The effect of unilateral blood flow restriction on temporal and spatial gait parameters.

Blood flow restriction walking (BFR-W) is becoming more frequently used in aerobic and strength training and it has been proposed that BFR-W can be used in clinical populations. BFR-W may change gait stability yet few studies have assessed gait changes during or following BFR-W. The aim of this study was to assess if spatial-temporal gait parameters change during and following BFR-W. Twenty-four participants completed two walking sessions (>48-hours apart); 1) Unilateral BFR-W applied at the dominant thigh, 2) walking without BFR. In each session participants performed a 5-min warmup, 15-min walking intervention and 10-min active recovery. The warmup and active recovery were performed without BFR on both days. Measurements were attained at baseline, during the intervention and post-intervention using the GAITRite®. Linear mixed models were applied to each measured variable. Fixed factors were timepoint (warmup, intervention, and active recovery), condition (BFR-W and control walking) and condition × timepoint. Random factors were subject and subject × condition. Participants took shorter (3.2-cm (mean difference), CI95%: 0.8-5.6-cm) and wider strides (1.4-cm, CI95%: 0.9-1.9-cm) during BFR-W. For single leg measures, participants took shorter steps (2.8-cm, CI95%: 1.7-4.0-cm) with a faster single support time (7.5-ms, CI95%: 2.9-12.0-ms) on the non-dominant (unoccluded) leg during BFR-W compared to the non-dominant leg during control walking. There were no differences in step length and single support time between the dominant (occluded) leg during BFR-W compared to the dominant leg during control walking. There were no significant changes in velocity, cadence or double support time between BFR-W and control walking (P > 0.05). BFR-W caused small transient changes to several gait parameters. These changes should be considered when using BFR-W in clinical populations.

Evaluation of circulating microparticles in healthy medical workers occupationally exposed to ionizing radiation: A preliminary study.

OBJECTIVES: Ionizing radiation was known to cause disruption of cytoskeleton. However, the disorganization of the cytoskeleton leads to form microparticles (MP) that carry membrane and cytoplasmic constituents from their parent cells they are released from. Therefore, authors investigated the effect of the occupational exposure to low doses of ionizing radiation on MP levels. MATERIAL AND METHODS: The current study was conducted on 38 healthy medical workers occupationally exposed to low doses of ionizing radiation and 29 controls matched by gender, age, and smoking habits. The MP levels measured by flow cytometry were classified as positive or negative phosphatidylserine (PS+ or PS-), and phenotyped according to their cellular origin. RESULTS: Total MP (PS-/PS+) levels, regardless of phenotype, were significantly higher in workers occupationally exposed to ionizing radiation than in healthy individuals (p = 0.0004). Negative phosphatidylserine microparticles were predominant in medical exposed workers and, to a lesser extent, in controls (68% and 57%, respectively). With regard to phenotypic characterization of cellular origin, MP derived from platelets (CD41a+), endothelial (CD146+), leucocytes (CD45+) and erythrocytes (CD235a+) MP were significantly enhanced in exposed workers compared with controls (p < 0.0001). However, no significant difference was found in the proportion of the other blood elements in the peripheral circulation between the 2 groups. Serum levels of C-reactive protein were normal for all individuals. In addition, no association was observed between MP levels and the studied confounding factors. CONCLUSIONS: The results suggest that elevated circulating MP levels represent an indicator of cellular damage caused by medical exposure to low doses of ionizing radiation. By consequence, the quantification of MP seems to be a useful biomarker for assessing the negative effects of occupational exposure to ionizing radiation. Int J Occup Med Environ Health 2018;31(6):783-793.

Circulating endothelial cells and microparticles as diagnostic and prognostic biomarkers in small-cell lung cancer.

