Reliability and Validity of the Rate of Force Development for Quadriceps in Older Patients with Cardiovascular Disease.

Background/Objectives: The rate of force development (RFD), which is the change in force over a period of time during muscle contraction, quantifies rapid muscle contractions. RFD may serve as a measure of physical rehabilitation in patients with cardiovascular disease (CVD); however, its reliability and validity in older patients remain unclear. This study examined the reliability and validity of quadricep RFD in older patients with CVD. Methods: This prospective study enrolled 30 outpatients undergoing cardiac rehabilitation (median age, 77 years) and 30 inpatients hospitalized for CVD (median age, 76 years). The quadricep RFD values at three time points (RFD50, 0-50 ms; RFD100, 0-100 ms; and RFD200, 0-200 ms) were calculated from the slope of the force-time curve. Physical performance was assessed using the Short Physical Performance Battery (SPPB). Intra- and inter-rater correlation coefficients were assessed for outpatients. The correlation coefficients between RFD values and physical performance indicators were assessed separately for outpatients and inpatients. Results: The intraclass correlation coefficients (1,1) and (2,1) for RFD50, RFD100, and RFD200 were 0.742, 0.893, and 0.873 and 0.810, 0.918, and 0.930, respectively. The correlation coefficients for SPPB with RFD50, RFD100, and RFD200 were 0.553, 0.547, and 0.597 (all p < 0.05), respectively, for inpatients; similar moderate correlations were observed for gait speed and the chair stand test. Conclusions: The test-retest reliability of the RFD was excellent in older patients with CVD. The RFD was positively correlated with physical function indicators, suggesting its validity as a measure of physical rehabilitation.

Association between preoperative phase angle and all-cause mortality after cardiovascular surgery: A retrospective cohort study.

BACKGROUND: The importance of preoperative physical function assessment for post-operative intervention has been reported in older patients undergoing cardiovascular surgery. Phase angle (PhA), measured using bioelectrical impedance analysis, is an indicator of cellular health and integrity and is reported as a prognostic factor in several chronic diseases; however, its association with the long-term prognosis of cardiovascular surgery remains unclear. This study aimed to investigate the prognostic value of PhA for long-term mortality in patients undergoing cardiovascular surgery. METHODS: This retrospective cohort study included consecutive patients who underwent elective cardiovascular surgery between October 2016 and March 2021 at Nagoya Heart Center, Japan. PhA was assessed using bioelectrical impedance analysis before surgery, and physical function measures (gait speed, grip strength and short physical performance battery [SPPB]) were measured synchronously. The association between PhA and all-cause mortality after discharge was assessed using Kaplan-Meier and multivariate Cox regression analyses. The incremental prognostic value of PhA was compared with other physical function measures using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 858 patients were included in the present analysis (mean age = 68.4 ± 11.9 years, 67.6% male). PhA positively correlated with body mass index (ρ = 0.38, P < 0.001), skeletal muscle mass index (ρ = 0.58, P < 0.001), usual gait speed (ρ = 0.44, P < 0.001), grip strength (ρ = 0.73, P < 0.001) and SPPB (ρ = 0.51, P < 0.001). The mean follow-up period, within which 44 (4.7%) died, was 908.9 ± 499.9 days for the entire cohort. Kaplan-Meier survival curves based on the PhA tertiles showed that higher PhA was associated with better survival (log-rank test, P < 0.001). The Cox regression analysis showed the independent association of PhA with mortality risk (hazard ratio: 0.91 per 0.1° increment; 95% confidence interval [CI]: 0.87-0.95; P < 0.001). The NRI and IDI showed significant improvements in predicting mortality after adding PhA to the clinical model consisting of age, sex and cardiac and renal function (NRI: 0.426, 95% CI: 0.124-0.729, P = 0.006; IDI: 0.037, 95% CI: 0.012-0.062, P = 0.003). The predictive model consisting of the clinical model and PhA was superior to the model consisting of the clinical model and each of the other physical function indicators (P < 0.05). CONCLUSIONS: PhA correlated with physical function and independently predicted long-term mortality after cardiovascular surgery. The additive prognostic value of PhA compared with the other physical function measures suggests the clinical usefulness of preoperative PhA for risk stratification in planning post-operative treatment and rehabilitation.

