Senescent endothelial progenitor cells from dogs with pulmonary arterial hypertension: a before–after self-controlled study

Previous studies have underlined the importance of endothelial dysfunction and microvascular occlusion in the pathogenesis of pulmonary artery hypertension (PAH). Since the endothelial progenitor cells (EPCs) are involved in maintaining endothelial homeostasis, we observed the change of peripheral EPCs in canines before and after PAH onset. PAH was induced by intra-pulmonary artery injection of dehydromonocrotaline (DHMC) in nine beagles. Before and 48 h and 6 weeks after DHMC injection, 40 ml peripheral blood was obtained from the femoral vein. Circulating EPCs were identified as CD133 + KDR + cells and numerated by fluorescence-activated cell sorter; the EPCs functional capacity was determined by in vitro tubule-forming assay. The senescence of EPCs was determined by β-galactosidase staining. At each time point, 2 ml blood from femoral artery was obtained for arterial oxygen pressure (PaO₂). Forty-eight  hours after DHMC injection, treated beagles suffered from hypoxemia; however, both the number and the tubule-forming capacity of EPCs were transiently raised. Six weeks later, PAH was confirmed by obviously high mean pulmonary arterial pressure (20.2 ± 1.64 vs. 11.3 ± 2.0 mmHg, p < 0.05) and low PaO₂ (69.30 ± 9.15 vs. 95.94 ± 1.43 mmHg, p < 0.01) in beagles after DHMC treatment, and their EPCs exhibited a predominant decrease in either the number (206.1 ± 26.8 vs. 632.8 ± 42.8 cells/ml blood, p < 0.01) or the tubule-forming capacity (21.1 ± 2.8 vs. 11.2 ± 2.8 tubules/×200 field, p < 0.01). Additionally, senescence-associated β-galactosidase-positive EPCs were significantly increased. Our data suggested that, after the acute stage of DHMC injury to pulmonary vessels, the EPCs from PAH beagles suffered from exhaustion and senescence.     

Synchronous whole-body vibration increases VO₂ during and following acute exercise

Single bout whole-body vibration (WBV) exercise has been shown to produce small but significant increases in oxygen consumption (VO₂). How much more a complete whole-body exercise session (multiple dynamic exercises targeting both upper and lower body muscles) can increase VO₂ is unknown. The purpose of this study was to quantify VO₂ during and for an extended time period (24 h) following a multiple exercise WBV exercise session versus the same session without vibration (NoV). VO₂ of healthy males (n = 8) was measured over 24 h on a day that included a WBV exercise session versus a day with the same exercise session without vibration (NoV), and versus a control day (no exercise). Upper and lower body exercises were studied (five, 30 s, 15 repetition sets of six exercises; 1:1 exercise:recovery ratio over 30 min). Diet was controlled. VO₂ was 23% greater (P = 0.002) during the WBV exercise session versus the NoV session (62.5 ± 12.0 vs. 50.7 ± 8.2 L O₂) and elicited a higher (P = 0.033) exercise heart rate versus NoV (139 ± 6 vs. 126 ± 11 bpm). Total O₂ consumed over 8 and 24 h following the WBV exercise was also increased (P < 0.010) (240.5 ± 28.3 and 518.9 ± 61.2 L O₂) versus both NoV (209.7 ± 22.9 and 471.1 ± 51.6 L O₂) and control (151.4 ± 20.7 and 415.2 ± 51.6 L O₂). NoV was also increased versus control (P < 0.003). A day with a 30-min multiple exercise, WBV session increased 24 h VO₂ versus a day that included the same exercise session without vibration, and versus a non-exercise day by 10 and 25%, respectively.     

