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Abstract: The hydrothermal synthesis of anatase-type TiO2 films on Ti and Ti–Nb substrates was examined with a focus on crystallinity and surface morphology of the films. The substrates were chemically treated with H2O2/HCl or H2O2/HNO3 solution to prepare amorphous-like TiO2. The hydrothermal treatment of the resultant films was performed in an autoclave with deionized water or NH3 aqueous solution. The synthesized anatase-type TiO2 films showed high crystallinity and rectangular morphology. The (Ti, Nb)O2 film could be obtained by using Ti–Nb alloys as substrates. [Copyright &y& Elsevier]

Purpose: To investigate the association between comorbidities associated with diabetes and higher-level functional status as well as the relationship between comorbidities associated with diabetes and higher-level functional status in older patients with type 2 diabetes mellitus who have better social networks., Methods: Participants were outpatients with type 2 diabetes aged ≥ 65 years, excluding individuals with severe cardiovascular or respiratory illness, hyperglycaemic crisis, type 1 diabetes, or diabetic foot. The Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) was used to evaluate the higher-level functional status. A TMIG-IC score of ≤ 9, instrumental activities of daily living (IADL) ≤ 4, intellectual activity or social role ≤ 3 were defined as decline in higher-level functional status. The comorbidities investigated included peripheral neuropathy, retinopathy, nephropathy, cognitive impairment, depression, frailty, sarcopenia, low muscle strength, stroke, heart disease, and arthritis., Results: The analysis included 198 patients (mean age 75.9 ± 5.7 years, male 60.1%). After adjusting for potential confounders, depression was associated with TMIG-IC (Prevalence ratio (PR) 2.34, 95% confidence interval (CI) 1.44-3.82), low muscle strength was associated with IADL (PR 2.85, 95% CI 1.30-6.27), and frailty was associated with intellectual activity (PR 1.38, 95% CI 1.10-1.74). In the model with social networks added as a confounder, the relationship between depression or low muscle strength and higher-level functional status was not statistically significant., Conclusion: Comorbidities of depression and low muscle strength for older patients with type 2 diabetes mellitus increase the risk of malfunctioning of higher-level functional status. Increased interactions with family, friends and neighbours may reduce this event., (© 2024. The Author(s).)

Abstract: 99m Tc-3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) scintigraphy and 99m Tc-pyrophosphate (PYP) scintigraphy are highly sensitive modalities for imaging both myocardial and extracardiac amyloid transthyretin in patients with wild-type transthyretin (ATTRwt) amyloidosis. "Loss of bone signal" on planar imaging of 99m Tc-DPD scintigraphy, in which the tracer uptake in bone is obscured by marked tracer uptake in the overlying skeletal muscles, is reported. However, this phenomenon has not yet been documented on 99m Tc-PYP scintigraphy. We describe an 89-year-old woman with ATTRwt amyloidosis in whom "loss of bone signal" together with marked tracer uptake into the skeletal muscles was clearly demonstrated on 99m Tc-PYP scan., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims/hypothesis: Fatty acid-binding protein 4 (FABP4) has been reported to act as a hepatic insulin resistance factor. We previously reported that fasting FABP4 was correlated with insulin resistance measurements derived from the glucose clamp, and another study reported that postprandial FABP4 levels were decreased in healthy volunteers but were not reported (or known) in participants with type 2 diabetes. We have limited knowledge about the direct effect of FABP4 on muscle cells. We investigated the postprandial FABP4 levels in participants with type 2 diabetes, and the basic mechanism of muscle insulin resistance and FABP4., Methods: We performed a meal tolerance test and hyperinsulinaemic-euglycaemic clamp in 22 participants with type 2 diabetes and 26 participants without diabetes. We measured fasting and postprandial serum FABP4. We cultured mouse C2C12 muscle cells, and investigated the effect of FABP4 on glucose uptake. We analysed insulin signalling by western blot and insulin binding assay., Results: The postprandial FABP4 level in participants with type 2 diabetes was higher than that in participants without diabetes. Participants without diabetes had lower postprandial FABP4 than fasting except for one participant, whereas one-third of participants with type 2 diabetes had higher postprandial FABP4 than fasting. Postprandial FABP4 was correlated with the muscle insulin resistance M/I value from a glucose clamp in participants without diabetes (r=-0.42, p<0.05). The increase in FABP4 after a meal correlated with the muscle insulin resistance M/I value (r=-0.44, p<0.05) and the difference between fasting and postprandial glucagon in participants with type 2 diabetes (r=0.36, p<0.05). FABP4 alone appears to increase glucose uptake, and the combination of FABP4 and insulin decreases glucose uptake when compared with insulin alone. FABP4 inhibits insulin signalling of muscle cells through decreases in phosphorylation of insulin receptor substrate 1 and Akt. The physiological concentration of FABP4 did not inhibit insulin binding to muscle cells., Conclusions/interpretation: These results suggested that the postprandial FABP4 level is associated with insulin resistance, and FABP4 may suppress insulin signals., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Epidemiological studies have reported that Asian dust (AD), a type of desert dust, has harmful effects on human health. This study aimed to examine the association between AD exposure and hospitalization due to pneumonia. Data on patients in Western Japan admitted for pneumonia were included from a real-world database derived from electronic medical records. We used the meteorological observatory data of the most populous city in each prefecture, in which AD event was defined as a loss of visibility from a distance ≤10 km. A case-crossover design and conditional logistic regression model were used. Overall, 12 938 patients were included, and AD exposure events were observed for 557 days. Exposure to an AD event five days prior to hospitalization was significantly associated with hospitalization for pneumonia after adjusting for weather variables (odds ratio = 1.17; 95% confidence interval = [1.01, 1.36]). These findings suggest that AD exposure is associated with an increased rate of admission for pneumonia in Western Japan., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Percutaneous coronary intervention (PCI) for lesions with eruptive calcified nodules (CNs) is associated with worse outcomes compared with that for other calcified lesions. We aimed to clarify the relationship between eruptive CNs at index PCI, optical coherence tomography (OCT) findings at the 8-month follow-up, and clinical outcomes using serial OCT., Methods: This retrospective observational study used data from a prospective, single-centre registry. We conducted consecutive PCI for calcified lesions requiring rotational atherectomy (RA) with OCT guidance. We categorized 51 patients (54 lesions) into those with (16 patients [16 lesions]) and without eruptive CNs (35 patients [38 lesions])., Results: Post-PCI, stent expansion was comparable between the 2 groups, and CN-like protrusion was found in 75% of lesions with eruptive CNs. Follow-up OCT at 8 months revealed in-stent CNs in 54% of treated eruptive CN lesions, whereas lesions without eruptive CNs lacked in-stent CNs. Multivariate linear regression analysis demonstrated that eruptive CN was associated with maximum neointimal tissue (NIT) thickness (regression coefficient 0.303; 95% confidence interval, 0.057-0.549; P = 0.02). Consequently, patients with eruptive CNs exhibited a higher clinically driven target lesion revascularization (TLR) rate than did those without at 1 year (31.3% vs 2.9%, P = 0.009) and 5 years (43.8% vs 11.4%, P = 0.02). TLR primarily occurred in lesions with maximum eruptive CN arc angles > 180°., Conclusions: Following RA treatment with acceptable stent expansion, eruptive CNs before PCI correlated with greater NIT formation with in-stent CNs, resulting in a higher TLR rate, particularly in lesions with maximum eruptive CN arc angles exceeding 180°., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Lactononadecapeptide (LNDP; NIPPLTQTPVVVPPFLQPE), a casein-derived peptide comprising 19 residues, is known for its capacity to enhance cognitive function. This study aimed to explore the transepithelial transport and stability of LNDP. Results showed that LNDP retained over 90% stability after 2 h of treatment with gastrointestinal enzymes. The stability of LNDP on Caco-2 cell monolayers ranged from 93.4% ± 0.9% to 101.1% ± 1.2% over a period of 15-60 min, with no significant differences at each time point. The permeability of LNDP across an artificial lipid membrane was very low with the effective permeability of 3.6 × 10 -11 cm/s. The Caco-2 assay demonstrated that LNDP could traverse the intestinal epithelium, with an apparent permeability of 1.22 × 10 -6 cm/s. Its transport was significantly inhibited to 67.9% ± 5.0% of the control by Gly-Pro, a competitor of peptide transporter 1 (PEPT1). Furthermore, PEPT1 knockdown using siRNA significantly inhibited LNDP transport by 77.6% ± 1.9% in Caco-2 cell monolayers. The LNDP uptake in PEPT1-expressing HEK293 cells was significantly higher (54.5% ± 14.6%) than that in mock cells. These findings suggest that PEPT1 plays a crucial role in LNDP transport, and LNDP exhibits good resistance to gastrointestinal enzymes.

