Search

Housing structures differ according to the local culture, climate, and lifestyle, and these unique characteristics usually act as potential hazards for falls, trips, and slips. The purpose of this study was to identify environmental hazards in a Japanese house and their association with falls, trips, and slips among older people.A total of 97 older people aged ≥75 years were included in this cross-sectional study. The number of environmental hazards was measured using a 46-item tool designed specifically for this study, and the associations of environmental hazards with falls, trips, and slips were analyzed using univariate and multivariate logistic regressions.All houses had at least one environmental hazard, and 3-30 environmental hazards were identified. Although the number of environmental hazards was not associated with falls experienced during the past 6 months, a greater number of environmental hazards at home was correlated with the daily experience of trips and slips (odds ratio [OR]: 1.10; 95% confidence interval [CI]: 1.02-1.18). The association remained significant even after adjusting for demographic characteristics and other fall risk factors (OR: 1.11; 95% CI: 1.02-1.21).We found that Japanese housing structures had unique environmental hazards that might cause trips and slips in older people. Appropriate housing assessments and modifications may help to promote aging-in-place among older people. Geriatr Gerontol Int 2022; 22: 305-310.

New three macrocyclic diolides, named bispolides C-E (1-3), were isolated from a fermentation broth of the actinomycete strain MG372-hF19, which produces an indole glycoside and leptomycins as we reported previously. The absolute structures of compounds 1-3 were elucidated by NMR and X-ray crystallography. Compounds 1-3 diverge from the known nine bispolides in their different alkylation patterns on the 20-membered macrocyclic diolide skeleton and the side chain in their planar structures. Furthermore, compounds 1-3 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci and cytotoxic activity against human cancer cell lines. Among them, compound 3 has the most potent biological activities against bacteria and tumor cells. Additionally, using a membrane-potential-sensitive fluorescence probe, we found that compounds 1-3 and elaiophylin have a similar effect on membrane potential in A549 human lung cancer cells.

Specific inhibitors of protein phosphatase 2A (PP2A) mediate anticancer effects by augmenting the tumor-killing activity of natural killer (NK) cells. In this study, new PP2A inhibitors, aminocytostatins A-E, were isolated from Kitasatospora sp. MJ654-NF4 and structurally characterized. Aminocytostatins are derivatives of cytostatin, which is a specific PP2A inhibitor isolated from the same organism, and aminocytostatins have a characteristic amino group within the lactone moiety. Compared to cytostatin, aminocytostatin A showed a stronger inhibitory activity against PP2A in vitro and augmented the tumor-killing activity of NK cells in vivo. Furthermore, a docking model was generated to demonstrate the favorable activities of aminocytostatin A.

In the course of screening for new antimicrobial compounds, a new antibiotic substance named saccharobipyrimicin was isolated from the leaf-litter actinomycete Saccharothrix sp. MM696L-181F4. The structure of saccharobipyrimicin was elucidated by various spectral methods, mainly single-crystal X-ray analysis and chemical degradation. It revealed that saccharobipyrimicin contained a 2,2'-bipyridine skeletal structure. Saccharobipyrimicin showed moderate and broad-spectrum antimicrobial activity. Two chemical derivatives of saccharobipyrimicin showed weaker antimicrobial activities than that of saccharobipyrimicin against most test microorganisms except two tolC mutants of Escherichia coli and Neisseria gonorrhoeae.

A Nonomuraea sp. strain MM565M-173N2 was isolated from deep-sea sediment off the Sanriku coast, and new antibiotics were evaluated against carbapenem-resistant Enterobacteriaceae (CRE), which is a problematic group of bacteria because of their antimicrobial resistance. From 220 l of fermented broth from strain MM565M-173N2, we isolated four new antibiotics by gel filtration and HPLC, designated as sealutomicins A (1.8 mg), B (1.5 mg), C (0.8 mg), and D (0.8 mg). Their structures were determined from MS, NMR, and CD spectra. Sealutomicin A was found to be a new enediyne antibiotic, while sealutomicins B-D were aromatized products from sealutomicin A. Sealutomicin A showed strong antibacterial activity (MIC 0.05-0.2 μg ml-1) against CRE.