The effect of acute exercise on endothelial function following a high-fat meal

The transient impairment of endothelial function following a high-fat meal is well established. Brachial artery flow-mediated dilation (FMD) decreases between 2 and 6 h post ingestion. Whether this impairment can be reduced with acute aerobic exercise has not been investigated. The purpose of this study was to investigate if a single sustained aerobic exercise session can counteract the postprandial attenuation in brachial artery FMD associated with the ingestion of a high-fat meal. Eight apparently healthy adults (five men, three women), age 25.5 ± 0.8 years, performed three treatment conditions in a counter-balanced design: (1) low-fat meal alone (LFM), (2) high-fat meal alone (HFM), and (3) one session of aerobic exercise presented 2 h after ingesting a high-fat meal (HFM-EX). The examination of brachial artery FMD was performed at baseline and 4 h following the ingestion of the meal for each treatment condition. A 3 × 2 (treatment × time) repeated measures ANOVA exhibited a significant interaction (P = 0.019). Preprandial FMDs were similar (P = 0.863) among all three treatment conditions. The FMDs following the LFM (7.18 ± 1.31%) and HFM-EX (8.72 ± 0.94%) were significantly higher (P = 0.001) than the FMD following the HFM (4.29 ± 1.64%). FMD was significantly elevated above preprandial values following the HFM-EX (5.61 ± 1.54 to 8.72 ± 0.94%, P = 0.005) but was unchanged following the LFM (6.17 ± 0.94 to 7.18 ± 1.31%, P = 0.317) and the HFM (5.73 ± 1.23 to 4.29 ± 1.64%, P = 0.160). These findings suggest that a single aerobic exercise session cannot only counteract the postprandial endothelial dysfunction induced by the ingestion of a high-fat meal, but also increase brachial artery FMD in apparently healthy adults.     

A single bout of breast milk expression does not increase resting metabolic rate

Introduction

Breastfeeding women have elevated resting metabolic rate (RMR); however, whether a single bout of lactation increases RMR is unknown. This study aimed to determine if a single bout of lactation acutely increased RMR.

Methods

Twenty-two lactating women (age: 31 ± 0.9 year, body mass index: 27.3 ± 1.2 kg/m²) were recruited. RMR was assessed at baseline and at 1- and 2-h following breast milk expression.

Results

RMR was unchanged in lactating women following a single bout of lactation (baseline: 1437 ± 39; 1 h: 1425 ± 37 2 h: 1440 ± 31 kcal/day) (p > .05). RMR was not correlated to daily milk produced (r = 0.05, p > .05), but was correlated to body mass (r = 0.74, p < .001), fat-free mass (kg) (r = 0.61, p < .01), and fat mass (kg) (r = 0.71, p < .01).

Conclusion

RMR in lactating women appears to be more related to body mass or composition in the postpartum period rather than lactation.     

Mobilization of circulating endothelial progenitor cells after endovascular therapy for ruptured cerebral aneurysms

Emerging evidence shows that circulating endothelial progenitor cells (EPCs) promote regeneration of the endothelium at sites of vessel injury. This study was designed to test the hypothesis that EPCs are mobilized in patients who had ruptured cerebral aneurysm (CA) and underwent endovascular therapy. Fourteen patients with ruptured CAs were recruited and blood samples were analyzed after coil embolization surgery. Blood samples were also obtained from 18 healthy control subjects who had no evidence of CAs and did not undergo endovascular surgery. We measured the numbers of circulating EPCs, levels of plasma vascular endothelial growth factor (VEGF) and platelet counts. EPCs significantly increased in patients with ruptured CAs and underwent surgical coil embolization, reaching a peak level on day 14 post operation. The levels of plasma VEGF and platelet counts also significantly increased in parallel with the increase in EPCs, leading to significant positive correlations of circulating EPCs with VEGF in plasma (r = 0.636, P < 0.01) and platelet counts (r = 0.721, P < 0.001), respectively. The finding suggests that EPCs are mobilized upon surgery and may play a critical role in repairing injured vascular endothelium. Levels of EPCs in peripheral blood could also serve as a prognostic marker for the outcomes of ruptured cerebral aneurysms after surgical repair.     