To assess the pharmacologically relevant and selective muscarinic receptor occupancy in the bladder mucosa, we considered not only plasma drug concentrations but also urinary drug concentrations. The purpose of this study was to predict muscarinic receptor occupancy in the human bladder mucosa based on urinary concentrations in response to clinical dosages of antimuscarinic agents used to treat overactive bladder. The calculated mean plasma or serum unbound steady state concentrations were 0.06-11 nM in clinical dosages of five antimuscarinic agents. Urinary concentrations calculated from the mean plasma or serum and renal clearance ranged between 19 nM and 2 μM, which were >10-fold higher than the K i values for bladder muscarinic receptors excluding propiverine. Bladder mucosal muscarinic receptor occupancy estimated from the urinary concentrations and the K i values was >90 % at a steady state in clinical dosages of five antimuscarinic agents. The bladder muscarinic receptor occupancy was higher than that in the parotid gland calculated based on the mean plasma or serum unbound concentrations and K i values for muscarinic receptors in the parotid gland. These results suggest that sufficient and selective muscarinic receptor occupancy by antimuscarinic agents, to exert pharmacological effects, in the bladder mucosa can be predicted using urinary concentrations., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (© 2024 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background/aim: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells., Materials and Methods: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of α-smooth muscle actin (α-SMA), senescence-associated β-galactosidase (SA-β-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets., Results: IGC cells significantly induced α-SMA+ myCAFs by secreting transforming growth factor-β, whereas DGC cells induced SA-β-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients., Conclusion: sCAFs promote peritoneal metastasis of DGC via IL-8-mediated crosstalk., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Weight loss following vertical sleeve gastrectomy (VSG) in youth can range from 10% to 50%. We examined whether there are differences in demographic or metabolic parameters before VSG in youth who achieve above-average weight loss (AAWL) versus below-average weight loss (BAWL) at 1 year post VSG and if youth with BAWL still achieve metabolic health improvements at 1 year post VSG., Methods: Demographic, anthropometric, and clinical lab data were collected before VSG and at 1, 3, 6, and 12 months after VSG., Results: Forty-three youth with a mean age of 16.9 (SD 1.7) years before VSG were studied; 70% were female, 19% non-Hispanic Black, 58% non-Hispanic White, and 23% mixed/other race. Mean baseline BMI was 51.1 (SD 10.5) kg/m 2 . Average weight loss was 25.8%. The AAWL group lost 18.6 kg/m 2 (35.3%) versus the BAWL group, who lost 8.8 kg/m 2 (17.5%). BMI, age, race, sex, and socioeconomic status at baseline were similar between AAWL and BAWL groups; however, the BAWL group had a higher frequency of pre-VSG dysglycemia, steatotic liver disease, and dyslipidemia. At 1 year post VSG, fewer youth in the BAWL group achieved ideal health parameters, and they had less resolution of comorbidities., Conclusions: The presence of comorbidities before VSG is associated with less weight loss and reduced resolution of metabolic conditions at 1 year post VSG., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

In patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), the uptake of the tracer on technetium-99m-labeled pyrophosphate ( 99m Tc-PYP) scintigraphy, which indicates amyloid transthyretin (ATTR) per se, is often observed in skeletal muscles, such as the abdominal oblique and gluteal muscles. Among extracardiac biopsies for confirming ATTR deposition in ATTRwt-CA, a 99m Tc-PYP imaging-based computed tomography (CT)-guided core needle biopsy of the internal oblique muscle has relatively high sensitivity. In some patients, the 99m Tc-PYP uptake is more pronounced in the gluteal muscles than in oblique muscles. We herein report two cases of ATTRwt-CA in which a CT-guided biopsy of the gluteus medius muscle with 99m Tc-PYP uptake confirmed the presence of ATTR deposits.

We herein report an 80-year-old man showing a downsloping TP segment together with an increase in the height of the T wave in the precordial leads on a standard 12-lead electrocardiogram (ECG). Separately, an 87-year-old woman showed only a downsloping TP segment in the precordial leads on a standard 12-lead ECG. Neither patient reported chest pain or dyspnea when ECGs was obtained. This downsloping TP segment in the precordial leads on the standard 12-lead ECG is thought to be due to a cardiac impulse-tapping artifact. Differential diagnoses are also discussed.

The 12-lead electrocardiographic findings in hypothermia include the presence of J waves; prolongation of the PR, QRS, and QT intervals; and atrial and ventricular dysrhythmias. Among these findings, the J wave, known as the Osborn wave, is considered pathognomonic. In 1953, the J wave was reported as a specific response to hypothermia in dogs, representing the current at the site of injury instead of a widening of the QRS complex that occurs caused by a conduction delay. The J wave is often accompanied by ventricular fibrillation. For the past 28 years, it was assumed that the hypothermia-induced J wave was mediated by the transient outward current. However, it was recently been reported that the J waves in some patients with hypothermia can be considered delayed conduction-related waveforms. Here, we present a case of hypothermia-induced J waves together with giant R waves, which have not been previously reported during hypothermia, augmented by short RR intervals arising from premature atrial contractions. Our observations indicate that the underlying mechanism for the genesis of J waves is indeed conduction delay and not transient outward currents., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Takahashi et al.)

Paramyxo- and filovirus genomes are equipped with bipartite promoters at their 3 ' ends to initiate RNA synthesis. The two elements, the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2), are separated by a spacer region that must be precisely a multiple of 6 nucleotides (nts), indicating these viruses adhere to the "rule of six." However, our knowledge of PE2 has been limited to a narrow spectrum of virus species. In this study, a comparative analysis of 1,647 paramyxoviral genomes from a public database revealed that the paramyxovirus PE2 can be clearly categorized into two distinct subcategories: one marked by C repeats at every six bases (exclusive to the subfamily Orthoparamyxovirinae ) and another characterized by CG repeats every 6 nts (observed in the subfamilies Avulavirinae and Rubulavirinae ). This unique pattern collectively mirrors the evolutionary lineage of these subfamilies. Furthermore, we showed that PE2 of the Rubulavirinae , with the exception of mumps virus, serves as part of the gene-coding region. This may be due to the fact that the Rubulavirinae are the only paramyxoviruses that cannot propagate without RNA editing. Filoviruses have three to eight consecutive uracil repeats every six bases (UN 5 ) in PE2, which is located in the 3 ' end region of the genome. We obtained PE2 sequences from 2,195 filoviruses in a public database and analyzed the sequence conservation among virus species. Our results indicate that the continuity of UN 5 hexamers is consistently maintained with a high degree of conservation across virus species., Importance: The genomic intricacies of paramyxo- and filoviruses are highlighted by the bipartite promoters-promoter element 1 (PE1) and promoter element 2 (PE2)-at their 3 ' termini. The spacer region between these elements follows the "rule of six," crucial for genome replication. By a comprehensive analysis of paramyxoviral genome sequences, we identified distinct subcategories of PE2 based on C and CG repeats that were specific to Orthoparamyxovirinae and Avulavirinae / Rubulavirinae , respectively, mirroring their evolutionary lineages. Notably, the PE2 of Rubulavirinae is integrated into the gene-coding region, a unique trait potentially linked to its strict dependence on RNA editing for virus growth. This study also focused on the PE2 sequences in filovirus genomes. The strict conservation of the continuity of UN 5 among virus species emphasizes its crucial role in viral genome replication., Competing Interests: The authors declare no conflict of interest.

