Granulomatosis with polyangiitis (GPA) is a rare granulomatous vasculitis affecting small- and medium-sized blood vessels. In optimally treated patients with long-standing disease, the common cause of death is atherosclerosis even in the absence of typical risk factors.To evaluate endothelial dysfunction in GPA patients.44 patients (21 men and 23 women) diagnosed with GPA and 53 controls matched for age, sex, BMI and typical risk factors for cardiovascular diseases (22 men and 31 women) were enrolled in the study. We measured each participant’s serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also studied flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness (IMT) of the common carotid artery and aortic stiffness using echocardiography.p = 0.01), 66% of IL-6 (p < 0.001) and 50.9% of thrombomodulin (p < 0.001) compared to controls. FMD% was 48.9% lower in patients with GPA in comparison to controls (p < 0.001), after adjustment for potential confounders, with no differences regarding IMT or aortic stiffness. FMD% was negatively associated with duration of the disease (β = − 0.18 [95% CI: − 0.32 to − 0.04]), C-reactive protein (β = − 0.17 [95% CI: − 0.27 to − 0.07]), IL-6 (β = − 0.29 [95% CI: − 0.39 to − 0.19]), blood creatinine level (β = − 0.2 [95% CI: − 0.3 to − 0.1]), and IMT (β = − 0.14 (− 0.24 to − 0.04). In a multiple linear regression model, kidney function, IMT, pack-years of smoking, diabetes and level of VCAM-1 were independent predictors of lower FMD%.Patients with GPA showed a 15.9% increase in serum levels of VCAM-1  contains supplementary material, which is available to authorized users. Endothelium plays a key role in vascular homeostasis. It acts as a barrier between tissues and circulating blood and as a signal transducer that regulates vasomotor activity . ActivatGranulomatosis with polyangiitis  is the common vasculitis with a prevalence of 3 per 100, 000 and peak incidence at the age of 50–60. Anti-neutrophil cytoplasmic antibodies (ANCA) are considered as the marker of the disease and are targeted against proteinase 3 (PR3). Its most common clinical features are granulomatous lesions of the upper and lower airways accompanied by the kidney failure . CardiacThe increased morbidity from ischemic heart disease in GPA suggests that not only small vessels but also big ones are affected .Atherosclerosis and its complications are one of the leading cause of death even in properly treated patients with long-standing ANCA-associated vasculitis (AAVs) , 11. HowThe relationship between inflammation, vascular dysfunction and atherosclerosis is well-established. Premature atherosclerosis has been observed in patients with chronic inflammatory diseases such as systemic lupus erythematosus , 13, sysPreviously, a few studies have analyzed the endothelial damage and progression of atherosclerosis in patients with systemic vasculitis –21. TheiA case–control observational, retrospective study was carried out with approval of the Bioethics Committee of XXXX University Medical College . The patients were recruited from the population of patients at the Department of Allergy and Clinical Immunology at the University Hospital in XXXXX in the period between 2014 and 2017 who were in the disease flare or symptomatic. The control group was enrolled from the hospital personnel and relatives. They were selected according to matching criteria. All participants received a detailed brief of the methodology and safety protocols for the study and provided written consent for their participation.The case group constituted 44 patients with GPA—21 men and 23 women.The control group consist of 53 individuals, 22 men and 31 women, matched to GPA patients by gender, age, body mass index (BMI) and smoking habit, as well as comorbidities, including hypertension, hypercholesterolemia, and diabetes mellitus.Each patient had a current or previous diagnosis of GPA based on the criteria of the American College of Rheumatology . We analIn this case–control study, we analyzed whether GPA is associated with vascular endothelial damage. We measured flow-mediated dilatation of the brachial artery, intima-media thickness of the common carotid artery, aortic stiffness as well as evaluated serum levels of thrombomodulin and VCAM-1 in GPA patients and matched control subjects.Fasting blood samples were drawn in the morning from the antecubital vein using minimal stasis. Lipid profile, glucose, liver enzymes, urine, creatinine with eGFR, complete blood cell and platelet count were analyzed by routine laboratory techniques. C-reactive protein (CRP) was measured using analyzer VITROS 250 Johnson & Johnson. Blood samples were drawn into serum separation tubes, centrifuged at 2000×g for 20 min at room temperature, within 2 h from sampling. The supernatant was frozen in aliquots and stored at -70 °C until analysis. Interleukin-6 (IL-6), VCAM-1, and soluble thrombomodulin were measured using standardized ELISA method . Anti-PR3 IgG was measured in all GPA subjects using ELISA assay .Ultrasound examinations were performed in a darkened, quiet, room, after at least 10 min rest in a supine position, using high-quality ultrasonograph . Before examination, the subjects refrained from eating for at least 10 h. Examinations were conducted by two independent ultrasonography experts and considered parameters constituted a mean of three subsequent measurements. A complete transthoracic echocardiogram (TTE) was performed in every participant with estimation of ejection fraction of the left ventricle (EF) and systolic pulmonary artery pressure in accordance to standard methods . Flow-meU test. Categorical variables were presented as numbers (percentages) and compared by χ2 test. Potential confounders were identified as: age, BMI, sex, and comorbidities such as arterial hypertension, diabetes mellitus and hypercholesterolemia. To adjust for these, obtained results of FMD%, IMT, aortic stiffness%, IL-6, VCAM-1, and thrombomodulin were log-transformed and a one way covariance analysis (ANCOVA) was performed, to achieve the overall p value. The univariate linear regression tests (with adjustment for aforementioned confounders) were used to analyze associations between two selected parameters. Independent determinants of FMD% were established in multiple linear regression model, built by a forward stepwise selection procedure, verified by F Snedecore’s statistics, with F > 1. The R2 was used as a measure of the variance. To calculate odds ratios (ORs) with 95% confidence intervals (CIs), unconditional multivariate logistic regression was performed. The cut-off values for IL-6, VCAM-1, FMD%, and thrombomodulin were determined based on receiver operating characteristic (ROC) curves. Results were considered statistically significant when the p value was less than 0.05.The results were compared between the case and control groups using STATISTICA 12.5 Software. Continuous variables, all non-normal distributed values (verified by the Shapiro–Wilk test), were given as median and interquartile range and compared by the Mann–Whitney Demographic, clinical and laboratory characteristics of the studied subjects, including basic laboratory tests, ultrasound parameters, and cardiovascular risk factors were given in Table As expected, GPA patients were characterized by higher inflammatory markers, such as CRP, IL-6 (reference range: 0.45–9.96 pg/ml) and white blood cells, as well as impaired kidney function and lower hemoglobin level Table . MoreoveIn TTE GPA subjects had larger left and right ventricles and left atria, thicker posterior walls and interventricular septa, as well as lower ejection fraction and higher systolic pulmonary artery pressure.p = 0.01) and a 50.9% increased thrombomodulin concentrations (p < 0.001) in peripheral blood, comparing to healthy individuals. However, in ANCOVA analysis we documented that only thrombomodulin levels remained higher in GPA subjects after adjustment for potential confounders . The VCAM-1 was similar in GPA and control groups in this analysis (p = 0.54). Moreover, patients with GPA had increased risk of elevated VCAM-1 , and thrombomodulin  compared to the healthy individuals . As expected, both endothelial injury markers were related to the CRP  and IL-6 level . Moreover, we demonstrated strong positive association between white blood cells and thrombomodulin (β = 0.2 [95% CI: 0.11–0.29]). Table GPA patients had a 15.9% higher levels of VCAM-1 (p = 0.02) and 41% higher thrombomodulin levels  than the remaining GPA patients. Moreover, GPA patients with chronic kidney disease were characterized by higher thrombomodulin level (11.7 [9.4–17.6) vs. 5.4 [4.4–6.9] ng/ml, p < 0.001) and VCAM-1 level . Other comorbidities had no impact on laboratory markers of endothelial damage. Patients taking statins and antihypertensive medications had increased thrombomodulin blood level , Moreover, those treated with antihypertensives had higher level of VCAM-1 .GPA patients with hypertension had 30. 