Chronic pain in older adults with disabilities is associated with fall-related injuries: a prospective cohort study.

PURPOSE: Previous studies have shown an association between chronic pain and the occurrence of falls in community-dwelling older adults; however, the association between chronic pain and fall-related injuries in older adults with disabilities is unclear. This study aimed to determine the association between chronic pain and fall-related injuries in older adults with disabilities. METHODS: This 24-month prospective cohort study included older adults aged 65 years or older using Japanese long-term care insurance services. Chronic pain, defined as "pain that has persisted for more than three months to date," was assessed using a face-to-face questionnaire. Fall-related injuries, defined as "injuries requiring hospitalization or outpatient treatment due to a fall," were assessed using a fall calendar. Data were analyzed using a Cox proportional hazards model, with fall-related injury as the dependent variable, chronic pain as the independent variable, and confounders as covariates. RESULTS: Among 133 included participants, 15 experienced fall-related injuries. After adjusting for age and sex as covariates, chronic pain was significantly associated with fall-related injuries (hazard ratio: 5.487, 95% confidence interval: 1.211-24.853, p = 0.027). CONCLUSIONS: Chronic pain was associated with fall-related injuries in older adults with disabilities. In this population, a greater focus should be placed on treating chronic pain to reduce the occurrence of falls.

Accurate ligand-protein docking in CASP15 using the ClusPro LigTBM server.

In the ligand prediction category of CASP15, the challenge was to predict the positions and conformations of small molecules binding to proteins that were provided as amino acid sequences or as models generated by the AlphaFold2 program. For most targets, we used our template-based ligand docking program ClusPro ligTBM, also implemented as a public server available at https://ligtbm.cluspro.org/. Since many targets had multiple chains and a number of ligands, several templates, and some manual interventions were required. In a few cases, no templates were found, and we had to use direct docking using the Glide program. Nevertheless, ligTBM was shown to be a very useful tool, and by any ranking criteria, our group was ranked among the top five best-performing teams. In fact, all the best groups used template-based docking methods. Thus, it appears that the AlphaFold2-generated models, despite the high accuracy of the predicted backbone, have local differences from the x-ray structure that make the use of direct docking methods more challenging. The results of CASP15 confirm that this limitation can be frequently overcome by homology-based docking.

Effect of Pre-Hospitalization Fall History on Physical Activity and Sedentary Behavior After the Implementation of a Behavioral Change Approach in Patients with Minor Ischemic Stroke: A Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: We aimed to determine whether a history of falls before admission affected physical activity levels and sedentary behavior negatively after implementing a behavior modification approach in patients with minor ischemic stroke. METHODS: This study constituted a secondary analysis of an intervention trial. In the intervention study, patients with minor ischemic stroke were randomly assigned to two groups: intervention and control groups. The intervention group was encouraged to reduce sedentary behavior during hospitalization and after discharge, while the control group was encouraged to increase physical activity levels solely during hospitalization. The study included 52 patients who completed the intervention trial. The exposure factor examined was a history of falls. Upon admission, patients were queried about any falls experienced in the year preceding admission and subsequently classified into fall and non-fall groups based on their responses. The primary outcome of interest focused on changes in physical activity levels (step count, light-intensity physical activity, and moderate-to-vigorous-intensity physical activity) and sedentary behavior. Measurements were obtained at two time points: before the intervention, during hospitalization (baseline), and 3 months after discharge (post-intervention). RESULTS: Only a significantly lower change in the number of steps taken in the fall group than in the non-fall group was found. CONCLUSION: Those with a history of falls showed a lesser change in the number of steps taken before and after implementing a behavior change approach compared with those without a history of falls. Those with a history of falls may have engaged in activities other than walking.

Effects on sedentary behaviour of an approach to reduce sedentary behaviour in patients with minor ischaemic stroke: A randomised controlled trial.

