Feeding Assistance Skill Score: development and verification of reliability and validity.

PURPOSE: Feeding assistance should be safe and improve the assisted individual's ability to feed, yet objective tools for evaluating these skills are lacking. This study focuses on developing a tool for assessing feeding assistance skills. METHODS: A group consisting of 25 experts employed the Delphi method to achieve a consensus on the essential items necessary for assessing feeding assistance skills. Subsequently, a draft score using a three-point scale was developed. To test the reliability of the draft scores, a group of 20 patients and 20 nurses was matched to record a meal assistance scene, which were independently evaluated by three raters. We computed the AC1 statistic to assess both intra- and inter-rater reliability, and further examined correlations between the Feeding Assistance Skill Score (FASS) scores and outcome items to verify validity. RESULTS: Initially, an 18-item draft score was generated using the Delphi method. Subsequently, seven items were omitted from the intra- or inter-rater reliability analysis. Furthermore, after discussion, researchers removed one item that assessed food cognition, because the agreement score between the two items was 91%. Finally, the 10-item FASS was developed, showing a correlation with dietary intake upon validation. CONCLUSIONS: We successfully developed a scoring system for peer evaluation of feeding assistance skills. Future studies should aim to validate the FASS. The implementation of the FASS aims to assess the effectiveness of feeding assistance training and care quality, potentially improving safety and satisfaction for those receiving feeding assistance.

Association between sarcopenia and urinary dysfunction in patients with dysphagia.

INTRODUCTION: The objective was to determine the relationship between sarcopenia and urinary dysfunction in patients with dysphagia. MATERIAL AND METHODS: A cross-sectional study was conducted on 460 Japanese Sarcopenic Dysphagia Database participants. Urinary dysfunction was defined as either urinary incontinence or urethral catheter use. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria. Univariate and multivariate analyses assessed the association between urinary dysfunction and sarcopenia, calf circumference (CC), handgrip strength (HGS), and Barthel Index (BI). Logistic regression analysis was performed for urinary dysfunction adjusted for age, sex, setting, and CCI in addition to BI and HGS or CC or sarcopenia (model 1) or FILS and BI (model 2). RESULTS: The mean age was 80.8 ± 10.5 years and urinary dysfunction in 137 participants. Urinary dysfunction was not associated with sarcopenia (123 versus 281, p = 0.440) but was associated with CC (27.4 ± 4.2 versus 28.5 ± 3.9, p = 0.009), HGS (9.7 ± 7.9 versus 14.4 ± 9.3, p < 0.001), and BI (19.9 ± 0.3 versus 20.3 ± 0.2, p < 0.001). Logistic regression analysis showed urinary dysfunction was associated with HGS (OR: 0.968, CI: 0.938, 0.998) and BI (OR: 0.955, CI: 0.943, 0.966). The cutoff was 19 kg for men (sensitivity 0.786, specificity 0.56, Area Under Curve (AUC) 0.689) and 6.1 kg for women (sensitivity 0.493, specificity 0.774, AUC 0.639) in HGS and 27.5 points in BI (sensitivity 0.781, specificity 0.604, AUC 0.740). CONCLUSION: Sarcopenia was not associated with urinary dysfunction. However, HGS and BI were related to urinary dysfunction.

Changes in Health-Related Quality of Life by Patient Education and Rehabilitation Based on a Behavior Change Program in Knee Osteoarthritis.

OBJECTIVE: The purpose of this study was to examine how rehabilitation and patient education for knee osteoarthritis improves health-related quality of life (HRQOL) and to identify factors influencing HRQOL. METHODS: Between May 2020 and March 2022, 30 patients with osteoarthritis of the knee were treated conservatively and rehabilitated with a patient education program. The patient education program was based on the health belief model by Sedlak et al., and patient education using pamphlets was provided during the rehabilitation intervention. The survey items were patient basic information, instrumental activities of daily living (ADL) (FAI), fear of falling (FES), degree of depression (GDS), HRQOL (SF-8), knee function assessment (JOA score), and X-ray classification (K-L classification), and the survey method was a self-administered questionnaire at the start of rehabilitation, 1 month after the intervention, and at the end of the rehabilitation intervention. We examined factors affecting the physical component summary (PCS) and mental component summary (MCS) of HRQOL scores. RESULTS: JOA score, FES, FAI, GDS, and SF-8 improved significantly (p<0.01). MCS was also negatively correlated with FES and age (r=-0.486, -0.368). Sex was extracted as a factor for PCS as a factor affecting HRQOL (p<0.01). MCS was extracted with FES as a factor (p=0.046). CONCLUSION: A rehabilitation intervention incorporating patient education in osteoarthritis of the knee showed improvement in HRQOL and may be useful for improving depression, fear of falling, and instrumental ADL.