Large regions in tumor tissues, particularly pancreatic cancer, are hypoxic and nutrient-deprived because of unregulated cell growth and insufficient vascular supply. Certain cancer cells, such as those inside a tumor, can tolerate these severe conditions and survive for prolonged periods. We hypothesized that small molecular agents, which can preferentially reduce cancer cell survival under nutrient-deprived conditions, could function as anticancer drugs. In this study, we constructed a high-throughput screening system to identify such small molecules and screened chemical libraries and microbial culture extracts. We were able to determine that some small molecular compounds, such as penicillic acid, papyracillic acid, and auranofin, exhibit preferential cytotoxicity to human pancreatic cancer cells under nutrient-deprived compared with nutrient-sufficient conditions. Further analysis revealed that these compounds target to redox systems such as GSH and thioredoxin and induce accumulation of reactive oxygen species in nutrient-deprived cancer cells, potentially contributing to apoptosis under nutrient-deprived conditions. Nutrient-deficient cancer cells are often deficient in GSH; thus, they are susceptible to redox system inhibitors. Targeting redox systems might be an attractive therapeutic strategy under nutrient-deprived conditions of the tumor microenvironment.

NMR spectroscopy has recently been utilized to determine the absolute amounts of organic molecules with metrological traceability since signal intensity is directly proportional to the number of each nucleus in a molecule. The NMR methodology that uses hydrogen nucleus (1H) to quantify chemicals is called quantitative 1H-NMR (1H qNMR). The quantitative method using 1H qNMR for determining the purity or content of chemicals has been adopted into some compendial guidelines and official standards. However, there are still few reports in the literature regarding validation of 1H qNMR methodology. Here, we coordinated an international collaborative study to validate a 1H qNMR based on the use of an internal calibration methodology. Thirteen laboratories participated in this study, and the purities of three samples were individually measured using 1H qNMR method. The three samples were all certified via conventional primary methods of measurement, such as butyl p-hydroxybenzoate Japanese Pharmacopeia (JP) reference standard certified by mass balance; benzoic acid certified reference material (CRM) certified by coulometric titration; fludioxonil CRM certified by a combination of freezing point depression method and 1H qNMR. For each sample, 1H qNMR experiments were optimized before quantitative analysis. The results showed that the measured values of each sample were equivalent to the corresponding reference labeled value. Furthermore, assessment of these 1H qNMR data using the normalized error, En-value, concluded that statistically 1H qNMR has the competence to obtain the same quantification performance and accuracy as the conventional primary methods of measurement.

Objective To investigate whether kinesiophobia with pregnancy-related lumbopelvic pain at late pregnancy influenced depressive symptoms at 1 month after delivery. Method Final participants were 43 pregnant women who experienced pregnancy-related lumbopelvic pain at late pregnancy and completed self-reported questionnaires at late pregnancy and 1 month after delivery. The Tampa Scale for Kinesiophobia was used to evaluate kinesiophobia, and depressive symptoms were assessed using the Self-Rating Depression Scale. We divided participants into two groups (depression and no-depression) using the score of the Self-Rating Depression Scale at 1 month after delivery. Univariate analysis and multiple logistic regression analysis identified kinesiophobia at late pregnancy as an independent predictor of depression at 1 month after delivery. Results In univariate analysis, kinesiophobia at late pregnancy was significantly higher in the depression group than in the no-depression group (P= .033). In multiple logistic regression analysis, kinesiophobia at late pregnancy were significantly associated with depression at 1 month after delivery even after adjusting for confounding factors (Odds Ratio, 1.25; 95% Confidence Interval, 1.03-1.52). Conclusion Results found that kinesiophobia at late pregnancy negatively influenced depressive symptoms at 1 month after delivery, suggesting that approaches to treat kinesiophobia at late pregnancymight reduce the risk of onset of postpartum depressive symptoms.

Objectives: The purpose of this cross-sectional study was to investigate the association between daily physical activity and sonographically measured bone status among women during the lactation period. Methods: Final participants were 152 women 4 months after childbirth. Bone status of the participants was measured using quantitative ultrasonometry of the calcaneus (speed of sound). Daily physical activity was assessed using the Japanese version of International Physical Activity Questionnaire short version. After getting the International Physical Activity Questionnaire results, we classified participants into three categories (low/moderate/high) according to a protocol. Participants categorized into the low group according to the International Physical Activity Questionnaire were considered to be in the low physical activity group and those categorized into the moderate and high groups were considered to be in the moderate to vigorous physical activity group. Results: Speed of sound was significantly higher in the moderate to vigorous physical activity group (moderate to vigorous physical activity versus low physical activity, 1533 m/s versus 1523 m/s, p = 0.03). Daily physical activity was significantly associated with speed of sound, even after adjustment for confounding factors and prognosticators ( β = 0.195, p = 0.02). Conclusion: Sonographically measured bone status was significantly higher in women who were physically active than in those who were physically inactive, suggesting that daily physical activity might help to maintain good bone status.

