ABSTRACT
AIM: To investigate the association between low-density lipoprotein-cholesterol (LDL-C) levels and coronary artery disease (CAD) incidence based on combining high-density lipoprotein-cholesterol (HDL-C) levels and glucose status. MATERIALS AND METHODS: In this retrospective cohort study, we used data from a nationwide claims database (1,524,289 individuals without a history of CAD or familial hypercholesterolaemia; 2008-2019). Cox proportional hazards modelling identified the risk of incident CAD by a novel combination of four HDL-C levels, seven LDL-C levels and glucose status. RESULTS: During the follow-up period (mean: 5.5 years), 8301 (0.99/1000 person-years) events occurred. The risk of CAD increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of the glucose status. Using the most favourable levels of HDL-C and LDL-C (i.e. 60-99 mg/dL and <80 mg/dL, respectively) as references, the hazard ratios (95% confidence interval) for the group with HDL-C levels <40 mg/dL and LDL-C levels <80 mg/dL were 2.74 (1.47-5.11), 2.52 (1.30-4.91) and 2.85 (1.68-4.84) for normoglycaemia, borderline glycaemia and diabetes, respectively. Comparison of the most favourable levels of HDL-C and LDL-C with their least favourable levels (i.e. <40 mg/dL and 180-199 mg/dL, respectively) revealed that the risk of new-onset CAD exhibited a 19-, nine- and seven-fold increase in individuals with normoglycaemia, borderline glycaemia and diabetes, respectively. CONCLUSIONS: To prevent CAD, LDL-C levels should be strictly controlled in patients with low HDL-C levels regardless of glucose tolerance. Individualized treatment, which involves setting target LDL-C levels based on glucose tolerance and HDL-C values, is required.
Subject(s)
Blood Glucose , Cholesterol, HDL , Cholesterol, LDL , Coronary Artery Disease , Humans , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Male , Cholesterol, LDL/blood , Female , Retrospective Studies , Middle Aged , Cholesterol, HDL/blood , Blood Glucose/metabolism , Blood Glucose/analysis , Adult , Aged , Risk Factors , Incidence , Risk AssessmentABSTRACT
BACKGROUND: Recurrent laryngeal nerve paralysis (RLNP) after esophagectomy can cause aspiration because of incomplete glottis closure, leading to pneumonia. However, patients with RLNP often have preserved swallowing function. This study investigated factors that determine swallowing function in patients with RLNP. METHODS: Patients with esophageal cancer who underwent esophagectomy and cervical esophagogastric anastomosis were enrolled between 2017 and 2020. Videofluoroscopic examination of swallowing study (VFSS) and acoustic voice analysis were performed on patients with suspected dysphagia including RLNP. Dysphagia in VFSS was defined as score ≥ 3 of the 8-point penetration-aspiration scale VFSS and acoustic analysis results related to dysphagia were compared between patients with and without RLNP. RESULTS: Among 312 patients who underwent esophagectomy, 74 developed RLNP. The incidence of late-onset pneumonia was significantly higher in the RLNP group than in the non-RLNP (18.9 vs. 8.0%, P = .008). Detailed swallowing function was assessed by VFSS in 84 patients, and patients with RLNP and dysphagia showed significantly shorter maximum diagonal hyoid bone elevation (10.62 vs. 16.75 mm; P = .003), which was a specific finding not seen in patients without RLNP. For acoustic voice analysis, the degree of hoarseness was not closely related to dysphagia. The length of oral intake rehabilitation for patients with and without RLNP was comparable if they did not present with dysphagia (8.5 vs. 9.0 days). CONCLUSIONS: Impaired hyoid bone elevation is a specific dysphagia factor in patients with RLNP, suggesting compensatory epiglottis inversion by hyoid bone elevation is important for incomplete glottis closure caused by RLNP.
