Ultrasonic Elastography Research Based on a Multicenter Study: Adding Strain Ratio after 5-Point Scoring Evaluation or Not

Background

This study aimed to confirm whether strain ratio should be added after evaluation of lesions with 5-point elasticity scoring for differentiating benign and malignant breast lesions on ultrasonographic elastography(UE).

Materials and Methods

From June 2010 to March 2012, 1080 consecutive female patients with breast lesions were recruited into a multicenter retrospective study, which involved 8 centers across China. Each institutional ethic review board approved the study, and all the patients gave written informed consent. All the patients underwent the UE procedure and the strain ratios were calculated and the final diagnosis was made by histological findings. The sensitivity, specificity, accuracy, PPV and NPV were calculated for each of the two evaluation systems and the areas under the ROC curve were compared.

Results

The strain ratios of benign lesions (mean, 2.6±2.0) and malignant lesions (mean,7.9±5.8) were significantly different (p <0.01). When the cutoff point was 3.01, strain ratio method had 79.8% sensitivity, 82.8% specificity, and 81.3% accuracy, while the 5-point scoring method had 93.1% sensitivity, 73.0% specificity, and 76.8% accuracy. The areas under the ROC curve with the strain ratio method and 5-point scoring method were 0.863 and 0.865, respectively(p>0.05). The strain ratio method shows better a diagnosis performance of the lesions with elasticity score 3 and 4.

Conclusions

Although the two UE methods have similar diagnostic performance, separate calculation of the strain ratios seems compulsory, especially for the large solid breast lesions and the lesions with elasticity score 3 and 4.     

Complement Alternative Pathway Activation in Human Nonalcoholic Steatohepatitis

The innate immune system plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently we reported complement activation in human NASH. However, it remained unclear whether the alternative pathway of complement, which amplifies C3 activation and which is frequently associated with pathological complement activation leading to disease, was involved. Here, alternative pathway components were investigated in liver biopsies of obese subjects with healthy livers (n = 10) or with NASH (n = 12) using quantitative PCR, Western blotting, and immunofluorescence staining. Properdin accumulated in areas where neutrophils surrounded steatotic hepatocytes, and colocalized with the C3 activation product C3c. C3 activation status as expressed by the C3c/native C3 ratio was 2.6-fold higher (p<0.01) in subjects with NASH despite reduced native C3 concentrations (0.94±0.12 vs. 0.57±0.09; p<0.01). Hepatic properdin levels positively correlated with levels of C3c (r_s = 0.69; p<0.05) and C3c/C3 activation ratio (r_s = 0.59; p<0.05). C3c, C3 activation status (C3c/C3 ratio) and properdin levels increased with higher lobular inflammation scores as determined according to the Kleiner classification (C3c: p<0.01, C3c/C3 ratio: p<0.05, properdin: p<0.05). Hepatic mRNA expression of factor B and factor D did not differ between subjects with healthy livers and subjects with NASH (factor B: 1.00±0.19 vs. 0.71±0.07, p = 0.26; factor D: 1.00±0.21 vs. 0.66±0.14, p = 0.29;). Hepatic mRNA and protein levels of Decay Accelerating Factor tended to be increased in subjects with NASH (mRNA: 1.00±0.14 vs. 2.37±0.72; p = 0.22; protein: 0.51±0.11 vs. 1.97±0.67; p = 0.28). In contrast, factor H mRNA was downregulated in patients with NASH (1.00±0.09 vs. 0.71±0.06; p<0.05) and a similar trend was observed with hepatic protein levels (1.12±0.16 vs. 0.78±0.07; p = 0.08). Collectively, these data suggest a role for alternative pathway activation in driving hepatic inflammation in NASH. Therefore, alternative pathway factors may be considered attractive targets for treating NASH by inhibiting complement activation.     