OBJECTIVES: To determine the effects on sedentary behaviour of an approach that promotes reduction in sedentary behaviour in patients with minor ischaemic stroke after intervention and at follow-up. DESIGN: A randomised controlled trial. SETTING: During hospitalisation and after hospital discharge. SUBJECTS: In total, 86 patients with minor ischaemic stroke admitted to an acute care hospital were assigned to the intervention (n = 43) and control (n = 43) groups. INTERVENTION: An intervention group that received an approach to reduce sedentary behaviour upon hospital admission until 3 months after discharge (education, self-monitoring, phone calls, etc.) and a control group that received the usual care during hospitalisation. From 3 to 6 months after discharge, no group received any intervention. MAIN OUTCOME: The primary outcome was the change (%) in sedentary behaviour from baseline to post-intervention (3 months after discharge) and follow-up (6 months after discharge). Sedentary behaviour was measured at baseline (upon hospital admission), post-intervention, and at follow-up using accelerometers. RESULTS: At the post-intervention stage, the intervention group showed a significantly greater change in sedentary behaviour from baseline than that shown by the control group (sedentary behaviour: intervention group, -22.7%; control group, -14.9%; P = 0.013; effect size = 0.58). At follow-up too, the intervention group showed a significantly greater change in sedentary behaviour from baseline than that shown by the control group (sedentary behaviour: intervention group, -20.4%; control group, -13.6%; P = 0.025; effect size = 0.54). CONCLUSIONS: An approach to reduce sedentary behaviour in patients with minor ischaemic stroke effectively reduces sedentary behaviour, which is sustained up to follow-up. TRIAL REGISTRATION: This study is registered at www.umin.ac.jp/ctr/index/htm UMIN000038616.

Effect of chronic pain on the occurrence of falls in older adults with disabilities: a prospective cohort study.

BACKGROUND: The relationship between chronic pain and the occurrence of falls in healthy older adults has been clarified in previous studies, but its relationship in older adults with disabilities has not. OBJECTIVE: This study aimed to determine whether chronic pain is related to the occurrence of falls in older adults with disabilities. METHODS: The participants were 101 older adults above 65 years old who used long-term care insurance services in Japan. Of these, 30 were fallers and 71 were non-fallers. Chronic pain, defined as pain lasting more than three months, was assessed using questionnaires, and the falls' occurrence was followed up for six months using a fall calendar. Logistic regression analysis was used to analyze the data, with falls as the dependent variable, chronic pain as the independent variable, and age, sex, body mass index, number of drugs, sleep disorders, and depression as covariates. RESULTS: After adjusting for covariates, chronic pain significantly influenced the occurrence of falls (odds ratio: 3.168, 95% confidence interval: 1.057-9.495, p = .04). CONCLUSION: Chronic pain was related to the occurrence of falls in older adults with disabilities. There is a need to focus on chronic pain presence in falls' prevention among older adults with disabilities.

Sarcopenia Affects Functional Independence Measure motor Scores in Elderly Patients with Stroke.

OBJECTIVES: There is no unified view of the relationship between sarcopenia and the activities of daily living (ADL) in stroke patients. This study aimed to determine whether sarcopenia affects the ADL in elderly patients with stroke. MATERIALS AND METHODS: This case-control study included 472 stroke patients aged ≥ 65 years who were admitted to the convalescent rehabilitation ward. Sarcopenia was defined as a decrease in both the skeletal muscle mass index and handgrip strength, based on the Asian Working Group for Sarcopenia 2019 criteria cut-off, which was assessed on admission. ADL was assessed using the Functional Independence Measure-motor (FIM-m) score at discharge. The Charlson comorbidity index, Mini Nutritional Assessment-Short Form, Brunnstrom recovery stage of the upper limb, Brunnstrom recovery stage of the lower limb and total amount of rehabilitation during hospitalization were evaluated as confounding factors. To clarify whether sarcopenia affects the ADL in patients with stroke, we conducted a multiple regression analysis with the presence of sarcopenia as the independent variable and FIM-m at discharge as the objective variable. RESULTS: The final analysis included 283 patients; among them, 163 (57.6%) patients had sarcopenia at the time of admission to the convalescent rehabilitation ward. In the multiple regression analysis, sarcopenia was independently associated with FIM-m at hospital discharge, even after adjusting for confounders (ß = -0.100, p = 0.034). CONCLUSIONS: Sarcopenia at admission in elderly patients with stroke affected the FIM-m at discharge, even after adjusting for multiple confounders.