The Japanese Breast Cancer Society clinical practice guidelines for epidemiology and prevention of breast cancer, 2022 edition.

The Japanese Breast Cancer Society Clinical Practice Guidelines for Epidemiology and Prevention of Breast Cancer, 2022 Edition.

Association between outpatient cardiac rehabilitation and all-cause mortality after cardiovascular surgery: A propensity score-matched analysis.

Objectives: Cardiac rehabilitation (CR) is a class I recommendation in the treatment guidelines for cardiovascular disease; however, its postoperative prognostic effects after surgery are not fully understood. Therefore, this study aimed to examine the effect of multidisciplinary outpatient CR on postdischarge all-cause mortality in patients who underwent cardiovascular surgery. Methods: This retrospective cohort study included consecutive patients who underwent elective cardiovascular surgery between April 2015 and March 2021. Patients were categorized into CR and non-CR groups. The primary outcome measure was all-cause mortality. Propensity score-matching analysis was performed to minimize selection bias and differences in clinical characteristics. The propensity score for each patient was produced using logistic regression analysis, with the CR group and the subsequent 27 variables as the dependent and independent variables, respectively. Results: In our cohort (n = 1095), 51 patients (4.7%) died during the follow-up period (mean, 1042 days). The CR group had a significantly lower mortality rate than the non-CR group (hazard ratio, 0.45; 95% CI, 0.21-0.95; P = .036). After propensity score matching adjusted for confounders, the association between CR and reduced risk of all-cause mortality remained (hazard ratio, 0.35; 95% CI, 0.14-0.85; P = .02). Conclusions: Postdischarge multidisciplinary outpatient CR in patients who underwent cardiovascular surgery was associated with a substantial survival benefit, which persisted after adjusting for variables, including age, operative factors, physical and cognitive functions, and nutritional status.

Metabolic Oscillations and Glycolytic Phenotypes of Cancer Cells.

Cancer cells show several metabolic phenotypes depending on the cancer types and the microenvironments in tumor tissues. The glycolytic phenotype is one of the hallmarks of cancer cells and is considered to be one of the crucial features of malignant cancers. Here, we show glycolytic oscillations in the concentrations of metabolites in the glycolytic pathway in two types of cancer cells, HeLa cervical cancer cells and DU145 prostate cancer cells, and in two types of cellular morphologies, spheroids and monolayers. Autofluorescence from nicotinamide adenine dinucleotide (NADH) in cells was used for monitoring the glycolytic oscillations at the single-cell level. The frequencies of NADH oscillations were different among the cellular types and morphologies, indicating that more glycolytic cancer cells tended to exhibit oscillations with higher frequencies than less glycolytic cells. A mathematical model for glycolytic oscillations in cancer cells reproduced the experimental results quantitatively, confirming that the higher frequencies of oscillations were due to the higher activities of glycolytic enzymes. Thus, glycolytic oscillations are expected as a medical indicator to evaluate the malignancy of cancer cells with glycolytic phenotypes.

Impact of arm circumference on clinical outcomes in patients undergoing transcatheter aortic valve replacement.

Background: Although Arm circumference (AC) is considered to be a predictor of clinical outcomes of transcatheter aortic valve replacement (TAVR), limited data are available on the impact of this anthropometric measurement. This study aimed to investigate the clinical impact of AC on the outcomes of patients who underwent TAVR. Methods: AC was investigated in consecutive patients who underwent TAVR between March 2014 and May 2018. Patients were divided into low AC (n = 220) and high AC (n = 127) groups by a classification and regression tree (CART) survival model, and their baseline characteristics and mortality were compared. The correlations of AC with other frailty markers were also evaluated. Results: One-year clinical follow-up was completed in 100% of cases, and 89 patients (31 men, 58 women) died during the median follow-up period of 825 days. The low AC group was more fragile than the high AC group, and the AC value was significantly correlated with each frailty marker (all p < 0.05). The Cox regression analysis demonstrated the independent association of mortality with low AC (HR: 2.56, 95% confidence interval [CI]: 1.47-4.46, p < 0.001). When AC was compared to conventional prediction models of survival, the net reclassification improvement and the integrated discrimination improvement analysis showed significant improvements in predicting outcomes after including the AC with other frailty markers (all p < 0.05). Conclusions: The AC is related to frailty markers and is an important surrogate marker for predicting worse clinical outcomes after TAVR. Assessment of AC may be considered when deciding on TAVR.