Subject(s)
Deglutition Disorders , Pneumonia , Vocal Cord Paralysis , Humans , Deglutition Disorders/epidemiology , Deglutition Disorders/etiology , Deglutition/physiology , Esophagectomy/adverse effects , Recurrent Laryngeal Nerve , Vocal Cord Paralysis/epidemiology , Vocal Cord Paralysis/etiology , Respiratory AspirationABSTRACT
BACKGROUND AND OBJECTIVES: To clarify whether the presence or absence of fast walking and habitual physical activity are independently associated with the incidence of functional disability. METHODS: This historical cohort study was comprised of 9,652 (4,412 men, mean age 65 years) individuals aged 39-98 years without functional disability at baseline. Functional disability was determined based on the Japanese long-term care insurance system, which specified requirements for assistance in the activities of daily living. The impact of fast walking and habitual physical activity on the incidence of functional disability was analysed by Cox proportional hazards models. RESULTS: The follow-up period was a median of 3.7 years during which 165 patients were newly certified as having functional disability. In the multivariate analysis, baseline age in 5-year increments (hazard ratio 2.42 [95% confidence interval 2.18-2.69]), no habitual physical activity (1.56 [1.07-2.27]), and not fast walking (1.89 [1.32-2.69]) significantly increased the risk of functional disability after adjustment for covariates. The stratified analysis showed that compared with physical activity (+), the impact of physical activity (-) on the incidence of functional disability was observed in those aged ≥75 years regardless of fast walking (+). Fast walking (-) significantly increased the risk of disability compared with fast walking (+) in those aged <75 years regardless of a physical activity habit. CONCLUSION: In Japanese, slow walking speed and lack of a physical activity habit were shown to be independent risk factors for incident functional disability, with their impact differing according to age.
Subject(s)
Activities of Daily Living , Walking , Male , Humans , Aged , Cohort Studies , Exercise , Proportional Hazards ModelsABSTRACT
BACKGROUND: To determine the impact of metabolic syndrome (MetS) and/or metabolic dysfunction-associated fatty liver disease (MAFLD), which are pathophysiologically similar and include insulin resistance, on the development of new-onset cardiovascular disease with and without type 2 diabetes and according to sex. METHODS: This study included 570,426 individuals without a history of cardiovascular disease who were enrolled in a nationwide claims database from 2008 to 2016 and were classified by the presence or absence of MetS and/or MAFLD stratified by the presence or absence of type 2 diabetes and sex. The fatty liver index was used to determine the presence or absence of fatty liver that required a diagnosis of MAFLD. Risks of developing coronary artery disease (CAD) and cerebrovascular disease (CVD) in each category were analyzed using a multivariate Cox proportional hazard model. RESULTS: During a median follow-up of 5.2 years, 2252 CAD and 3128 CVD events occurred. Without type 2 diabetes the hazard ratio (HR) (95% CI) for CAD/CVD compared with neither MAFLD nor MetS was 1.32 (1.17-1.50)/1.41(1.28-1.57) for MAFLD only (without MetS), 1.78 (1.22-2.58)/1.66 (1.34-2.06) for MetS only (without MAFLD), and 2.10 (1.84-2.39)/1.73 (1.54-1.95) for MAFLD + MetS. For those with type 2 diabetes, the HR for CAD for MAFLD only (compared with neither MAFLD nor MetS) was 1.29 (1.06-1.58), for MetS only 1.34 (0.84-2.13), and for MAFLD + MetS 1.22 (1.02-1.47). For CVD, there was a significant increase in HR only in MAFLD + MetS [1.44 (1.18-1.76)]. The results of the analysis stratified by sex showed that MAFLD had a greater impact in men, and MetS had a greater impact in women regarding the development of CAD. CONCLUSIONS: Distinguishing between MetS and/or MAFLD in the presence or absence of type 2 diabetes and according to sex may aid in accurately identifying patients at high risk of cardiovascular disease.
