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Background Systemic inflammation is associated with poor functional outcomes. However, the effects of improved inflammation on functional indicators remain unclear. This study aimed to clarify the relationship between improvements in systemic inflammation and activities of daily living in patients after stroke. Methods This retrospective cohort study included patients post stroke with systemic inflammation upon admission. Systemic inflammation was defined as a modified Glasgow Prognostic Score (mGPS) score of 1–2. Improvement in systemic inflammation was defined as a reduction in mGPS score or blood C-reactive protein (CRP) levels during hospitalization. The primary outcomes were the motor items of the Functional Independence Measure (FIM-motor) at discharge. We applied multiple linear regression analysis to examine whether reduced systemic inflammation was associated with outcomes after adjusting for confounding factors. Results Of the 1,490 patients recruited, 158 (median age of 79 years; 88 men) had systemic inflammation on admission and were included in the study. Among these patients, 131 (82.9%) and 147 (93.0%) exhibited reduced mGPS and CRP levels, respectively. The median change in CRP was 2.1 mg/dL (interquartile range, 1.1–3.8). Multivariate analysis revealed that improvements in mGPS (β=0.125, p=0.012) and CRP levels (β=0.108, p=0.108) were independently and positively associated with FIM-motor at discharge. Conclusions Improvement in systemic inflammation was positively associated with functional outcomes in patients post stroke. Early detection and therapeutic intervention for systemic inflammation may further improve outcomes in these patients.

Background Sarcopenia negatively affects the short-term prognosis of hospitalized older adults. However, no evidence currently supports a direct relationship between sarcopenia and readmission among individuals who have experienced an acute stroke. Therefore, we investigated whether sarcopenia is associated with readmission after discharge. Methods This retrospective cohort study included patients who had experienced acute stroke. Sarcopenia was defined as the coexistence of low skeletal muscle mass index (SMI) and grip strength. We applied the log-rank test and Cox proportional hazards regression analysis to analyze whether sarcopenia, low SMI, and low grip strength were associated with readmission within 6 months. Results Among 228 included patients (mean age, 72.8 years; 146 males), the prevalence of sarcopenia was 24.6% (n=56; male 17.8%; female 36.6%). Cox proportional hazards regression analysis using the propensity score as a covariate revealed that sarcopenia (hazard ratio [HR]=7.21; 95% confidence interval [CI] 1.45–35.8; p=0.016) and low skeletal muscle mass (HR=7.40; 95% CI 1.14–48.1; p=0.036), but not low grip strength (HR=1.42; 95% CI 0.281–7.21; p=0.670), were significantly associated with readmission for stroke within 6 months. Conclusions Sarcopenia was negatively associated with readmission within 6 months of stroke onset in patients in Japan who had experienced an acute stroke. These findings suggest that the identification of sarcopenia may facilitate prognostic prediction from the acute stage and intervention(s) to prevent rehospitalization.

Background This study aimed to determine whether changes in phase angle during rehabilitation are associated with clinical outcomes such as activities of daily living (ADL), skeletal muscle mass index (SMI), and strength in patients with osteoporotic fractures. Methods This retrospective observational study included patients with osteoporotic fractures admitted to convalescent rehabilitation wards. Changes in phase angle were defined as the difference between the phase angle values at discharge and on admission. The primary outcome was the Functional Independence Measure motor (FIM-motor) score at discharge. The secondary outcomes were SMI and handgrip strength at discharge. We used multivariate analysis to adjust for confounding factors and examine the association between changes in the phase angle and outcomes. Results We analyzed a total of 115 patients (97 women, mean age of 81.0±10.0 years), with a median change in phase angle of 0° during hospitalization. We observed increased phase angles in 49 patients (43%), with a median increase of 0.2°. Multiple regression analysis showed that changes in phase angle were independently associated with FIM-motor score at discharge (β=0.238, p=0.027). Changes in phase angle were not significantly associated with SMI (β=0.059, p=0.599) or handgrip strength (β=-0.032, p=0.773) at discharge. Conclusion An increased phase angle during rehabilitation was positively associated with ADL improvement in patients with osteoporotic fractures. These findings may help clinicians make informed decisions regarding patient care and treatment strategies for better outcomes.