This study aimed to investigate whether abnormal gait patterns are associated with experiencing an elevated degree of pain after daily walking. In this preliminary, cross-sectional study, 223 community-dwelling older adults were assessed for pain experienced after daily walking using a simple question that involved asking the subject about their past experiences of an elevated degree of pain after walking for 400 m or more. Gait patterns were assessed using the Comprehensive Gait Assessment using InerTial Sensor score (C-GAITS score), derived from the data measured by Inertial sensors attached to the lower trunk and heel when subjects walked along a 15 m walkway at a self-selected preferred speed. The score was the sum of 10 gait parameter scores. The lower scores indicated more and worse abnormal gait patterns. In total, 24 older adults (10.8%) reported that they experienced pain after daily walking. According to the multiple logistic regression analyses, older adults with a lower total C-GAITS score had a significantly greater probability of having past experiences of pain after walking (odds ratio = 1.11, 95% confidence interval = 1.03–1.20). The findings of this study suggest that more and worse abnormal gait patterns among older adults in a clinical walking test are associated with an elevated degree of pain after daily walking.

An association between respiratory muscle weakness and sarcopenia may provide a clue to the mechanism of sarcopenia development. We aimed to clarify this relationship among community-dwelling older adults. In total, 117 community-dwelling older adults were assessed and classified into 4 groups: robust, respiratory muscle weakness, sarcopenia, and respiratory sarcopenia. The respiratory sarcopenia group (12%) had a significantly higher percentage of males and had lower BMI, skeletal muscle index, skeletal muscle mass, phase angle, and oral function than the robust group (32.5%). All physical functions were significantly lower. The respiratory muscle weakness group (54.7%) had a significantly lower BMI and slower walking speed, compared with the robust group. The sarcopenia group (0.8%) was excluded from the analysis. The percent maximum inspiratory pressure was significantly lower in both the respiratory muscle weakness and respiratory sarcopenia groups, compared with the robust group. Almost all participants with sarcopenia showed respiratory muscle weakness. In addition, approximately 50% had respiratory muscle weakness, even in the absence of systemic sarcopenia, suggesting that respiratory muscle weakness may be the precursor of sarcopenia. The values indicating physical function and skeletal muscle mass in the respiratory muscle weakness group were between those in the robust and the respiratory sarcopenia groups.

An acyldipeptide, micromonosporamide A, was isolated from the fermentation broth of

BACKGROUND Commercially available active video games (AVGs) have recently been used for rehabilitation in some specific patient populations but rarely in those with cardiovascular disease (CVD). Commercially available AVGs are designed to increase motivation for continuous play, which could be applicable to the long-term cardiac rehabilitation process. OBJECTIVE The objective of this scoping review was to assess the effectiveness of AVG-induced physical exercise, safety management, and patient adherence by applying commercially available AVGs to cardiac rehabilitation. METHODS Four databases (CINAHL, MEDLINE, PubMed, and SPORTDiscus) were searched for all years up to August 12, 2020. Articles were retained if they were written in English, included patients with CVD who were aged 18 years or older, and used AVGs as part of a physical exercise program. The included studies were then evaluated from the viewpoints of effectiveness as physical exercise, safety, and adherence management. RESULTS Among 120 nonduplicate articles reviewed, 5 (4.2%) were eligible for inclusion, of which 3 (2.5%) were reported by the same research group. The AVG consoles used were Xbox Kinect and Nintendo Wii, and sports-related programs were adopted for the intervention. No adverse cardiac events occurred in the identified studies, and dropout rates tended to be low. CONCLUSIONS AVGs appear to be safe and feasible for promoting an active lifestyle in patients with CVD. However, the effectiveness of AVGs alone as a therapeutic exercise to improve physical function may be limited.

Leucinostatin Y, a new peptaibiotic, was isolated from the culture broth of the entomoparasitic fungus Purpureocillium lilacinum 40-H-28. The planar structure was elucidated by detailed analysis of its NMR and MS/MS data. The absolute configurations of the amino acids were partially determined by an advanced Marfey's method. The biological activities of leucinostatin Y were assessed using human pancreatic cancer cells, revealing the importance of the C-terminus of leucinostatins for preferential cytotoxicity to cancer cells under glucose-deprived conditions and inhibition of mitochondrial function.