Differential serum cytokine profile in patients with systemic lupus erythematosus and posterior reversible encephalopathy syndrome

Systemic lupus erythematosus (SLE) patients are susceptible to the development of posterior reversible encephalopathy syndrome (PRES). The main theory concerning the physiopathology of PRES suggests that there is brain–blood barrier damage, which is associated with endothelial dysfunction, and characterized by vasogenic oedema. However, current evidence regarding its physiopathogenic mechanisms is quite scant. The aim of this study was to analyse the expression of different serum cytokines, as well as vascular endothelial growth factor (VEGF) and soluble CD40 ligand (sCD40L), in patients with PRES/systemic lupus erythematosus (SLE) and to compare them with levels in SLE patients without PRES and in healthy controls. We performed a transversal study in a tertiary care centre in México City. We included 32 subjects (healthy controls, n = 6; remission SLE, n = 6; active SLE, n = 6 and PRES/SLE patients, n = 14). PRES was defined as reversible neurological manifestations (seizures, visual abnormalities, acute confusional state), associated with compatible changes by magnetic resonance imaging (MRI). Serum samples were obtained during the first 36 h after the PRES episode and were analysed by cytometric bead array, Luminex multiplex assay or enzyme‐linked immunosorbent assay (ELISA). Interleukin (IL)‐6 and IL‐10 levels were significantly higher in PRES/SLE patients (P = 0·013 and 0·025, respectively) when compared to the other groups. Furthermore, IL‐6 and IL‐10 levels displayed a positive correlation (r = 0·686, P = 0·007). There were no differences among groups regarding other cytokines, sCD40L or VEGF levels. A differential serum cytokine profile was found in PRES/SLE patients, with increased IL‐6 and IL‐10 levels. Our findings, which are similar to those described in other neurological manifestations of SLE, support the fact that PRES should be considered among the SLE‐associated neuropsychiatric syndromes.     

Post-concurrent exercise hemodynamics and cardiac autonomic modulation

Concurrent training is recommended for health improvement, but its acute effects on cardiovascular function are not well established. This study analyzed hemodynamics and autonomic modulation after a single session of aerobic (A), resistance (R), and concurrent (A + R) exercises. Twenty healthy subjects randomly underwent four sessions: control (C:30 min of rest), aerobic (A:30 min, cycle ergometer, 75% of VO₂ peak), resistance (R:6 exercises, 3 sets, 20 repetitions, 50% of 1 RM), and concurrent (AR: A + R). Before and after the interventions, blood pressure (BP), heart rate (HR), cardiac output (CO), and HR variability were measured. Systolic BP decreased after all the exercises, and the greatest decreases were observed after the A and AR sessions (−13 ± 1 and −11 ± 1 mmHg, respectively, P < 0.05). Diastolic BP decreased similarly after all the exercises, and this decrease lasted longer after the A session. CO also decreased similarly after the exercises, while systemic vascular resistance increased after the R and AR sessions in the recovery period (+4.0 ± 1.7 and +6.3 ± 1.9 U, respectively, P < 0.05). Stroke volume decreased, while HR increased after the exercises, and the greatest responses were observed after the AR session (SV, A = −14.6 ± 3.6, R = −22.4 ± 3.5 and AR = −23.4 ± 2.4 ml; HR, A =+13 ± 2, R =+15 ± 2 vs. AR =+20 ± 2 bpm, P < 0.05). Cardiac sympathovagal balance increased after the exercises, and the greatest increase was observed after the AR session (A = +0.7 ± 0.8, R = +1.0 ± 0.8 vs. AR = +1.2 ± 0.8, P < 0.05). In conclusion, the association of aerobic and resistance exercises in the same training session did not potentiate post-exercise hypotension, and increased cardiac sympathetic activation during the recovery period.     