Phenolic Acid Composition,Antiatherogenic and Anticancer Potential of Honeys Derived from Various Regions in Greece

The phenolic acid profile of honey depends greatly on its botanical and geographical origin. In this study, we carried out a quantitative analysis of phenolic acids in the ethyl acetate extract of 12 honeys collected from various regions in Greece. Our findings indicate that protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid and p-coumaric acid are the major phenolic acids of the honeys examined. Conifer tree honey (from pine and fir) contained significantly higher concentrations of protocatechuic and caffeic acid (mean: 6640 and 397 µg/kg honey respectively) than thyme and citrus honey (mean of protocatechuic and caffeic acid: 437.6 and 116 µg/kg honey respectively). p-Hydroxybenzoic acid was the dominant compound in thyme honeys (mean: 1252.5 µg/kg honey). We further examined the antioxidant potential (ORAC assay) of the extracts, their ability to influence viability of prostate cancer (PC-3) and breast cancer (MCF-7) cells as well as their lowering effect on TNF- α-induced adhesion molecule expression in endothelial cells (HAEC). ORAC values of Greek honeys ranged from 415 to 2129 µmol Trolox equivalent/kg honey and correlated significantly with their content in protocatechuic acid (p<0.001), p-hydroxybenzoic acid (p<0.01), vanillic acid (p<0.05), caffeic acid (p<0.01), p-coumaric acid (p<0.001) and their total phenolic content (p<0.001). Honey extracts reduced significantly the viability of PC-3 and MCF-7 cells as well as the expression of adhesion molecules in HAEC. Importantly, vanillic acid content correlated significantly with anticancer activity in PC-3 and MCF-7 cells (p<0.01, p<0.05 respectively). Protocatechuic acid, vanillic acid and total phenolic content correlated significantly with the inhibition of VCAM-1 expression (p<0.05, p<0.05 and p<0.01 respectively). In conclusion, Greek honeys are rich in phenolic acids, in particular protocatechuic and p-hydroxybenzoic acid and exhibit significant antioxidant, anticancer and antiatherogenic activities which may be attributed, at least in part, to their phenolic acid content.     

Increased Circulating ANG II and TNF-α Represents Important Risk Factors in Obese Saudi Adults with Hypertension Irrespective of Diabetic Status and BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m²), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m²), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m²) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m²). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk.     

Intravascular Ultrasound Observation of the Mechanism of No-Reflow Phenomenon in Acute Myocardial Infarction

Objective

To study the mechanism of the no-reflow phenomenon using coronary angiography (CAG) and intravascular ultrasound (IVUS).

Methods

A total of 120 patients with acute myocardial infarction (AMI) who successfully underwent indwelling intracoronary stent placement by percutaneous coronary intervention (PCI). All patients underwent pre- and post-PCI CAG and pre-IVUS. No-reflow was defined as post-PCI thrombolysis in myocardial infarction (TIMI) grade 0, 1, or 2 flow in the absence of mechanical obstruction. Normal reflow was defined as TIMI grade 3 flow. The pre-operation reference vascular area, minimal luminal cross-sectional area, plaque cross-sectional area, lesion length, plaque volume and plaque traits were measured by IVUS.

Results

The no-reflow group was observed in 14 cases (11.6%) and normal blood-flow group in 106 cases (89.4%) based on CAG results. There was no statistically significant difference in the patients’ medical history, reference vascular area (no-flow vs. normal-flow; 15.5 ± 3.2 vs. 16.2 ± 3.3, p> 0.05) and lesion length (21.9 ± 5.1 vs. 19.5 ± 4.8, p> 0.05) between the two groups. No-reflow patients had a longer symptom onset to reperfusion time compared to normal blood-flow group [(6.6 ± 3.1) h vs (4.3 ± 2.7) h; p< 0.05] and higher incidence of TIMI flow grade< 3 (71.4% vs 49.0%, p< 0.05). By IVUS examination, the no-reflow group had a significantly increased coronary plaque area and plaque volume compared to normal blood-flow group [(13.7 ± 3.0) mm² vs (10.2 ± 2.9) mm²; (285.4 ± 99.8) mm³ vs (189.7 ± 86.4) mm³; p< 0.01]. The presence of IVUS-detected soft plaque (57.1% vs. 24.0%, p< 0.01), eccentric plaque (64.2% vs. 33.7%, p< 0.05), plaque rupture (50.0% vs. 21.2%, p< 0.01), and thrombosis (42.8% vs. 15.3%) were significantly more common in no-reflow group.