Subject(s)
Cardiovascular Diseases , Coronary Artery Disease , Diabetes Mellitus, Type 2 , Fatty Liver , Metabolic Syndrome , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Coronary Artery Disease/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Female , Heart Disease Risk Factors , Humans , Male , Metabolic Syndrome/complications , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Risk FactorsABSTRACT
AIM: To compare the long-term efficacy of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors as second-line drugs after metformin for patients not at high risk of atherosclerotic cardiovascular disease (ASCVD). MATERIALS AND METHODS: In a 52-week randomized open-label trial, we compared ipragliflozin and sitagliptin in Japanese patients diagnosed with type 2 diabetes, without prior ASCVD and treated with metformin. The primary endpoint was a glycated haemoglobin (HbA1c) reduction of ≥0.5% (5.5 mmol/mol) without weight gain at 52 weeks. RESULTS: Of a total of 111 patients (mean age 59.2 years, mean body mass index [BMI] 26.6 kg/m2 , 61.3% men), 54 patients received ipragliflozin and 57 received sitagliptin. After 52 weeks, achievement of the primary endpoint was not significantly different (37.0% and 40.3%; P = 0.72). HbA1c reduction rate at 24 weeks was greater for sitagliptin (56.1%) than for ipragliflozin (31.5%; P = 0.01). From 24 to 52 weeks, the HbA1c reduction with sitagliptin was attenuated, with no significant difference in HbA1c reduction after 52 weeks between sitagliptin (54.4%) and ipragliflozin (38.9%; P = 0.10). Improvements in BMI, C-peptide and high-density lipoprotein cholesterol were greater with ipragliflozin than with sitagliptin. Adverse events occurred in 17 patients with ipragliflozin and in 10 patients with sitagliptin (P = 0.11). CONCLUSION: The HbA1c-lowering effect at 24 weeks was greater with sitagliptin than with ipragliflozin, but with no difference in efficacy related to HbA1c and body weight at 52 weeks. However, some ASCVD risk factors improved with ipragliflozin.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Metformin , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Glucosides , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Male , Metformin/therapeutic use , Middle Aged , Sitagliptin Phosphate/therapeutic use , Thiophenes , Treatment OutcomeABSTRACT
PURPOSE: This network meta-analysis aimed to assess the current efficacy of decreasing the uric acid (UA) level with drugs to reduce mortality in patients with heart failure (HF). METHODS: Electronic literature searches using EMBASE and MEDLINE of studies published from 1 Jan 1950 to 26 Dec 2019 were conducted for randomized controlled trials or non-randomized cohort studies that included at least one group of patients who took UA-lowering drugs and with a study outcome of all-cause mortality. A random-effects network meta-analysis was performed within a frequentist framework. Hierarchy of treatments was expressed as the surface under the cumulative ranking curve (SUCRA) value, which is in proportion to mean rank (best is 100%). RESULTS: Nine studies, which included seven different types of groups, were eligible for analysis. The "untreated uricemia" group in which patients had hyperuricemia but without treatment had a significantly higher risk of mortality than the "no uricemia" group in which patients had no hyperuricemia (relative risk (RR)(95% confidence interval (CI), 1.43 (1.08-1.89)). The "start-allo" group wherein patients started to take allopurinol did not have a significantly lower risk of mortality than the "untreated uricemia" group (RR (95% CI), 0.68 (0.45-1.01)). However, in the "start-allo" group the SUCRA value was comparable to that in the "no uricemia" group (SUCRA: 65.4% for "start-allo"; 64.1% for "no uricemia"). CONCLUSIONS: Results suggested that allopurinol therapy was not associated with a significantly improved prognosis in terms of mortality but could potentially counteract the adverse effects associated with longstanding hyperuricemia in HF patients.
Subject(s)
Allopurinol/therapeutic use , Gout Suppressants/therapeutic use , Heart Failure/mortality , Uric Acid/blood , Allopurinol/administration & dosage , Gout Suppressants/administration & dosage , Heart Failure/epidemiology , Humans , Hyperuricemia/drug therapy , Hyperuricemia/epidemiology , Network Meta-AnalysisABSTRACT
PURPOSE: To evaluate the accuracy of various claims-based definitions of diabetes-related complications (coronary artery disease [CAD], heart failure, cerebrovascular disease and dialysis). METHODS: We evaluated data on 1379 inpatients who received care at the Niigata University Medical & Dental Hospital in September 2018. Manual electronic medical chart reviews were conducted for all patients with regard to diabetes-related complications and were used as the gold standard. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each claims-based definition associated with diabetes-related complications based on Diagnosis Procedure Combination (DPC), International Classification of Diseases, Tenth Revision (ICD-10) codes, procedure codes and medication codes were calculated. RESULTS: DPC-based definitions had higher sensitivity, specificity, and PPV than ICD-10 code definitions for CAD and cerebrovascular disease, with sensitivity of 0.963-1.000 and 0.905-0.952, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. Sensitivity, specificity, and PPV were high using procedure codes for CAD and dialysis, with sensitivity of 0.963 and 1.000, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. DPC and/or ICD-10 codes + medication were better for heart failure than the ICD-10 code definition, with sensitivity of 0.933, specificity of 1.000, and PPV of 1.000. The PPVs were lower than 60% for all diabetes-related complications using ICD-10 codes only. CONCLUSION: The DPC-based definitions for CAD and cerebrovascular disease, procedure codes for CAD and dialysis, and DPC or ICD-10 codes with medication codes for heart failure could accurately identify these diabetes-related complications from claims databases.