Glycolytic oscillations in HeLa cervical cancer cell spheroids.

Previous studies have unravelled glycolytic oscillations in cancer cells, such as HeLa cervical and DU145 prostate cancer cells, using a monolayer culture system. Here, we demonstrate glycolytic oscillations in HeLa cervical cancer cell spheroids. Experiments revealed that a small number of HeLa cells in spheroids exhibited heterogeneous oscillations with a higher frequency than those in monolayers. Model analyses and our previous experiments indicated that the higher frequencies of oscillations in spheroids were mostly due to the increase in glycolytic enzyme activity in the cells, and to the decrease in glucose concentration by diffusional transport of glucose from the surface to inside the spheroids, as well as the increase in cell density through spheroid formation. These results and our previous studies imply that more malignant cancer cells tend to exhibit glycolytic oscillations with higher frequencies than less malignant cells. Adjacent cells in spheroids oscillated within a 10% difference in frequency, but did not synchronize with each other. This suggests that weak cell-to-cell interactions might exist among HeLa cells connected with cadherins in the spheroid microenvironment; however, the interactions were not strong enough to induce synchronization of glycolytic oscillations.

Obesity May Not Be a Risk of Non-Target Lesion Revascularization in the Elderly Patients.

Obesity is assumed to be one of the robust risk factors for coronary artery disease. However, the effects of obesity on the progression of atherosclerosis in patients in different age groups after percutaneous coronary intervention (PCI) remain unclear. This study aimed to examine the effect of obesity on prognosis in different age groups.Consecutive patients who underwent urgent or elective PCI were surveyed for this study and were then divided into the elderly group and middle-aged group with a cut-off age of 70 years. All patients underwent coronary angiography or coronary computed tomography angiography 1 year after PCI to examine the progression of atherosclerosis. The primary endpoint was revascularization for a new lesion within 2 years after PCI. In addition, the main effects and correlations between obesity and age were examined. Multivariate logistic regression analysis was conducted to identify independent predictors of non-target lesion revascularization (non-TLR).Of the 711 patients who met the criteria and were available for follow-up analysis, the incidence of non-TLR within 2 years was 97/711 (13.6%). The higher incidence of non-TLR in patients with obesity was observed only in the middle-aged group. Furthermore, in the multivariate analysis, obesity was independently associated with non-TLR only in the middle-aged group.The findings of the present study would enable us to construct the hypothesis that obesity in elderly patients may not be an independent predictor of the incidence of non-TLR, indicating that the management to prevent non-TLR may vary depending on the age of the patient.

[A case of cerebral embolism with Coronavirus disease 2019].

A 63-year-old man, who had persistent fever for a month, was admitted to the hospital with sudden left arm palsy with a National Institutes of Health Stroke Scale score of 3. Consequently, brain MRI showed hyperintensity of the bilateral occipital, right parietal, and right frontal lobes on diffusion-weighted imaging. Moreover, FLAIR presented hyperintensity of the left occipital lobe. Magnetic resonance angiography detected the deficit of the blood-flow signal of the horizontal segment of the middle cerebral artery. He was diagnosed with acute ischemic stroke. In addition, chest CT showed ground-glass opacities, and test to detect SARS-CoV-2 was positive. Cerebral embolism was suspected. However, the source was unknown. His ischemic stroke was possibly associated with coagulation abnormality caused by coronavirus disease 2019.

Clinical Outcomes of Subcutaneous and Visceral Adipose Tissue Characteristics Assessed in Patients Underwent Transcatheter Aortic Valve Replacement.