Conclusion

There was no obvious relationship between the coronary risk factors and no-reflow phenomenon. The symptom onset to reperfusion time, TIMI flow grade before stent deployment, plaque area, soft plaques, eccentric plaques, plaque rupture and thrombosis may be risk factors for the no-reflow phenomenon after PCI.     

Global and Regional Left Ventricular Contractile Impairment in Patients with Wolff-Parkinson-White Syndrome

Background

To assess regional systolic function and global contractile function in patients with WPW Syndrome.

Method

Eleven cases with manifest Wolff-Parkinson-White (WPW) syndrome in sinus rhythm were compared to 11 age matched controls. 2D strain analysis was performed and peak segmental radial strain (pRS) values obtained from basal ventricular parasternal short-axis images (70 ± 5 frames/sec) using a dedicated software package. Heterogeneity of radial strain pattern in six circumferential basal left ventricular segments was measured in terms of standard deviations of peak RS (SD^pRS) or range (difference between maximum and minimum peak RS i.e. Range^pRS). Spectral Doppler (continuous wave) measurements were acquired through the left ventricular outflow tract to determine Pre Ejection Period (PEP), Left Ventricular Ejection Time (LVET) and measures of left ventricular systolic performance.

Results

LV segmental radial strain was profoundly heterogeneous in WPW cases in contrast to fairly homogenous strain pattern in normal subjects. Wide SD^pRS values 17.5 ± 8.9 vs 3.3 ± 1.4, p<0.001 and Range^pRS 42.7 ± 20.8 vs.8.5 ± 3.6 , p<0.001 were observed among WPW and healthy subjects respectively. PEP (132.4 ± 14.7 vs 4.7 ± 0.5ms, p<0.001) and corrected PEP (76.1 ± 8.0 vs 2.7 ± 0.4ms, p<0.001) were significantly longer in WPW patients compared to controls. The PEP/LVET ratio was also significantly greater in WPW cohort (0.49 ± 0.04 vs. 0.28 ± 0.05, p <0.001) suggesting global systolic dysfunction.

Conclusions

Patients with manifest preexcitation (predominantly those with right-sided pathways) have regional and global contractile dysfunction resulting from aberrant impulse propagation inherent to the preexcited state.     

Low Density Lipoproteins Promote Unstable Calcium Handling Accompanied by Reduced SERCA2 and Connexin-40 Expression in Cardiomyocytes

The damaging effects of high plasma levels of cholesterol in the cardiovascular system are widely known, but little attention has been paid to direct effects on cardiomyocyte function. We therefore aimed at testing the hypothesis that Low Density Lipoprotein (LDL) cholesterol affects calcium dynamics and signal propagation in cultured atrial myocytes. For this purpose, mRNA and protein expression levels were determined by real time PCR and western blot analysis, respectively, and intracellular calcium was visualized in fluo-4 loaded atrial HL-1 myocyte cultures subjected to field stimulation. At low stimulation frequencies all cultures had uniform calcium transients at all tested LDL concentrations. However, 500 µg LDL/mL maximally reduced the calcium transient amplitude by 43% from 0.30±0.04 to 0.17±0.02 (p<0.05). Moreover, LDL-cholesterol dose-dependently increased the fraction of alternating and irregular beat-to-beat responses observed when the stimulation interval was shortened. This effect was linked to a concurrent reduction in SERCA2, RyR2, IP3RI and IP3RII mRNA levels. SERCA2 protein levels were also reduced by 43% at 200 µg LDL/mL (p<0.05) and SR calcium loading was reduced by 38±6% (p<0.001). By contrast, HDL-cholesterol had no significant effect on SERCA expression or SR calcium loading. LDL-cholesterol also slowed the conduction velocity of the calcium signal from 3.2+0.2 mm/s without LDL to 1.7±0.1 mm/s with 500 µg LDL/mL (p<0.05). This coincided with a reduction in Cx40 expression (by 44±3%; p<0.05 for mRNA and by 79±2%; p<0.05 for Cx40 protein at 200 µg/ml LDL) whereas the Cx-43 expression did not significantly change. In conclusion, LDL-cholesterol destabilizes calcium handling in cultured atrial myocytes subjected to rapid pacing by reducing SERCA2 and Cx40 expression and by slowing the conduction velocity of the calcium signal.     