Subject(s)
Diabetes Complications , Diabetes Mellitus , Databases, Factual , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Humans , International Classification of Diseases , Japan/epidemiology , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
Dysphagia after esophagectomy is the main cause of a prolonged postoperative stay. The present study investigated the effects of a swallowing intervention led by a speech-language-hearing therapist (SLHT) on postoperative dysphagia. We enrolled 276 consecutive esophageal cancer patients who underwent esophagectomy and cervical esophagogastric anastomosis between July 2015 and December 2018; 109 received standard care (control group) and 167 were treated by a swallowing intervention (intervention group). In the intervention group, swallowing function screening and rehabilitation based on each patient's dysfunction were led by SLHT. The start of oral intake, length of oral intake rehabilitation, and length of the postoperative stay were compared in the two groups. The patient's subgroups in the 276 patients were examined to clarify the more effectiveness of the intervention. The start of oral intake was significantly earlier in the intervention group (POD: 11 vs. 8 days; P = 0.009). In the subgroup analysis, the length of the postoperative stay was also significantly shortened by the swallowing intervention in patients without complications (POD: 18 vs. 14 days; P = 0.001) and with recurrent laryngeal nerve paralysis (RLNP) (POD: 30 vs. 21.5 days; P = 0.003). A multivariate regression analysis identified the swallowing intervention as a significant independent factor for the earlier start of oral intake and a shorter postoperative stay in patients without complications and with RLNP. Our proposed swallowing intervention is beneficial for the earlier start of oral intake and discharge after esophagectomy, particularly in patients without complications and with RLNP. This program may contribute to enhanced recovery after surgery.
Subject(s)
Deglutition Disorders , Esophageal Neoplasms , Deglutition , Deglutition Disorders/etiology , Esophageal Neoplasms/complications , Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Humans , Length of Stay , Postoperative Complications/etiology , Retrospective StudiesABSTRACT
BACKGROUND AND OBJECTIVES: Pediatric obesity is associated with clustered cardiometabolic risk and the future incidence of cardiovascular disease. However, few studies have determined the effect of pediatric obesity in Asia, where obesity is less common than in Western countries. We aimed to clarify whether weight status including underweight and slightly overweight is associated with metabolic risk factors in Japanese adolescents. METHODS AND STUDY DESIGN: We performed a cross-sectional analysis of 2241 adolescents aged 13-14 years. Participants were classified as underweight, normal weight, slightly overweight, overweight, or obese according to the International Obesity Task Force. The clustered cardiometabolic risk (Z-CMR) was estimated by summing standardized sex-specific Z scores of mean arterial pressure (MAP), non-high-density lipoprotein cholesterol (non-HDLC), and HbA1c. RESULTS: Linear regression analysis showed that MAP, non-HDL-C, and Z-CMR were higher in the slightly overweight, overweight, and obese groups than in the normal weight group after adjusting for confounders. Compared with the normal weight group, the slightly overweight, overweight, and obese groups had higher prevalence of high BP [odds ratios (ORs): 1.38 (95% CI, 1.03, 1.85); 2.63 (1.77, 3.91); and 2.39 (1.57, 3.64), respectively]. Compared with the normal weight group, underweight boys, but not girls, had a lower prevalence of high Z-CMR [OR=0.20 (0.05, 0.84)]. CONCLUSIONS: Adolescents classified as slightly overweight had higher levels of BP, serum lipids, and clustered cardiometabolic risk than those classified as normal weight. This observation showed significant associations between weight status and cardiometabolic risk factors during adolescence even in East Asians.
Subject(s)
Cardiovascular Diseases , Pediatric Obesity , Adolescent , Body Mass Index , Cardiovascular Diseases/epidemiology , Child , Cross-Sectional Studies , Female , Humans , Japan/epidemiology , Male , Overweight/epidemiology , Pediatric Obesity/epidemiology , Risk FactorsABSTRACT
AIMS: To determine incidence and predictors of starting dialysis in patients with diabetes emphasizing blood pressure variables. METHODS: A nationwide database with claim data on 18 935 people (15 789 men and 3146 women) with diabetes mellitus aged 19 to 72 years in Japan was used to elucidate predictors for starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modelling, interactions between glycaemic and blood pressure values were determined. RESULTS: During a median follow-up of 5.3 years, incidence of dialysis was 0.81 per 1000 person-years. Multivariate analysis of a model involving systolic and diastolic blood pressure (SBP and DBP) simultaneously as covariates showed that hazard ratios (HRs) for starting dialysis for each 1-SD elevation in SBP and DBP were 2.05 (95% confidence interval 1.58-2.64) and 0.66 (0.50-0.88), respectively, implying that pulse pressure (PP) was a promising predictor. For confirmation, a model involving SBP and PP simultaneously as covariates demonstrated that HRs for each 1-SD elevation in SBP and PP were 1.09 (0.81-1.48) and 1.54 (1.14-2.08), respectively, with PP the more potent predictor. Compared with HbA1c <8% and PP <60 mmHg, the HR for those with HbA1c ≥8% and PP ≥60 mmHg was 6.32 (3.42-11.7). CONCLUSIONS: In our historical cohort analysis, SBP and PP were independent predictors for starting dialysis. PP was the more potent, suggesting the contribution of increased arterial stiffness to the incidence of dialysis. Future studies are needed to conclude the independent influence of PP and HbA1c on dialysis considering other risk factors.