Assessment of immune function after short-term administration of recombinant human growth hormone in healthy young males

Growth hormone (GH) is a commonly used drug aimed at improving sport performance. The aim of this study is to evaluate the immunomodulatory effects of short-term administration of recombinant GH (rhGH) in healthy young males. NK cell number, activity and phenotype, T cell number, CD4⁺ (Th1/Th2) cytokine production of IL2, IL4, IL6, IL10, TNF-α and IFN-γ and CD4⁺/CD8⁺ ratio with particular attention to the possible correlation to IGF-I production were investigated. 30 males (27 ± 9 years) were randomly assigned to placebo (n = 15) or drug (rhGH) 1 mg/day groups (n = 15) with daily injection for 7 days. IGF-I plasma concentration and flow cytometry data were generated at baseline and days 8, 15, 22 and 29 post injection. Data analysis used General Linear Model with repeated measures, Bonferroni correction factor and significance at p ≤ 0.05. Serum IGF-I levels (ng/mL) increased significantly (p ≤ 0.01) on day 8 (0.48 ± 0.78) after injections compared to baseline (0.31 ± 0.07) and days 15 (0.33 ± 0.06), 22 (0.29 ± 0.05) and 29 (0.29 ± 0.06). A significant time effect was noted in IL10 secretion (pg/mL) from day 15 (P = 35.14 ± 19.93, rhGH = 26.63 ± 16.39) to days 22 (P = 61.32 ± 20.41, rhGH = 74.99 ± 46.91) and 29 (P = 101.98 ± 67.25, rhGH = 107.74; ± 122.58). There was no correlation between IGF-I and NK activity, phenotype or number along with T lymphocyte number, CD4⁺/CD8⁺ ratio or Th1 and Th2 cytokine production. In conclusion, cytokine secretion spectrum was not affected by short-term rhGH administration in young males.     

Rituximab‐induced interleukin‐15 reduction associated with clinical improvement in rheumatoid arthritis

Rituximab therapy alters all aspects of B‐cell participation in the disturbed immune response of rheumatoid arthritis patients. To determine the impact of B‐cell depletion on other immune compartments, we analysed levels of soluble and surface interleukin‐15 (IL‐15) along with the frequency of IL‐15‐related subsets after rituximab treatment. We then studied the correlation of observed changes with clinical activity. Heparinized blood samples from 33 rheumatoid arthritis patients were collected on days 0, 30, 90 and 180 after each of three rituximab cycles. Serum cytokine levels were determined by ELISA. Interleukin‐15 trans‐presentation was analysed by cytometry. Flow cytometry with monoclonal antibodies was performed to analyse circulating cell subsets. Interleukin‐15 was detected in the serum of 25 patients before initiating the treatment. Rituximab then progressively reduced serum IL‐15 (138 ± 21 pg/ml at baseline, 48 ± 18 pg/ml after third cycle, P = 0·03) along with IL‐17 (1197 ± 203 pg/ml at baseline, 623 ± 213 pg/ml after third cycle, P = 0·03) and tended to increase the frequency of circulating regulatory T cells (3·1 ± 1 cells/μl at baseline, 7·7 ± 2 cells/μl after third cycle). Rituximab also significantly decreased IL‐15 trans‐presentation on surface monocytes of patients negative for IL‐15 serum (mean fluorescence intensity: 4·82 ± 1·30 at baseline, 1·42 ± 0·69 after third cycle P = 0·05). Reduction of serum IL‐15 was associated with decrease in CD8⁺ CD45RO⁺/RA⁺ ratio (1·17 ± 0·21 at baseline, 0·36 ± 0·06 at third cycle, P = 0·02). DAS28, erythrocyte sedimentation rate and C‐reactive protein correlated significantly with CD8⁺ CD45RO⁺/RA⁺ ratio (R = 0·323, R = 0·357, R = 0·369 respectively, P < 0·001). Our results suggest that sustained clinical improvement after rituximab treatment is associated with IL‐15/memory T‐cell‐related mechanisms beyond circulating B cells.     

Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans

Shear stress is the frictional force of blood against the endothelium, a stimulus for endothelial activation and the release of von Willebrand factor (vWF). This study tested the hypothesis that the increase in shear stress associated with exercise correlates with plasma vWF. Young (n = 14, 25.7 ± 5.4 years) and older (n = 13, 65.6 ± 10.7 years) individuals participated in 30 min of dynamic handgrip exercise at a moderate intensity. Brachial artery diameter and blood flow were measured using ultrasound Doppler and blood samples were collected before, immediately after, and following 30 min of recovery from exercise with plasma levels of vWF. Plasma levels of vWF increased (P < 0.05) by 6 ± 2% in young individuals and 4 ± 1% in older individuals immediately after exercise. The change in plasma vWF was linearly correlated with the increase in shear stress during exercise in older individuals (post-exercise: r = 0.78, 30 min recovery: r = 0.77, P < 0.01), but no association was found in the young individuals. These changes in plasma levels of vWF in humans suggest that aging influences endothelial activation and hemostasis.     

No evidence for a thermic effect of the dietary flavonol quercetin: a pilot study in healthy normal-weight women

Our objective was to investigate the effect of quercetin supplementation on fasting resting energy expenditure (REE) and respiratory quotient (RQ) in humans. Six healthy, normal-weight women (mean age 25.5 ± 1.6 years, body mass index 21.4 ± 1.5 kg/m²) participated in a randomized, placebo-controlled, double-blinded crossover study. Treatments were administered as capsules of 150 mg quercetin (aglycone) or placebo. The acute response was measured by indirect calorimetry for 3 h following ingestion. Blood pressure and pulse rate were assessed in 30-min intervals. On the following day, 24 h after capsule intake, a follow-up measurement was performed. Baseline (t ₀) REE adjusted for fat-free mass was 4.7 ± 0.26 kJ/min (quercetin) and 4.8 ± 0.35 kJ/min (placebo) and did not significantly change between baseline and end (t ₁₈₀) in either group (P = 0.992 for time effect in repeated measures analysis of variance; P = 0.581 for time × treatment interaction). Mean RQ was 0.78 ± 0.04 (quercetin) and 0.77 ± 0.04 (placebo). RQ values decreased slowly and to a similar extent during both treatments (P < 0.001 for time; quercetin, −0.09 ± 0.05; placebo, −0.08 ± 0.03; P = 0.877 for time × treatment interaction). Resting systolic and diastolic blood pressure, pulse pressure as well as resting pulse rate did not significantly change between baseline and end in either treatment group. No significant differences were found between the results of the baseline measurement and 24 h after treatment. In conclusion, the present pilot study provides no evidence for a thermic effect of quercetin in humans.     

Both flow-mediated vasodilation procedures and acute exercise improve endothelial function in obese young men

Obesity is associated with impaired endothelial function assessed as flow-mediated vasodilation (FMD), the procedure of which involves transient brachial artery occlusion and following reactive hyperemia. Acute aerobic exercise can improve FMD. This study examined the effects of repeated FMD procedures and acute aerobic exercise on FMD in obese young men. Upper arm cuff inflation of 200 mmHg for 5 min and subsequent deflation was induced at 0, 1 and 2 h to examine effects of repeated FMD procedures on FMD in obese subjects, as well as in lean controls. To observe the combined effects of FMD procedures and acute exercise on FMD in obese subjects, 45 min moderate exercise was performed immediately after FMD procedure at 0 h, with the procedure repeated at 1 and 2 h. The results showed that, after repeated FMD procedures, FMD in obese subjects increased from 5.9 ± 4.0% to 6.5 ± 3.2% and 8.4 ± 2.8% (P = 0.017), whereas FMD demonstrated no changes in lean controls (P = 0.90). After repeated FMD procedures and exercise, FMD in the obese subjects increased from 7.3 ± 3.5% to 9.5 ± 4.0% and 11.0 ± 4.3% (P = 0.0004). The present findings demonstrate that both repeated FMD procedures and acute aerobic exercise improve FMD in obese subjects.     