Impact of body mass index on outcomes of inpatients with vertebral compression fractures in Japan: A retrospective cohort study.

AIM: The present study examined the relationship between body mass index and the ability to perform the activities of daily living in patients with vertebral compression fractures. METHODS: A retrospective cohort analysis of patients aged >65 years hospitalized with a vertebral compression fracture was carried out using a nationwide database in Japan. Body mass index was categorized as underweight (<18.5 kg/m2 ), normal weight (18.5-22.9 kg/m2 ), overweight (23.0-27.4 kg/m2 ) and obese (≥27.5 kg/m2 ) according to the World Health Organization criteria for the Asia-Pacific region. The primary outcome was Barthel Index gain, namely, the change in the Barthel Index score at discharge from that at admission. Secondary outcomes were the length of hospital stay and readmission within 30 days of discharge. RESULTS: Among 41 423 participants, 24.5% were classified as underweight, excluding those with missing body mass index data. The underweight group had a significantly lower Barthel Index gain than the normal, overweight and obese groups (median 20 vs 25 vs 30 vs 30, respectively, P < 0.001). The underweight group also had longer hospital stays and higher 30-day readmission rates than the other groups. A multivariable analysis showed that being underweight was independently associated with a Barthel Index gain -3.63 points (95% confidence interval -4.58 to -2.68) lower than normal weight. Furthermore, being underweight was an independent variable affecting the length of hospital stay and readmission within 30 days (P < 0.001). CONCLUSIONS: In patients with vertebral compression fractures, being underweight leads to lower Barthel Index scores, longer hospital stays and increased readmissions within 30 days of discharge. Geriatr Gerontol Int 2023; 23: 788-794.

Association between board-certified physiatrist involvement and functional outcomes in sarcopenic dysphagia patients: a retrospective cohort study of the Japanese Sarcopenic Dysphagia Database.

Objective: Dysphagia rehabilitation is an important area in geriatric nutrition due to the commonality of sarcopenic dysphagia in older adults. However, there have been no reports on the efficacy of treatment by board-certified physiatrists (BCP) in patients with sarcopenic dysphagia. This study therefore aimed to investigate whether intervention by board-certified physiatrists affects the functional prognosis of patients with sarcopenic dysphagia. Materials and Methods: Of 467 patients enrolled in the Japanese Sarcopenic Dysphagia database between November 2019 and March 2021, 433 met the study eligibility criteria. The patients were divided into two groups based on whether or not they received intervention by a BCP. The clinical characteristics and outcomes of the two groups were compared. Statistical analyses were performed by inverse probability weighting (IPW). Results: BCPs were involved in the management of 57.0% of patients with sarcopenic dysphagia. These patients had a significantly higher increase in the Barthel index both before and after IPW correction than those not managed by a BCP (P=0.001 and P=0.016, respectively). However, sarcopenic dysphagia significantly improved in the non-BCP group before IPW correction (P<0.001), although there was no significant difference after IPW correction (P=0.301). Conclusion: BCP management was significantly associated with higher activities of daily living (ADL), but not with an improvement in sarcopenic dysphagia. To provide and manage effective rehabilitation, it is necessary to familiarize patients with the management and training of sarcopenic dysphagia rehabilitation for BCP in order to cope in regions with few rehabilitation units.

Relationship Between Start of Feeding and Functional Outcome in Aspiration Pneumonia: A Retrospective Cohort Study.