Subject(s)
Diabetes Mellitus/physiopathology , Renal Dialysis/statistics & numerical data , Adult , Aged , Blood Pressure , Cohort Studies , Female , Follow-Up Studies , Humans , Japan , Male , Middle Aged , Prognosis , Young AdultABSTRACT
BACKGROUND: Efficacy of programs for patients with diabetes mellitus (DM) that have promoted family members to help with patients' self-care activities has been largely inconsistent. This meta-analysis aims to assess the effect of family-oriented diabetes programs for glycemic control (GC). METHODS: Electronic literature searches were conducted for clinical trials with a parallel design wherein there were two groups according to whether family members were included (intervention group) or not included (control group) and changes in glycohemoglobin A1C (A1C) were assessed as a study outcome. Each effect size (i.e. difference in A1C change between the intervention and control group) was pooled with a random-effects model. RESULTS: There were 31 eligible trials consisting of 1466 and 1415 patients in the intervention and control groups, respectively. Pooled A1C change [95% confidence interval (CI)] was -0.45% (-0.64% to -0.26%). Limiting analyses to 21 trials targeted at patients with type 1 DM or 9 trials targeted at patients with type 2 DM, the pooled A1C changes (95% CI) were -0.35% (-0.55% to -0.14%) and -0.71% (-1.09% to -0.33%), respectively. CONCLUSION: This meta-analysis suggests that focusing on the family as well as the individual patient in self-management diabetes programs to improve the performance of self-care activities of patients with DM is effective in terms of proper GC.
Subject(s)
Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/therapy , Disease Management , Glycated Hemoglobin/analysis , Patient Education as Topic , Blood Glucose/metabolism , Family , Humans , Self CareABSTRACT
OBJECTIVE: To examine the independent and combined associations of cardiorespiratory fitness (CRF) and muscular fitness (MF) with cardiometabolic risk factors in Japanese adolescents. METHODS: A cross-sectional study including 993 Japanese adolescents (aged 13-14 years) was undertaken. Height, body mass, blood pressure, lipid profile (non-fasting), and HbA1c were measured. The physical fitness (PF) test included measurements of CRF (20 m multistage shuttle run test), upper limb strength (hand grip strength), lower limb strength (standing long jump), and muscular endurance (sit-ups). The clustered cardiometabolic risk (CCMR) was estimated by summing standardized Z-scores of body mass index (BMI), mean arterial pressure (MAP), non-high-density lipoprotein cholesterol (non-HDL-C), and HbA1c. RESULTS: Linear regression analysis showed that all PF factors except for muscular endurance were inversely correlated with CCMR (P < .001). Among metabolic risk components, HbA1c was unrelated to PF, while non-HDL-C was inversely associated with CRF (B = -2.40; P < .001), upper limb strength (B = -1.77; P < .05), and lower limb strength (B = -1.53; P < .05) after adjustment for lifestyle factors. Logistic regression showed that the probability of having high CCMR (≥1SD) was synergistically higher in those with the lowest tertiles of both CRF and upper limb strength (P for interaction = .001); however, a substantially lower likelihood of having high CCMR was observed among individuals with the lowest tertile of upper limb strength but moderate CRF. CONCLUSIONS: Lower CRF and MF were significantly and synergistically associated with an unhealthier metabolic risk profile.