Receptor occupancy is an indicator of antipsychotic efficacy and safety. It is desirable to simultaneously determine the occupancy of multiple brain receptors as an indicator of the efficacy and central side effects of antipsychotics because many of these drugs have binding affinities for various receptors, such as dopamine 2 (D 2 ), histamine 1 (H 1 ), and muscarinic acetylcholine (mACh) receptors. The purpose of this study was to develop a method for the simultaneous measurement of multiple receptor occupancies in the brain by the simultaneous quantification of unlabeled tracer levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rats were pre-administered with a vehicle, displacer, or olanzapine, and mixed solutions of raclopride, doxepin, and 3-quinuclidinyl benzilate (3-QNB) were administered (3, 10, and 30 μg/kg). The brain tissue and plasma tracer concentrations were quantified 45 min later using LC-MS/MS, and the binding potential was calculated. The highest binding potential was observed at 3 μg/kg raclopride, 10 μg/kg doxepin, and 30 μg/kg 3-QNB. Tracer-specific binding at these optimal tracer doses in the cerebral cortex was markedly reduced by pre-administration of displacers. D 2 , H 1, and mACh receptor occupancy by olanzapine increased in a dose-dependent manner, reaching 70-95%, 19-43%, and 12-45%, respectively, at an olanzapine dose range of 3-10 mg/kg. These results suggest that simultaneous determination of in vivo D 2 , H 1 , and mACh receptor occupancy is possible using LC-MS/MS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Intraperitoneal tumor-associated macrophages (TAMs) are involved in evading anti-tumor immunity and promoting the peritoneal metastasis (PM) of gastric cancer (GC). Oncolytic viruses are known to induce the activation of host anti-tumor immunity in addition to tumor lysis. This study investigated whether a wild-type p53 -loading telomerase-specific oncolytic adenovirus (OBP-702) could elicit the remodeling of intraperitoneal macrophages and enhance the efficacy of immune therapy. Increased numbers of CD163 TAMs and few CD8 + lymphocytes were immunohistochemically observed in clinical samples with PM, which suggested that TAMs were associated with the suppression of anti-tumor immunity. OBP-702 induced immunogenic cell death and upregulated PD-L1 expression in human and murine GC cell lines. Intraperitoneal administration of OBP-702 increased recruitment of CD8 + lymphocytes into the PM via the functional remodeling of intraperitoneal macrophages from TAM toward a pro-inflammatory phenotype, resulting in significantly suppressed tumor growth for the in vivo model. Furthermore, the combination of intraperitoneal OBP-702 with anti-programmed cell death-1 antibody enhanced anti-tumor immunity and prolonged the survival of mice bearing PM. Intraperitoneal immunotherapy using OBP-702 restores anti-tumor immunity via the remodeling of intraperitoneal macrophages in addition to direct tumor lysis and cooperates with immune checkpoint inhibitors to suppress PM in GC., Competing Interests: Y.U. is the president and CEO of Oncolys BioPharma, Inc., the manufacturer of OBP-702. H.T. and T.F. are consultants for Oncolys BioPharma, Inc., (© 2024 The Author(s).)

Immunological testing to detect neutralizing antibodies (NAbs) is important in measles (MV) infection control. Currently, the plaque reduction neutralization test is the only credible method for measuring actual virus NAbs; however, its feasibility is hampered by drawbacks, such as long turnaround times, low throughput, and the need for laboratory biosafety equipment. To solve these problems, we developed a simple and rapid MV-NAb detection system using lentivirus-based virus-like particles incorporated with the NanoLuc fragment peptide HiBiT comprising the MV fusion protein and hemagglutinin on their exterior surface. Overall, this simple, safe, and rapid method could be used to detect MV NAbs., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

Background: Technetium-99m-pyrophosphate ( 99m Tc-PYP) uptake in the internal oblique muscle (IOM), which is often observed in patients with wild-type transthyretin cardiac amyloidosis (ATTR-CA), indicates amyloid transthyretin (ATTR) deposition., Objective: This study aimed to assess the safety and efficacy of 99m Tc-PYP imaging-based computed tomography (CT)-guided core-needle biopsy of the IOM as a new extracardiac screening biopsy for confirming the presence of ATTR deposits., Methods: Patients with suspected ATTR-CA in whom myocardial tracer uptake was detected on chest- and abdomen-centered images of 99m Tc-PYP scintigraphy underwent CT-guided core-needle biopsy at the site with the highest tracer uptake in the IOM between September 2021 and November 2022., Results: All 18 consecutive patients (mean age, 86.3 years ± 6.5; 61.1% male) enrolled in the study showed 99m Tc-PYP uptake into the IOM. Adequate tissue samples were obtained from all patients except one without serious complications. Immunohistochemical analysis confirmed ATTR deposits in 16/18 (88.9%) patients. In the remaining two patients, ATTR deposits were observed via endomyocardial biopsy. All patients were diagnosed with wild-type ATTR-CA based on transthyretin gene sequence testing results., Conclusion: In wild-type ATTR-CA, 99m Tc-PYP imaging-based CT-guided core-needle biopsy of the IOM could be used as an extracardiac screening biopsy to confirm the presence of ATTR deposits.