Objectives: This study aimed to examine the reliability and validity of the Japanese version of the Physical Activity Questionnaire for Older Children (PAQ-C) in Japanese children aged 9 to 12 years. Methods: A total of 210 children aged between 9 and 12 years participated. Internal consistency and test-retest reliability were evaluated using Cronbach alpha coefficient and intraclass correlation coefficient (ICC), respectively. Validity was evaluated using athletic competence (AC), self-efficacy (SE), body mass index (BMI), body fat percentage (%BF), cardiovascular fitness (CVF), and World Health Organization Health Behavior in School-aged Children (WHO HBSC) physical activity questionnaire. Results: Internal consistency was acceptable (alpha = 0.80) and test-retest reliability showed excellent agreement (ICC = 0.83). The PAQ-C score was significantly correlated with AC ( r = 0.41), SE ( r = 0.65), %BF ( r = 0.19), and CVF ( r = −0.32). The PAQ-C score of the active group classified by the WHO HBSC physical activity questionnaire (mean score ± standard deviation [SD] = 3.03 ± 0.57) was significantly higher than that of the inactive group (mean score ± SD = 2.27 ± 0.63, P Conclusions: The PAQ-C had acceptable reliability and validity. The PAQ-C is a useful instrument to evaluate physical activity for Japanese children aged 9 to 12 years.

Influenza virus RNA polymerase has cap-dependent endonuclease activity that produces capped RNA fragments for priming viral mRNA synthesis. This enzymatic activity is essential for viral propagation, but it is not present in any host cellular enzyme, making it an attractive target for the development of anti-influenza drugs. Here, we isolated a novel inhibitor of cap-dependent endonuclease, named flupyranochromene, from the fermentation broth of the fungus Penicillium sp. f28743. Structural analysis revealed that this compound bears a putative pharmacophore that chelates divalent metal ion(s) present in the endonuclease active site in the PA subunit of the polymerase. Consistently, in vitro endonuclease assays showed that flupyranochromene exerts its inhibitory effects by blocking endonucleolytic cleavage by the PA subunit of viral RNA polymerase complex.

BACKGROUND Heart failure is one of the world’s most frequently diagnosed cardiovascular diseases. An important element of heart failure management is cardiac rehabilitation, the goal of which is to improve patients’ recovery, functional capacity, psychosocial well-being, and health-related quality of life. Patients in cardiac rehabilitation may lack sufficient motivation or may feel that the rehabilitation process does not meet their individual needs. One solution to these challenges is the use of telerehabilitation. Although telerehabilitation has been available for several years, it has only recently begun to be utilized in heart failure studies. Especially within the past 5 years, we now have several studies focusing on the effectiveness of telerehabilitation for heart failure management, all with varying results. Based on a review of these studies, this paper offers an assessment of the effectiveness of telerehabilitation as applied to heart failure management. OBJECTIVE The aim of this scoping review was to assess the effects of telerehabilitation in the management of heart failure by systematically reviewing the available scientific literature within the period from January 1, 2015, to December 31, 2020. METHODS The literature search was carried out using PubMed and EMBASE. After duplicates were removed, 77 articles were screened and 12 articles were subsequently reviewed. The review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews) guidelines. As measures of the effectiveness of telerehabilitation, the following outcomes were used: patients’ quality of life, physical capacity, depression or anxiety, and adherence to the intervention. RESULTS A total of 12 articles were included in this review. In reviewing the effects of telerehabilitation for patients with heart failure, it was found that 4 out of 6 randomized controlled trials (RCTs), a single prospective study, and 4 out of 5 reviews reported increased quality of life for patients. For physical capacity, 4 RCTs and 3 systematic reviews revealed increased physical capacity. Depression or depressive symptoms were reported as being reduced in 1 of the 6 RCTs and in 2 of the 5 reviews. Anxiety or anxiety-related symptoms were reported as reduced in only 1 review. High adherence to the telerehabilitation program was reported in 4 RCTs and 4 reviews. It should be mentioned that some of the reviewed articles described the same studies although they employed different outcome measures. CONCLUSIONS It was found that there is a tendency toward improvement in patients’ quality of life and physical capacity when telerehabilitation was used in heart failure management. The outcome measures of depression, anxiety, and adherence to the intervention were found to be positive. Additional research is needed to determine more precise and robust effects of telerehabilitation.

A series of analogs of vegfrecine, a natural quinone vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, was synthesized via oxidative amination of 2,5-dihydroxybenzamide with functionalized arylamine followed by ammonolysis and substitution of the quinone ring. The inhibitory activities of the analogs against the VEGFR-1 and -2 tyrosine kinases were assayed in vitro with the aim to identify a compound suitable to treat cancer and inflammatory diseases. Alterations of the functionality of the phenyl group, substitution of the quinone ring, and oxidative cyclization of the 1-carboxamide-2-aminoquinone moiety to form an isoxazole quinone ring were examined. Introduction of halo- and alkyl-substituents at the 5'-position of the phenyl ring resulted in potent inhibition of the VEGFR-1 and -2 tyrosine kinases. In particular, structural modification at C-5' on the phenyl ring was shown to significantly affect the selectivity of the inhibition between the VEGFR-1 and -2 tyrosine kinases. Compound 8, 5'-methyl-vegfrecine, showed superior selectivity toward the VEGFR-2 tyrosine kinase over the VEGFR-1 tyrosine kinase.