The Higher Temperature in the Areola Supports the Natural Progression of the Birth to Breastfeeding Continuum

Numerous functional features that promote the natural progression of the birth to breastfeeding continuum are concentrated in the human female’s areolar region. The aim of this study was to look more closely into the thermal characteristics of areola, which are said to regulate the local evaporation rate of odors and chemical signals that are uniquely important for the neonate’s ‘breast crawl’. A dermatological study of the areolae and corresponding intern breast quadrants was undertaken on the mothers of 70 consecutive, healthy, full-term breastfed infants. The study took place just after the births at the Policlinico Abano Terme, in Italy from January to February 2014. Temperature, pH and elasticity were assessed one day postpartum using the Soft Plus 5.5 (Callegari S.P.A., Parma, Italy). The mean areolar temperature was found to be significantly higher than the corresponding breast quadrant (34.60 ±1.40°C vs. 34.04 ±2.00°C, p<0.001) and the pH was also significantly higher (4.60±0.59 vs. 4.17±0.59, p<0.001). In contrast, the elasticity of the areolar was significantly lower (23.52±7.83 vs. 29.02±8.44%, p<0.003). Our findings show, for the first time, that the areolar region has a higher temperature than the surrounding breast skin, together with higher pH values and lower elasticity. We believe that the higher temperature of the areolar region may act as a thermal signal to guide the infant directly to the nipple and to the natural progression of the birth to breastfeeding continuum.     

Gender Differences in In-Hospital Clinical Outcomes after Percutaneous Coronary Interventions: An Insight from a Japanese Multicenter Registry

Background

Gender differences in clinical outcomes after percutaneous coronary intervention (PCI) among different age groups are controversial in the era of drug-eluting stents, especially among the Asian population who are at higher risk for bleeding complications.

Methods and Results

We analyzed data from 10,220 patients who underwent PCI procedures performed at 14 Japanese hospitals from September 2008 to April 2013. A total of 2,106 (20.6%) patients were women. Women were older (72.7±9.7 vs 66.6±10.8 years, p<0.001), and had a lower body mass index (23.4±4.0 vs 24.3±3.5, p<0.001), with a higher prevalence of hypertension (p<0.001), hyperlipidemia (p<0.001), insulin-dependent diabetes (p<0.001), renal failure (p<0.001), and heart failure (p<0.001) compared with men. Men tended to have more bifurcation lesions (p = 0.003) and chronic totally occluded lesions (p<0.001) than women. Crude overall complications (14.8% vs 9.5%, p<0.001) and the rate of bleeding complications (5.3% vs 2.8%, p<0.001) were significantly higher in women than in men. On multivariate analysis in the total cohort, female sex was an independent predictor of overall complications (OR, 1.47; 95% CI, 1.26–1.71; p<0.001) and bleeding complications (OR, 1.74; 95% CI, 1.36–2.24; p<0.001) after adjustment for confounding variables. A similar trend was observed across the middle-aged group (≥55 and <75 years) and old age group (≥75 years).

Conclusions

Women are at higher risk than men for post-procedural complications after PCI, regardless of age.     

Cross-Sectional Comparison of Small Animal [18F]-Florbetaben Amyloid-PET between Transgenic AD Mouse Models