INTRODUCTION: Aspiration pneumonia is the predominant form of pneumonia in the elderly. Low oral intake levels and malnutrition have been reported to be associated with increased mortality and loss of function in aspiration pneumonia. However, the relationship between start of feeding and readmission, which is associated with malnutrition and low oral intake levels, has not been reported. The purpose of this study was to clarify the relationship between start of feeding and functional prognosis in aspiration pneumonia. METHODS: Patients' basic information, comorbidities, severity of pneumonia, swallowing function, time from admission to the start of feeding, geriatric nutritional risk index (GNRI), readmission, and Barthel index (BI) were evaluated in 160 patients. The patients were divided into two groups-a readmission group and a non-readmission group-and statistical verification was performed. RESULTS: The readmission group was 62 cases (38.8%). Univariate analysis showed that the time from admission to the start of feeding was significantly longer in the readmission group (p < 0.001). Age was significantly higher and nutrition parameters were lower in the readmission group (p = 0.001, 0.006). Furthermore, according to logistic regression analysis, readmission was associated with age (odds ratio, 1.063; p = 0.007; 95% confidence interval (CI) 1.017-1.111) and time from admission to the start of feeding (odds ratio 1.080; p < 0.001; 95% CI 1.025-1.137). CONCLUSION: The time from admission to the start of feeding was significantly longer in the readmitted patients. A comprehensive intervention with multidisciplinary collaboration should be performed from the early stage of hospitalization. TRIAL REGISTRATION: This study is registered in the UMIN-Clinical Trials Registry (UMIN-CTR). UMIN-CTR meets the criteria of the International Committee of Medical Journal Editors (ICMJE). (Registration number: 000047141).

Aspiration pneumonia is the predominant form of pneumonia in the elderly. Low oral intake levels and malnutrition have been reported to be associated with increased mortality and loss of function in aspiration pneumonia. However, the relationship between start of feeding and readmission, which is associated with malnutrition and low oral intake levels, has not been reported. The purpose of this study was to clarify the relationship between start of feeding and functional prognosis in aspiration pneumonia. Patients' basic information, comorbidities, severity of pneumonia, swallowing function, time from admission to the start of feeding, geriatric nutritional risk index (GNRI), readmission, and Barthel index (BI) were evaluated in 160 patients. The patients were divided into two groups: a readmission group and a non-readmission group. The readmission group was 62 cases (38.8%). Univariate analysis showed that the time from admission to the start of feeding was significantly longer in the readmission group. Age was significantly higher and nutrition parameters were lower in the readmission group. According to logistic regression analysis, readmission was associated with age and time from admission to the start of feeding. The time from admission to the start of feeding was significantly longer in the readmitted patients. A comprehensive intervention with multidisciplinary collaboration should be performed from the early stage of hospitalization. It is necessary to carry out indirect swallowing training from the time of hospitalization, nursing care such as feeding assistance, oral care, and functional training; to periodically evaluate intention; to identify problems by conference; and to decide on a treatment plan.

Functional prognosis in patients with sarcopenic dysphagia: An observational cohort study from the Japanese sarcopenic dysphagia database.

AIM: In sarcopenic dysphagia, confirmation of recovery of the swallowing function and activity of daily living is insufficient. The aim of this study was to examine differences in the recovery of the swallowing function and activities of daily living between sarcopenic dysphagia patients and non-sarcopenic dysphagia patients. METHODS: The registry data of the Japanese Sarcopenic Dysphagia Database were used for the analysis; 440 patients met the eligibility criteria of the study. Dysphagia was evaluated according to the Food Intake Level Scale and a five-step diagnostic algorithm for the disorder. Patients were divided into two groups according to the presence or absence of sarcopenic dysphagia. RESULTS: Sarcopenic dysphagia was found in 268 cases (60.9%). The rate of improvement in the Food Intake Level Scale was 47.4% in sarcopenic dysphagia patients and 62.2% in non-sarcopenic dysphagia patients. The rate of improvement in the Food Intake Level Scale was lower in the sarcopenic dysphagia patients (P = 0.008). A multiple regression analysis showed that the presence of sarcopenic dysphagia had a significant influence on changes in the Food Intake Level Scale and Barthel Index (ß = -0.191, 95% confidence interval, -1.484 to -0.530, P < 0.001, ß = 0.112, 95% confidence interval, 0.587 to 10.450, P = 0.028). CONCLUSION: Improvement in the swallowing function was poor in patients with sarcopenic dysphagia. Sarcopenic dysphagia should be examined to improve swallowing function. Geriatr Gerontol Int 2022; 22: 839-845.