Animals navigate their environment by manipulating their movements and adjusting their trajectory which requires a sophisticated integration of sensory data with their current motor status. Here, we utilize the nematode Caenorhabditis elegans to explore the neural mechanisms of processing the sensory and motor information for navigation. We developed a microfluidic device which allows animals to freely move their heads while receiving temporal NaCl stimuli. We found that C. elegans regulates neck bending direction in response to temporal NaCl concentration changes in a way which is consistent with a C. elegans' navigational strategy which regulates traveling direction toward preferred NaCl concentrations. Our analysis also revealed that the activity of a neck motor neuron is significantly correlated with neck bending and activated by the decrease in NaCl concentration in a phase-dependent manner. By combining the analysis of behavioral and neural response to NaCl stimuli and optogenetic perturbation experiments, we revealed that NaCl decrease during ventral bending activates the neck motor neuron which counteracts ipsilateral bending. Simulations further suggest that this phase-dependent response of neck motor neurons can facilitate curving toward preferred salt concentrations. [ABSTRACT FROM AUTHOR]

Ship motion responses and added resistance in waves have been predicted by a wide variety of computational tools. However, validation of the computational flow field still remains a challenge. In the previous study, the flow field around the Korea Research Institute for Ships and Ocean Engineering (KRISO) Very Large Crude-oil Carrier 2 tanker model with and without propeller condition and without rudder condition was measured by the authors, as well as the resistance and self-propulsion tests in waves. In this study, the KRISO container shipmodel appended with a rudder was used for the higher Froude number .26 and smaller block coefficient .65. The experiments were conducted in the Osaka University towing tank using a 3.2-m-long ship model for resistance and self-propulsion tests in waves. Viscous flow simulation was performed by using CFDShip-Iowa. The wave conditions proposed in Computational Fluid Dynamics (CFD) Workshop 2015 were considered, i.e., the wave-ship length ratio λ/L = .65, .85, 1.15, 1.37, 1.95, and calm water. The objective of this study was to validate CFD results by Experimental Fluid Dynamics (EFD) data for ship vertical motions, added resistance, andwake flowfield. The detailed flowfield for nominalwake and self-propulsion condition will be analyzed for λ/L = .65, 1.15, 1.37, and calm water. Furthermore, bilge vortex movement and boundary layer development on propeller plane, propeller thrust, and wake factor oscillation in waves will be studied. [ABSTRACT FROM AUTHOR]

Obesity is accompanied by chronic, low-grade inflammation in adipose tissue, which is associated with insulin resistance and consequent multiple metabolic diseases. In addition to M1 macrophage infiltration, multiple involvements of adipose tissue T lymphocytes in the progression of inflammation have been highlighted recently. Here, we isolated a specific Vɑ5/Vβ8.2 TCR-bearing T cell that accumulated in obese adipose tissue of mice, and generated transgenic mice expressing this TCR. Under lean conditions with a normal chow diet, CD4+FoxP3+ Treg cells and M2 macrophages increased in adipose tissue with ageing in wild-type mice, but not in transgenic mice. However, both mice exhibited no obvious adipose tissue inflammation such as the formation of crown-like structures (CLSs) of infiltrating macrophages. When fed a high-fat diet, the proportion of adipose tissue Treg cells was markedly small at a similar level in transgenic and wild-type mice. Both types of mice exhibited comparable inflammatory states in adipose tissue, including vast formation of macrophage CLSs, accompanied by insulin resistance. Together, our findings suggest that the absence of an increase in Treg cells and M2 macrophages is not sufficient to initiate inflammatory macrophage infiltration in lean adipose tissue and also provide a new view about the involvement of T cells in promoting obesity-associated inflammation. [ABSTRACT FROM AUTHOR]

Introduction Loss of histone H4 lysine 20 trimethylation (H4K20me3) is associated with multiple cancers, but its role in breast tumors is unclear. In addition, the pathological effects of global reduction in H4K20me3 remain mostly unknown. Therefore, a major goal of this study was to elucidate the global H4K20me3 level in breast cancer tissue and investigate its pathological functions. Methods Levels of H4K20me3 and an associated histone modification, H3 lysine 9 trimethylation (H3K9me3), were evaluated by immunohistochemistry in a series of breast cancer tissues. Univariate and multivariate clinicopathological and survival analyses were performed. We also examined the effect of overexpression or knockdown of the histone H4K20 methyltransferases, SUV420H1 and SUV420H2, on cancer-cell invasion activity in vitro. Results H4K20me3, but not H3K9me3, was clearly reduced in breast cancer tissue. A reduced level of H4K20me3 was correlated with several aspects of clinicopathological status, including luminal subtypes, but not with HER2 expression. Multivariate analysis showed that reduced levels of H4K20me3 independently associated with lower disease-free survival. Moreover, ectopic expression of SUV420H1 and SUV420H2 in breast cancer cells suppressed cell invasiveness, whereas knockdown of SUV420H2 activated normal mammary epithelial-cell invasion in vitro. Conclusions H4K20me3 was reduced in cancerous regions of breast-tumor tissue, as in other types of tumor. Reduced H4K20me3 level can be used as an independent marker of poor prognosis in breast cancer patients. Most importantly, this study suggests that a reduced level of H4K20me3 increases the invasiveness of breast cancer cells in a HER2-independent manner. [ABSTRACT FROM AUTHOR]