[Purpose] This study aimed to determine the relationship between acceleration parameters in the sit-to-stand (STS) movement and falls, and the strength of the association between acceleration in STS movements and falls in older adults. [Participants and Methods] In total, 330 older adults were included. Four acceleration parameters were measured in STS movement: maximum acceleration (MA), velocity (MV), power (MP), and stand-up time (ST). For the conventional STS tests, 5 times STS test (5xSTS) and ground reaction force (maximal rate of force development per body weight: RFD/w, peak reaction force per body weight: F/w, chair-rise time: T) were measured. Poisson regression analysis adjusted for confounding factors was used. [Results] In the model adjusted for confounders, significant associations were observed among MV (Prevalence ratio (PR): 0.75; 95% confidence interval (CI): 0.58-0.98), MP (PR: 0.67; 95% Cl: 0.68-0.93), RFD/w (PR: 0.70; 95% Cl: 0.56-0.87), and T (PR: 1.14; 95% Cl: 1.05-1.24). [Conclusion] Among the acceleration parameters, MP was most strongly associated with falls and was considered the most useful parameter for evaluation. In addition, comparisons with the conventional chair rise tests suggested that MP was stronger than the 5xSTS test and may be equally related to the RFD/w., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Mononegaviruses are promising tools as oncolytic and transgene vectors for gene therapy and regenerative medicine. However, when mononegaviruses are used for therapeutic applications, the viral activity must be strictly controlled due to concerns about toxicity and severe side effects. With this technology, mononegavirus vectors can be grown where they are intended and can be easily removed when they are no longer needed. In particular, a photoswitch protein called Magnet (consisting of two magnet domains) is incorporated into the hinge region between the connector and methyltransferase domains of the mononegavirus polymerase protein (L protein) to disrupt the L protein functions. Blue light (470 ± 20 nm) irradiation causes the dimerization of the two magnet domains, and the L protein is restored to activity, allowing viral gene expression and virus replication. Since the magnet domains' dimerization is reversible, viral gene expression and replication cease when blue light irradiation is stopped., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: This study clarified the association between the amount of physical activity and apathy after one year among community-dwelling older adults., Methods: Two hundred community-dwelling older adults (mean age: 74.3±5.0 years old, female: 52.5%) who participated in the 2018 and 2019 "Kasama Longevity Health Examination" were included. Apathy was assessed using the Apathy Scale (0-42 points; the higher the score, the lower the motivation), physical activity by Physical Activity Scale for the Elderly (PASE), and Geriatric Depression Scale-15 (GDS). The 2018 PASE data were grouped into tertiles. A multiple regression analysis was performed with the 2019 Apathy Scale as the dependent variable and the 2018 PASE as the independent variable, and the sex, age, years of education, economic situation, body mass index, chronic illness, smoking history, alcohol drinking habits, physical function, cognitive function, GDS, and the 2018 Apathy Scale as adjustment variables. The PASE subcategories (leisure-time, household, and work-related activities) were examined using a similar method., Results: The mean Apathy Scale in 2019 was 14.0±6.2 for the low physical activity group, 12.8±6.0 for the medium physical activity group, and 10.1±5.9 for the high physical activity group. The high physical activity group showed a significant negative association with the Apathy Scale (B=-1.56, 95% confidence interval=-2.91 to -0.21, p=0.023). No association was found for any activity of the PASE sub-items., Conclusions: A high level of physical activity may protect against apathy among community-dwelling older adults.

Background: Hepatic insulin clearance (HIC) is an important pathophysiology of type 2 diabetes mellitus (T2DM). HIC was reported to decrease in patients with type 2 diabetes and metabolic syndrome. HIC is originally calculated by post-load insulin and C-peptide from the oral glucose tolerance test (OGTT). However, OGTT or meal tolerance tests are a burden for patients, and OGTT is not suitable for overt diabetes due to the risk of hyperglycemia. If we can calculate the HIC from the fasting state, it is preferable. We hypothesized that fasting HIC correlates with postprandial HIC in both participants with T2DM and without diabetes. We investigated whether fasting HIC correlates with postprandial HIC in overt T2DM and nondiabetes subjects (non-DM) evaluated by using glucose clamp and meal load., Methods: We performed a meal tolerance test and hyperinsulinemic-euglycemic clamp in 70 subjects, 31 patients with T2DM and 39 non-DM subjects. We calculated the postprandial C-peptide AUC-to-insulin AUC ratio as the postprandial HIC and the fasting C-peptide-to-insulin ratio as the fasting HIC. We also calculated whole-body insulin clearance from the glucose clamp test., Results: The fasting HIC significantly correlated with postprandial HIC in T2DM (r&#95;S = 0.82, P < 0.001). Nondiabetes subjects also showed a significant correlation between fasting and postprandial HIC (r&#95;S = 0.71, P < 0.001). Fasting HIC in T2DM was correlated with BMI, HbA1c, gamma-glutamyl transpeptidase, HOMA-IR, HOMA-beta, M/I, and whole-body insulin clearance. Fasting HIC in nondiabetes subjects was correlated with HOMA-IR and HOMA-beta., Conclusions: These results suggest that fasting HIC is strongly correlated with postprandial HIC in both overt T2DM and non-DM patients, as evaluated by the meal test and glucose clamp method. Fasting HIC could be a convenient marker of HIC., (© 2023. The Author(s).)

Acceleration parameters in sit-to-stand (STS) movements are useful for measuring lower-limb function in older adults. The purpose of this study was to examine the relationship between acceleration in STS movements and physical function and the test-retest reliability of acceleration parameters in older adults. We performed cross-sectional analyses on 244 older adults including 107 men (mean age: 77.4 ± 4.7) and 137 women (mean age: 75.6 ± 5.3). Four acceleration parameters were measured in STS movements: maximum acceleration (MA), maximum velocity (MV), maximum power (MP), and stand-up time (ST). Good intraclass correlation coefficients (ICC > 0.70) were observed for all parameters. For the acceleration parameters, MA, MV, and MP were relatively strongly associated with the 5-time STS test (men: r = -0.36~-0.47; women: r = -0.37~-0.45) and the timed up and go test (men: r = -0.39~0.47, women: r = -0.43~-0.51): MP was also strongly associated with grip strength (men: r = 0.48, women: r = 0.43). All acceleration parameters were poorer in participants reporting mobility limitations than in those reporting no mobility limitations. These findings support the usefulness of sensor-based STS measurement. The system is expected to be useful in various settings where care prevention is addressed.