Association Among Geriatric Nutritional Risk Index and Functional Prognosis in Elderly Patients with Osteoporotic Vertebral Compression Fractures.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) are common among the elderly, and malnutrition has also been identified as a poor prognostic factor in elderly patients with fractures. However, the relationship between nutrition status and functional prognosis in OVCF is unclear. The aim of this study was to investigate the association between nutritional status using geriatric nutritional risk index (GNRI), activities of daily living (ADL), and fall after fracture in patients with OVCF. METHODS: The clinical information of 187 conservatively treated OVCF patients was retrospectively examined. This information included: age, sex, body mass index, total number of drugs used for treatment at admission, bone mineral density, use of drugs for osteoporosis, fracture type, comorbidity severity, nutritional status, Barthel Index (BI), and fall after OVCF. Subjects were divided into two groups according to their GNRI. Propensity score matching was used to confirm factors affecting BI and falls after OVCF. RESULTS: Sixty-eight patients (36.4%) presented with malnutrition at fracture. According to multiple linear regression analysis, GNRI positively affected BI gain (ß = 0.283, 95% confidence interval [CI] - 122.2 to - 0.706, p = 0.001). Furthermore, on logistic regression analysis, fall after OVCF was associated with GNRI (odds ratio = 0.896, 95% CI 0.832-0.964, p = 0.003). CONCLUSIONS: Malnutrition in elderly OVCF patients decreases the acquisition of ADL and increases fall risk. Improvement of nutritional status during OVCF treatment may lead to improvement of ADL and prevention of falls.

Influence of potentially inappropriate medications on activities of daily living for patients with osteoporotic vertebral compression fractures: A retrospective cohort study.

PURPOSE: Potentially inappropriate medications (PIMs) are a major concern in geriatric care. Osteoporotic vertebral compression fractures (OVCFs) are more common among the elderly, who are more likely to receive long-term analgesics for pain and additional medications for complications, but no studies have examined the effects of PIMs on OVCFs. The purpose of our study was to clarify the association between PIMs and activities of daily living (ADL) among patients with OVCFs. METHODS: The subjects were 170 patients aged 65 years or older with OVCFs treated conservatively who underwent rehabilitation between October 2014 and August 2019. Patients' clinical information, including age, sex, body mass index, total number of drugs used for treatment at admission, number and type of PIMs used at admission, bone mineral density, use of drugs for osteoporosis, fracture type, comorbidity severity, nutritional status, Barthel Index (BI), presence and extent of lower back pain, and length of hospital stay were examined retrospectively. The possible association between these clinical factors and the BI and use of PIMs was assessed. RESULTS: Ninety-seven patients (57.1%) were prescribed PIMs at admission. Mean BI at discharge was significantly lower among patients receiving PIMS (70 points vs. 83 points; p < 0.001). Multivariate analysis for BI gain after propensity score matching showed that the number of PIMs and BI at admission affected the BI gain. CONCLUSION: The use of PIMs hindered the improvement in ADL. Our results demonstrate the importance of appropriate drug control for patients with OVCFs.

Relationship between potentially inappropriate medications and functional prognosis in elderly patients with distal radius fracture: a retrospective cohort study.

BACKGROUND: Potentially inappropriate medications (PIMs) are a major concern in geriatric care. PIMs increase the risk of falls in elderly patients. However, the relationship between PIMs, subsequent falls, and functional prognosis for distal radius fracture (DRF) remains unclear. The aim of this study was to examine the relationship between PIMs, activities of daily living, and subsequent falls in elderly DRF patients. METHODS: The study included 253 patients aged ≥ 65 years who required surgical treatment for DRF. Clinical characteristics of patients obtained included age, sex, body mass index, number of medicines used at admission, number and type of PIMs used at admission, bone mineral density, use of drugs for osteoporosis, severity of comorbidities, nutritional status, Barthel Index (BI), length of hospital stay, subsequent falls, fracture type, and Mayo wrist score. Subjects were divided into two groups according to PIMs use and no use. Propensity score matching was used to assess patient characteristics and confirm factors affecting BI and subsequent falls. RESULTS: One hundred seven patients (42.3%) were prescribed PIMs upon hospital admission. The mean BI gain was significantly lower in patients prescribed PIMs than in those who were not (p = 0.006), as was the rate of falls post-surgery (p = 0.009). Multivariate analysis of BI gain showed that PIMs affected BI gain (95% confidence interval [CI], - 1.589 to - 0.196, p = 0.012), and logistic regression analysis revealed that PIMs influenced subsequent falls (odds ratio, 0.108, 95% CI, 1.246 to 2.357, p < 0.001). CONCLUSIONS: PIM use hindered the improvement in activities of daily living and increased the incidence of subsequent falls in patients assessed. These results demonstrate the importance of appropriate drug control for patients with DRF.