Four new quinofuracins F - I were isolated from the culture broth of Staphylotrichum boninense PF1444. The structures of quinofuracins F - I were elucidated by extensive spectroscopic analysis. These quinofuracins induced tumor suppressor protein p53-dependent cell death in human glioblastoma LNZTA3 cells.

Background The COVID-19 pandemic has required an increased need for rehabilitation activities applicable to patients with chronic diseases. Telerehabilitation has several advantages, including reducing clinic visits by patients vulnerable to infectious diseases. Digital platforms are often used to assist rehabilitation services for patients in remote settings. Although web portals for medical use have existed for years, the technology in telerehabilitation remains a novel method. Objective This scoping review investigated the functional features and theoretical approaches of web portals developed for telerehabilitation in patients with chronic diseases. Methods PubMed and Web of Science were reviewed to identify articles associated with telerehabilitation. Of the 477 nonduplicate articles reviewed, 35 involving 14 portals were retrieved for the scoping review. The functional features, targeted diseases, and theoretical approaches of these portals were studied. Results The 14 portals targeted patients with chronic obstructive pulmonary disease, cardiovascular, osteoarthritis, multiple sclerosis, cystic fibrosis diseases, and stroke and breast cancer survivors. Monitoring/data tracking and communication functions were the most common, followed by exercise instructions and diary/self-report features. Several theoretical approaches, behavior change techniques, and motivational techniques were found to be utilized. Conclusions The web portals could unify and display multiple types of data and effectively provide various types of information. Asynchronous correspondence was more favorable than synchronous, real-time interactions. Data acquisition often required assistance from other digital tools. Various functions with patient-centered principles, behavior change strategies, and motivational techniques were observed for better support shifting to a healthier lifestyle. These findings suggested that web portals for telerehabilitation not only provided entrance into rehabilitation programs but also reinforced participant-centered treatment, adherence to rehabilitation, and lifestyle changes over time.

Nonreducing disaccharide trehalose is used as a stabilizer and humectant in various products and is a potential medicinal drug, showing curative effects on the animal models of various diseases. However, its use is limited as it is hydrolyzed by trehalase, a widely expressed enzyme in multiple organisms. Several trehalose analogs are prepared, including a microbial metabolite 4-trehalosamine, and their high biological stability is confirmed. For further analysis, 4-trehalosamine is selected as it shows high producibility. Compared with trehalose, 4-trehalosamine exhibits better or comparable protective activities and a high buffer capacity around the neutral pH. Another advantage of 4-trehalosamine is its chemical modifiability: simple reactions produce its various derivatives. Labeled probes and detergents are synthesized in one-pot reactions to exemplify the feasibility of their production, and their utility is confirmed for their respective applications. The labeled probes are used for mycobacterial staining. Although the derivative detergents can be effectively used in membrane protein research, long-chain detergents show 1000-3000-fold stronger autophagy-inducing activity in cultured cells than trehalose and are expected to become a drug lead and research reagent. These results indicate that 4-trehalosamine is a useful trehalose substitute for various purposes and a material to produce new useful derivative substances.

Background/Objective: To elucidate the effects of walking exercise using a wearable device and functional wear on spinal alignment and jump performance. Methods: In total, 27 female college soccer players were randomly divided into two groups: trunk solution (TS) and compression garments (CGs). Spinal alignment, jump performance, and electromyography activity during the jump performance of the two groups were measured after a 20-min walking exercise. The values for each group were compared t pre- and post-intervention. Results: The flexibility of the lower thoracic vertebrae in spinal alignment was increased during extension in the TS group. However, the post-value of the abdominal external oblique muscle during a countermovement jump (CMJ) was significantly lower than its pre-value (p

Metacytofilin (MCF) was isolated from the fungus Metarhizium sp. TA2759. Although MCF possesses anti-Toxoplasma activity, the effects of this compound against other parasites are unknown. Here, we evaluated the in vitro anti-malarial activity of MCF against the 3D7 strain and the chloroquine-resistant K1 strain of Plasmodium falciparum. The half maximal inhibitory concentrations (IC50) of MCF against the 3D7 and K-1 strains following culture for 48 h were 666 nM and 605 nM, respectively. Artemisinin was more potent than MCF against both strains (3D7 IC50: 17.4 nM; K-1 IC50: 18.3 nM), while chloroquine was ineffective against the chloroquine-resistant strain (3D7 IC50: 39.1 nM; K-1 IC50: 1.62 μM). MCF affected the ring stage of the parasites, resulting in their death as shown by spots within red blood cells. MCF also inhibited parasite growth following culture for 72 h (3D7 IC50, 285 nM). Four optical isomers of cyclo[Leu-Phe]-diketopiperazine derivatives with modified methoxy and/or hydroxyl groups lost anti-malarial activity, suggesting that the spatial positions of the methoxy and hydroxyl groups in MCF play an important role in its anti-malarial effects. Together, these data suggest that MCF may represent a promising lead compound for treatment of drug-resistant malarial parasites.