Background/aim: Diffuse-type gastric cancer (GC) frequently exhibits peritoneal metastasis, leading to poor prognosis. However, efforts to develop antitumor strategies for preventing the peritoneal metastasis of GC have been unsuccessful. As diffuse-type GC cells often carry a genetic alteration in the tumor suppressor p53 gene, p53 restoration may be a potent strategy for preventing peritoneal metastasis of GC. In this study, we investigated the therapeutic potential of p53-expressing adenoviral vectors against peritoneal metastasis of diffuse-type GC cells., Materials and Methods: Three diffuse-type human GC cell types with different p53 statuses (p53-wild type NUGC-4, p53-mutant type GCIY, and p53-null type KATOIII) were used to evaluate the therapeutic potential of p53 activation induced by the p53-expressing, replication-deficient adenovirus Ad-p53 and oncolytic adenovirus OBP-702. Viability, apoptosis, and autophagy of virus-treated GC cells were analyzed under normal and sphere-forming culture conditions using the XTT assay and western blot analysis. The in vivo antitumor effects of OBP-702 and Ad-p53 were assessed using xenograft tumor models involving peritoneal metastasis of NUGC-4 and GCIY cells., Results: Under normal and sphere-forming culture conditions, OBP-702 induced a significantly greater antitumor effect in GC cells compared with Ad-p53 by strongly inducing p53-mediated apoptosis and autophagy and receptor tyrosine kinase suppression. In vivo experiments demonstrated that intraperitoneal administration of OBP-702 significantly suppressed the peritoneal metastasis of NUGC-4 and GCIY cells compared with Ad-p53, leading to prolonged survival of mice., Conclusion: Intraperitoneal administration of OBP-702 inhibits the peritoneal metastasis of GC cells by inducing p53-mediated cytopathic activity., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To investigate the efficacy of sagittal ultrasonography of the median nerve in diagnosing carpal tunnel syndrome (CTS)., Methods: Seventy-six hands with idiopathic CTS and 80 hands of asymptomatic subjects were included. All patients with CTS underwent ultrasonographic examination, electrodiagnostic testing, and CTS-6 assessment. In the sagittal ultrasonographic examination, the maximum and minimum median nerve diameters (MNDs) were measured at the proximal and distal ends of the carpal tunnel, respectively. The median nerve stenosis rate (MNSR) was computed as (1 - minimum MND/maximum MND) × 100 (%). The cross-sectional area (CSA) of the median nerve at the level of the pisiform was measured., Results: In the sagittal ultrasonographic examination, the mean maximum MNDs were 0.252 cm and 0.202 cm, mean minimum MNDs were 0.145 cm and 0.165 cm, and mean MNSRs were 41.83% and 17.35% in the CTS and control groups, respectively; the mean maximum MND and MNSR were considerably larger in the CTS group. The maximum MND and MNSR were correlated with the electrodiagnostic testing results and CTS-6 score. The MNSR with a cut-off value of 34.0% had a higher sensitivity and specificity than the CSA in diagnosing CTS., Conclusions: Sagittal ultrasonographic examination is useful in diagnosing CTS., (© 2023 The Authors. Journal of Clinical Ultrasound published by Wiley Periodicals LLC.)