BACKGROUND: Adipose tissue (AT) characteristics are considered to be a marker for predicting clinical outcomes. This study aimed to investigate the prognostic value of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) computed tomography (CT) assessment in patients who underwent transcatheter aortic valve replacement (TAVR). METHODS: We used the Japanese multicentre registry data of 1372 patients (age: 84.5 ± 5.0 years, women: 70.6%) who underwent TAVR. The SAT and VAT were assessed according to the preprocedural CT area and density. Baseline characteristics and clinical outcomes were compared based on the differences in AT characteristics. The independent associations with all-cause mortality after TAVR were evaluated according to the CT area and density of AT. RESULTS: Low-volume area of SAT and VAT was associated with worse clinical outcomes compared with high-volume area of SAT and VAT in patients who underwent TAVR (log-rank test P = 0.016 and P = 0.014). High CT density of SAT and VAT was associated with increasing mortality in comparison with low CT density of SAT and VAT (log-rank test P < 0.001 and P = 0.007). The Cox regression multivariate analysis demonstrated the independent association of increased all-cause mortality in the high SAT and VAT density (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.06-1.88, P = 0.019, and HR: 1.34, 95% CI: 1.03-1.76, P = 0.031, respectively), but not in the low SAT and VAT area (HR: 0.85, 95% CI: 0.74-1.29, P = 0.85, and HR: 0.78, 95% CI: 0.60-1.03, P = 0.085, respectively). CONCLUSIONS: CT-derived AT characteristics, particularly the qualitative assessments, were useful for predicting the prognosis in patients after TAVR.

INTRODUCTION: Les caractéristiques du tissu adipeux (TA) sont considérées comme un marqueur de la prédiction des résultats cliniques. La présente étude avait pour objectif d'examiner la valeur pronostique de l'évaluation par tomodensitométrie (TDM) du tissu adipeux sous-cutané (TASC) et du tissu adipeux viscéral (TAV) des patients qui subissaient un remplacement valvulaire aortique par cathéter (RVAC). MÉTHODES: Nous avons utilisé les données du registre multicentrique japonais de 1 372 patients (âge : 84,5 ± 5,0 ans, femmes : 70,6 %) qui subissaient un RVAC. Nous avons évalué le TASC et le TAV selon la surface et la densité à la TDM préinterventionnelle. Nous avons comparé les caractéristiques initiales et les résultats cliniques en nous basant sur les différences dans les caractéristiques du TA. Nous avons évalué les associations indépendantes à la mortalité toutes causes confondues après le RVAC selon la surface et la densité du TA à la TDM. RÉSULTATS: La surface de faible volume du TASC et du TAV était associée à de plus mauvais résultats cliniques que la surface de grand volume du TASC et du TAV chez les patients qui subissaient le RVAC (test logarithmique par rangs P = 0,016 et P = 0,014). La densité du TASC et du TAV à la TDM était associée à l'augmentation de la mortalité en comparaison d'une faible densité du TASC et du TAV à la TDM (test logarithmique par rangs P < 0,001 et P = 0,007). L'analyse multivariée selon le modèle de régression de Cox démontrait l'association indépendante de l'augmentation de la mortalité toutes causes confondues lors de densité élevée du TASC et du TAV (rapport de risque [RR] 1,41, intervalle de confiance [IC] à 95 %, 1,06-1,88, P = 0,019, et RR 1,34, IC à 95 %, 1,03-1,76, P = 0,031, respectivement), mais non lors de faible surface du TASC et du TAV (RR 0,85, IC à 95 %, 0,74-1,29, P = 0,85, et RR 0,78, IC à 95 % : 0,60-1,03, P = 0,085, respectivement). CONCLUSIONS: Les caractéristiques du TA acquises par TDM, particulièrement les évaluations qualitatives, étaient utiles à la prédiction du pronostic des patients après le RVAC.

Methotrexate-induced Transient Encephalopathy in an Adolescent and Young Adult Patient with Acute Lymphoblastic Leukemia.

A 17-year-old girl was diagnosed with acute lymphoblastic leukemia (ALL). After the administration of high-dose methotrexate (MTX) or intrathecal MTX, the patient experienced transient hemiparesis and motor aphasia. Diffusion-weighted magnetic resonance imaging showed a high-intensity lesion in the bilateral centrum semiovale, and a vasospasm was detected in the proximal segment of bilateral A1 on magnetic resonance angiography. Edaravone was administered, and leucovorin rescue treatment was continued; eventually, the patient's neurological symptoms completely resolved. This finding suggested that vasospasm might be a mechanism underlying MTX-induced transient encephalopathy in adolescent and young adult patients with ALL.

Smoking status and unruptured intracranial aneurysm among brain health check-up examinees: a cross-sectional study in Japan.