The influence of electrical stimulation on calpain and ubiquitin-proteasome systems was examined in the denervated and unloaded tibialis anterior muscles of male Wistar rats. Animals were divided into 5 groups: control, denervation, denervation plus electrical stimulation, unloading, and hindlimb unloading plus electrical stimulation groups. Due to denervation and unloading for 14 days, muscle atrophy markedly occurred in the denervated and unloading animals, and the atrophy in the former was significantly more severe than that in the latter. In the denervated muscle, the atrophy was significantly attenuated by the electrical stimulation, but not in the unloaded muscle. Overexpression of calpain-2 and ubiquitinated proteins was observed only in denervated muscles. In the unloaded animals, though the expression level of calpain-2 appeared to be slightly higher than that in the control, the expression level of ubiquitinated proteins was almost the same as that in the control. The overexpression of calpain-1, calpain-2, and ubiquitinated proteins in the denervated muscle was inhibited by the electrical stimulation. However, there was no difference in these expressions between the unloaded and unloaded plus electrical stimulation groups. The mechanism of the preventive effect of the electrical stimulation on muscle atrophy might differ between the denervated and unloaded muscles. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia negatively affects the short-term prognosis of hospitalized older adults. However, no evidence currently supports a direct relationship between sarcopenia and readmission among individuals who have experienced an acute stroke. Therefore, we investigated whether sarcopenia is associated with readmission after discharge. Methods: This retrospective cohort study included patients who had experienced acute stroke. Sarcopenia was defined as the coexistence of low skeletal muscle mass index (SMI) and grip strength. We applied the log-rank test and Cox proportional hazards regression analysis to analyze whether sarcopenia, low SMI, and low grip strength were associated with readmission within 6 months. Results: Among 228 included patients (mean age, 72.8 years; 146 males), the prevalence of sarcopenia was 24.6% (n=56; male 17.8%; female 36.6%). Cox proportional hazards regression analysis using the propensity score as a covariate revealed that sarcopenia (hazard ratio [HR]=7.21; 95% confidence interval [CI] 1.45–35.8; p=0.016) and low skeletal muscle mass (HR=7.40; 95% CI 1.14–48.1; p=0.036), but not low grip strength (HR=1.42; 95% CI 0.281–7.21; p=0.670), were significantly associated with readmission for stroke within 6 months. Conclusions: Sarcopenia was negatively associated with readmission within 6 months of stroke onset in patients in Japan who had experienced an acute stroke. These findings suggest that the identification of sarcopenia may facilitate prognostic prediction from the acute stage and intervention(s) to prevent rehospitalization. [ABSTRACT FROM AUTHOR]

Purpose: Potentially inappropriate prescribing (PIP) is commonly encountered in older adults; yet, there is limited information on the occurrence of PIP among older adults with hypertension. This study aims to determine and compare the prevalence of PIP and its association with comorbidities in older adult outpatients with hypertension across hospitals and community health centers (CHCs). Methods: This 3-year (2015-2017) repeated cross-sectional study used electronic medical records from Shenzhen, China, involving 62 hospitals and 678 primary medical institutions. PIP was defined using the 2019 Beers Criteria. Older adults (≥65 years) with hypertension and at least one outpatient prescription were included. Modified Poisson regression analysis was used to assess the association between chronic comorbidities, healthcare settings, and PIP. Results: The prevalence of PIP in old adult outpatients with hypertension in 2015, 2016, and 2017 was 46.32%, 46.98%, and 46.58% in hospitals, with a sample size of 38,411, 46,235, and 50,495, respectively, and 29.14%, 26.66%, and 29.84% in CHCs, with a sample size of 26,876, 29,434, and 34,775 respectively. The top four most popular PIP in hospitals and CHCs was proton-pump inhibitors (PPIs), diuretics, benzodiazepines, and non-cyclooxygenase-selective non-steroidal anti-inflammatory drugs (NSAIDs), respectively. PIP was most associated with chronic gastrointestinal disease (adjusted prevalence ratio = 1.54, 95% confidence interval [CI] = 1.50-1.59) and mental and behavioral disorders (adjusted prevalence ratio = 1.49, 95% CI = 1.46-1.53) in hospitals and with mental and behavioral disorders (adjusted prevalence ratio = 1.99; 95% CI = 1.95-2.03) andmusculoskeletal systemand connective tissue disorders (adjusted prevalence ratio = 1.33; 95% CI = 1.31-1.36) in CHCs. The prevalence of PIP was significantly higher in hospital settings than in CHCs (adjusted prevalence ratio = 1.65; 95% CI = 1.63-1.66). Conclusion: Among older adult outpatients with hypertension in Shenzhen, PIP was more prevalent in hospitals than in CHCs. The comorbidities most strongly associated with PIP were chronic gastrointestinal disease and mental and behavioral disorders in hospitals and mental and behavioral disorders in CHCs. Clinical pharmacy integration needs to be considered to reduce inappropriate prescribing in this vulnerable population. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine whether changes in phase angle during rehabilitation are associated with clinical outcomes such as activities of daily living (ADL), skeletal muscle mass index (SMI), and strength in patients with osteoporotic fractures. Methods: This retrospective observational study included patients with osteoporotic fractures admitted to convalescent rehabilitation wards. Changes in phase angle were defined as the difference between the phase angle values at discharge and on admission. The primary outcome was the Functional Independence Measure motor (FIM-motor) score at discharge. The secondary outcomes were SMI and handgrip strength at discharge. We used multivariate analysis to adjust for confounding factors and examine the association between changes in the phase angle and outcomes. Results: We analyzed a total of 115 patients (97 women, mean age of 81.0±10.0 years), with a median change in phase angle of 0° during hospitalization. We observed increased phase angles in 49 patients (43%), with a median increase of 0.2°. Multiple regression analysis showed that changes in phase angle were independently associated with FIM-motor score at discharge (β=0.238, p=0.027). Changes in phase angle were not significantly associated with SMI (β=0.059, p=0.599) or handgrip strength (β=-0.032, p=0.773) at discharge. Conclusion: An increased phase angle during rehabilitation was positively associated with ADL improvement in patients with osteoporotic fractures. These findings may help clinicians make informed decisions regarding patient care and treatment strategies for better outcomes. [ABSTRACT FROM AUTHOR]