Oxidative stress, inflammation and recovery of muscle function after damaging exercise: effect of 6-week mixed antioxidant supplementation

There is no consensus regarding the effects of mixed antioxidant vitamin C and/or vitamin E supplementation on oxidative stress responses to exercise and restoration of muscle function. Thirty-eight men were randomly assigned to receive either placebo group (n = 18) or mixed antioxidant (primarily vitamin C & E) supplements (n = 20) in a double-blind manner. After 6 weeks, participants performed 90 min of intermittent shuttle-running. Peak isometric torque of the knee flexors/extensors and range of motion at this joint were determined before and after exercise, with recovery of these variables tracked for up to 168 h post-exercise. Antioxidant supplementation elevated pre-exercise plasma vitamin C (93 ± 8 μmol l⁻¹) and vitamin E (11 ± 3 μmol l⁻¹) concentrations relative to baseline (P < 0.001) and the placebo group (P ≤ 0.02). Exercise reduced peak isometric torque (i.e. 9–19% relative to baseline; P ≤ 0.001), which persisted for the first 48 h of recovery with no difference between treatment groups. In contrast, changes in the urine concentration of F₂-isoprostanes responded differently to each treatment (P = 0.04), with a tendency for higher concentrations after 48 h of recovery in the supplemented group (6.2 ± 6.1 vs. 3.7 ± 3.4 ng ml⁻¹). Vitamin C & E supplementation also affected serum cortisol concentrations, with an attenuated increase from baseline to the peak values reached after 1 h of recovery compared with the placebo group (P = 0.02) and serum interleukin-6 concentrations were higher after 1 h of recovery in the antioxidant group (11.3 ± 3.4 pg ml⁻¹) than the placebo group (6.2 ± 3.8 pg ml⁻¹; P = 0.05). Combined vitamin C & E supplementation neither reduced markers of oxidative stress or inflammation nor did it facilitate recovery of muscle function after exercise-induced muscle damage.     

Shine light on sleep: Morning bright light improves nocturnal sleep and next morning alertness among college students

The relationship between daytime light, especially morning light and sleep, has not been well documented. People who work in an office spend most of their time indoors and thus have less access to high-level daylight. The current study employed a field intervention approach to investigate whether exposure to 1.5 h of bright electric light in the early morning for 1 workweek would benefit sleep among students who spent most of their time in an office at the university. Twelve students (24.92 ± 1.78 years) underwent a 2 workday baseline measurement and two inconsecutive 5 workday interventions (with 1 week washout) with morning bright light and regular office light (1000 lx, 6500 K vs. 300 lx, 4000 K, at eye level). The sleep outcomes were recorded with actigraphy and a sleep diary. In addition, self-ratings of daytime sleepiness, mood, mental fatigue, perceived effort, and next morning sleepiness were measured each workday. The results showed that exposure to morning bright light versus regular office light yielded a higher sleep efficiency (83.82% ± 1.60 vs. 80.35% ± 1.57, p = 0.02), a smaller fragmentation index (15.26% ± 1.31 vs. 17.18% ± 1.28, p = 0.05), and a shorter time in bed (7.12 ± 0.13 vs. 7.51 ± 0.12, p = 0.03). Meanwhile, an earlier sleep onset time, shorter sleep latency, and lower morning sleepiness were observed after a 5 workday morning bright light intervention compared with the baseline (ps <0.05), no such benefit was found for self-ratings (ps >0.05). These findings support existing evidence that morning bright light could function as an enhancer of sleep and alertness for office occupants.     

Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction

This study was designed to determine the levels of early endothelial progenitor cells(EPCs),apelin,vascu-lar endothelial growth factor(VEGF) and stromal cell-derived growth factor-1(SDF-1) after acute myocardial infarction(AMI),and to investigate the relationships between these cytokines and early EPCs.Early EPCs,de-fined as CD133+,KDR+,and CD34+ cells,were quantified by flow cytometry.The levels of early EPCs and those cytokines in AMI patients were significantly different from those with coronary artery disease or controls(P < 0.05).Plasma apelin levels were inversely correlated with Gensini score and early EPCs(both P < 0.01).Early EPCs,VEGF and SDF-1 showed different patterns of changes in AMI patients during the first 24 h.The trend in the change of early EPCs was proportionally correlated with that of VEGF(P < 0.05).AMI patients exhibited in-creased early EPCs with remarkably decreased apelin levels and enhanced VEGF levels.     