Nutrition status and functional prognosis among elderly patients with distal radius fracture: a retrospective cohort study.

BACKGROUND: Distal radius fractures (DRF) are common in the elderly and are typically caused falls. Malnutrition has also been identified as a poor prognostic factor in elderly patients with fractures. However, the relationship between nutritional status and subsequent falls and functional prognosis for DRF in the elderly is not clear. The aim of the present study was to investigate the association between nutritional status and functional prognosis in elderly patients with DRF. METHODS: Study participants included 229 outpatients who required surgical treatment for DRF. The patients' clinical information, including age, sex, body mass index, bone mineral density, geriatric nnutritional risk index (GNRI), total number of drugs being treated with on admission, use of drugs for osteoporosis, comorbidity severity, the Barthel Index (BI), presence of subsequent falls, fracture type, postoperative follow-up period, and Mayo wrist score was reviewed. Subjects were further divided into two groups according to their GNRI: the malnutrition group and the normal group. Propensity score matching was used to confirm factors affecting the BI and subsequent falls. RESULTS: Thirty-one patients (13.5%) presented with malnutrition before surgery for DRF. According to multiple liner regression analysis, the GNRI positively affected the efficiency of the BI (ß = 0.392, 95% confidence interval [CI], 0.001 to 0.351, p = 0.039). Furthermore, on logistic regression analysis, subsequent falls were associated with serum albumin levels (odds ratio = 0.033, 95% CI, 0.002 to 0.477, p = 0.012). CONCLUSION: Malnutrition impaired improvement of activities of daily living (ADL) and increased the incidence of subsequent falls. Improvement of nutritional status before DRF surgery may further improve ADL and prevent falls.

Verification of phycological factors related to health-related quality of life in elderly knee osteoarthritis: A prospective cohort study.

BACKGROUND: In recent years, locomotive syndrome, which is a condition requiring nursing care due to musculoskeletal disease, has been reported, and interest in knee osteoarthritis has been increasing. Several studies have reported the physical factors influencing the relationship between knee osteoarthritis and health-related quality of life (HRQOL), but there have been no reports verifying the changes over time in the relationship between psychosocial factors and HRQOL. This study aimed to investigate the influence of psychosocial factors on HRQOL in elderly patients with knee osteoarthritis. METHODS: Evaluations were conducted at four time points: before exercise therapy intervention, 1 month into intervention, 3 months into intervention, and 1 month after completion of intervention. The items investigated were (1) Japanese Orthopedic Association (JOA) score, (2) Kellgren-Lawrence (K-L) grading system, (3) Fall Efficacy Scale (FES), (4) Frenchay Activities Index (FAI), (5) Geriatric Depression Scale (GDS), and (6) Short Form-8 (SF-8). RESULTS: No significant differences were seen between each time point of exercise therapy intervention in depression and HRQOL scale but a significant improvement was seen in instrumental ADL and fear of falling at 3 months into intervention. On multiple regression analysis with SF-8 subscales, fear of falling and degree of depression were determined as significant factors affecting physical and mental summary scores. CONCLUSION: Elderly patients with knee osteoarthritis require not only intervention for knee function, but also psychological intervention to address decreased activity and depression to improve their HRQOL.

Neuropathic Characteristics In Patients With Persistent Idiopathic Facial Pain.