NMR spectroscopy has recently been utilized to determine the absolute amounts of organic molecules with metrological traceability since signal intensity is directly proportional to the number of each nucleus in a molecule. The NMR methodology that uses hydrogen nucleus (

Two new dimeric cyclohexapeptides, chloptosins B and C, were discovered from the culture broth of Embleya sp. MM621-AF10 together with the known compounds chloptosin and L-156,602. The structures of the new chloptosins were determined by spectroscopic studies and advanced Marfey’s methods. The stereo structure of the constituent isoleucine was determined by C3 Marfey’s analysis. Chloptosins demonstrated potent antimicrobial activity against Gram-positive bacteria including drug-resistant strains of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci with MICs of 0.5–2 µg ml−1. The antimicrobial activities of chloptosins were enhanced by addition of co-producing compound L-156,602, as shown by checkerboard analysis.

Stereospecific β-l-rhamnopyranosylations were conducted using a 1,2-anhydro-l-rhamnopyranose donor and mono-ol or diol acceptors in the presence of a glycosyl-acceptor-derived borinic or boronic ester. Reactions proceeded smoothly to provide the corresponding β-l-rhamnopyranosides (β-l-Rhap) with complete stereoselectivity in moderate to high yields without any further additives under mild conditions. Mechanistic studies of the borinic ester mediated glycosylation using 13 C kinetic isotope effect (KIE) measurements and DFT calculations were consistent with a concerted SN i mechanism with an exploded transition state. In addition, the present glycosylation method was applied successfully to the synthesis of a trisaccharide, α-l-Rhap-(1,2)-β-l-Rhap-(1,4)-Glcp, derived from Streptococcus pneumoniae serotypes 7B, 7C, and 7D.

Objectives Fear of falling (FoF) is common in older adults. Physical activity decreases as FoF increases. However, this association between physical activity and FoF may vary depending on activity intensity. The current study was performed to explore the associations between FoF and step count, light-intensity physical activity (LPA), and moderate/vigorous-intensity physical activity (MVPA) in community-dwelling older adults. Methods This cross-sectional observational study was held at a local community association center, with 242 older adults living independently in the community (mean age: 75.1 ± 5.4 years). FoF was defined using the Falls Efficacy Scale-International and categorized into three levels (low, moderate, and high). Physical activity was measured using a uniaxial accelerometer worn for 7 consecutive days, and by calculating daily step count, LPA, and MVPA, over this period. Results Step count and physical activity intensity showed significant linear trends across FoF severity (p < .01, respectively). High FoF decreased step count by approximately 2,000 steps/day. Further, high FoF was significantly associated with short durations of both LPA and MVPA. In addition, moderate FoF was associated with decreased LPA duration, even after adjustment for confounding variables. Discussion Physical activity decreased concomitantly with a rise in FoF severity. Moreover, the association between physical activity and FoF differed by physical activity intensity level in community-dwelling older adults. Further studies are needed to investigate the causal relationship between FoF and objective physical activity in this population.

OBJECTIVE Physical inactivity is recognized as a pandemic health problem. The association of pain with physical activity, particularly when measured objectively, in older adults is unclear. This study investigates the association of number of chronic musculoskeletal pain sites and pain severity with objectively measured physical activity in community-dwelling older adults. DESIGN Observational study. SETTING Community. SUBJECTS We analyzed 267 community-dwelling older adults (mean age = 75.3 years, 67.0% women). METHODS Number of chronic musculoskeletal pain sites and pain severity were measured using a self-reported questionnaire. Mean steps per day and mean minutes of light physical activity per day and moderate to vigorous physical activity per day were measured using an accelerometer. Linear regression models were applied to analyze the association of number of chronic musculoskeletal pain sites and pain severity with physical activity. RESULTS The results suggest that a higher number of chronic musculoskeletal pain sites is associated with lower step count (beta = -333.5, 95% confidence interval = -655.9 to -11.0, P

