[Risk factors for the onset of aspiration pneumonia among stroke patients in the recovery stage].

AIM: Post-stroke aspiration pneumonia is one of the most common complications among stroke patients. Although the onset of aspiration pneumonia is caused by a disruption of the balance between invasion (the type and amount of oral flora and aspiration) and host resistance (the protective airway reflex and immune function), several previous studies have focused on invasion, such as aspiration and dysphagia. In this study, we examined the importance of the host resistance to aspiration pneumonia among stroke patients with dysphagia. METHODS: The study subjects included 76 stroke patients (mean age, 74.7±8.4 years) with dysphagia chosen from 175 stroke patients who were newly admitted to four rehabilitation hospitals. We divided the subjects into two groups based on the onset of pneumonia during the period of admission and compared their status. RESULTS: Ten patients (13.2%) developed pneumonia at the hospital, and all of the affected patients were over 65 years old. Significant differences existed between the two groups with respect to the gender, activity level, albumin level, nutrition method and severity of dysphagia (p<0.05). CONCLUSIONS: Our study revealed that recumbency, malnutrition, tube feeding, severe dysphagia and female sex were risk factors for pneumonia. In particular, dysphagia was closely associated with aspiration pneumonia. Moreover, host resistance factors, such as recumbency and malnutrition, also play important roles in the development of aspiration pneumonia.

Activities of daily living limitation and functional decline during hospitalization predict 180-day readmission and mortality in older patients with pneumonia: A single-center, retrospective cohort study.

BACKGROUND: The role of activities of daily living (ADL) as a predictor of adverse outcomes in patients with pneumonia is unclear. This study aimed to assess the association between ADL, including physical and cognitive function, and death or readmission in older inpatients with pneumonia. METHODS: This retrospective, single-center, observational study included consecutive older inpatients with pneumonia between October 2018 and December 2019. ADL was assessed using the Functional Independence Measure (FIM). Functional decline during hospitalization was defined as a decrease of at least 1 point in FIM at discharge from admission. The primary outcome was the time to composite 180-day mortality and readmission from any cause after discharge. RESULTS: In total, 363 patients (median [interquartile range] age: 80 [73-86] years, male: 68 %) were divided according to the median FIM scores (≥100, n = 183 and < 100, n = 180). Among the patients, 25 experienced functional decline during hospitalization, 69 were readmitted, and 17 died. In the Kaplan-Meier analysis, both the lower FIM group and the functional decline group had significantly lower event-free rates than the higher FIM groups and the non-functional decline groups (log-rank test, p < 0.001), respectively. After multivariate analysis, both the lower FIM (adjusted HR, 2.11; 95 % CI, 1.24-3.58; p = 0.006) and functional decline (adjusted HR, 3.18; 95 % CI, 1.44-7.05; p = 0.005) were significantly associated with the primary outcome. CONCLUSIONS: In older patients hospitalized with pneumonia, ADL limitations at discharge and a decline in ADL were associated with poor outcomes.

Feasibility and informativeness of the Canadian occupational performance measure for identifying priorities in patients with Parkinson's disease.

OBJECTIVE: The aim of this study was to examine the feasibility and informativeness of the Canadian Occupational Performance Measure (COPM) for identifying the priorities of patients with Parkinson's disease (PD). METHODS: The COPM was administered in patients with PD who were admitted to the hospital. Feasibility was investigated by confirming the acceptability and practicality of the COPM interview. To investigate informativeness, identified priorities were classified according to the International Classification of Functioning, Disability and Health (ICF) and were cross-referenced with data from similar studies using the Patient-Specific Functional Scale (PSFS) and the Patient-Specific Index for PD (PSI-PD). RESULTS: All 61 patients who participated in this study completed the COPM, and a total of 197 priorities were identified. The most frequently identified priorities were "Recreation and leisure," "Preparing meals," "Walking," "Doing housework," and "Caring for household objects." The priorities identified using the PSFS and the PSI-PD were less diverse and focused on "Mobility" or "Self-care." CONCLUSIONS: The COPM is a feasible and informative tool for identifying priorities in patients with PD. Its informativeness was demonstrated by its ability to identify diverse priorities across the ICF domains of "Activity and participation" that had not been identified in the studies using the PSFS and PSI-PD.

Metabolic and ventilatory changes during postural change from the supine position to the reclining position in bedridden older patients.