Subject(s)
Cardiorespiratory Fitness/physiology , Cardiovascular Diseases/epidemiology , Metabolic Diseases/epidemiology , Muscle Strength/physiology , Physical Fitness/physiology , Adolescent , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Exercise Test , Female , Humans , Japan/epidemiology , Male , Mass Screening , Metabolic Diseases/etiology , Noncommunicable Diseases/epidemiology , Noncommunicable Diseases/prevention & control , Risk FactorsABSTRACT
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by the expansion of a CAG repeat in the androgen receptor (AR) gene. Mutant AR has been postulated to alter the expression of genes important for mitochondrial function and induce mitochondrial dysfunction. Here, we show that the expression levels of peroxisome proliferator-activated receptor-γ (PPARγ), a key regulator of mitochondrial biogenesis, were decreased in mouse and cellular models of SBMA. Treatment with pioglitazone (PG), an activator of PPARγ, improved the viability of the cellular model of SBMA. The oral administration of PG also improved the behavioral and histopathological phenotypes of the transgenic mice. Furthermore, immunohistochemical and biochemical analyses demonstrated that the administration of PG suppressed oxidative stress, nuclear factor-κB (NFκB) signal activation and inflammation both in the spinal cords and skeletal muscles of the SBMA mice. These findings suggest that PG is a promising candidate for the treatment of SBMA.
Subject(s)
Muscle, Skeletal/drug effects , Muscular Disorders, Atrophic/drug therapy , Neurons/drug effects , Peptides/metabolism , Receptors, Androgen/genetics , Thiazolidinediones/administration & dosage , Animals , Disease Models, Animal , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Muscle, Skeletal/metabolism , Muscular Disorders, Atrophic/genetics , Muscular Disorders, Atrophic/metabolism , Neurons/metabolism , Peroxisome Proliferator-Activated Receptors/genetics , Peroxisome Proliferator-Activated Receptors/metabolism , Pioglitazone , Receptors, Androgen/metabolism , Spinal Cord/drug effects , Spinal Cord/metabolism , Trinucleotide Repeat Expansion/drug effectsABSTRACT
PURPOSE: Changes in acoustic features in the perioperative phase for elucidating the mechanisms of articulation disorder and the effect of perioperative rehabilitation were studied prospectively. MATERIALS AND METHODS: Sixty-two patients with 62 tongue cancer were divided into a partial glossectomy group (n = 40) and a reconstruction group (n = 22). Acoustic characteristics were analyzed during the preoperative and postoperative periods and after rehabilitation using the first and second formants of the vowels /a/, /i/, and /u/; the triangular vowel space area (tVSA); and the slopes of formant transitions. RESULTS: In the 2 groups, decreases in the tVSA and formant slopes were found from the preoperative to the postoperative period, and the acoustic characteristics of the reconstruction group especially improved to preoperative values after rehabilitation. Analysis of the postoperative period showed that acoustic characteristics were altered at the site of surgical resection. CONCLUSION: Changes of acoustic variables are related to excision size and site, suggesting the distinctive tongue portion for the articulation of each speech sound. Perioperative rehabilitation could activate the articulators and increase the range of movement of the remaining tongue, especially the preserved anterior tongue.
Subject(s)
Articulation Disorders/physiopathology , Articulation Disorders/rehabilitation , Glossectomy/rehabilitation , Postoperative Complications/physiopathology , Postoperative Complications/rehabilitation , Speech Acoustics , Tongue Neoplasms/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome , Young AdultABSTRACT
The psychogenic vertigo has been diagnosed based on subjective dizzy symptom without abnormal findings of oculomotor tests and vestibular tests. We investigated the characteristics of the postural control system in patients with psychogenic vertigo using stabilometry and Body Tracking Tests with a visual feedback test to assess the dynamic body balance. This study consisted of 14 patients with psychogenic vertigo and 92 aged-match healthy subjects. They were instructed to keep the center of pressure constantly in the target circle displayed on the screen in front of the subjects. The dynamic body balance was evaluated by the proportion of the center of pressure (COP) including in the target circle during the test. The psychogenic vertigo group showed a larger area and a smaller locus length per unit area in comparison with the healthy subject group (p<0.01). In spectral analysis with the maximum entropy method (MEM), the power of the medio-lateral and antero-posterior positional power spectrum under eyes open condition were significantly largest at around 0.125 Hz in the psychogenic vertigo group. No significant difference in the result of Body Tracking Tests with a visual feedback test was found between both groups. Our results suggest that the patients with psychogenic vertigo maintain body balance with extremely slowly and large movements for quiet stance during eyes open condition. The results of Body Tracking Tests with a visual feedback test may indicate that the spontaneous postural control itself in patients with psychogenic vertigo does not differ from that in healthy individuals. We believe that this test could be useful as one of the significant diagnostic tests for psychogenic vertigo.