Aim: The effects of statins on muscle health are not well established. Therefore, this study investigated the impact of statin use on muscle strength and mass recovery in patients with sarcopenia after stroke. Methods: This retrospective cohort study included stroke patients with sarcopenia hospitalized between 2015 and 2021 at a post‐acute rehabilitation hospital. Sarcopenia was diagnosed using handgrip strength and skeletal muscle mass index measured using bioelectrical impedance analysis according to the 2019 criteria of the Asian Working Group for Sarcopenia. The study outcomes included handgrip strength and skeletal muscle mass index at hospital discharge. We used multivariate analyses to examine whether statin use was independently associated with the outcomes. Statistical significance was set at P < 0.05. Results: Of the 586 patients enrolled, 241 (mean age 79.3 years, 44.4% men) presented with sarcopenia and were included in the analysis. Statin use was observed in 61 (25.3%) patients. Statin use was independently negatively associated with handgrip strength at discharge (β = −0.095, P = 0.032), but not with skeletal muscle mass index at discharge (β = 0.019, P = 0.692). Conclusions: Statin use was negatively associated with muscle strength recovery, but not with muscle mass in patients with sarcopenia who underwent rehabilitation after stroke. To maximize outcomes, sufficient consideration is needed for statin use in these patients. Geriatr Gerontol Int 2023; 23: 676–683. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to calculate the cut‐off values for severe decline in muscle strength and skeletal muscle mass in post‐acute patients with sarcopenia and to determine their effect on activities of daily living. Methods: This retrospective cohort study included patients with sarcopenia consecutively admitted to a Japanese rehabilitation hospital between 2014 and 2016. Sarcopenia was diagnosed based on handgrip strength and skeletal muscle mass index. The outcome was the functional independence measure of motor function at discharge. Cut‐off values for predicting severe decline in handgrip strength and skeletal muscle mass index were calculated separately by sex. Values below the cut‐off were used to define severely low handgrip strength and severely low skeletal muscle mass index. Results: Overall, 451 patients (median age, 83 years; 61.4% women) were evaluated. The median functional independence measure of motor function score at discharge was 57. The optimal cut‐off values for severely low handgrip strength were 9.0 kg for women and 14.6 kg for men, and those for severely low skeletal muscle mass index were 4.6 kg/m2 for women and 5.6 kg/m2 for men. Severely low handgrip strength and skeletal muscle mass index were independently associated with the functional independence measure of motor function score at discharge (β = −0.178, P = 0.005). Conclusions: In post‐acute patients with sarcopenia, a severe decline in muscle strength and skeletal muscle mass is further negatively associated with an improvement in activities of daily living. The cut‐off values herein can serve as indicators to assess sarcopenia severity. Geriatr Gerontol Int 2023; 23: 493–499. [ABSTRACT FROM AUTHOR]

Energy intake and rehabilitation time individually contribute to the improvement of activities of daily living (ADL). This study aimed to investigate the additive effect of energy intake and rehabilitation time on ADL improvement in acute stroke patients with sarcopenia. The study included 140 patients (mean age 82.6 years, 67 men) with stroke. Energy intake during the first week of hospitalization was classified as "Sufficiency" or "Shortage" based on the reported cutoff value and rehabilitation time was classified as "Long" or "Short" based on the median. The study participants were categorized into four groups based on the combination of energy intake and rehabilitation time. The primary outcome was the gain of functional independence measure (FIM) motor during hospitalization. The secondary outcomes were length of stay and home discharge rates. Multivariate analysis was performed with primary/secondary outcomes as the dependent variable, and the effect of each group on the outcome was examined. Multivariate analysis showed that "long rehabilitation time and sufficient energy intake" (β = 0.391, p < 0.001) was independently associated with the gain of FIM motor items. The combination of high energy intake and sufficient rehabilitation time was associated with ADL improvement in acute stroke patients with sarcopenia. [ABSTRACT FROM AUTHOR]