Objective: Although it is well known that smoking is a risk factor for subarachnoid hemorrhage, the association between smoking and unruptured intracranial aneurysms remains unclear. The aim of the present study was to investigate whether smoking status was associated with unruptured intracranial aneurysms among Japanese brain health check-up examinees. Materials and Methods: We conducted a cross-sectional study of 1,496 adults (aged 26-90 years) undergoing brain health check-ups at a single community medical support hospital in Akita, Japan between 2009 and 2013. In Japan, people can discretionarily undergo a brain health check-up for early detection of unruptured intracranial aneurysms or subarachnoid hemorrhages. Participants responded to a questionnaire on lifestyle, such as smoking status, and were classified into three groups: never, former, and current smoker. The evaluation of unruptured intracranial aneurysms detected by magnetic resonance angiography was performed by an expert physician. Multiple logistic regression models were used to estimate the odds ratio for unruptured intracranial aneurysms. We performed statistical analyses by age, sex, and family history of stroke. Results: The number of participants with unruptured intracranial aneurysms was 43 (2.9%). The mean age (standard deviation) and proportion of males was 55.8 (9.5) years and 53.3%, respectively. The adjusted odds ratios (95% confidence intervals) for unruptured intracranial aneurysms of 1.21 (0.48-3.08) among former smokers and 2.88 (1.10-7.50) among current smokers were compared to those of never smokers (p-trend = 0.041). After stratifying by age, sex, and family history of stroke, no interactions were found. Conclusion: This cross-sectional study conducted in Japan showed that smoking was positively associated with unruptured intracranial aneurysms among brain health check-up examinees.

The Cellular and Mechanical Basis for Response Characteristics of Identified Primary Afferents in the Rat Vibrissal System.

Compared to our understanding of the response properties of receptors in the auditory and visual systems, we have only a limited understanding of the mechanoreceptor responses that underlie tactile sensation. Here, we exploit the stereotyped morphology of the rat vibrissal (whisker) array to investigate coding and transduction properties of identified primary tactile afferents. We performed in vivo intra-axonal recording and labeling experiments to quantify response characteristics of four different types of identified mechanoreceptors in the vibrissal follicle: ring-sinus Merkel; lanceolate; clublike; and rete-ridge collar Merkel. Of these types, only ring-sinus Merkel endings exhibited slowly adapting properties. A weak inverse relationship between response magnitude and onset response latency was found across all types. All afferents exhibited strong "angular tuning," i.e., their response magnitude and latency depended on the whisker's deflection angle. Although previous studies suggested that this tuning should be aligned with the angular location of the mechanoreceptor in the follicle, such alignment was observed only for Merkel afferents; angular tuning of the other afferent types showed no clear alignment with mechanoreceptor location. Biomechanical modeling suggested that this tuning difference might be explained by mechanoreceptors' differential sensitivity to the force directed along the whisker length. Electron microscopic investigations of Merkel endings and lanceolate endings at the level of the ring sinus revealed unique anatomical features that may promote these differential sensitivities. The present study systematically integrates biomechanical principles with the anatomical and morphological characterization of primary afferent endings to describe the physical and cellular processing that shapes the neural representation of touch.

Diagnostic utility of CD205 in breast cancer: Simultaneous detection of myoepithelial cells and dendritic cells in breast tissue by CD205.

BACKGROUND: CD205 can be used to detect myoepithelial cells (MECs) and dendritic cells (DCs) in breast tissue. However, the usefulness of CD205 immunostaining in the pathological diagnosis of breast tumors is not fully understood. The objective of this study was to re-evaluate CD205 co-expression with other MEC markers, such as p63 and CD10, in nonneoplastic and neoplastic breast tissue and to evaluate its pathological diagnostic utility in these types of breast cancer. MATERIAL AND METHODS: Nonneoplastic breast tissue samples with a terminal duct lobular unit and duct were obtained from fibroadenoma and mastopathy patients. Neoplastic breast tissue samples included ductal carcinoma in situ (DCIS) (n=43) and invasive ductal carcinoma (IDC) (n=60), including the tubule-forming type (n=20). These specimens were investigated by CD205, p63, and CD10 immunostaining. RESULTS: In addition to p63 and CD10, CD205 was expressed on MECs in nonneoplastic breast and DCIS tissue samples; CD205 was simultaneously detected on DCs that had infiltrated DCIS and IDC tumor nests. CD205 was expressed on cancer cells themselves in only 7.3% of the breast cancer samples. The number of intratumoral CD205⁺ DCs in tubular IDC was significantly higher than that in DCIS (P<0.01). CONCLUSION: Because CD205 was simultaneously detected on MECs and DCs in the same breast tissue sections, it may be useful for distinguishing tubular IDC from DCIS.