We aimed to compare [¹⁸F]-florbetaben PET imaging in four transgenic mouse strains modelling Alzheimer’s disease (AD), with the main focus on APPswe/PS2 mice and C57Bl/6 mice serving as controls (WT). A consistent PET protocol (N = 82 PET scans) was used, with cortical standardized uptake value ratio (SUVR) relative to cerebellum as the endpoint. We correlated methoxy-X04 staining of β-amyloid with PET results, and undertook ex vivo autoradiography for further validation of a partial volume effect correction (PVEC) of PET data. The SUVR in APPswe/PS2 increased from 0.95±0.04 at five months (N = 5) and 1.04±0.03 (p<0.05) at eight months (N = 7) to 1.07±0.04 (p<0.005) at ten months (N = 6), 1.28±0.06 (p<0.001) at 16 months (N = 6) and 1.39±0.09 (p<0.001) at 19 months (N = 6). SUVR was 0.95±0.03 in WT mice of all ages (N = 22). In APPswe/PS1G384A mice, the SUVR was 0.93/0.98 at five months (N = 2) and 1.11 at 16 months (N = 1). In APPswe/PS1dE9 mice, the SUVR declined from 0.96/0.96 at 12 months (N = 2) to 0.91/0.92 at 24 months (N = 2), due to β-amyloid plaques in cerebellum. PVEC reduced the discrepancy between SUVR-PET and autoradiography from −22% to +2% and increased the differences between young and aged transgenic animals. SUVR and plaque load correlated highly between strains for uncorrected (R = 0.94, p<0.001) and PVE-corrected (R = 0.95, p<0.001) data. We find that APPswe/PS2 mice may be optimal for longitudinal amyloid-PET monitoring in planned interventions studies.     

Notch-1 Mediated Cardiac Protection following Embryonic and Induced Pluripotent Stem Cell Transplantation in Doxorubicin-Induced Heart Failure

Doxorubicin (DOX), an effective chemotherapeutic drug used in the treatment of various cancers, is limited in its clinical applications due to cardiotoxicity. Recent studies suggest that transplanted adult stem cells inhibit DOX-induced cardiotoxicity. However, the effects of transplanted embryonic stem (ES) and induced pluripotent stem (iPS) cells are completely unknown in DOX-induced left ventricular dysfunction following myocardial infarction (MI). In brief, C57BL/6 mice were divided into five groups: Sham, DOX-MI, DOX-MI+cell culture (CC) media, DOX-MI+ES cells, and DOX-MI+iPS cells. Mice were injected with cumulative dose of 12 mg/kg of DOX and 2 weeks later, MI was induced by coronary artery ligation. Following ligation, 5×10⁴ ES or iPS cells were delivered into the peri-infarct region. At day 14 post-MI, echocardiography was performed, mice were sacrificed, and hearts were harvested for further analyses. Our data reveal apoptosis was significantly inhibited in ES and iPS cell transplanted hearts compared with respective controls (DOX-MI+ES: 0.48±0.06% and DOX-MI+iPS: 0.33±0.05% vs. DOX-MI: 1.04±0.07% and DOX-MI+CC: 0.96±0.21%; p<0.05). Furthermore, a significant increase in levels of Notch-1 (p<0.05), Hes1 (p<0.05), and pAkt (p<0.05) were observed whereas a decrease in the levels of PTEN (p<0.05), a negative regulator of Akt, was evident following stem cell transplantation. Moreover, hearts transplanted with stem cells demonstrated decreased vascular and interstitial fibrosis (p<0.05) as well as MMP-9 expression (p<0.01) compared with controls. Additionally, heart function was significantly improved (p<0.05) in both cell-transplanted groups. In conclusion, our data show that transplantation of ES and iPS cells blunt DOX-induced adverse cardiac remodeling, which is associated with improved cardiac function, and these effects are mediated by the Notch pathway.     

High-Intensity Endurance Training Results in Faster Vessel-Specific Rate of Vasorelaxation in Type 1 Diabetic Rats