Subject(s)
Feedback, Sensory , Vertigo/psychology , Adolescent , Adult , Female , Healthy Volunteers , Humans , Male , Middle Aged , Young AdultABSTRACT
The accumulation of abnormal proteins is a common characteristic of neurodegenerative diseases. This accumulation reflects a severe disturbance of cellular homeostasis in pathogenic protein clearance. Here, we demonstrated that the activation of the two major proteolytic machineries, the molecular chaperone-ubiquitin proteasome system (UPS) and the autophagy system, were simultaneously enhanced by paeoniflorin (PF), a major component of Paeonia plants, and exerted therapeutic effects in models of spinal and bulbar muscular atrophy (SBMA). PF significantly increased the expression of nuclear factor-YA (NF-YA), which strongly upregulated the molecules involved in the proteolytic machinery [molecular chaperones, carboxyl terminus of Hsc70-interacting protein and transcription factor EB], which thus mitigated the behavioral and pathological impairments in an SBMA mouse model through the upregulation of pathogenic androgen receptor protein clearance in motor neurons and muscles. These findings demonstrated that PF is able to enhance both the UPS and autophagy systems by upregulating the expression of NF-YA, which promotes therapeutic effects in an SBMA model.
Subject(s)
Glucosides/therapeutic use , Monoterpenes/therapeutic use , Receptors, Androgen/genetics , Animals , Cell Line , Cell Survival/genetics , Cell Survival/physiology , Cell Survival/radiation effects , Immunohistochemistry , Mice , Muscular Atrophy, Spinal , Proteolysis/drug effects , Real-Time Polymerase Chain ReactionABSTRACT
BACKGROUND: The purpose of this study was to elucidate the relationships among communication self-efficacy (SE), communication burden, and the mental health of the families of persons with aphasia using structural equation modeling (SEM). METHODS: This study examined 110 pairs of persons with aphasia receiving home care and 1 family caregiver per person with aphasia. The survey items for this study consisted of the Communication Self-efficacy Scale, the Communication Burden Scale, the Geriatric Depression Scale-Short Form-Japanese, and the Health-Related Quality of Life: SF-8 Health Survey. The relationships between the constructive concept of "communication self-efficacy" and "communication burden," and "mental-health status" were analyzed using SEM. RESULTS: The results of the SEM analysis revealed that a high communication SE of the families was associated with low burden of communication and good mental-health status. CONCLUSIONS: Psychoeducational programs that address the communication SE of family caregivers may have the potential to reduce the burden of communication and to improve the mental health of caregivers. These programs could lead to an enhanced quality of life for both persons with aphasia and their families.
Subject(s)
Aphasia/psychology , Caregivers/psychology , Communication , Family/psychology , Mental Health , Adult , Aged , Aged, 80 and over , Female , Health Services Needs and Demand , Humans , Japan , Male , Middle Aged , Patient Education as Topic , Self Efficacy , Severity of Illness Index , Stress, Psychological/etiology , Stress, Psychological/psychology , Surveys and QuestionnairesABSTRACT
OBJECTIVES: To elucidate the phenotypes and pathophysiology of speech and voice disorders in Parkinson's disease (PD) with subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: We conducted a cross-sectional study on 76 PD patients treated with bilateral STN-DBS (PD-DBS) and 33 medically treated PD patients (PD-Med). Speech and voice functions, electrode positions, motor function and cognitive function were comprehensively assessed. Moreover, speech and voice functions were compared between the on-stimulation and off-stimulation conditions in 42 PD-DBS patients. RESULTS: Speech and voice disorders in PD-DBS patients were significantly worse than those in PD-Med patients. Factor analysis and subsequent cluster analysis classified PD-DBS patients into five clusters: relatively good speech and voice function type, 25%; stuttering type, 24%; breathy voice type, 16%; strained voice type, 18%; and spastic dysarthria type, 17%. STN-DBS ameliorated voice tremor or low volume; however, it deteriorated the overall speech intelligibility in most patients. Breathy voice did not show significant changes and stuttering exhibited slight improvement after stopping stimulation. In contrast, patients with strained voice type or spastic dysarthria type showed a greater improvement after stopping stimulation. Spastic dysarthria type patients showed speech disorders similar to spastic dysarthria, which is associated with bilateral upper motor neuron involvement. Strained voice type and spastic dysarthria type appeared to be related to current diffusion to the corticobulbar fibres. CONCLUSIONS: Stuttering and breathy voice can be aggravated by STN-DBS, but are mainly due to aging or PD itself. Strained voice and spastic dysarthria are considered corticobulbar side effects.