Endovascular Stenting Following Stereotactic Radiosurgery for Meningioma Involving the Superior Sagittal Sinus.

Objective: Surgical removal of meningiomas that have partially invaded the superior sagittal sinus (SSS) is difficult because it requires reconstruction of the SSS, which can lead to SSS occlusion and venous infarction. The present report details the case of an SSS-involved meningioma treated by stereotactic radiosurgery (SRS) and stenting. Case Presentation: A 60-year-old woman was admitted to the hospital with blurred vision and papilledema. Lumbar puncture showed markedly increased intracranial pressure (ICP; 340 mm H2O). Gadolinium-enhanced T1-weighted imaging revealed a 1-cm meningioma located mainly in the SSS. Digital subtraction angiography revealed severe stenosis, at the posterior part of the SSS, and no collateral flow. The ICP was considered a result of the stenosis caused by the meningioma. A combined therapy comprising transarterial embolization (for tumor growth suppression), endovascular stenting of the SSS (for intracranial hypertension improvement), and SRS (for tumor control) was planned. SRS was performed first to avoid interference by the metal artifacts caused by the stent. After placement of a self-expanding stent, partial recanalization was achieved. Two months after stenting, SSS stenosis improved and MRI results showed shrinkage of the meningioma. Thirty months after the treatment, no tumor recurrence was observed. Conclusion: The treatment strategy of SRS followed by stenting was successful for a SSS-involved meningioma. ICP and a pressure gradient between the pre- and post-stenotic segments should be considered indications for stenting.

[A case of possible elderly onset rheumatoid meningitis without arthritis].

A 93-year-old man was admitted to our hospital with disturbance of consciousness. Brain magnetic resonance imaging (MRI) showed hyperintensity of the subarachnoid space in the left frontal and parietal lobes on diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR). Gadolinium-enhancement of the pia mater was also observed. We did not perform biopsy because of a high risk of perioperative complication. Although physical examination found no evidence of the rheumatoid arthritis, rheumatoid factors and anti-cyclic citrullinated peptides antibodies were elevated. He was suspected to have rheumatoid meningitis. We treated him with intravenous methylprednisolone (0.5 g/day) for 3 days. Rheumatoid meningitis often shows hyperintensity of the subarachnoid space on the DWI and FLAIR, and steroid therapy is effective.

The 6-Minute Walk Test: DIFFERENCE IN EXPLANATORY VARIABLES FOR PERFORMANCE BY COMMUNITY-DWELLING OLDER ADULTS AND PATIENTS HOSPITALIZED FOR CARDIAC DISEASE.

PURPOSE: To examine the use of 10-m usual walking speed as an explanatory variable of the 6-min walk test distance (6MWD) in cardiac patients and community-dwelling older adults. METHODS: This was a cross-sectional secondary analysis correlational study. Participants of the present study were 119 patients hospitalized for cardiac disease and 109 community-dwelling older adults. Data including 6MWD, 10-m usual walking speed, age, sex, grip strength, height, weight, and cognitive function were obtained from the medical records of patients in 2 acute care hospitals and a cohort of community-dwelling Japanese older adults. Multiple linear regression models for the 6MWD were examined in each group. RESULTS: The mean ± standard deviation for 6MWDs were 276 ± 106 m in hospitalized patients and 466 ± 81 m in community-dwelling older adults. In both groups, 10-m usual walking speed was the strongest factor correlated with 6MWD. On univariate analysis, the correlation between walking tests was stronger in the hospitalized group (ß = .855) than in the community-dwelling elderly (ß = .627). When age and sex were added into the models, the determination coefficients improved (adjusted R = 0.745 and 0.463 in the hospitalized patients and the community-dwelling elderly, respectively). CONCLUSIONS: The present findings indicated that the 6MWD was more strongly associated with 10-m usual walking speed in patients hospitalized for cardiac disease than in community-dwelling older adults. The predictive validity of 10-m walking speed for future adverse outcomes among cardiac patients is an issue for future research.

Modeling studies of heterogeneities in glycolytic oscillations in HeLa cervical cancer cells.