A mobile,web‐based system can improve positive airway pressure adherence

SleepMapper is a mobile, web‐based system that allows patients to self‐monitor their positive airway pressure therapy, and provides feedback and education in real time. In addition to the usual, comprehensive support provided at our clinic, we gave the SleepMapper to 30 patients initiating positive airway pressure. They were compared with patients initiating positive airway pressure at our clinic without SleepMapper (controls) to determine whether SleepMapper affected adherence. A total of 61 patients had polysomnographic and adherence data analysed, 30 were given SleepMapper and 31 received our standard of care. The two groups were well matched at baseline to include no significant differences in age, apnea–hypopnea index, percentage receiving split‐night polysomnographs and starting pressures. Patients in the control group received significantly more non‐benzodiazepine sedative hypnotics the night of their polysomnography and during positive airway pressure initiation. At 11 weeks, patients in the SleepMapper group had a greater percentage of nights with any use (78.0 ± 22.0 versus 55.5 ± 24.0%; P < 0.001) and >4 h positive airway pressure use (78.0 ± 22.0 versus 55.5 ± 24.0%; P = 0.02). There was a trend toward more patients in the SleepMapper group achieving >4 h of use for at least 70% of nights [9/30 (30%) versus 3/31 (9.7%); P = 0.06]. In multivariate linear regression, the SleepMapper remained significantly associated with percentage of nights >4 h positive airway pressure use (β coefficient = 0.18; P = 0.02). Added to our usual, comprehensive programme to maximize positive airway pressure adherence in new users, the SleepMapper was independently associated with an 18% increase in nights >4 h of use.     

High‐level expression of periostin is significantly correlated with tumour angiogenesis and poor prognosis in osteosarcoma

Periostin (PN), originally named as osteoblast‐specific factor‐2 (OSF‐2), has been involved in regulating adhesion and differentiation of osteoblasts. Recently many studies have shown that high‐level expression of PN is correlated significantly with tumour angiogenesis and prognosis in many kinds of human cancer. However, whether and how periostin expression influences prognosis in osteosarcoma remains unknown. This study aimed to examine the expression of PN in patients with osteosarcoma and explore the relationship of PN expression with clinicopathologic factors, tumour angiogenesis and prognosis. Immunohistochemistry was performed to determine the expression of PN in osteosarcoma and osteochondroma respectively. Vascular endothelial growth factor (VEGF) and CD34 were also examined in tissues from the osteosarcoma patients mentioned above. The results showed that PN expression was significantly (P < 0.05) higher in osteosarcoma (80.9%) than in osteochondroma (14.7%). Increased PN protein expression was associated with histological subtype (P = 0.000), Enneking stage (P = 0.027) and tumour size (P = 0.009). The result also showed that high expression of PN correlated with VEGF expression (r = 0.285; P = 0.019) and that tumours with PN‐positive expression significantly had higher microvessal density (44.6 ± 13.7 vs. 20.6 ± 6.5; P = 0.000) compared to those in normal bone tissues. Additionally, the expression of PN was found to be an independent prognostic factor in osteosarcoma patients. In conclusion, our findings suggest that PN may have an important role in tumour progression and may be used as a prognostic biomarker for patients with osteosarcoma.     