This study examined the effects of 6 weeks of moderate- (MD) and high-intensity endurance training (HD) and resistance training (RD) on the vasorelaxation responsiveness of the aorta, iliac, and femoral vessels in type 1 diabetic (D) rats. Vasorelaxation to acetylcholine was modeled as a mono-exponential function. A potential mediator of vasorelaxation, endothelial nitric oxide synthase (e-NOS) was determined by Western blots. Vessel lumen-to-wall ratios were calculated from H&E stains. The vasorelaxation time-constant (τ) (s) was smaller in control (C) (7.2±3.7) compared to D (9.1±4.4) and it was smaller in HD (5.4±1.5) compared to C, D, RD (8.3±3.7) and MD (8.7±3.8) (p<0.05). The rate of vasorelaxation (%·s⁻¹) was larger in HD (2.7±1.2) compared to C (2.0±1.2), D (2.0±1.5), RD (2.0±1.0), and MD (2.0±1.2) (p<0.05). τ vasorelaxation was smaller in the femoral (6.9±3.7) and iliac (6.9±4.7) than the aorta (9.0±5.0) (p<0.05). The rate of vasorelaxation was progressively larger from the femoral (3.1±1.4) to the iliac (2.0±0.9) and to the aorta (1.3±0.5) (p<0.05). e-NOS content (% of positive control) was greater in HD (104±90) compared to C (71±64), D (85±65), RD (69±43), and MD (76±44) (p<0.05). e-NOS normalized to lumen-to-wall ratio (%·mm⁻¹) was larger in the femoral (11.7±11.1) compared to the aorta (3.2±1.9) (p<0.05). Although vasorelaxation responses were vessel-specific, high-intensity endurance training was the most effective exercise modality in restoring the diabetes-related loss of vascular responsiveness. Changes in the vasoresponsiveness seem to be endothelium-dependent as evidenced by the greater e-NOS content in HD and the greater normalized e-NOS content in the smaller vessels.     

Maternal Lineage of Warmblood Mares Contributes to Variation of Gestation Length and Bias of Foal Sex Ratio

Maternal lineage influences performance traits in horses. This is probably caused by differences in mitochondrial DNA (mtDNA) transferred to the offspring via the oocyte. In the present study, we investigated if reproductive traits with high variability—gestation length and fetal sex ratio—are influenced by maternal lineage. Data from 142 Warmblood mares from the Brandenburg State Stud at Neustadt (Dosse), Germany, were available for the study. Mares were grouped according to their maternal lineage. Influences on the reproduction parameters gestation length and sex ratio of offspring were analyzed by simple and multiple analyses of variance. A total of 786 cases were included. From the 142 mares, 119 were assigned to six maternal lineages with n≥10 mares per lineage, and 23 mares belonged to smaller maternal lineages. The mean number of live foals produced per mare was 4.6±3.6 (±SD). Live foal rate was 83.5%. Mean gestation length was 338.5±8.9 days (±SD) with a range of 313 to 370 days. Gestation length was affected by maternal lineage (p<0.001). Gestation length was also significantly influenced by the individual mare, age of the mare, year of breeding, month of breeding and sex of the foal (p<0.05). Of the 640 foals born alive at term, 48% were male and 52% female. Mare age group and maternal lineage significantly influenced the sex ratio of the foals (p<0.05). It is concluded that maternal lineage influences reproductive parameters with high variation such as gestation length and foal sex ratio in horses. In young primiparous and aged mares, the percentage of female offspring is higher than the expected 1:1 ratio.     

Hemodynamic Impact of Absent or Reverse End-Diastolic Flow in the Two Umbilical Arteries in Growth-Restricted Fetuses

Objective

To determine if bilateral absent or reverse end-diastolic (ARED) flow in the two umbilical arteries (UAs) at the perivesical (PVC) segment represents a more severe degree of hemodynamic compromise than unilateral ARED flow at the PVC segment in singleton pregnancies complicated by intrauterine growth restriction (IUGR).

Methods

This was a prospective observational study. One hundred nine fetuses with IUGR underwent a total of 225 ultrasound (US) examinations. We measured the pulsatility index (PI) from the two UAs at the PVC segment, UA in the free floating cord (FFC), middle cerebral artery (MCA), ductus venosus (DV) and the aortic isthmus blood flow index (IFI). Three groups were classified according to bilateral positive end-diastolic (PED) flow, unilateral ARED flow or bilateral ARED flow in the UAs at the PVC segment.