6% higher levels of VCAM-1 .In the subgroups analysis, patients in persistent disease or in active disease had similar results of laboratory parameters of endothelial injury , and markedly higher risk of diminished FMD% defined as values below the cut-off point of 8.51 (OR 4.9 [95% CI: 2.88–8.23]).GPA patients had 48.9% decrease in FMD% compared to controls (β = − 0.24 [95% CI: − 0.32 to − 0.15]), CRP (β = − 0.17 [95% CI: − 0.27 to − 0.07]), IL-6 (β = − 0.29 [95% CI: − 0.39 to − 0.19]) and the blood creatinine level (β = − 0.2 [95% CI:− 0.3 to − 0.1]) in univariate linear regression models. Interestingly, FMD% was also negatively related to smoking (packs/years) (β = − 0.33 [95% CI: − 0.44 to − 0.12)], duration of the disease (β = − 0.18 [95% CI: − 0.32 to − 0.04]), as well as posterior wall and interventricular septum thickness .In Table β = − 0.41 [95% CI: − 0.55 to − 0.27]), pack-years of smoking (β = − 0.14 [95% CI: − 0.29 to − 0.01]), IMT (β = − 0.34 [95% CI: − 0.5 to − 0.18]), serum urea (β = − 0.41 [95% CI: − 0.61 to − 0.21]) or VCAM-1 (β = − 0.33 [95% CI: − 0.53 to − 0.13]), , diabetes  and smoking currently or in the past (4.3 [2.9–5] vs. 6.7 [5–0.3]). Interestingly, only those treated with azathioprine had lower FMD%  without influence of other immunosuppressive drugs. Patients treated with statins were also characterized by decrease in FMD% .Among GPA patients, lower FMD% was observed in those with hypertension , blood creatinine level (β = 0.18 [95% CI: 0.08 to 0.28]), duration of steroid treatment (β = 0.19 [95% CI: 0.03 to 0.35]) duration of the disease (β = 0.27 [95% CI: 0.14 to 0.41]), posterior wall thickness (β = 0.16 [95% CI:0.05 to 0.27]), and interventricular septum thickness (β = 0.12 [95% CI:0.01 to 0.23]) . GPA subjects treated with statins and with hypertension had higher IMT than remaining GPA patients . Only one patient had an atherosclerotic plaque in the left common carotid artery.In the subgroup of GPA patients with chronic kidney disease IMT was higher .Ultrasound parameters of endothelial injury were comparable between the patients in the disease flare and in the persistent disease  . MoreoveSmoking currently or in the past also influenced lower FMD in GPA patients and it was an independent predictor of lower FMD.Described changes may lead to the increased risk of cardiovascular events, what has been previously demonstrated by Faurschou et al. . In his The limited number of GPA patients decreases the power of our findings. However, our study group is one of the biggest evaluated in the literature so far in terms of endothelial dysfunction. Moreover, the GPA is a rare disease and in our opinion every report is valuable. Patients with GPA had some comorbidities , which in the majority of analyzed subjects were related to the systemic complications of vasculitis and might be considered as a consequence of GPA. We attempted to eliminate these confounding variables by an adjustment for comorbidities  during statistical analysis and recruitment of controls with similar common cardiovascular risk factors. GPA patients were younger than controls, but this difference did not reach statistical significance. Finally, patients with vasculitis were being treated with many medications, notably immunosuppressive drugs and corticosteroids. The impact of the medications used on endothelial dysfunction was beyond the scope of our study; however, decreased values of FMD% in patients on statins and antihypertensive medications seemed to be related more to comorbidities  than the drugs themselves. Nevertheless, we believe that the presented results reflect true intergroup differences.In summary, the patients with GPA are characterized by endothelial dysfunction, which is likely related to the chronic systemic inflammation observed in autoimmune diseases. Although large observational studies are needed to verify whether lower FMD% is associated with increased risk of cardiovascular events in GPA patients, this noninvasive and simple ultrasound test seems to represent a new tool/predictor of endothelial injury for clinical practice.Below is the link to the electronic supplementary material.Supplementary material 1 (DOCX 13 KB)


We present our experience with hypothermic machine perfusion (HMP) versus cold storage (CS) in relation to kidney transplant outcomes. Retrospective analysis of 33 consecutive HMP kidney transplant outcomes matched with those of 33 cold stored: delayed graft function (DGF), length of hospital stay (LOS), estimated glomerular filtration rate (eGFR), and patient and graft survival were compared. Renal Resistive Indexes (RIs) during HMP in relation to DGF were also analysed. In the HMP group, mean HMP time was 5.7 ± 3.9 hours with a mean cold ischaemic time (CIT) of 15 ± 5.6 versus 15.1 ± 5.3 hours in the CS group. DGF was lower in the HMP group (p=0.041), and donation after Circulatory Death (DCD) was a predictor for DGF (p<0.01). HMP decreased DGF in DCD grafts (p=0.036). Patient and graft survival were similar, but eGFR at 365 days was higher in the HMP cohort (p<0.001). RIs decreased during HMP (p<0.01); 2-hours RI ≥ 0.45 mmHg/mL/min predicted DGF in DCD kidneys ; 2-hours RI ≥ 0.2 mmHg/ml/min predicted DGF in DBD grafts . HMP decreased DGF compared to CS, offering viability assessment pretransplant and improving one-year renal function of the grafts. Worldwide, the increasing demand for renal allografts and growing waiting lists has led to the utilization of organs through donation after Circulatory Death (DCD), although these organs are associated with higher rates of discard, retrieval associated injury , and up In order to achieve the optimum outcome from each donated kidney and increase the survival benefit compared to the dialysis population , optimalThe process underlying DGF include several pathophysiologic mechanisms derived from the donor ischemic injury and inflammatory signalling; it is the clinical manifestation of the acute kidney injury which affects the transplant parenchyma and, subsequently, renal function . Animal One of the flow parameters in HMP, the Renal Resistance Index (RI), has been previously identified as a marker of the whole-organ microcirculatory damage after the retrieval ischaemic injury . MonitorThe aim of the present study was to evaluate the effect of HMP during kidney transplant preservation in comparison to static cold storage based on a single centre experience.The study is a single centre retrospective cohort analysis of hypothermic machine perfused kidneys  transplanted from March 2012 to April 2018 versus cold storage only. It was conducted in accordance with institutional ethics regulations; since it was a retrospective chart analysis, no informed consent was required.The case controls were matched on 1:1 basis according to graft type (DBD or DCD), donor age, cold ischaemic time (CIT), and number of Human Leukocyte Antigen (HLA) mismatches between donor and recipients.As soon as the kidneys were delivered into our centre and there was an impediment to proceed immediately with the transplant, HMP was chosen as the preservation method.The University of Wisconsin solution was used for HMP, at a temperature between 4-5°C and at an initial peak systolic pressure of 45 mmHg. After 30 minutes of cold perfusion, the pressure was held constant ≥ 40 mmHg. RIs were recorded to monitor kidney parenchymal recovery.CIT was defined the time from the start of cold perfusion during organ retrieval to the time of reperfusion during the transplant, including the HMP time. DGF was defined as the need for dialysis within 1 week of transplantation with a perfused graft. Furthermore, we compared the mean Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR)  until daAll the patients received a steroid sparing immunosuppressive regimen (7-day course of steroids) with alemtuzumab induction and long-term Tacrolimus (TAC) monotherapy  and neither the renal replacement therapy nor the immunosuppression protocol of our centre changed over the last 10 years. p was considered significant at less than 0.05. We used a linear regression model with stepwise procedure to test which parameters were acting as independent predictors for DGF. A generalised linear model of univariate repeated ANOVA with post hoc Bonferroni correction was used to determine whether mean eGFR differed statistically significantly during follow up. A receiver operator characteristic (ROC) curve was constructed to investigate the predictive accuracy of RI for DGF.Continuous variables are presented as mean ± standard deviation and were compared using one way ANOVA. Independent t-test was used to analyse RI trend during machine perfusion. The confidence interval was set to 95%, andAnalysis was performed using SPSS .Sixty-six transplanted kidney outcomes were analysed. Donor and recipient demographics are shown in p=ns).The mean HMP time was 5.7 ± 3.9 hours; in the HMP group, the mean CIT of 15 ± 5.6 hours and 15.1 ± 5.3 hours in the CS group  in the whole cohort, occurring in 24/66 kidneys (36%): 8/33 (24%) machine perfused and 16/33 (48%) cold stored (p=0.041). The DCD kidneys that developed DGF in the HMP group were 5/12 versus 10/12 in the CS control cohort (p=0.036), confirming a protective effect of the HMP preservation for the grafts retrieved from DCD donors.The patients receiving grafts with subsequent DGF had higher length of hospital stay (LOS): 11.6 ± 5.8 days versus 29.1 ± 18.1 days (p<0.001).The RI decreased statistically significantly during HMP: mean RI at baseline (R0) was 0.65 ± 0.25 mmHg/ml/min