OBJECTIVES: It has been proposed that circulating endothelial cells (CECs) and microparticles (MPs) may be useful for the assessment of patients with non-small-cell lung cancer (NSCLC). However, little is known about the potential clinical relevance of these biomarkers in small-cell lung cancer (SCLC). Therefore, we investigated the utility of baseline levels of CECs and MPs in SCLC patients. MATERIALS AND METHODS: An immunomagnetic separation (IMS) technique was used to isolate and quantify CECs in the peripheral blood, while plasma samples were analyzed using flow cytometry for the measurement of circulating MPs. RESULTS: We prospectively collected data from 56 patients and 41 healthy individuals. Forty-three patients presented at initial diagnosis and 13 patients presented at relapse. Baseline levels of CECs and MPs were significantly higher in SCLC patients either at initial diagnosis or at relapse than in healthy subjects (p < 0.0002 and p < 0.007, respectively). However, estimated tumor volume (ETV) was significantly correlated with basal MP values (p < 0.0001) but not with pretreatment CECs (p = 0.57). The amount of baseline CECs and MPs was significantly lower in patients with an objective response (OR, n = 23) than in those with progressive disease (PD, n = 15) after treatment (p = 0.016 and 0.05, respectively). With cut-off values of 110 cells/mL for CECs and 1257 events/µL for MPs according to receiver operating characteristics (ROC) analysis, baseline levels of these biomarkers were not significantly correlated with either progression-free survival (PFS) or overall survival (OS). However, patients with 6-month PFS displayed significantly decreased pretreatment CEC counts (p = 0.042), whereas basal MP values significantly increased in 1-year survivors compared with those in non-survivors (p = 0.05). CONCLUSION: Our results suggest that baseline CECs and MPs may be predictive biomarkers of tumor response and long-term survival in SCLC patients.

Between session reliability of heel-to-toe progression measurements in the stance phase of gait.

The objective of the current study was to determine the test-retest reliability of heel-to-toe progression measures in the stance phase of gait using intraclass correlation coefficient (ICC) analysis. It has been proposed that heel-to-toe progression could be used as a functional measure of ankle muscle contracture/weakness in clinical populations. This was the first study to investigate the test-retest reliability of this measure. Eighteen healthy subjects walked over the GAITRite® mat three times at a comfortable speed on two sessions (≥ 48 hours apart). The reliability of the heel-to-toe progression measures; heel-contact time, mid-stance time and propulsive time were assessed. Also assessed were basic temporal-spatial parameters; velocity, cadence, stride length, step length, stride width, single and double leg support time. Reliability was determined using the ICC(3,1) model and, fixed and proportional biases, and measures of variability were assessed. Basic gait temporal-spatial parameters were not different between sessions (p > 0.05) and had excellent reliability (ICC(3,1) range: 0.871-0.953) indicating that subjects walked similarly between sessions. Measurement of heel-to-toe progression variables were not different between sessions (p > 0.05) and had excellent reliability (ICC(3,1) range: 0.845-0.926). However, these were less precise and more variable than the measurement of standard temporal-spatial gait variables. As the current study was performed on healthy populations, it represents the 'best case' scenario. The increased variability and reduced precision of heel-to-toe progression measurements should be considered if being used in clinical populations.

Circulating endothelial cells and microparticles for prediction of tumor progression and outcomes in advanced non-small cell lung cancer.