The prevention of pneumonia in bedridden older patients is important, and its recurrence in these patients is a relevant issue. Patients who are bedridden and inactive, and have dysphagia are considered to be at risk for pneumonia. Efforts to reduce the bedridden state and low activity may be necessary to reduce the risk of developing pneumonia in bedridden older patients. This study aimed to clarify the effects of postural change from the supine position to the reclining position on metabolic and ventilatory parameters and on safety in bedridden older patients. Using a breath gas analyzer and other tools, we assessed the following 3 positions: lying on the back (supine), resting in the Fowler position (Fowler), and resting in an 80° recline wheelchair (80°). Measurements were oxygen uptake, carbon dioxide output, gas exchange ratio, tidal volume (VT), minute volume, respiratory rate, inspiratory time, expiratory time, total respiratory time, mean inspiratory flow, metabolic equivalents, end-expiratory oxygen, and end-expiratory carbon dioxide as well as various vital signs. The study analysis included 19 bedridden participants. The change in oxygen uptake driven by changing the posture from the supine position to the Fowler position was as small as 10.8 mL/minute. VT significantly increased from the supine position (398.4 ±â€…111.2 mL) to the Fowler position (426.9 ±â€…106.8 mL) (P  = .037) and then showed a decreasing trend in the 80° position (416.8 ±â€…92.5 mL). For bedridden older patients, sitting in a wheelchair is a very low-impact physical activity, similar to that in normal people. The VT of bedridden older patients was maximal in the Fowler position, and the ventilatory volume did not increase with an increasing reclining angle, unlike that in normal people. These findings suggest that appropriate reclining postures in clinical situations can promote an increase in the ventilatory rate in bedridden older patients.

Reliability and Validity of the Japanese Version of the Barthel Index Dyspnea Among Patients with Respiratory Diseases.

Purpose: Japan has only a few respiratory disease-specific activity of daily living scales that are accepted outside of Japan, and they are not widely used. The Barthel Index dyspnea (BI-d), an improved version of the Barthel Index (BI), may be popular in Japan. The purpose of this study was to develop the Japanese version of BI-d (J-BI-d) and investigate its reliability and validity. Patients and Methods: The J-BI-d was developed using the basic guidelines for scale translation. The study included patients with chronic respiratory disease, receiving outpatient care at two centers between January 2019 and February 2020. Scores on the J-BI-d, modified Medical Research Council scale (mMRC scale), BI, respiratory function tests, and 6-minute walk distance (6MWD) test were measured. To verify the test-retest reliability, the J-BI-d was re-administered, and the intraclass correlation coefficient (ICC) was obtained. Internal consistency was verified by Cronbach's alpha reliability coefficient, and criterion-related validity was verified through a correlation analysis of the J-BI-d with mMRC scale and 6MWD test. Divergent validity was verified through correlation analysis between the J-BI-d and BI. Results: Data for 57 participants (mean age 74.4 ± 8.3 years) were analyzed, and reliability testing was performed with 42 of them. The mean time to retest was 8.1 ± 3.0 days, and the ICC (2, 1) was 0.76 (95% CI: 0.62-0.85), indicating high reliability. Cronbach's alpha reliability coefficient was 0.81, indicating high internal consistency. Correlation coefficients of the J-BI-d with 6MWD test (r = -0.46, p < 0.01) and mMRC scale (ρ = 0.76, p < 0.01) indicated high criterion-related validity. The J-BI-d and BI had a weak negative correlation (r = -0.29, p < 0.05), indicating high divergent validity. Conclusion: The results of this study demonstrate high reliability and appropriate validity of the J-BI-d in patients with chronic respiratory disease.

Relationship between the Functional Independence Measure and Mann Assessment of Swallowing Ability in hospitalized patients with pneumonia.

AIM: Pneumonia ranks high among the causes of death worldwide. However, the predictive values of activities of daily living, the nutrition index and the aspiration index measured objectively remain unclear. The present study aimed to examine the associations of activity, nutrition and dysphagia with pneumonia. METHODS: We assessed 992 hospitalized patients. Logistic regression analysis was used to examine the predictors of pneumonia. Receiver operating characteristic curve analysis was used to determine the cut-off values of variables. Kaplan-Meier and Cox hazards regression analyses were used to examine the incidence of pneumonia and the factors associated with pneumonia. RESULTS: We finally enrolled 393 inpatients. Of the 393 patients, 102 (26.0%) had pneumonia. On logistic regression analysis, age, Functional Independence Measure (FIM)-motor score and Mann Assessment of Swallowing Ability (MASA) score were independent predictors of pneumonia. The FIM-motor and MASA cut-off values were 19.5 (area under the curve 0.83, P < 0.01) and 170.5 (area under the curve 0.82, P < 0.01), respectively. Kaplan-Meier analysis showed that the no pneumonia rate was significantly lower among patients with FIM-motor scores <20 than among those with FIM-motor scores ≥20 (log-rank test, P < 0.01), and was significantly lower among patients with MASA scores <171 than among those with MASA scores ≥171 (log-rank test, P < 0.01). Cox regression analysis showed that FIM-motor (hazard ratio 0.97, P = 0.009) and MASA scores (hazard ratio 0.99, P < 0.01) were significantly associated with pneumonia. CONCLUSIONS: In addition to the infectious risk, the FIM-motor and MASA scales are useful tools to predict the development of pneumonia in older adults. Geriatr Gerontol Int 2018; 18: 1620-1624.

Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance.

BACKGROUND: Epimagnolin A is an ingredient of the Chinese crude drug Shin-i, derived from the dried flower buds of Magnolia fargesii and Magnolia flos, which has been traditionally used for the treatment of allergic rhinitis and nasal congestion, empyema, and sinusitis. The pharmacokinetic activity of epimagnolin A remains to be evaluated. PURPOSE: In this study, we examined the possible interactions of epimagnolin A with human ATP-binding cassette (ABC) transporter ABCB1, a membrane protein vital in regulating the pharmacokinetics of drugs and xenobiotics. STUDY DESIGN/METHODS: The interaction of epimagnolin A with ABCB1 was evaluated in calcein, ATPase, and MTT assays by using Flp-In-293/ABCB1 cells and purified ABCB1 and simulated in molecular docking studies. RESULTS: Epimagnolin A inhibited calcein export by Flp-In-293/ABCB1 cells in a concentration-dependent manner in a calcein assay. ATPase assay revealed a concentration-dependent stimulation of the ATPase activity of ABCB1 by epimagnolin A. Epimagnolin A also showed saturation kinetics in the relationship between the compound-stimulated ATPase activity and the compound concentration, suggesting Michaelis-Menten kinetics similar to those of the control drug, verapamil. Km and Vmax values were calculated from Hanes-Woolf plots of (compound concentration) × (compound-stimulated ATPase activity)-1 vs. (compound concentration); the Km of epimagnolin and verapamil was 42.9 ±â€¯7.53  µM and 12.3 ±â€¯4.79  µM, respectively, and the corresponding Vmax values were 156 ±â€¯15.0  µM and 109 ±â€¯3.18  µM. Molecular docking studies on human ABCB1 showed that epimagnolin A docked to the same binding pocket as verapamil, and 3-(4,5-dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays showed that the sensitivities of Flp-In-293/ABCB1 cells against anti-cancer drugs were enhanced upon exposure to 10  µM epimagnolin A. CONCLUSION: These results strongly suggest that epimagnolin A affects the transport activity of ABCB1 as a substrate.

Relationship between functional independence measure and geriatric nutritional risk index in pneumonia patients in long-term nursing care facilities.

AIM: The prevention of pneumonia is an urgent issue among Japanese older adults. However, little has been reported on the relationship between a Functional Independence Measure (FIM) and the Geriatric Nutrition Risk Index (GNRI) for the prevention of pneumonia in patients in long-term care facilities in Japan. We aimed to clarify the relevance of FIM and GNRI for inpatients with and without pneumonia. METHODS: We identified 233 patients who were hospitalized in our long-term nursing hospital from April 2012 to September 2013. We compared differences in FIM among GNRI classes for four groups: (i) pneumonia/high GNRI; (ii) pneumonia/low GNRI; (iii) no pneumonia/high GNRI; and (iv) no pneumonia/low GNRI. To assess the pneumonia predictors, we used a logistic regression for long-term nursing patients. Receiver operating characteristic analysis showed cut-off values and the area under the curve. RESULTS: A total of 88 (37.8%) of 233 inpatients had pneumonia. FIM of the pneumonia/low GNRI groups was significantly lower than that of the no pneumonia/high and low GNRI groups. Logistic regression showed that FIM (P < 0.001; OR -1.035, 95% CI -1.019-1.051) and GNRI (P = 0.017; OR -1.038, 95% CI -1.007-1.070) were predictors of pneumonia. The cut-off values for FIM and GNRI were 26.6 (P < 0.001, the area under the curve 0.70) and 80.5 (P < 0.001, the area under the curve 0.65), respectively. CONCLUSION: Low activity and malnutrition might lead to the development of pneumonia. FIM and GNRI are useful predictor tools that could help to prevent pneumonia in Japanese patients in long-term care facilities. Geriatr Gerontol Int 2017; 17: 1617-1622.

Usefulness of the desaturation-distance ratio from the six-minute walk test for patients with COPD.