Regio- and 1,2-cis-stereoselective chemical glycosylation of unprotected glycosyl acceptors has been in great demand for the efficient synthesis of natural glycosides. However, simultaneously regulating these selectivities has been a longstanding problem in synthetic organic chemistry. In nature, glycosyl transferases catalyze regioselective 1,2-cis-glycosylations via the SNi mechanism, yet no useful chemical glycosylations based on this mechanism have been developed. In this paper, we report a highly regio- and 1,2-cis-stereoselective SNi-type glycosylation of 1,2-anhydro donors and unprotected sugar acceptors using p-nitrophenylboronic acid (10e) as a catalyst in the presence of water under mild conditions. Highly controlled regio- and 1,2-cis-stereoselectivities were achieved via the combination of boron-mediated carbohydrate recognition and the SNi-type mechanism. Mechanistic studies using the KIEs and DFT calculations were consistent with a highly dissociative concerted SNi mechanism. This glycosylat...

Background Heart failure is one of the world’s most frequently diagnosed cardiovascular diseases. An important element of heart failure management is cardiac rehabilitation, the goal of which is to improve patients’ recovery, functional capacity, psychosocial well-being, and health-related quality of life. Patients in cardiac rehabilitation may lack sufficient motivation or may feel that the rehabilitation process does not meet their individual needs. One solution to these challenges is the use of telerehabilitation. Although telerehabilitation has been available for several years, it has only recently begun to be utilized in heart failure studies. Especially within the past 5 years, we now have several studies focusing on the effectiveness of telerehabilitation for heart failure management, all with varying results. Based on a review of these studies, this paper offers an assessment of the effectiveness of telerehabilitation as applied to heart failure management. Objective The aim of this scoping review was to assess the effects of telerehabilitation in the management of heart failure by systematically reviewing the available scientific literature within the period from January 1, 2015, to December 31, 2020. Methods The literature search was carried out using PubMed and EMBASE. After duplicates were removed, 77 articles were screened and 12 articles were subsequently reviewed. The review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews) guidelines. As measures of the effectiveness of telerehabilitation, the following outcomes were used: patients’ quality of life, physical capacity, depression or anxiety, and adherence to the intervention. Results A total of 12 articles were included in this review. In reviewing the effects of telerehabilitation for patients with heart failure, it was found that 4 out of 6 randomized controlled trials (RCTs), a single prospective study, and 4 out of 5 reviews reported increased quality of life for patients. For physical capacity, 4 RCTs and 3 systematic reviews revealed increased physical capacity. Depression or depressive symptoms were reported as being reduced in 1 of the 6 RCTs and in 2 of the 5 reviews. Anxiety or anxiety-related symptoms were reported as reduced in only 1 review. High adherence to the telerehabilitation program was reported in 4 RCTs and 4 reviews. It should be mentioned that some of the reviewed articles described the same studies although they employed different outcome measures. Conclusions It was found that there is a tendency toward improvement in patients’ quality of life and physical capacity when telerehabilitation was used in heart failure management. The outcome measures of depression, anxiety, and adherence to the intervention were found to be positive. Additional research is needed to determine more precise and robust effects of telerehabilitation.

Drug-resistant bacteria are still emerging, and screening of new skeletal antibiotics is important. During our continuous screening for antimicrobial agents, we discovered a new antimicrobial, named quadoctomycin, from solid culture of Streptomyces sp. MM168-141F8. The substance was purified by solvent extraction, silica gel chromatography and HPLC. Structural elucidation of quadoctomycin was performed by MS and NMR analyses and chemical degradation. Quadoctomycin possesses a 48-membered polyol macrolide skeleton in which an α-D-mannoside is connected to C-22 by an O-glycosidic linkage. The structure of quadoctomycin was found to be related to that of monazomycin A based on the analyses of NMR spectra in the same solvent (pyridine-d5). Quadoctomycin showed potent antibacterial activity against Staphylococcus aureus, including methicillin-resistant S. aureus, and other Gram-positive pathogenic bacteria such as Enterococcus faecalis and E. faecium (including drug-resistant strains), but did not show activity toward Gram-negative bacteria or Candida albicans.The Journal of Antibiotics advance online publication 15 November 2017; doi:10.1038/ja.2017.140.

In the course of optimizing pargamicin A production in Amycolatopsis sp. ML1-hF4, we discovered novel cyclic depsipeptide compounds in the broth and designated them valgamicins A, C, T and V. The structures of these molecules were determined by spectroscopic studies, advanced Marfey's method and X-ray crystal structural analysis. Valgamicin C contains the extremely rare amino acid cleonine. To our knowledge, this is the first report of a cleonine-containing metabolite from a naturally isolated microorganism without any breeding or mutation treatment. None of the valgamicins showed potent antibacterial activity against either Gram-positive or -negative bacteria. Valgamicins A, C and T exhibited moderate cytotoxicity against human tumor cell lines.The Journal of Antibiotics advance online publication, 15 November 2017; doi:10.1038/ja.2017.135.