Background: Evidence is lacking on the association between antibiotic use and risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Asians., Objective: We assessed the risk of SJS/TEN associated with different antibiotic classes in Japanese., Methods: We conducted a case-crossover study using a claims database. Firth conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of SJS/TEN associated with antibiotic use in a 56-day hazard period versus 3 control periods. We created 18 cohorts for each antibiotic class and calculated 56-day cumulative incidence per 100,000 new users. The association between antibiotic class and SJS/TEN was also evaluated in each case using the ALgorithm of Drug causality for Epidermal Necrolysis (ALDEN)., Results: Our case-crossover study included 170 SJS/TEN cases. Increased ORs were observed for lincomycins (OR, 33.00 [95% CI, 3.74-4332.05]), trimethoprim-sulfamethoxazole (21.20 [6.73-105.98]), penicillins (14.39 [6.95-34.21]), glycopeptides (14.37 [3.17-136.10]), cephalosporins (7.06 [4.25-12.21]), aminoglycosides (6.55 [1.97-26.84]), quinolones (5.98 [3.34-11.20]), fosfomycin (5.40 [1.20-30.97]), carbapenems (5.09 [1.85-15.64]), tetracyclines (4.95 [1.78-15.27]), and macrolides (3.78 [2.13-6.83]). Cumulative incidence of SJS/TEN was 67.4 for trimethoprim-sulfamethoxazole, 86.2 for glycopeptides, and below 10.0 for the others. Despite the high incidence, only 2 cases had a probable causal relationship with glycopeptides., Conclusion: Some antibiotic classes, including lincomycins, glycopeptides, aminoglycosides, fosfomycin, and carbapenems, were newly suggested to be associated with risk of SJS/TEN; considered together with the high incidence for trimethoprim-sulfamethoxazole and glycopeptides, these findings warrant caution in clinical practice., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the association between whole-body (WB), arm, and leg extracellular-to-intracellular water resistance (Recw/Ricw) ratios and various physical functions of each segment and muscle mass using segmental multifrequency bioelectrical impedance analysis., Methods: In total, 988 community-dwelling older adults were included in the analysis. Physical function was assessed using hand grip, 5-repetition sit-to-stand, 5-m habitual walk, Timed Up and Go, and single-leg balance with eyes open tests. Each segmental Recw/Ricw ratio and muscle mass were assessed at 5 and 250 kHz resistances using a segmental multifrequency bioelectrical impedance analysis device. Pearson's correlation between the segmental Recw/Ricw ratio and muscle mass and physical function was calculated, and the difference in correlation coefficients was tested using Bonferroni correction. Multiple linear regression analysis was conducted using physical function as the dependent variable and the segmental Recw/Ricw ratio as the independent variable, adjusting for sex, age, body mass index, and segmental muscle mass., Results: WB and leg Recw/Ricw ratios were significantly positively correlated with good hand grip performance, gait speed, mobility, balance, and standing power (p < 0.05), after adjusting for sex, age, body mass index, and muscle mass. Furthermore, the leg Recw/Ricw ratio was positively associated with lower extremity physical function compared with WB and arm Recw/Ricw ratios and muscle mass (p < 0.01). Conversely, WB muscle mass was more strongly related to grip strength than WB, arm, and leg Recw/Ricw ratios (p < 0.01)., Conclusions: The Recw/Ricw ratio is useful for identifying older adults with worse physical function. The Recw/Ricw ratio allows for easy and timely screening of older adults with worse physical function in clinical settings., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Radiohalogens with a short half-life are useful radioisotopes for radiotheranostics. Astatine-211 is an α-emitting radiohalogen and is expected to be applicable to targeted α therapy. A neopentyl labeling group is an effective hydrophilic labeling unit for various radiohalogens, which includes 211 At. In this study, a 1-( N , N -dialkylcarbamoyl)-1,1-difluoromethanesulfonyl (CDf) ester was developed as a stable precursor for labeling with 211 At, 77 Br and 125 I through a neopentyl labeling group. The CDf ester remained stable in an acetonitrile solution at room temperature and enabled the successful syntheses of 211 At-labeled compounds in a highly radiochemical conversion in the presence of K 2 CO 3 . 77 Br- and 125 I-labeled compounds can be prepared from the CDf ester without a base. The utility of the CDf ester was demonstrated in the synthesis of a benzylguanidine with a neopentyl 211 At-labeling group. The developed method afforded a 32% radiochemical yield of 211 At-labeled benzylguanidine. However, a partial deastatination was observed under acidic conditions during the removal of an N -Boc protecting group. Deprotecting these groups under milder acidic conditions may improve the radiochemical yield. In conclusion, the CDf ester facilitates the syntheses of 211 At, 125 I and 77 Br-labeled compounds that use a neopentyl labeling group for radiotheranostic applications. Further optimization of protecting groups and reaction conditions should enhance the total radiochemical yield of the 211 At-labeled compounds.

The Japanese population has the world's longest life expectancy but faces the challenge of extending the healthy life expectancy without developing chronic diseases. Therefore, the effectiveness of products derived from olives used in the Mediterranean diet as a potential dietary solution has attracted attention. This study examined the effects of desert olive tree pearls (DOTPs), which contain 162 times more polyphenol hydroxytyrosol than olive oil, on the cognitive function of middle-aged and older adults using the Cognitrax test. Participants (aged 51-82 years) were assigned to the DOTP intake ( n = 36) or placebo group ( n = 36) in a randomized, double-blind, placebo-controlled, parallel-group study. The participants received 3 g of DOTPs or placebo in olive oil twice daily for 12 weeks. Among cognitive domains, complex attention had a significant time × group interaction effect ( p = 0.049) between the DOTP and placebo groups. The simple main effect for this item was significantly different ( p < 0.001 and p = 0.572, respectively). Time effects were significant ( p < 0.05) for the psychomotor speed, reaction time, cognitive flexibility, processing speed, and executive function domains. Therefore, DOTPs have the potential to alleviate cognitive problems faced by middle-aged and older adults in Japan.

Background: Phase angle (PhA) is an indicator of cellular conditions. Recent studies have suggested that PhA supports healthy aging. Identifying modifiable lifestyle factors for PhA is important. The associations of PhA in 24-h movement behaviors, including physical activity (PA), sedentary behavior (SB), and sleep, have not been studied in older adults., Objectives: We investigated the cross-sectional associations between 24-h movement behaviors and PhA in community-dwelling older adults while appropriately considering the co-dependent nature of daily time use using compositional data analysis., Methods: The participants were 113 healthy older adults. PhA was measured using a bioelectrical impedance device. Time spent in light-intensity PA (LPA), moderate- to vigorous-intensity PA (MVPA), and SB was measured using a tri-axial accelerometer. Sleep duration information was self-reported in a questionnaire. Compositional multiple linear regression and compositional isotemporal substitution were performed to examine the associations of 24-h movement behaviors with PhA and hypothetical time reallocation in movement behaviors with PhA, respectively., Results: Even after adjusting for potential confounders, relative to other behaviors more time spent in MVPA was significantly associated with higher PhA (p < 0.001). The 30 min/day of time reallocation from the other behaviors (SB, LPA, and sleep) to MVPA was predicted to be 0.12 higher PhA (corresponding to 2.3% increase; 95% CI 0.01, 0.24)., Conclusions: Our results suggest that increasing or maintaining the daily time spent in MVPA is important for managing PhA in older adults, regardless of the other behaviors time consumed instead., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Epstein-Barr virus (EBV) is a human herpes virus that latently infects B lymphocytes. When EBV is reactivated, host B cells differentiate into plasma cells and produce IgM-dominant antibodies as well as many progeny virions. The aims of the present study were to confirm the IgM dominance of thyrotropin-receptor antibodies (TRAbs) produced by EBV reactivation and investigate the roles of TRAb-IgM in Graves' disease. Peripheral blood mononuclear cells (PBMCs) containing TRAb-producing cells were stimulated for EBV reactivation, and TRAb-IgM and TRAb-IgG were measured by ELISA. TRAb-IgM were purified and TSH-binding inhibitory activities were assessed using a radio-receptor assay. Porcine thyroid follicular epithelial cells were cultured with TRAb-IgM and/or complements to measure the intracellular levels of cAMP and the amount of LDH released. TRAb-IgM/TRAb-IgG (the MG ratio) was examined in sequential serum samples of Graves' disease and compared among groups of thyroid function. The results obtained showed that IgM-dominant TRAb production was induced by EBV reactivation. TRAb-IgM did not inhibit TSH binding to TSH receptors and did not transduce hormone-producing signals. However, it destroyed thyroid follicular epithelial cells with complements. The MG ratio was significantly higher in samples of hyperthyroidism or hypothyroidism than in those with normal function or in healthy controls. A close relationship was observed between TRAb-IgM produced by EBV reactivation and the development and exacerbation of Graves' disease. The present results provide novel insights for the development of prophylaxis and therapeutics for Graves' disease.

