitigate chronic disease risk. Trial registration - Optimizing Mothers' Milk for Preterm Infants Program of Research: Study 1 - Impact of Donor Milk at Kindergarten, NCT02759809, https://clinicaltrials.gov/ct2/show/NCT02759809. Novelty: Overall diet quality and body composition did not differ between VLBW children with poor vs. typical social-emotional functioning. Most had diets "needing improvement" or "poor" according to the Healthy Eating Index-2010. Diet counselling may help mitigate chronic disease risk in this vulnerable population.
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First-in-Human Phase 1 Study of MORAb-202, an Antibody-Drug Conjugate Comprising Farletuzumab Linked to Eribulin Mesylate, in Patients with Folate Receptor-α-Positive Advanced Solid Tumors.
Shimizu, T, Fujiwara, Y, Yonemori, K, Koyama, T, Sato, J, Tamura, K, Shimomura, A, Ikezawa, H, Nomoto, M, Furuuchi, K, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021;(14):3905-3915
Abstract
PURPOSE MORAb-202, an antibody-drug conjugate containing farletuzumab and eribulin with a cathepsin-B cleavable linker, targets folate receptor α (FRα)-expressing tumor cells. The primary objective of this first-in-human study was to evaluate the safety and tolerability of MORAb-202 in patients with solid tumors. PATIENTS AND METHODS Patients ≥20 years with adequate organ function and FRα-positive solid tumors who failed to respond to standard therapy were eligible. Patients received MORAb-202 intravenously at doses of 0.3 to 1.2 mg/kg once every three weeks. Endpoints included dose-limiting toxicities, safety, tumor responses, pharmacokinetics, and pharmacodynamics. TRIAL REGISTRATION NUMBER NCT03386942 (ClinicalTrials.gov). RESULTS Between November 28, 2017 and June 4, 2019, 22 patients (median age, 58.0 years) with advanced solid tumors were enrolled. Treatment-emergent adverse events occurred in 21 (95%) patients, with leukopenia and neutropenia in 10 (45%) patients each. One patient (0.9 mg/kg cohort) experienced two grade 3 dose-limiting toxicities: serum alanine aminotransferase and γ-glutamyl transferase increases. Following review by an independent adjudication committee, grade 1/2 interstitial lung disease thought to be related to MORAb-202 was identified in five (23%) patients. Complete response, partial response, and stable disease were observed in one, nine, and eight patients, respectively. The normalized predose serum FRα tended to be positively correlated with the maximum tumor shrinkage (R 2 = 0.2379; P = 0.0291). CONCLUSIONS The MTD of MORAb-202 was not reached. MORAb-202 demonstrated promising antitumor activity in FRα-positive solid tumors and was generally well-tolerated at the tested doses. Further investigations are required to establish appropriate dosage and clinical utility of MORAb-202.