Previous experiments demonstrated that a population of HeLa cells starved of glucose or both glucose and serum exhibited a strong heterogeneity in the glycolytic oscillations in terms of the number of oscillatory cells, periods of oscillations, and duration of oscillations. Here, we report numerical simulations of this heterogeneous oscillatory behavior in HeLa cells by using a newly developed mathematical model. It is simple enough that we can apply a mathematical analysis, but capture the core of the glycolytic pathway and the activity of the glucose transporter (GLUT). Lognormal distributions of the values of the four rate constants in the model were obtained from the experimental distributions in the periods of oscillations. Thus, the heterogeneity in the periods of oscillations can be attributed to the difference in the rate constants of the enzymatic reactions. The activity of GLUT is found to determine whether the HeLa cells were oscillatory or non-oscillatory under the same experimental conditions. Simulation with the log-normal distribution of the maximum uptake velocity of glucose and the four randomized rate constants based on the log-normal distributions successfully reproduced the time-dependent number of oscillatory cells (oscillatory ratios) under the two starving conditions. The difference in the initial values of the metabolites has little effect on the simulated results.

Differential expression of estrogen receptor-α on follicular dendritic cells from patients with grade 1-2 and grade 3 follicular lymphoma.

Hormone therapy has been used for patients with estrogen receptor alpha (ERα)-positive breast cancers. Recently, some studies reported the expression of ERα on neoplastic cells from B-cell lymphomas. However, there has been only one report of ERα expression on the follicular dendritic cells (FDCs) that structurally and functionally support the microenvironment of follicular lymphomas (FLs). The objective of this study was to investigate the frequency of ERα expression on FDCs in nonneoplastic reactive lymphoid tissues and to compare the frequency of ERα expression on FDCs in the axillary lymph nodes between patients with and without antiestrogen therapy and among patients with grades 1-3 of FL. Reverse transcription-polymerase chain reaction was performed to detect ERα mRNA in FL. In nonneoplastic germinal centers (GCs) from patients with tonsillitis or reactive lymphadenitis, ERα was expressed in the light zone. ERα-positive cells strongly correlated with the width of GCs (rs  = 0.81, P < 0.01) and the CD21-positive (rs  = 0.69, P < 0.01) and CD23-positive (rs  = 0.83, P < 0.01) FDC meshwork. The axillary lymph nodes had fewer ERα-positive cells, smaller GCs, and a looser CD21- and CD23-positive FDC meshwork with hormone therapy than without hormone therapy (P < 0.01). Neoplastic follicles of G1-2 FL had more ERα-positive cells and a larger CD23+ FDC meshwork than those of G3 FL (P < 0.01). ERα mRNA was detected in both G1-2 FL and G3 FL by reverse transcription-polymerase chain reaction. In conclusion, these results suggested that antiestrogen hormone therapy may decrease the number of ERα-positive FDCs and that the responses mediated by the estrogen-ERα interaction on FDCs may differ between G1-2 FL and G3 FL.

Effect of Perioperative Neuromuscular Electrical Stimulation in Patients Undergoing Cardiovascular Surgery: A Pilot Randomized Controlled Trial.

A randomized, controlled trial was conducted to examine the effects of perioperative neuromuscular electrical stimulation on muscle proteolysis and physical function using blinded assessment of physical function. Consecutive patients undergoing cardiovascular surgery were screened for eligibility as study subjects. Participants were randomly assigned to receive either neuromuscular electrical stimulation or the usual postoperative mobilization program. The intervention group received neuromuscular electrical stimulation on bilateral legs 8 times before and after surgery. The primary outcomes were the mean 3-methylhistidine concentration corrected for urinary creatinine content from baseline to postoperative day 6, and knee extensor isometric muscle strength on postoperative day 7. Secondary outcomes were usual walking speed and grip strength. Physical therapists blinded to patient allocation performed measurements of physical function. Of 498 consecutive patients screened for eligibility, 119 participants (intervention group, n = 60; control group, n = 59) were enrolled. In the overall subjects, there were no differences in any outcomes between the intervention and control groups. The results demonstrated no significant effects of neuromuscular electrical stimulation on muscle proteolysis and physical function after cardiovascular surgery, suggesting the need to explore indications for neuromuscular electrical stimulation and to clarify the effects in terms of the dose-response relationship.