Core body temperature (CBT) shows a diurnal rhythm, and the nocturnal decrease in CBT is blunted in older people. The physiological mechanisms responsible for the blunted nocturnal decrease in CBT in older people remain to be revealed. The aim of this study was to compare heat production and heat dissipation in young and old subjects during sleep, as assessed by indirect calorimetry and the distal-proximal temperature gradient (DPG) of skin temperature. A complete dataset of 9 young (23.3 ± 1.1 years) and 8 old (72.1 ± 2.5 years) females was analyzed. CBT and energy metabolism were monitored during sleep using an ingestible temperature sensor in a metabolic chamber maintained at 25 °C. Skin temperature was measured at proximal and distal parts of the body. CBT, distal skin temperature, and DPG in older subjects were higher than in young subjects. Protein oxidation was similar between the two groups, but fat oxidation was lower and carbohydrate oxidation was higher in old subjects compared to young subjects. On the other hand, energy expenditure was similar between the two age groups. Thus, the elevated CBT in older subjects was not attributed to deteriorated heat dissipation or enhanced heat production, suggesting an alternative explanation such as deteriorated evaporative heat loss in old subjects., (© 2023. The Author(s).)

Background: The relationship between manual dexterity and cognitive function among older adults is well known; however, few studies have focused on manual dexterity training that confirms cognitive load of training in older adults through functional near-infrared spectroscopy (fNIRS) and verifies the effect of training. This study examined the effects of home-based manual dexterity training on cognitive function in older adults using a digital trail-making peg test device combining two conventional assessment tools namely, the peg and trail-making tests., Methods: For 12 weeks, 57 healthy older adults aged 65-88 years participated in a parallel-group, randomized controlled trial, wherein home-based manual dexterity training was performed for approximately 20 min daily. To quantify the cognitive load in different manual dexterity conditions, we assessed the cortical activation patterns of the prefrontal cortex via a wearable four-channel fNIRS device. Participants in the control group were asked to continue their usual daily routines during the intervention period. Cognitive function was assessed using the Stroop Color and Word and Cognitive Impairment Tests. Manual dexterity was assessed using the Purdue Pegboard Test. All outcomes were estimated before and after the intervention., Results: We observed significant differences in prefrontal cortical activation between the different manual dexterity conditions. Only the intervention group showed a significant improvement in Stroop interference (169.0-108.9 ms, p = 0.032) and an executive function and assembly task of the Purdue Pegboard Test (22.5-26.4 counts, p < 0.001). Additionally, except the clock drawing task, cognitive function had a larger effect size (Cohen's d) in the intervention group (d = 0.26-0.45) than in the control group (d = 0.11-0.28)., Conclusions: Home-based manual dexterity training can improve performance in a complex manual dexterity task and executive functioning in older adults., Trial Registration: UMIN-CTR Clinical Trial, UMIN000047203. Registered 17 March 2022 - Retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000053844&type=summary&language=E., (© 2023. The Author(s).)

Background: Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme involved in alcohol metabolism. ALDH2 polymorphism has been reported as a risk factor for type 2 diabetes mellitus (T2DM) and is associated with liver insulin resistance due to alcohol consumption in non-diabetic individuals. Herein, we investigated the association between ALDH2 polymorphisms and insulin resistance in patients with T2DM., Methods: We performed a meal tolerance test and the hyperinsulinemic-euglycemic clamp on 71 Japanese participants: 34 patients with T2DM, and 37 non-diabetic participants. We analyzed the ALDH2 polymorphism (ALDH2 rs67); GG type was defined as the T2DM high-risk group, compared with the low-risk AG and AA groups., Results: Glucose levels were similar in the high- and low-risk T2DM groups. The high-risk group for T2DM showed a significantly higher BMI (p < 0.005), insulin resistance in HOMA-IR (p < 0.05), and Insulin sensitivity index (p < 0.05); however, there were no significant differences in insulin resistance in the clamp test (p = 0.10). Alcohol consumption did not differ significantly between groups (p = 0.66). Non-diabetic participants also showed higher HOMA-IR insulin resistance in the high-risk group (p < 0.05), but insulin resistance levels in the glucose clamp tests (p = 0.56) and insulin secretion were not significant., Conclusion: The results suggest that ALDH2 is an important gene associated with insulin resistance and obesity in Japanese patients with type 2 diabetes., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. Published by Elsevier Inc.)