BACKGROUND: Persistent idiopathic facial pain (PIFP) is a subtype of painful cranial neuropathies and other facial pains. The involvement of neuropathic mechanisms in PIFP, however, remains controversial. Using the Douleur Neuropathique 4 (DN4) questionnaire, the present study examined neuropathic characteristics in patients with PIFP. METHODS: The multi-institutional retrospective study collected the following clinical data from 205 consecutive patients with adult chronic pain: gender, age, BMI, diseases causing chronic pain, disease duration, visual analogue scale score of pain strength, and DN4 score. To compare neuropathic characteristics between PIFP and postherpetic neuralgia (PHN), we selected patients with PIFP (n=19) and patients with PHN (n=33), and performing a case-control study in which each patient with PHN or PIFP was matched by age and gender (n=16 in each group). RESULTS: DN4 score was significantly lower in the PIFP group than in the PHN group before and after matching. The incidence when DN4 was ≥4 was 10.5% before matching and 12.5% after matching in the PIFP group, both of which were significantly lower than those in the PHN group before and after matching (66.7% and 75.0%). CONCLUSION: Ten percent of the PIFP patients likely show neuropathic pain characteristics.

N-Acetyl-seryl-aspartyl-lysyl-proline is a potential biomarker of renal function in normoalbuminuric diabetic patients with eGFR ≥ 30 ml/min/1.73 m2.

BACKGROUND: A biomarker, by which we can predict alterations of renal function in normoalbuminuric diabetic patients, is not available. Here, we report that endogenous anti-fibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) represents a potential biomarker to predict alterations in eGFR in normoalbuminuric diabetic patients. METHODS: We analyzed 21 normoalbuminuric diabetic patients with eGFR ≥ 30 ml/min/1.73 m2 and measured AcSDKP levels in first morning void urine. We divided patients into two groups based on the median values: low or high urinary AcSDKP groups (uAcSDKP/Crlow or uAcSDKP/Crhigh). At baseline, no significant differences in sex, age, HbA1c, BMI, serum creatinine levels, etc., were observed between the two groups. RESULTS: During ~ 4 years, the alteration in eGFR [ΔeGFRop (ΔeGFR observational periods)] was significantly stable in uAcSDKP/Crhigh group compared with uAcSDKP/Crlow group over time (P = 0.003, χ2 = 8.58). We also evaluated urine kidney injury molecule-1 (uKim-1) levels and found that ΔeGFRop was also stable in low uKim-1 group compared with high uKim-1 group over time (P = 0.004, χ2 = 8.38). Patients who fulfilled the criteria for both uAcSDKP/Crhigh and uKim-1low exhibited stable ΔeGFRop (P < 0.001, χ2 = 30.4) when compared to the remaining patients. Plasma AcSDKP (P = 0.015, χ2 = 5.94) and urine ß2-microglobulin (P = 0.038, χ2 = 4.31) also display weak but significant predictor of ΔeGFRop as well. CONCLUSION: AcSDKP represents a potentially useful biomarker to predict alterations in the renal function of patients with diabetes presenting normoalbuminuria.

Severe electrolytes disorders with the interstitial kidney alterations in the patient with the history of total thyroidectomy and parathyroidectomy: possible role of vitamin D deficiency.

Vitamin D plays vital role for the health, and its deficiency has been implicated in the diverse pathological conditions such as hypomagnesemia and abnormal immune system. Here, we present a case of severe electrolytes disorders (hypokalemia and hypomagnesemia etc.) and kidney damages associated with vitamin D deficiency.

Echo Findings of Intraoperative Surgical Glue Remnant on the Aortic Valve: A Case Report.

Surgical adhesive agents are frequently applied to reinforce aortic sutures in cardiac and aortic surgery. They are thought to provide hemostasis and safely and effectively reduce morbidity. Complications owing to surgical glue remnants, however, have been reported. In our recent case, a surgical glue remnant was detected on the aortic valve by transesophageal echocardiography. For detection of such surgical glue remnants, and to prevent associated serious potential complications, comprehensive transesophageal echocardiography is important. If surgical glue is applied during operative procedures, the heart and aorta should be carefully examined by transesophageal echocardiography.

FGFR1 is essential for N-acetyl-seryl-aspartyl-lysyl-proline regulation of mitochondrial dynamics by upregulating microRNA let-7b-5p.