Association between physical activity levels and depressive symptoms in patients with minor ischemic stroke.

OBJECTIVE: Post-stroke depression is associated with stroke recurrence and it is necessary to identify its influencing factors. The study aims to determine whether physical activity during hospitalization, as measured by accelerometer, was associated with depression after discharge in patients with minor ischemic stroke. MATERIALS AND METHODS: This prospective observational study assessed 76 patients with minor ischemic stroke (aged 71.2 years) admitted to an acute care hospital. Depressive symptoms 3 months after discharge from the hospital was assessed using a questionnaire sent by mail. Baseline was set during hospitalization, and accelerometers were used to measure sedentary behavior, light and moderate-to-vigorous physical activities during hospitalization. RESULTS: Three months after hospital discharge, 14 patients (18.4%) were placed in the depressive symptom group, with significantly more sedentary behavior (p = 0.021), less light physical activity (p = 0.016) and more depressive symptoms during hospitalization (p = 0.005) than in the non-depressive symptom group. Logistic regression analysis showed that sedentary behavior (odds ratio = 1.130, 95% confidence interval = 1.013‒1.281, p = 0.028) and light-intensity physical activity (odds ratio = 0.853, 95% confidence interval = 0.746‒0.976, p = 0.021) were independent factors for depressive symptoms at three months after discharge. Moderate to vigorous physical activity was not an independent factor. CONCLUSIONS: Sedentary behavior and light-intensity physical activity during hospitalization were associated with depressive symptoms in patients with minor ischemic stroke after discharge. Reducing sedentary behavior and increasing light-intensity physical activity as part of inpatient rehabilitation may help prevent post-stroke depression.

Chronic pain in the frail elderly mediates sleep disorders and influences falls.

AIM: Previous studies have highlighted the causation between chronic pain and falls in the elderly, but the mediator variables between chronic pain and falls in the frail elderly have not been identified. The purpose of this study was to identify the mediator variable of chronic pain and falls. METHODS: This study is a prospective cohort study. Participants were 116 frail elderly individuals living in a community. Chronic pain (pain lasting more than 3 months) was assessed using a questionnaire, and the occurrence of falls was tracked using a falls calendar. Using logistic regression, a model was created with falls as the dependent variable and chronic pain and confounders as independent variables. The mediation analysis was conducted with chronic pain as the independent variable, falls as the dependent variable, and factors that showed significant differences between the chronic pain group and the non-chronic pain group as candidate mediators. RESULTS: Even after adjusting for covariates, chronic pain significantly influenced the occurrence of falls (odds ratio: 3.004, 95% CI [1.226, 7.363], p=0.016). The results of mediation analysis showed a significant direct effect between chronic pain and falls, and a significant indirect effect (partial mediation) of sleep disorders on the relationship between chronic pain and falls. CONCLUSIONS: Chronic pain in frail elderly mediates sleep disorders and influences falls. It is suggested that interventions for chronic pain and sleep disorders should focus on preventing falls in the frail elderly.