PURPOSE: A straightforward, noninvasive method is needed to assess emphysema and pulmonary hypertension (PH) in COPD patients. The desaturation-distance ratio (DDR) is an index derived from the distance traveled and level of desaturation during a six-minute walk test (6MWT); it has previously been shown to be associated with percentage of forced expiratory volume in the first second of expiration (%FEV1.0) and percentage of diffusion capacity of the lung for carbon monoxide (%DLCO). The aim of this study was to examine the associations between DDR and emphysema and PH. PATIENTS AND METHODS: We collected the following data for 74 stable COPD outpatients: lung function tests (%FEV1.0 and %DLCO), 6MWT distance and desaturation, and area of emphysema on computed tomography (percentage of low attenuation area). Enlargement of the pulmonary artery (PA) was assessed by the ratio of the diameter of the PA to that of the aorta (PA:A ratio) as an index of PH. DDR was calculated by the distance traveled and the degree of desaturation reached during a 6MWT. The relationships between study outcomes were assessed with Spearman's rank-correlation analysis. Receiver operating characteristic (ROC) curves were used to determine the threshold values with the optimum cutoff points for predicting severe or very severe airway obstruction, pulmonary diffusing capacity disorder, moderate or severe emphysema, and enlargement of the PA. RESULTS: DDR correlated significantly with %FEV1.0, %DLCO, %LAA, and PA:A ratio. DDR showed high accuracy (area under the ROC curve >0.7) for predicting severe or very severe airway obstruction, pulmonary diffusing capacity disorder, moderate or severe emphysema, and enlargement of the PA. CONCLUSION: The results suggest that DDR is a good index of emphysema and PH in COPD patients. The 6MWT is widely used to assess COPD, and DDR could help with the early diagnosis of COPD.

Usefulness of the 6-minute walk test as a screening test for pulmonary arterial enlargement in COPD.

PURPOSE: Pulmonary hypertension and exercise-induced oxygen desaturation (EID) influence acute exacerbation of COPD. Computed tomography (CT)-detected pulmonary artery (PA) enlargement is independently associated with acute COPD exacerbations. Associations between PA to aorta (PA:A) ratio and EID in patients with COPD have not been reported. We hypothesized that the PA:A ratio correlated with EID and that results of the 6-minute walk test (6MWT) would be useful for predicting the risk associated with PA:A >1. PATIENTS AND METHODS: We retrospectively measured lung function, 6MWT, emphysema area, and PA enlargement on CT in 64 patients with COPD. The patients were classified into groups with PA:A ≤1 and >1. Receiver-operating characteristic curves were used to determine the threshold values with the best cutoff points to predict patients with PA:A >1. RESULTS: The PA:A >1 group had lower forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1:FVC ratio, diffusion capacity of lung carbon monoxide, 6MW distance, and baseline peripheral oxygen saturation (SpO2), lowest SpO2, highest modified Borg scale results, percentage low-attenuation area, and history of acute COPD exacerbations ≤1 year, and worse BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index results (P<0.05). Predicted PA:A >1 was determined for SpO2 during 6MWT (best cutoff point 89%, area under the curve 0.94, 95% confidence interval 0.88-1). SpO2 <90% during 6MWT showed a sensitivity of 93.1, specificity of 94.3, positive predictive value of 93.1, negative predictive value of 94.3, positive likelihood ratio of 16.2, and negative likelihood ratio of 0.07. CONCLUSION: Lowest SpO2 during 6MWT may predict CT-measured PA:A, and lowest SpO2 <89% during 6MWT is excellent for detecting pulmonary hypertension in COPD.

Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens.

Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein/MDR1) is one of the major obstacles in chemotherapy. To understand the mechanism of MDR by ABCB1 and circumvent the MDR, in the present study, we established human ABCB1-expressing cells (Flp-In-293/ABCB1 cells) and examined the cytotoxic effects of four guanidine alkaloids from Pterogyne nitens (galegine, nitensidine A, pterogynidine and pterogynine) using Flp-In-293/Mock and Flp-In-293/ABCB1 cells. The activity of ABCB1 in Flp-In-293/ABCB1 cells were confirmed by typical substrates for ABCB1 (taxol and vinblastine) in MTT assay. Flp-In-293/ABCB1 cells were also resistant to the four guanidine alkaloids as well as taxol and vinblastine compared to Flp-In-293/Mock cells although the four guanidine alkaloids exhibited cytotoxicity against the two Flp-In-293 cells. Furthermore, the four guanidine alkaloids were also found to stimulate the ATPase activity of ABCB1 in ATPase assays. These results suggest that ABCB1 can confer the resistance to the cytotoxic guanidine alkaloids by transporting them.