BACKGROUND: Circulating endothelial cells (CECs) and microparticles (MPs) are proposed as useful biosensors for angiogenesis and membrane damage in cancer. OBJECTIVE: We investigated their predictive value for progression disease (PD) and clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with cytotoxic chemotherapy. METHODS: Peripheral blood samples were obtained from 60 patients. Immunomagnetic separation (IMS) and flow cytometry techniques were used to quantify CECs and MPs, respectively. Receiver operating characteristics (ROC) analysis was used to determine the optimal cutoff values for CECs and MPs counts according to their levels in patients with an objective response (OR) and non-responders after treatment. Baseline serum biomarkers levels and their kinetics after chemotherapy were correlated with tumor response and outcomes in advanced NSCLC patients. RESULTS: Forty-seven patients presented an OR after chemotherapy. Of these, 28 patients progressed within three months. Through an increase in their levels during or after chemotherapy, CECs and MPs correctly predicted PD in 57% and 61% of these patients, respectively. Regarding tumor stage, NSCLC patients with stage IV had significantly higher pretreatment CECs and MPs levels than stage III patients (p= 0.037 and 0.018, respectively). Moreover, progression-free survival (PFS) was significantly longer in patients with high baseline CECs levels than those with low pretreatment CECs values (p= 0.05). Moreover, patients with high percentage change in CECs count after chemotherapy had significantly longer time to progression (TTP) duration (p= 0.018). CONCLUSIONS: Our findings suggest the increase in CECs and MPs number during or after chemotherapy as predictive biomarkers of tumor progression in advanced NSCLC patients. An association of basal CECs and MPs values with tumor stage was also shown in advanced NSCLC patients. However, baseline CECs levels and their kinetics after chemotherapy seem to be prognostic factors in advanced NSCLC.

Circulating endothelial cells for evaluation of tumor response in non-small cell lung cancer patients receiving first-line chemotherapy.

BACKGROUND: Circulating endothelial cells (CECs) reflect the neovascularization in the tumor mass. We therefore investigated the potential role of CEC kinetics after first-line chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. METHODS: Peripheral blood samples were obtained from 45 healthy subjects and 51 naïve patients with advanced NSCLC. Quantification of CD146+ CECs was performed using immunomagnetic separation (IMS). RESULTS: Pretreatment and posttreatment CEC levels in NSCLC patients were significantly higher than in healthy subjects (p<0.0001). An objective response was achieved after chemotherapy with partial response (PR) or stable disease (SD) in 26 patients, whereas the remaining 25 patients had progressive disease (PD). Baseline CEC levels were significantly higher in PR/SD patients than in PD patients (p = 0.039). After chemotherapy, CEC count significantly decreased in PR/SD patients (p = 0.014) and increased in patients with PD (p = 0.019). Moreover, there was a significant difference in the percentage change of CEC counts between the 2 groups (p = 0.0016). No significant difference in the median progression-free survival and overall survival (OS) was observed between patients with high baseline CEC counts and those with low baseline CEC levels. However, patients with high percentage change in CEC count had longer OS than those with low percentage change after chemotherapy (p = 0.05). CONCLUSIONS: Changes in CEC counts after chemotherapy reflect tumor response in advanced NSCLC patients. Moreover, high percentage changes in CEC counts after chemotherapy may predict longer OS in advanced NSCLC. High baseline CEC levels might be an indicator of tumor response in advanced NSCLC patients after first-line chemotherapy.

Predictive and prognostic value of circulating endothelial cells in non-small cell lung cancer patients treated with standard chemotherapy.

PURPOSE: Monitoring circulating endothelial cells (CECs) count reflects the tumor vasculature in cancer patients and might be a predictor of response to chemotherapy. We therefore investigated the clinical significance of changes in CECs count after three cycles of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Peripheral blood samples were collected from 89 naive NSCLC patients at diagnosis and after chemotherapy. The CECs were quantified by an immuno-magnetic technique and fluorescent microscopy. After chemotherapy, patients were assessed according to the response evaluation criteria in solid tumors as partial response (PR), stable disease (SD) or progression disease (PD). RESULTS: Baseline CECs levels were significantly higher in PR patients (n = 62) than those in patients with SD/PD (n = 27) (p = 0.0007). Although there was no significant correlation between baseline CECs levels and progression-free survival (PFS) (p = 0.287), patients with high percentage change in CECs count after chemotherapy had significantly longer PFS than those with low percentage change (p = 0.048). Regarding treatment efficacy, CECs count significantly decreased after chemotherapy in comparison with CECs count at baseline in patients with PR (p < 0.0001). By contrast, CECs levels after chemotherapy were significantly higher than those at diagnosis in patients with PD (p = 0.002). Moreover, there was no significant change between pre- and post-treatment CECs amount in patients with SD (p = 0.681). CONCLUSIONS: Baseline CECs levels might be an early predictive biomarker for treatment efficacy in advanced NSCLC patients. Our results suggest the change in CECs count after chemotherapy as a prognostic factor for tumor response and PFS in NSCLC.