Approaches to Promote Reduction in Sedentary Behavior in Patients With Minor Ischemic Stroke: A Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to determine whether an approach that promotes reduction in sedentary behavior (SB) during hospitalization and after hospital discharge reduces SB in patients with minor ischemic stroke (MIS) compared with an approach that promotes an increase in physical activity levels. DESIGN: Randomized controlled trial design. SETTING: During hospitalization and after hospital discharge. PARTICIPANTS: We randomly assigned patients (N=61) with MIS (average age, 71.3±8.3y; 65.6% men) admitted to an acute hospital to either the intervention group (reduced SB, n=31) or the control group (increased physical activity levels, n=30). INTERVENTIONS: During hospitalization, the intervention group received education on reducing SB, goal setting for SB after hospital discharge, and self-monitoring of SB and step count. In contrast, the control group received education on increasing physical activity levels and self-monitoring of step count. Patients in both groups wore an accelerometer during hospitalization until 3 months after hospital discharge. The intervention group received self-monitoring of SB and step count, stickers including information about reducing their SB, and phone calls once every 2 weeks for encouragement and feedback. The control group only wore the accelerometer. MAIN OUTCOME MEASURES: The primary outcome was SB (in percentage) at 3 months after hospital discharge. RESULTS: There was an interaction between the 2 groups for SB. Compared with the control group, the intervention group showed a significantly reduced SB (intervention group: baseline, 70.5%; 3 months after hospital discharge, 48.6%; control group: baseline, 71.5%; 3 months after hospital discharge, 57.5%; F value=5.981; P=.018). CONCLUSIONS: The results suggested that an approach that promotes SB reduction during hospitalization and after hospital discharge is effective in reducing SB in patients with MIS 3 months after hospital discharge.

Depression Is Associated with Chronic Pain in Disabled Older Adults.

BACKGROUND: The association between depression and chronic pain has been clearly demonstrated in healthy older adults, but not in older adults with disabilities. This study thus aimed to clarify the association between depression and chronic pain in older adults with disabilities. METHODS: In total, 92 older adults aged 65 years or older subscribed to Japanese long-term care insurance services were included in this study. Depression was assessed using the Geriatric Depression Scale-Short Version-Japanese (GDS-S-J) and was diagnosed among respondents who scored 6 or more points. Chronic pain was assessed using a questionnaire and defined as a "pain that persists in the present and has lasted for more than three months." RESULTS: Chronic pain was associated with depression in older adults with disabilities (odds ratio: 3,355, 95% confidence interval: 1,232-9,135, p = 0,018). There was a strong association between severe chronic pain and depression (odds ratio: 3,699, 95% confidence interval: 1,345-10,173, p = 0,011). CONCLUSION: Our findings suggest that it is necessary to focus on intensity of chronic pain to improve depression in older adults with disabilities who are more difficult to treat than healthy older adults.

Assessing the binding properties of CASP14 targets and models.

An important question is how well the models submitted to CASP retain the properties of target structures. We investigate several properties related to binding. First we explore the binding of small molecules as probes, and count the number of interactions between each residue and such probes, resulting in a binding fingerprint. The similarity between two fingerprints, one for the X-ray structure and the other for a model, is determined by calculating their correlation coefficient. The fingerprint similarity weakly correlates with global measures of accuracy, and GDT_TS higher than 80 is a necessary but not sufficient condition for the conservation of surface binding properties. The advantage of this approach is that it can be carried out without information on potential ligands and their binding sites. The latter information was available for a few targets, and we explored whether the CASP14 models can be used to predict binding sites and to dock small ligands. Finally, we tested the ability of models to reproduce protein-protein interactions by docking both the X-ray structures and the models to their interaction partners in complexes. The analysis showed that in CASP14 the quality of individual domain models is approaching that offered by X-ray crystallography, and hence such models can be successfully used for the identification of binding and regulatory sites, as well as for assembling obligatory protein-protein complexes. Success of ligand docking, however, often depends on fine details of the binding interface, and thus may require accounting for conformational changes by simulation methods.

Conservation of binding properties in protein models.