Background: Evidence is scarce for potentially inappropriate medications (PIMs) in rehabilitation medicine. Aim: To examine the effect of PIMs on functional recovery in older patients with sarcopenia after stroke. Methods: We conducted a retrospective cohort study in a post-acute rehabilitation hospital. All patients diagnosed with sarcopenia aged ≥ 65 years among all post-stroke patients hospitalized from 2015 to 2020 were included. PIMs were defined based on the 2019 Beers criteria. Sarcopenia was diagnosed using handgrip strength (HG) and skeletal muscle mass index (SMI), according to the criteria of the Asian Working Group for Sarcopenia 2019. The outcomes included functional independence measure motor (FIM-motor), HG, and SMI values at discharge. Multiple linear regression analyses were used to determine whether PIMs used at admission were independently associated with outcomes. Results: Of the eligible patients, 361 were 65 years or older, of whom 196 (mean age 81.0 years, 44.4% male) presented with sarcopenia and were included in the analysis. Of these, 131 (66.8%) were prescribed PIMs at admission. The most frequently prescribed PIMs were proton pump inhibitors, antipsychotics, benzodiazepines, and nonsteroidal anti-inflammatory drugs. The number of PIMs on admission was independently associated with FIM-motor (β = − 0.132, P = 0.001) and HG (β = − 0.091, P = 0.048) at discharge, but not with SMI (β = − 0.055, P = 0.256). Conclusions: High admission PIMs prescription numbers are negatively associated with favorable discharge functional status and muscle strength in older patients with sarcopenia after stroke. [ABSTRACT FROM AUTHOR]

Evidence on polypharmacy in patients with sarcopenia is lacking. We aimed to examine the association of polypharmacy with swallowing function and nutritional risk in post-stroke patient with sarcopenia. This retrospective cohort study included hospitalized patients diagnosed with sarcopenia who needed convalescent rehabilitation following stroke onset. Study outcomes were the Food Intake Level Scale (FILS) as dysphagia assessment and geriatric nutritional risk index (GNRI) as nutritional status at hospital discharge, respectively. To examine the impact of admission polypharmacy, multivariate linear regression analyses were used to determine whether the number of drugs prescribed at hospital admission was associated with these outcomes. As a result, of the 586 patients enrolled, 257 (mean age 79.3 years, 44.0% male) were diagnosed with sarcopenia and were finally analyzed high admission drug prescription numbers were independently associated with FILS (β = −0.133, p = 0.017) and GNRI (β = −0.145, p = 0.003) at hospital discharge, respectively. Polypharmacy is associated with dysphagia and malnutrition in post-stroke patients with sarcopenia. In addition to the combination of nutritional and exercise therapies, review and optimization of prescription medications may be warranted to treat sarcopenia in order to maximize improvement in outcomes for these patients. [ABSTRACT FROM AUTHOR]

Sarcopenic obesity is of growing research and clinical interest; however, validated diagnostic criteria are lacking. We therefore aimed to examine the prevalence of sarcopenic obesity as diagnosed by the criteria recently proposed by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO), and its association with outcomes among patients after stroke. This study was based on a cohort of 760 Japanese patients after stroke admitted to a post-acute rehabilitation hospital. Sarcopenic obesity was diagnosed at admission according to the ESPEN and EASO criteria using reference values specific to Asians. Outcomes included the motor domain of the functional independence measure (FIM-motor) and the food intake level scale (FILS) at discharge. Multivariate linear regression models were used to assess the associations between sarcopenic obesity and outcomes. Among 760 patients (median age, 73 years; 352 women and 408 men), sarcopenic obesity was diagnosed in 34 patients (4.5%; 5.4% of women and 4.1% of men). In multivariate analyses, sarcopenic obesity was independently and negatively associated with FIM-motor (β = −0.048, p = 0.031) and FILS at discharge (β = −0.095, p = 0.046) in women. In contrast, in men, sarcopenic obesity showed an independent negative association with FIM-motor at discharge (β = −0.117, p < 0.001) but no statistically significant association with FILS at discharge (β = −0.004, p = 0.323). In conclusion, the prevalence of sarcopenic obesity diagnosed by the ESPEN and EASO-defined criteria was as low as 4.5% among Japanese patients after stroke. Furthermore, sarcopenic obesity was negatively associated with improvements in activities of daily living and dysphagia. [ABSTRACT FROM AUTHOR]

Keywords: amides; chlorination; dehydroamino acids; late-stage functionalization; peptides EN amides chlorination dehydroamino acids late-stage functionalization peptides 1 1 1 06/29/22 20220627 NES 220627 B A b I B N b i B -chloropeptide strategy b enables the rapid construction of AA-containing peptides. Cover Feature: Late-Stage Installation of Dehydroamino Acid Motifs into Peptides Enabled by an N-Chloropeptide Strategy (Chem. Eur. J. 36/2022) Amides, chlorination, peptides, dehydroamino acids, late-stage functionalization. [Extracted from the article]