p<0.01); after 60 minutes (RI60) was 0.62 ± 0.33 mmHg/ml/min (p<0.01); after 120 minutes (RI 120) was 0.46 ± 0.16 mmHg/ml/min (p<0.01); after 180 minutes (RI180) was 0.44 ± 0.22 mmHg/ml/min (p<0.01). The higher impact in decreasing the original RI value was observed between the first and the second hour of HMP (p< 0.01). Figures ; after 6Furthermore, we subanalysed the difference in RIs between DCD and DBD grafts. A 2-hours RI value ≥ 0.2 mmHg/ml/min was associated with 100% sensitivity and 91% specificity in DGF prediction for DBD grafts. The area under the curve was 0.87 .A 2-hours RI value ≥ 0.45 mmHg/ml/min was associated with 75% sensitivity and 80% specificity in DGF prediction for DCD grafts. The area under the curve was 0.78 .p=0.039), with the eGFRs for the HMP transplanted kidneys being persistently higher  at 120 days posttransplant and acute rejection (n=2), at 180 days posttransplant (p=0.31). One patient died in the HMP group with a nonfunctioning graft after 270 days posttransplant due to myocardial infarction; no patient died in the CS (p=0.32). Results are summarised in DGF is the Achille's heel of kidney transplantation from DCD donors, affecting more than half of the subsequently transplanted grafts . Our finThe use of cold pulsatile technology is a long-established alternative to static cold storage and it has been shown to be a better preservation method . There aNevertheless, an important advantage of RI monitoring could be the ability to estimate the risk of a particular kidney to develop DGF . RIs areKnowing the risk profile of a particular kidney earlier in the preservation process would be of great benefit for the postoperative management and it would provide objective information for selecting a particular recipient for a particular kidney, thus tailoring the offered renal replacement therapy to the patient who would benefit most. In the era of patient tailored consent  and patiWithin the limitations of the size of the HMP and CS groups, our study demonstrated that hypothermic machine perfusion offers an advantage in deceased donor renal transplantation of high risk kidneys, since it reduces significantly DGF rates and is associated with higher posttransplant eGFRs. This preservation modality has a positive impact in kidney transplant outcomes from DCD donors and offers an early viability assessment that allows prediction of short- and long-term posttransplant graft function. It represents a real time opportunity to recondition the retrieval ischaemic injury, plan the postoperative recovery, and enhance the decision-making process by offering the patients evidence that allow them to make an informed decision.


Dynamic properties of TA and AA were measured in the same rats, using echotracking recording of aortic diameter coupled with blood pressure (BP). Measurements were performed first at operating BP and then after BP reduction in hypertensive rats, thus in isobaric conditions. Histological staining and immunohistochemistry were used for structural analysis at both sites. At operating pressure, BP and pulse pressure (PP) were higher in SHRLN compared with SHR. Stiffness index was also increased and distensibility decreased in both TA and AA in SHRLN. At WKY-matched blood pressure, isobaric AA parameters remained specifically altered in SHRLN, whereas TA recovered to values identical to WKYs. Collagen, fibronectin, α5-selectin, and FAK were increased in SHRLN compared with SHR or WKY. Nevertheless, only the strong accumulations of fibronectin and collagen at the AA site in SHRLN were associated with intrinsic stiffening. In conclusion, we confirm that NO restriction associated with hypertension induces a severe pathological phenotype and shows that L-NAME induced stiffening is more pronounced in AA than in TA as a result of greater fibrosis.The spontaneously hypertensive rat model with reduced NO synthesis (SHRLN) shares features with aging and hypertension in humans, among other a severe aortic stiffening. The present The stiffening of large central arteries occurs naturally with aging. The reduction of aortic compliance leads to downstream damage to organs which receive high flow with low impedance such as the brain  and kidnRecently, we investigated the role of an increased salt diet in hypertensive rat on aortic stiffness . We obseIn the present study we aimed to evaluate thoracic and abdominal arterial compliance and composition in another experimental model of hypertensive aortic stiffness. For that purpose, we administered L-NAME in spontaneously hypertensive rats (SHR) over 5 weeks and studied aortic compliance using echotracking evaluation of