Results

The proportions of US examinations with PED flow, unilateral ARED flow and bilateral ARED flow in the UAs were 54.7%, 20.4%, and 24.9%, respectively. At the last US examination, the IFI z-scores were significantly lower in the bilateral ARED group (-6.28±4.30) compared to the unilateral ARED group (-1.72±3.18, p<0.05) and the bilateral PED group (-0.83±2.36, p<0.05), the DV-PI z-scores were significantly higher in the bilateral ARED group (2.15±3.79) compared to the bilateral PED group (0.64±1.50, p<0.05). Before 32 weeks of gestation, the interval between US examination and delivery was significantly shorter in the bilateral ARED group (8.9 days ±8.2) than the unilateral ARED group (15.9 days ±13.4, p<0.05) and the bilateral PED group (30.3 days±25.7, p<0.05).

Conclusion

There are significant differences in fetal blood fluxes between left and right UA. Doppler examination at the PVC segment significantly improves the comparability of UA-PI between two successive US examinations and allows a longitudinal and independent hemodynamic investigation of each UA. Examination of a single UA in free floating cord may miss a large fraction of unilateral ARED flow. In singleton IUGR fetuses, a bilateral ARED flow in the UAs at the PVC segment indicates more severe hemodynamic compromise and worse fetal conditions than unilateral ARED flow.     

Influence of Passive Muscle Tension on Electromechanical Delay in Humans

Background

Electromechanical delay is the time lag between onsets of muscle activation and muscle force production and reflects both electro-chemical processes and mechanical processes. The aims of the present study were two-fold: to experimentally determine the slack length of each head of the biceps brachii using elastography and to determine the influence of the length of biceps brachii on electromechanical delay and its electro-chemical/mechanical processes using very high frame rate ultrasound.

Methods/Results

First, 12 participants performed two passive stretches to evaluate the change in passive tension for each head of the biceps brachii. Then, they underwent two electrically evoked contractions from 120 to 20° of elbow flexion (0°: full extension), with the echographic probe maintained over the muscle belly and the myotendinous junction of biceps brachii. The slack length was found to occur at 95.5 ± 6.3° and 95.3 ± 8.2° of the elbow joint angle for the long and short heads of the biceps brachii, respectively. The electromechanical delay was significantly longer at 120° (16.9 ± 3.1 ms; p<0.001), 110° (15.0 ± 3.1 ms; p<0.001) and 100° (12.7 ± 2.5 ms; p = 0.01) of elbow joint angle compared to 90° (11.1 ± 1.7 ms). However, the delay between the onset of electrical stimulation and the onset of both muscle fascicles (3.9 ± 0.2 ms) and myotendinous junction (3.7 ± 0.3 ms) motion was not significantly affected by the joint angle (p>0.95).

Conclusion

In contrast to previous observations on gastrocnemius medialis, the onset of muscle motion and the onset of myotendinous junction motion occurred simultaneously regardless of the length of the biceps brachii. That suggests that the between-muscles differences reported in the literature cannot be explained by different muscle passive tension but instead may be attributable to muscle architectural differences.     

Effect of Acute Intermittent CPAP Depressurization during Sleep in Obese Patients

Background

Obstructive Sleep Apnea (OSA) describes intermittent collapse of the airway during sleep, for which continuous positive airway pressure (CPAP) is often prescribed for treatment. Prior studies suggest that discontinuation of CPAP leads to a gradual, rather than immediate return of baseline severity of OSA. The objective of this study was to determine the extent of OSA recurrence during short intervals of CPAP depressurization during sleep.

Methods

Nine obese (BMI = 40.4 ± 3.5) subjects with severe OSA (AHI = 88.9 ± 6.8) adherent to CPAP were studied during one night in the sleep laboratory. Nasal CPAP was delivered at therapeutic (11.1 ± 0.6 cm H₂0) or atmospheric pressure, in alternating fashion for 1-hour periods during the night. We compared sleep architecture and metrics of OSA during CPAP-on and CPAP-off periods.

Results

8/9 subjects tolerated CPAP withdrawal. The average AHI during CPAP-on and CPAP-off periods was 3.6 ± 0.6 and 15.8 ± 3.6 respectively (p<0.05). The average 3% ODI during CPAP-on and CPAP-off was 4.7 ± 2 and 20.4 ± 4.7 respectively (p<0.05). CPAP depressurization also induced more awake (p<0.05) and stage N1 (p<0.01) sleep, and less stage REM (p<0.05) with a trend towards decreased stage N3 (p = 0.064).