Nitensidine A, a guanidine alkaloid from Pterogyne nitens, induces osteoclastic cell death.

Nitensidine A is a guanidine alkaloid isolated from Pterogyne nitens, a common plant in South America. To gain insight into the biological activity of P. nitens-produced compounds, we examined herein their biological effects on osteoclasts, multinucleated giant cells that regulate bone metabolism by resorbing bone. Among four guanidine alkaloids (i.e., galegine, nitensidine A, pterogynidine, and pterogynine), nitensidine A and pterogynine exhibited anti-osteoclastic effects at 10 µM by reducing the number of osteoclasts on the culture plate whereas galegine and pterogynidine did not. The anti-osteoclastic activities of nitensidine A and pterogynine were exerted in a concentration-dependent manner, whereas nitensidine A exhibited an approximate threefold stronger effect than pterogynine (IC50 values: nitensidine A, 0.93 ± 0.024 µM; pterogynine, 2.7 ± 0.40 µM). In the present study, the anti-osteoclastic effects of two synthetic nitensidine A derivatives (nitensidine AT and AU) were also examined to gain insight into the structural features of nitensidine A that exert an anti-osteoclastic effect. The anti-osteoclastic effect of nitensidine A was greatly reduced by substituting the imino nitrogen atom in nitensidine A with sulfur or oxygen. According to the differences in chemical structures and anti-osteoclastic effects of the four guanidine alkaloids and the two synthetic nitensidine A derivatives, it is suggested that the number, binding site, and polymerization degree of isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their anti-osteoclastic effects.

Comparison of Geriatric Nutritional Risk Index scores on physical performance among elderly patients with chronic obstructive pulmonary disease.

OBJECTIVES: The Geriatric Nutritional Risk Index (GNRI) is a new prognostic indicator for nutritional status-related complications and mortality among the elderly. Here we aimed to compare 6-min walk distance (6MWD) between high and low GNRI groups for patients with COPD. METHODS: We enrolled 63 elderly men with COPD. These subjects were divided into two groups based on their GNRI scores: high GNRI group (≥92 points; n = 44) and low GNRI group (n = 19); we compared 6MWD between these groups. RESULTS: The subjects' characteristics between the high and the low GNRI groups were similar, except for BMI and serum albumin levels. 6MWD were significantly lower in the low GNRI group (279.5 ± 112.3 m versus 211.1 ± 125.3 m; p = 0.03). CONCLUSIONS: The GNRI has a more close relation with exercise tolerance and may be a useful nutritional assessment scale for elderly patients with COPD.

Nitensidine A, a guanidine alkaloid from Pterogyne nitens, is a novel substrate for human ABC transporter ABCB1.

The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibited some level of cytotoxicity against both CCRF-CEM and CEM/ADR5000 cells. In ATPase assays, three of the four guanidine alkaloids were found to stimulate the ATPase activity of ABCB1. Notably, nitensidine A was clearly found to stimulate the ATPase activity of ABCB1 as strongly as the control drug, verapamil. Furthermore, the cytotoxic effect of nitensidine A on CEM/ADR5000 cells was synergistically enhanced by verapamil. Nitensidine A inhibited the extrusion of calcein by ABCB1. In the present study, the possibility of interaction between ABCB1 and two synthetic nitensidine A analogs (nitensidine AT and AU) were examined to gain insight into the mechanism by which nitensidine A stimulates the ATPase activity of ABCB1. The ABCB1-dependent ATPase activity stimulated by nitensidine A was greatly reduced by substituting sulfur (S) or oxygen (O) for the imino nitrogen atom (N) in nitensidine A. Molecular docking studies on human ABCB1 showed that, guanidine alkaloids from P. nitens dock to the same binding pocket as verapamil. Nitensidine A and its analogs exhibit similar binding energies to verapamil. Taken together, this research clearly indicates that nitensidine A is a novel substrate for ABCB1. The present results also suggest that the number, binding site, and polymerization degree of the isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their stimulation of ABCB1's ATPase activity.

Wideband digital frequency detector with subtraction-based phase comparator for frequency modulation atomic force microscopy.

We have developed a wideband digital frequency detector for high-speed frequency modulation atomic force microscopy (FM-AFM). We used a subtraction-based phase comparator (PC) in a phase-locked loop circuit instead of a commonly used multiplication-based PC, which has enhanced the detection bandwidth to 100 kHz. The quantitative analysis of the noise performance revealed that the internal noise from the developed detector is small enough to provide the theoretically limited noise performance in FM-AFM experiments in liquid. FM-AFM imaging of mica in liquid was performed with the developed detector, showing its stability and applicability to true atomic-resolution imaging in liquid.