Transient Extremity Ischemia Augments CD34+ Progenitor Cell Availability

Peripheral blood is an easily accessed source for stem cell production; however, the number of cells produced is relatively low. We hypothesized that ischemic preconditioning may serve as a safe method to increase the number of CD34+ cells that can be harvested and cultured in a short period. This study was conducted to test this hypothesis by examining the safety and efficacy of brief, transient ischemia of the lower limbs to augment the number of cells that can be produced from blood of healthy volunteers. Following induction of ischemia, blood samples were withdrawn at baseline, 30 min, 12 h and 24 h. The number of progenitor cells was determined by flow cytometry after the harvested cells were cultured for 5 days. We also analyzed the blood samples to determine IL-8 and VEGF concentrations. No serious adverse events were observed. The total number of cells increased from 0.46 ± 0.1 × 10⁶ cells/ml in the pretreatment blood samples to 0.7 ± 0.1 × 10⁶ cells/ml in blood taken 12 h after the conclusion of transient ischemia, p = 0.0029. The number of CD34+ cells increased from 4.23 ± 0.8 × 10⁴ cells/ml in the pretreatment samples to 7.17 ± 1.34 × 10⁴ cells/ml in blood taken 12 h after ischemia, p = 0.0001. The harvested stem cells maintained their ability to construct tubular structures. The augmentation in the number of CD34+ cells was positively correlated with the increase of IL-8, but not with VEGF concentrations. Ischemic preconditioning is a safe and effective technique to increase the availability of stem cells for therapeutic purposes.     

Hemoglobin and hematocrit at the end of hemodialysis: a better way to adjust erythropoietin dose?

A severe disadvantage of administration of recombinant human erythropoietin to hemodialysis patients has been reported. A significant correlation has been shown with hemoglobin values determined online by use of the blood volume monitor (BVM) and by laboratory measurement. Online hemoglobin and hematocrit were measured by use of the BVM during hemodialysis session. Data were analyzed by t test and statistical significance was defined as a P of <0.05. Increases in the mean values of hemoglobin and hematocrit from 11.6 ± 1.9 to 13.9 ± 2.4 g/dL (17.4 ± 7.1%, P = 0.02) and from 34.4 ± 6.8 to 42 ± 8.3% (20.6 ± 8.8%, P = 0.022), respectively, were observed from the beginning to the end of dialysis. We hypothesize that a new strategy for adjusting erythropoietin dose may be based on hemoglobin and hematocrit values evaluated at the end of hemodialysis, when patients are no longer hypervolemic. Inadvertent high levels of hemoglobin could be one explanation why patients present higher rates of cardiovascular and access-related events, especially when monitored online by use of the BVM to achieve the dry weight.     

The effects of sodium oxybate on core body and skin temperature regulation in narcolepsy

Patients suffering from narcolepsy type 1 show altered skin temperatures, resembling the profile that is related to sleep onset in healthy controls. The aim of the present study is to investigate the effects of sodium oxybate, a widely used drug to treat narcolepsy, on the 24‐h profiles of temperature and sleep‐wakefulness in patients with narcolepsy and controls. Eight hypocretin‐deficient male narcolepsy type 1 patients and eight healthy matched controls underwent temperature measurement of core body and proximal and distal skin twice, and the sleep–wake state for 24 h. After the baseline assessment, 2 × 3 g of sodium oxybate was administered for 5 nights, immediately followed by the second assessment. At baseline, daytime core body temperature and proximal skin temperature were significantly lower in patients with narcolepsy (core: 36.8 ± 0.05 °C versus 37.0 ± 0.05 °C, F = 8.31, P = 0.01; proximal: 33.4 ± 0.26 °C versus 34.3 ± 0.26 °C, F = 5.66, P = 0.03). In patients, sodium oxybate administration increased proximal skin temperature during the day (F = 6.46, P = 0.04) to a level similar as in controls, but did not affect core body temperature, distal temperature or distal–proximal temperature gradient. Sodium oxybate administration normalised the predictive value of distal skin temperature and distal–proximal temperature gradient for the onset of daytime naps (P < 0.01). In conclusion, sodium oxybate administration resulted in a partial normalisation of the skin temperature profile, by increasing daytime proximal skin temperature, and by strengthening the known relationship between skin temperature and daytime sleep propensity. These changes seem to be related to the clinical improvement induced by sodium oxybate treatment. A causal relationship is not proven.