Conclusion

Acute intermittent depressurization of CPAP during sleep led to deterioration of sleep architecture but only partial re-emergence of OSA. These observations suggest carryover effects of CPAP.     

SDF1-A Facilitates Lin?/Sca1+ Cell Homing following Murine Experimental Cerebral Ischemia

Background

Hematopoietic stem cells mobilize to the peripheral circulation in response to stroke. However, the mechanism by which the brain initiates this mobilization is uncharacterized.

Methods

Animals underwent a murine intraluminal filament model of focal cerebral ischemia and the SDF1-A pathway was evaluated in a blinded manner via serum and brain SDF1-A level assessment, Lin−/Sca1+ cell mobilization quantification, and exogenous cell migration confirmation; all with or without SDF1-A blockade.

Results

Bone marrow demonstrated a significant increase in Lin−/Sca1+ cell counts at 24 hrs (272±60%; P<0.05 vs sham). Mobilization of Lin−/Sca1+ cells to blood was significantly elevated at 24 hrs (607±159%; P<0.05). Serum SDF1-A levels were significant at 24 hrs (Sham (103±14), 4 hrs (94±20%, p = NS) and 24 hrs (130±17; p<0.05)). Brain SDF1-A levels were significantly elevated at both 4 hrs and 24 hrs (113±7 pg/ml and 112±10 pg/ml, respectively; p<0.05 versus sham 76±11 pg/ml). Following administration of an SDF1-A antibody, Lin−/Sca1+ cells failed to mobilize to peripheral blood following stroke, despite continued up regulation in bone marrow (stroke bone marrow cell count: 536±65, blood cell count: 127±24; p<0.05 versus placebo). Exogenously administered Lin−/Sca1+ cells resulted in a significant reduction in infarct volume: 42±5% (stroke alone), versus 21±15% (Stroke+Lin−/Sca1+ cells), and administration of an SDF1-A antibody concomitant to exogenous administration of the Lin−/Sca1+ cells prevented this reduction. Following stroke, exogenously administered Lin−/Sca1+ FISH positive cells were significantly reduced when administered concomitant to an SDF1-A antibody as compared to without SDF1-A antibody (10±4 vs 0.7±1, p<0.05).

Conclusions

SDF1-A appears to play a critical role in modulating Lin−/Sca1+ cell migration to ischemic brain.     

Effects of Aminoguanidine on Lipid and Protein Oxidation in Diabetic Rat Kidneys

Nonenzymatic glycation of tissue and plasma proteins may stimulate the production of oxidant and carbonyl stress in diabetes. The aim of this study was to evaluate the effects of aminoguanidine (AG) on lipid peroxidation, protein oxidation and nitric oxide (NO) release in diabetic rat kidneys. After induction of diabetes with streptozotocin, female Wistar rats were divided into 2 groups. Group DAG (n=9) rats were given AG hydrogen carbonate (1 g/L) in drinking water and group D (n=8) was diabetic control rats given only tap water. Group H (n=8) was followed as healthy controls. At the end of an 8 week period, NO release, lipid and protein oxidation were determined in kidney tissues. NO release was significantly lower in diabetic rats compared with healthy controls (p<0.05). Lipid peroxidation was significantly high in group D (3.9 ± 0.3 nmol MDA/g tissue) compared with the group DAG (2.6 ± 0.1 nmol MDA/g tissue, p<0.01) and group H (2.4 ± 0.2 nmol MDA/g tissue). Protein oxidation was significantly higher in diabetics than healthy controls (563.8 ± 23.9, 655.8 ± 7.2 , 431.5 ± 8.8 mmol carbonyl / g tissue for group DAG, D and H, respectively, p< 0.05). A positive correlation between albuminuria and thiobarbituric acid reactive substance (TBARS) levels (r= 0.54,p<0.005) and carbonyl content (r=0.70, p<0.0005) in kidney homogenate were observed. Although AG treatment had no effect on NO release, it significantly decreased lipid peroxidation in diabetic rat cortices. Consequently increased lipid peroxidation -as well as- protein oxidation could be involved in the pathogenesis of diabetic albuminuria.