We study the models submitted to round 12 of the Critical Assessment of protein Structure Prediction (CASP) experiment to assess how well the binding properties are conserved when the X-ray structures of the target proteins are replaced by their models. To explore small molecule binding we generate distributions of molecular probes - which are fragment-sized organic molecules of varying size, shape, and polarity - around the protein, and count the number of interactions between each residue and the probes, resulting in a vector of interactions we call a binding fingerprint. The similarity between two fingerprints, one for the X-ray structure and the other for a model of the protein, is determined by calculating the correlation coefficient between the two vectors. The resulting correlation coefficients are shown to correlate with global measures of accuracy established in CASP, and the relationship yields an accuracy threshold that has to be reached for meaningful binding surface conservation. The clusters formed by the probe molecules reliably predict binding hot spots and ligand binding sites in both X-ray structures and reasonably accurate models of the target, but ensembles of models may be needed for assessing the availability of proper binding pockets. We explored ligand docking to the few targets that had bound ligands in the X-ray structure. More targets were available to assess the ability of the models to reproduce protein-protein interactions by docking both the X-ray structures and models to their interaction partners in complexes. It was shown that this application is more difficult than finding small ligand binding sites, and the success rates heavily depend on the local structure in the potential interface. In particular, predicted conformations of flexible loops are frequently incorrect in otherwise highly accurate models, and may prevent predicting correct protein-protein interactions.

Nonleisure-Time Physical Activity Guidance Following Minor Ischemic Stroke: A Randomized Clinical Trial.

The purpose of this single-masked randomized clinical trial was to examine whether nonleisure-time physical activity guidance (NLTPAG) improves physical activity levels in patients after minor ischemic stroke. Patients who had been hospitalized for minor ischemic stroke in an acute care hospital (National Health Institute Stroke Scale ≤ 5) were randomized to either an NLTPAG group (n = 17) or a leisure-time physical activity guidance group (n = 16). NLTPAG focused on reducing sedentary behavior and increasing the frequency of walking for shopping and household activities to improve physical activity levels in daily life. Physical activity levels significantly improved only in participants in the NLTPAG group (initial assessment: metabolic equivalents of task = 12.6; final assessment: metabolic equivalents of task = 14.8; p = .035, r = .51). These results suggest that NLTPAG may be effective for improving physical activity levels in patients after minor ischemic stroke.

ClusPro in rounds 38 to 45 of CAPRI: Toward combining template-based methods with free docking.

Targets in the protein docking experiment CAPRI (Critical Assessment of Predicted Interactions) generally present new challenges and contribute to new developments in methodology. In rounds 38 to 45 of CAPRI, most targets could be effectively predicted using template-based methods. However, the server ClusPro required structures rather than sequences as input, and hence we had to generate and dock homology models. The available templates also provided distance restraints that were directly used as input to the server. We show here that such an approach has some advantages. Free docking with template-based restraints using ClusPro reproduced some interfaces suggested by weak or ambiguous templates while not reproducing others, resulting in correct server predicted models. More recently we developed the fully automated ClusPro TBM server that performs template-based modeling and thus can use sequences rather than structures of component proteins as input. The performance of the server, freely available for noncommercial use at https://tbm.cluspro.org, is demonstrated by predicting the protein-protein targets of rounds 38 to 45 of CAPRI.

Effects of hydrogen bonding interactions on the redox potential and molecular vibrations of plastoquinone as studied using density functional theory calculations.

The effects of H-bonding on the redox potential and molecular vibrations of plastoquinone (PQ) that functions as a primary and a secondary quinone electron acceptor (QA and QB, respectively) in photosystem II (PSII) in plants and cyanobacteria were investigated using density functional theory calculations. Calculations were performed on the neutral and semiquinone anion forms of PQ and its H-bonded complexes, which form H-bonds with water molecules, or using amino acid models mimicking the interactions of QA and QB. The calculated redox potential (E(o)) of PQ showed a linear relationship with the number of H-bonds, and the E(o) increased by +100-200 mV with the addition of one H-bond. Vibrational analysis of the model PQ complexes showed that the CO stretching vibrations of neutral PQ are sensitive to the number and symmetry of H-bonding interactions, providing criteria to determine the H-bonding structure. Although no specific trend in the H-bonding dependency was found for anionic PQ, complex spectral features in the CO stretching region due to significant couplings with other PQ vibrations and the vibrations of H-bonding amino acids are useful monitors of the change in the H-bonding structure of anionic PQ in proteins. The calculated E(o) values and infrared spectra of the QA and QB models are consistent with the view that one additional H-bond to QB from D1-Ser264 largely contributes to the redox potential gap between QA and QB in PSII.