Subject(s)
Deep Brain Stimulation , Parkinson Disease/therapy , Speech Disorders/etiology , Subthalamic Nucleus , Voice Disorders/etiology , Aged , Cluster Analysis , Cross-Sectional Studies , Female , Humans , Male , Parkinson Disease/complications , Parkinson Disease/physiopathology , Phenotype , Subthalamic Nucleus/physiopathologyABSTRACT
Speech and voice disorders are one of the most common adverse effects in Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS). However, the pathophysiology of voice and laryngeal dysfunction after STN-DBS remains unclear. We assessed 47 PD patients (22 treated with bilateral STN-DBS (PD-DBS) and 25 treated medically (PD-Med); all patients in both groups matched by age, sex, disease duration, and motor and cognitive function) using the objective and subjective voice assessment batteries (GRBAS scale and Voice Handicap Index), and laryngoscopy. Laryngoscopic examinations revealed that PD-DBS patients showed a significantly higher incidence of incomplete glottal closure (77 vs 48 %; p = 0.039), hyperadduction of the false vocal folds (73 vs 44 %; p = 0.047), anteroposterior hypercompression (50 vs 20 %; p = 0.030) and asymmetrical glottal movement (50 vs 16 %; p = 0.002) than PD-Med patients. On- and off-stimulation assessment revealed that STN-DBS could induce or aggravate incomplete glottal closure, hyperadduction of the false vocal folds, anteroposterior hypercompression, and asymmetrical glottal movement. Incomplete glottal closure and hyperadduction of the false vocal folds significantly correlated with breathiness and strained voice, respectively (r = 0.590 and 0.539). We should adjust patients' DBS settings in consideration of voice and laryngeal functions as well as motor function.
Subject(s)
Deep Brain Stimulation/adverse effects , Larynx/physiopathology , Parkinson Disease/physiopathology , Parkinson Disease/therapy , Subthalamic Nucleus/physiopathology , Voice Disorders/physiopathology , Aged , Female , Follow-Up Studies , Humans , Laryngoscopy , Larynx/pathology , Male , Parkinson Disease/complications , Parkinson Disease/pathology , Severity of Illness Index , Voice/physiology , Voice Disorders/complications , Voice Disorders/pathologyABSTRACT
The greatly enhanced oxidation ability of dilute aqueous nitric acid (0.10-2.0 mol L(-1)) containing bromide and iodide salts as well as chloride salts has been examined based on the dissolution kinetics of pure gold at 30-60 °C. It has been found that bromide salts are more effective than chloride salts in gaining the ability of dissolving gold in dilute aqueous nitric acid solution. At 60 °C, a piece of gold-wire (ca. 20 mg) is dissolved in 20 mL of as low as 0.10 mol L(-1) HNO3 solution containing 1.0-5.0 mol L(-1) NaBr and the dissolution rate constant, log(k/s(-1)), increases linearly (from -5.78 to -4.52) with the increasing NaBr concentration. The addition of organic solvents, such as acetonitrile and acetic acid, causes acceleration of gold dissolution in LiBr and NaBr solutions. With increasing MeCN contents, for instance, the log(k/s(-1)) value of 0.10 mol L(-1) HNO3 solution containing 2.0 mol L(-1) NaBr increases linearly from -5.30 to -4.61 at 30% (v/v) MeCN. The bromide salts affect the gold dissolution rate constant in the order of KBr < NaBr < LiBr < CaBr2. With increasing NaI concentration (0.20-3.0 mol L(-1)), some acceleration in log(k/s(-1)) of 0.50 or 1.0 mol L(-1) HNO3 solution has been observed; however, the slope of acceleration as the function of NaI concentration is much smaller than that of NaCl or NaBr. The gold dissolution ability has been examined also for nitrous acid containing chloride and bromide ions at 35 °C. The NaNO2 solution containing twice or more amounts of HX (X = Cl, Br) gives the maximum efficiency for gold dissolution, according to the log(k/s(-1)) values of the mixed solutions of NaNO2 (0.10-2.0 mol L(-1)) and HX of various concentrations. The influence of oxidation by dilute nitric and nitrous acids on the gold dissolution is discussed from the standpoint of the redox potentials in "modified" aqueous solutions and not of the changes in the activity coefficients of ions.