Conventional methods for the construction of dehydroamino acids (ΔAAs), which are a unique class of non‐proteinogenic amino acids, require the pre‐installation of special amino acids. Herein, we report and demonstrate the practical utility of an N‐chloropeptide strategy for the rapid construction of ΔAA‐containing peptides. The electrophilic N‐chlorination of peptide bonds is drastically accelerated by a catalytic amount of quinuclidine (ABCO), and the subsequent β‐elimination of N‐chloroamide efficiently provides ΔAA‐containing peptides in high yield. The strategy enables, for the first time, the construction of a wide variety of ΔAA residues in peptides without any pre‐functionalized side chains and facilitates the late‐stage installation of ΔAA motifs into already‐constructed oligopeptides, including a medicinally important macrocyclic peptide. [ABSTRACT FROM AUTHOR]

Background Evidence is scarce regarding polypharmacy and potentially inappropriate medications (PIMs) in rehabilitation medicine. Aim To investigate the prevalence of polypharmacy and PIMs and their association with outcomes in stroke rehabilitation. Method A retrospective cohort study was conducted with 849 older inpatients post-stroke. Polypharmacy was defined as six or more medications, and PIMs were defined based on Beers criteria 2019. Study outcomes included functional independence measure (FIM)-motor, FIM-cognitive, energy intake, dysphagia, length of hospital stay, and the rate of home discharge. To consider the effect of pharmacotherapy during rehabilitation, multivariate analyses were used to determine whether the presence of polypharmacy or PIMs at discharge was associated with outcomes. Results After enrollment, 361 patients (mean age 78.3 ± 7.7 years; 49.3% male) were analyzed. Polypharmacy was observed in 43.8% and 62.9% of patients, and any PIMs were observed in 64.8% and 65.4% of patients at admission and discharge, respectively. The most frequently prescribed PIMs included antipsychotics, benzodiazepines, and proton pump inhibitors. Polypharmacy was negatively associated with FIM-motor score (β = − 0.062, P = 0.049), FIM-cognitive score (β = − 0.076, P = 0.014), energy intake (β = − 0.143, P = 0.005), and home discharge (OR: 0.458; 95% CI: 0.248, 0.847; P = 0.013). PIMs were negatively associated with home discharge (OR: 0.375; 95% CI: 0.195, 0.718; P = 0.003). Conclusion Polypharmacy and PIMs are commonly found among older patients undergoing stroke rehabilitation. Moreover, polypharmacy was negatively associated with activities of daily living (ADL) but not with PIMs and ADLs, and both were associated with home discharge. [ABSTRACT FROM AUTHOR]

sd1-d originating from ‘Dee-geo-woo-gen’ has been utilized to develop short-culmed indica varieties adaptable to higher fertilizer-application. Its tall alleles SD1-in and SD1-ja are harbored in indica and japonica subspecies, respectively. The sd1-d of indica IR36 was substituted with SD1-in or SD1-ja by recurrent backcrossing with IR36, and two tall isogenic lines (“5867-36” and “Koshi-36”) were developed. IR36, 5867-36 and Koshi-36 were grown in a paddy field in three years, and yield and related traits were measured, the effects of SD1-in and SD1-ja on yielding ability and related characteristics were examined on the genetic background of IR 36. SD1-in decreased panicle number per m2 but increased spikelet number per panicle, ripened-grain percentage and 1000-grain weight, compared with sd1-d, resulting in the increase of yield. The increase of 1000-grain weight by SD1-in, caused by the increases of length, width and thickness of grain, was due to the increases of the length and width of lemma. SD1-ja did not significantly affect yield, mainly because the decrease of panicle number per m2 was compensated by the enlarged 1000-grain weight owing to the increase of lemma length. Serious lodging was observed in long-culmed 5867-36, suggesting that sd1-d is indispensable for indica breeding programs. [ABSTRACT FROM AUTHOR]

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Despite CYP102A1 (P450BM3) representing one of the most extensively researched metalloenzymes, crystallisation of its haem domain upon modification can be a challenge. Crystal structures are indispensable for the efficient structure‐based design of P450BM3 as a biocatalyst. The abietane diterpenoid derivative N‐abietoyl‐l‐tryptophan (AbiATrp) is an outstanding crystallisation accelerator for the wild‐type P450BM3 haem domain, with visible crystals forming within 2 hours and diffracting to a near‐atomic resolution of 1.22 Å. Using these crystals as seeds in a cross‐microseeding approach, an assortment of P450BM3 haem domain crystal structures, containing previously uncrystallisable decoy molecules and diverse artificial metalloporphyrins binding various ligand molecules, as well as heavily tagged haem‐domain variants, could be determined. Some of the structures reported herein could be used as models of different stages of the P450BM3 catalytic cycle. [ABSTRACT FROM AUTHOR]