Fibroblast growth factor receptor (FGFR) 1 plays a key role in endothelial homeostasis by inducing microRNA (miR) let-7. Our previous paper showed that anti-fibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) were associated with restoring diabetes-suppressed expression of FGFR1 and miR let-7, the key contributor of mitochondrial biogenesis, which is regulated by mitochondrial membrane GTPase proteins (MFN2 and OPA1). Here, we found that the FGFR1 signaling pathway was critical for AcSDKP in maintaining endothelial mitochondrial biogenesis through induction of miR let-7b-5p. In endothelial cells, AcSDKP restored the triple cytokines (TGF-ß2, interleukin-1ß, tumor necrosis factor-α)-suppressed miR let-7b-5p and protein levels of the mitochondrial membrane GTPase. This effect of AcSDKP was lost with either fibroblast growth factor receptor substrate 2 (FRS2) siRNA or neutralizing FGFR1-treated cells. Similarly, AcSDKP had no effect on the miR let-7b-5p inhibitor-suppressed GTPase levels in endothelial cells. In addition, a miR let-7b-5p mimic restored the levels of FRS2 siRNA-reduced GTPases in endothelial cells. These findings were also confirmed using MitoTracker Green and an immunofluorescence assay. Our results demonstrated that the AcSDKP-FGFR1 signaling pathway is critical for maintaining mitochondrial dynamics by control of miR let-7b-5p in endothelial cells.

FGFR1 is critical for the anti-endothelial mesenchymal transition effect of N-acetyl-seryl-aspartyl-lysyl-proline via induction of the MAP4K4 pathway.

Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis, and we have reported that the anti-EndMT effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is associated with restoring expression of diabetes-suppressed fibroblast growth factor receptor (FGFR), the key anti-EndMT molecule. FGFR1 is the key inhibitor of EndMT via the suppression of the transforming growth factor ß (TGFß) signaling pathway, and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibits integrin ß1, a key factor in activating TGFß signaling and EndMT. Here, we showed that the close proximity between AcSDKP and FGFR1 was essential for the suppression of TGFß/smad signaling and EndMT associated with MAP4K4 phosphorylation (P-MAP4K4) in endothelial cells. In cultured human dermal microvascular endothelial cells (HMVECs), the anti-EndMT and anti-TGFß/smad effects of AcSDKP were lost following treatment with a neutralizing FGFR1 antibody (N-FGFR1) or transfection of FRS2 siRNA. The physical interaction between FGFR1 and P-MAP4K4 in HMVECs was confirmed by proximity ligation analysis and an immunoprecipitation assay. AcSDKP induced P-MAP4K4 in HMVECs, which was significantly inhibited by treatment with either N-FGFR1 or FRS2 siRNA. Furthermore, MAP4K4 knockdown using specific siRNAs induced smad3 phosphorylation and EndMT in HMVECs, which was not suppressed by AcSDKP. Streptozotocin-induced diabetic CD-1 mice exhibited suppression of both FGFR1 and P-MAP4K4 expression levels associated with the induction of TGFß/smad3 signaling and EndMT in their hearts and kidneys; those were restored by AcSDKP treatment. These data demonstrate that the AcSDKP-FGFR1-MAP4K4 axis has an important role in combating EndMT-associated fibrotic disorders.

Association between bone scan index and activities of daily living in patients with advanced non-small cell lung cancer.

PURPOSE: The aim of this retrospective cross-sectional study was to investigate the association between the bone scan index (BSI) and activities of daily living (ADL) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Among patients with advanced NSCLC, subjects who underwent bone scintigraphy were recruited from this study. Clinical information about patients, including the Barthel Index of ADL, was extracted from their medical charts. Variables including the age, sex, BSI, presence/absence skeletal-related events (SREs), diagnostic state (initial vs. relapse), and history of use of certain medications (e.g. opiates) were evaluated as factors possibly associated with the Barthel Index. In Addition, associations between these factors, including the Barthel Index, with the overall survival were also assessed. RESULTS: A total of 111 patients with bone metastases were selected. The BSI and Barthel Index of the patients were 1.59 ± 2.25 and 69.7 ± 19.6, respectively. Multivariable analysis identified age (≥70 years), a high BSI (≥1.0), and presence of SREs were as factors statistically significantly associated with lower values of the Barthel Index (<75). On the other hand, Cox proportional hazards analysis identified low values of the Barthel Index (<75), use of opiates, and male sex as significant factors associated with a shorter overall survival; the BSI was not associated with the overall survival in the patients with advanced NSCLC in this study. CONCLUSION: The results suggest that a high BSI (≥1.0) is an independent predictor of poor ADL in patients with NSCLC, while showing no correlation with the overall survival.