Circulating endothelial cells as a biomarker in non-small cell lung cancer patients: correlation with clinical outcome.

BACKGROUND: Circulating endothelial cells (CECs) have been proposed as a biomarker for the assessment of patients with solid tumors. However, few data are available in non-small cell lung cancer (NSCLC). We therefore analyzed the clinical significance of CECs in newly diagnosed NSCLC patients. In addition, we tried to determine the prognostic value of CECs in NSCLC. METHODS: In this prospective study, 151 newly diagnosed NSCLC patients and 25 healthy volunteers were included. Furthermore, 25 patients with a partial response (n=15) or stable disease (n=10) after treatment were evaluated at recurrence with a mean follow-up of 117 days (range: 47-364 days). CECs were counted using magnetic beads coupled to a specific antibody against CD146. RESULTS: The pre-treatment CEC count was significantly higher in patients with all histological subtypes of NSCLC than in healthy volunteers (p<0.0001). High baseline CEC counts were significantly correlated with advanced clinical stages (p=0.026), weight loss (p=0.03), and poorly differentiated NSCLC (p=0.02). The amount of CECs increased significantly at recurrence compared with their amount after treatment in 20/21 assessable patients (p=0.0001). Nevertheless, there was no significant correlation between baseline CEC count and median duration of progression-free survival (p=0.402). CONCLUSIONS: Increased CEC counts were present in patients with newly diagnosed NSCLC compared with healthy subjects. Elevated levels of baseline CECs correlated with high-risk factors in NSCLC. In addition, increased CEC count during follow-up seems to be correlated with recurrence in NSCLC patients.

Dietary K+ regulates apical membrane expression of maxi-K channels in rabbit cortical collecting duct.

The cortical collecting duct (CCD) is a final site for regulation of K(+) homeostasis. CCD K(+) secretion is determined by the electrochemical gradient and apical permeability to K(+). Conducting secretory K(+) (SK/ROMK) and maxi-K channels are present in the apical membrane of the CCD, the former in principal cells and the latter in both principal and intercalated cells. Whereas SK channels mediate baseline K(+) secretion, maxi-K channels appear to participate in flow-stimulated K(+) secretion. Chronic dietary K(+) loading enhances the CCD K(+) secretory capacity due, in part, to an increase in SK channel density (Palmer et al., J Gen Physiol 104: 693-710, 1994). Long-term exposure of Ambystoma tigrinum to elevated K(+) increases renal K(+) excretion due to an increase in apical maxi-K channel density in their CDs (Stoner and Viggiano, J Membr Biol 162: 107-116, 1998). The purpose of the present study was to test whether K(+) adaptation in the mammalian CCD is associated with upregulation of maxi-K channel expression. New Zealand White rabbits were fed a low (LK), control (CK), or high (HK) K(+) diet for 10-14 days. Real-time PCR quantitation of message encoding maxi-K alpha- and beta(2-4)-subunits in single CCDs from HK animals was greater than that detected in CK and LK animals (P < 0.05); beta(1)-subunit was not detected in any CCD sample but was present in whole kidney. Indirect immunofluorescence microscopy revealed a predominantly intracellular distribution of alpha-subunits in LK kidneys. In contrast, robust apical labeling was detected primarily in alpha-intercalated cells in HK kidneys. In summary, K(+) adaptation is associated with an increase in steady-state abundance of maxi-K channel subunit-specific mRNAs and immunodetectable apical alpha-subunit, the latter observation consistent with redistribution from an intracellular pool to the plasma membrane.