A photo-responsive nanoscroll composed of niobate nanosheets and a polyfluoroalkyl azobenzene derivative (C3F-Azo-C6H) is one of the most interesting layered materials because the reversible winding and unwinding motion could be efficiently induced by photo-irradiations. Previously, we have studied a double-walled nanoscroll (DWNS) of niobate that could be synthesized by the intercalation of a cationic polyfluorinated surfactant only into the interlayer I of the layered niobate among the two interlayers, I and II. In this study, we have successfully synthesized another novel photo-responsive single-walled nanoscroll (SWNS) of niobate by a stepwise guest–guest ion-exchange method. All niobate nanosheets that were exfoliated at both interlayers I and II were efficiently converted to nanoscrolls by the intercalation of C3F-Azo-C6H. The synthetic yield has been quantitatively estimated. Though the photo-isomerization reaction of C3F-Azo-C6H was induced in the SWNS, its photo-reactivity was the lowest when compared with those of the nanosheet-stacked film and the DWNS. The photo-reactivity of C3F-Azo-C6H decreased in the order of DWNS > nanosheet-stacked film > SWNS. The different flexibility of the layered miroenvironment might influence the photo-reactivity of C3F-Azo-C6H in the niobate hybrid. The SWNS exhibited a reversible expansion and shrinkage of its interlayer spaces upon photo-irradiation, while the winding and unwinding motion was not observed, contrary to the DWNS. The direction of the expansion and shrinkage of the interlayer of the SWNS was opposite to those of the nanosheet-stacked film and the DWNS. Based on the experimental results, the tilt angle of C3F-Azo-C6H against the nanosheet surface and the matching structures of the top and bottom surfaces of the nanosheet could be the probable key factors that control the photo-reactivity of C3F-Azo-C6H in the layered microenvironment; the morphological changes of the nano hybrids was also discussed. [ABSTRACT FROM AUTHOR]

A supervised machine learning algorithm, which is qualified for image classification and analyzing similarities, is based on multiple discriminative morphological features that are automatically assembled during the learning processes. The algorithm is suitable for population-based analysis of images of biological materials that are generally complex and heterogeneous. Here we used the algorithm wndchrm to quantify the effects on nucleolar morphology of the loss of the components of nuclear envelope in a human mammary epithelial cell line. The linker of nucleoskeleton and cytoskeleton (LINC) complex, an assembly of nuclear envelope proteins comprising mainly members of the SUN and nesprin families, connects the nuclear lamina and cytoskeletal filaments. The components of the LINC complex are markedly deficient in breast cancer tissues. We found that a reduction in the levels of SUN1, SUN2, and lamin A/C led to significant changes in morphologies that were computationally classified using wndchrm with approximately 100% accuracy. In particular, depletion of SUN1 caused nucleolar hypertrophy and reduced rRNA synthesis. Further, wndchrm revealed a consistent negative correlation between SUN1 expression and the size of nucleoli in human breast cancer tissues. Our unbiased morphological quantitation strategies using wndchrm revealed an unexpected link between the components of the LINC complex and the morphologies of nucleoli that serves as an indicator of the malignant phenotype of breast cancer cells. [ABSTRACT FROM PUBLISHER]

Chromosome elimination occurs frequently in interspecific hybrids between distantly related species in Poaceae. However, chromosomes from both parents behave stably in a hybrid of female oat ( Avena sativa L.) pollinated by pearl millet ( Pennisetum glaucum L.). To analyze the chromosome behavior in this hybrid, we cloned the centromere-specific histone H3 (CENH3) genes of oat and pearl millet and produced a pearl millet-specific anti-CENH3 antibody. Application of this antibody together with a grass species common anti-CENH3 antibody revealed the dynamic CENH3 composition of the hybrid cells before and after fertilization. Despite co-expression of CENH3 genes encoded by oat and pearl millet, only an oat-type CENH3 was incorporated into the centromeres of both species in the hybrid embryo. Oat CENH3 enables a functional centromere in pearl millet chromosomes in an oat genetic background. Comparison of CENH3 genes among Poaceae species that show chromosome elimination in interspecific hybrids revealed that the loop 1 regions of oat and pearl millet CENH3 exhibit exceptionally high similarity. [ABSTRACT FROM AUTHOR]