Osteoblast and adipocyte are differentiated from mesenchymal stem cells and dysregulation of the differentiation might result in disease, such as osteoporosis and diabetes. To find small compounds that induce osteoblast differentiation, we screened an in-house natural compounds library with mouse preosteoblastic MC3T3-E1 cells using alkaline phosphatase (ALP) expression as an early osteoblast marker. We found that phenazine-1-carboxylic acid (PCA), one of the major phenazine derivatives produced by Pseudomonas, induced osteoblast differentiation in the cells at micromolar concentrations. PCA acted synergistically with an agonist of hedgehog signaling in inducing ALP activity in the cells. We also found that 2-hydroxy-PCA (2H-PCA) induced osteoblast differentiation in the cells but 2-methoxy-PCA and 1-hydroxy-phenazine did not. Unexpectedly, treatment of mouse pluripotent mesenchymal C3H10T1/2 cells with PCA or 2H-PCA induced an obvious morphological change. Oil Red O staining and real-time reverse-transcription PCR analysis revealed that PCA induced not osteoblast differentiation but adipocyte differentiation in C3H10T1/2 cells. These compounds could allow us to investigate the mechanism of osteoblast and adipocyte differentiation in the two model cell systems through a chemical biology approach.

Two new 4’-acetylated analogs of chrysomycin were discovered during the screening for antitumor agents from the metabolites of actinomycetes. Their structures and physicochemical properties were determined by standard spectrometric analyses. Their cytotoxicities and antimicrobial activities were evaluated against a panel of cancer cell lines and microbes. While acetylation reinforced the cytotoxicity of chrysomycin B, it weakened the activity of chrysomycin A. Chrysomycin A and its acetylated analog showed high cytotoxicity toward most of the cancer cells with IC50s less than 10 ng ml−1. The 4’-acetyl-chrysomycin A was predominantly observed in nuclei at concentrations where the autofluorescence was observable. Chrysomycins were effective toward Gram-positive bacteria. The 4’-acetylated-chrysomycin A and B had MICs of 0.5–2 μg ml−1 and 2 to greater than 64 μg ml−1, respectively, toward Gram-positive bacteria including MRSA and VRE.

Mitogen-activated protein kinase (MAPK) pathways that direct cellular responses are involved in various biological processes; the RAS-RAF-MEK-ERK pathway is one of the most important MAPK pathways. It is frequently activated in human malignant tumors such as melanomas, thyroid tumors and colorectal carcinomas. Therefore, targeting this pathway has been considered an attractive strategy for new anticancer drugs. In particular, MEK is a promising target because it is a kinase that directly phosphorylates ERK. We performed a screening to discover new MEK inhibitors, and found a guanine derivative produced by Streptomyces sp. MK63-43F2. This guanine derivative was identified to be 2-amino-4-methoxy-5-cyanopyrrolo[2,3-d]pyrimidine (1) through spectroscopic analysis. Compound 1 inhibited MEK1 kinase activity in an ATP-dependent manner and suppressed the phosphorylation of ERK in cancer cells and cell proliferation. Therefore, 1 might be a potent lead compound for new MEK inhibitors.The Journal of Antibiotics advance online publication, 6 September 2017; doi:10.1038/ja.2017.100.

Background The association of quantitative gait characteristics, such as gait variability with musculoskeletal pain is poorly understood. We aimed to examine whether gait speed and gait variability are associated with musculoskeletal pain assessed by the severity and the number of sites in community-dwelling elderly individuals. Methods A total of 176 elderly individuals participated in this study. The wireless motion-recording sensor units were attached to the lower trunk and heel during gait, and an autocorrelation coefficient was calculated in three directions as parameters of gait variability of trunk movement. Musculoskeletal pain was assessed in two aspects: severity and the number of sites. Results Moderate/severe pain intensity was significantly associated with slow gait speed and low AC in a mediolateral direction ( P = 0.024 and 0.026, respectively). Participants with musculoskeletal pain in multiple sites had significantly lower autocorrelation coefficient in mediolateral direction than did those without pain ( P = 0.003). Conclusions Presence of moderate/severe pain intensity in at least one site or any-intensity pain in multiple sites is associated with slower gait speed and higher gait variability of trunk movement in well-functioning elderly individuals living in the community. Additional studies are necessary to elucidate the causal relationships between musculoskeletal pain and gait.

Structure and antibacterial activities of new cyclic peptide antibiotics, pargamicins B, C and D, from Amycolatopsis sp. ML1-hF4