Cancer cells exhibit a variety of features indicative of atypical nuclei. However, the molecular mechanisms underlying these phenomena remain to be elucidated. The linker of nucleoskeleton and cytoskeleton ( LINC) complex, a nuclear envelope protein complex consisting mainly of the SUN and nesprin proteins, connects nuclear lamina and cytoskeletal filaments and helps to regulate the size and shape of the nucleus. Using immunohistology, we found that a nuclear lamina component, lamin A/C and all of the investigated LINC complex components, SUN1, SUN2, and nesprin-2, were downregulated in human breast cancer tissues. In the majority of cases, we observed lower expression levels of these analytes in samples' cancerous regions as compared to their cancer-associated noncancerous regions (in cancerous regions, percentage of tissue samples exhibiting low protein expression: lamin A/C, 85% [ n = 73]; SUN1, 88% [ n = 43]; SUN2, 74% [ n = 43]; and nesprin-2, 79% [ n = 53]). Statistical analysis showed that the frequencies of recurrence and HER2 expression were negatively correlated with lamin A/C expression ( P < 0.05), and intrinsic subtype and ki-67 level were associated with nesprin-2 expression ( P < 0.05). In addition, combinatorial analysis using the above four parameters showed that all patients exhibited reduced expression of at least one of four components despite the tumor's pathological classification. Furthermore, several cultured breast cancer cell lines expressed less SUN1, SUN2, nesprin-2 mRNA, and lamin A/C compared to noncancerous mammary gland cells. Together, these results suggest that the strongly reduced expression of LINC complex and nuclear lamina components may play fundamental pathological functions in breast cancer progression. [ABSTRACT FROM AUTHOR]

Global histone modification patterns correlate with tumor phenotypes and prognostic factors in multiple tumor types. Recent studies suggest that aberrant histone modifications play an important role in cancer. However, the effects of global epigenetic rearrangements on cell functions remain poorly understood. In this study, we show that the histone H3 lysine 9 (H3K9) methyltransferase SUV39H1 is clearly involved in regulating cell migration in vitro. Overexpression of wild-type SUV39H1, but not enzymatically inactive SUV39H1, activated migration in breast and colorectal cancer cells. Inversely, migration was reduced by knockdown of SUV39H1 or chemical inhibition by chaetocin. In addition, H3K9 trimethylation (H3K9me3) was specifically increased in invasive regions of colorectal cancer tissues. Moreover, the presence of H3K9me3 positively correlated with lymph node metastasis in colorectal cancer patients. Furthermore, overexpression of SUV39H1 drove tumorigenesis in mouse, resulting in a considerable decrease in survival rate. These data indicate that H3K9 trimethylation plays an important role in human colorectal cancer progression, possibly by promoting collective cell invasion. [ABSTRACT FROM AUTHOR]

Currently, there is a lack of evidence to show that exercise therapy improves sarcopenia in older patients in clinical practice. We therefore conducted a retrospective cohort study to clarify the effects of chair-stand exercise on improving sarcopenia among patients diagnosed with sarcopenia undergoing convalescent rehabilitation after stroke. According to the latest Asian criteria, sarcopenia was diagnosed when both skeletal muscle mass index (SMI) and handgrip strength (HGS) were low. Patients were asked to perform a repeated chair-stand exercise as whole-body resistance training, in addition to the rehabilitation program. Outcomes included sarcopenia rates, SMI, HGS, and physical function at hospital discharge. Multivariate analyses were used to examine whether the frequency of daily chair-stand exercise was independently associated with the outcomes after adjustment for potential confounders. After enrollment, 302 patients with sarcopenia (mean age: 78.6 years; 46.4% male) were analyzed. Overall, sarcopenia prevalence decreased by 21.9%, from 100% at admission to 78.1% at discharge. Multivariate analyses showed that the frequency of the exercise was significantly associated with the presence of sarcopenia (odds ratio: 0.986, p = 0.010), SMI (β = 0.181, p < 0.001), and HGS (β = 0.101, p = 0.032) at discharge, respectively. The chair-standing exercise was effective in improving sarcopenia in these patients. [ABSTRACT FROM AUTHOR]

Evidence is scarce regarding the polypharmacy in patients with sarcopenia. The aim of this study was to investigate the effect of deprescribing for polypharmacy on the improvement of nutritional intake and sarcopenia in older patients with sarcopenia. A retrospective cohort study was conducted with hospitalized older patients with sarcopenia undergoing rehabilitation after stroke. Study outcomes included energy intake, protein intake, handgrip strength (HG) and skeletal muscle mass index (SMI) at hospital discharge. To consider the effects of deprescribing for polypharmacy, we used multivariate analyses to examine whether the change in the number of medications during hospitalization was associated with outcomes. Of 361 patients after enrollment, 91 (mean age 81.0 years, 48.4% male) presented with sarcopenia and polypharmacy and were eligible for analysis. The change in the number of medications was independently associated with energy intake (β = −0.237, p = 0.009) and protein intake (β = −0.242, p = 0.047) at discharge, and was not statistically significantly associated with HG (β = −0.018, p = 0.768) and SMI (β = 0.083, p = 0.265) at discharge, respectively. Deprescribing was associated with improved nutritional intake in older sarcopenic patients with polypharmacy undergoing stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI., AKI is characterized by impaired kidney-filtration function, caused by insults such as kidney ischemia-reperfusion injury (IRI), sepsis or nephrotoxins. Although most cases of AKI are reversible, it is believed to [...]