pressure-independent stiffening , 13 and This study was conducted in accordance with European Community Guidelines for the use of experimental animals and was approved by the ethical committee on Animal Experiments of the Servier Research Institute. All animals were provided by CERJ (France). Three groups were compared: Wistar Kyoto (WKY) rats (n=6), SHR (n=6), and SHR given N-nitro-L-arginine methyl ester  at 2 mg/kg in drinking water for 5 weeks, from 15 to 20 weeks of age (SHRLN) (n=8). Water consumption and body weight were measured every 3 days and L-NAME concentration was adjusted to maintain 2 mg/kg/day. The animals were housed 2 per cage in a temperature controlled room (20-21°C) with a 12/12 hour light/dark cycle.2O. Body temperature was maintained at 37°C with a homeothermic blanket (Harvard) connected to a rectal probe.Rats were anaesthetized with an intraperitoneal injection of sodium pentobarbital . The jugular vein was cannulated for constant administration of anesthetic and the penile vein was cannulated for administration of other drugs. The trachea was cannulated and ventilation was maintained with a pressure controlled respirator  at a frequency of 60-70 cycles per minute and a pressure of 9-12 cmHA microtip pressure catheter (Millar 1.2F) was inserted into the aorta via the right femoral artery. The blood pressure signal was visualized and analyzed with Biopac 4.2 Acknowledge acquisition and analysis system (CEROM). The aortic diameter was simultaneously measured as previously described , 10 withThoracic measurements were made at the lowest part of the TA, above renal artery bifurcation and below diaphragm and abdominal aorta measurements were made at the lowest abdominal site.μg/kg i.v.) to achieve the same blood pressure as the normotensive WKY rats; the effect of clonidine lasts approximately 10 min. In the SHRLN group two measurements were performed during clonidine effect, one matched BP with that of SHR and one matched BP with that of WKY. Following these measurements, the catheter and ultrasound probe were repositioned into and above the TA to obtain measurements at the baseline blood pressure of the normotensive rats. The changes induced by the reduction in BP represent the pressure dependent stiffness and the difference remaining versus normotensive animals after BP reduction represents the pressure-independent stiffening, i.e., intrinsic stiffening.The catheter was inserted first into the TA via the right femoral artery and measurements were made in the TA at baseline blood pressure. Then the catheter was withdrawn and placed in the AA just above the iliac bifurcation. The ultrasound was also moved to obtain an image of the catheter within the AA. For the SHR group, after the baseline recordings, a second series of measurements were taken within the AA when blood pressure was reduced using an injection of clonidine (3D) and diastolic diameter (dD); mean distension (in μm); compliance (ΔA/ΔP) in mm2/kPa, where A is the transsectional area of the vessel calculated from the diameter and P is pressure; distensibility (ΔA/ΔP XA) in 1/kPa; and stiffness index {[dD ln(SAP/DAP)]/(sD-dD)},where sD is systolic diameter, SAP is systolic arterial pressure, and DAP is diastolic arterial pressure. Aortic distension was expressed in percent vs. diastolic diameter (ΔD X100/dD). The local pulse wave velocity (PWV) is calculated from √−(A/ΔP/ρΔA), ρ= blood viscosity. Δ represents the systolodiastolic difference during the cardiac cycle.The parameters automatically calculated to determine the dynamic properties of the aortic wall were as follows: mean diameter  and one without (n=8), were implanted with a standard telemetric device  with a pressure transducer under short-term anesthesia with isoflurane. Blood pressure signals were continuously recorded by data analysis software . Systolic (SBP), diastolic (DBP), mean blood pressure (MBP), pulse pressure (PP), and heart rate (HR) were automatically detected beat to beat with analysis software ECG auto®  and averaged every minute.k-1 and BPk, (1 minute) and n is the number of BP readings in 24 hours .Data were analyzed 1 day before L-NAME treatment and then at days 7, 14, 21, and 28 of treatment and similarly for the control SHR group. Reported values of SBP, DBP, MBP, and PP, represented the mean of individual measurements over the 24 h recording period. Short-term variability of HR, SBP, DBP, and PP was calculated over 1-minute periods over 24h Average Real Variability (ARV), an index used in clinical studies, considered as the most potent index for short-term BP variability, evaluates the variability between consecutive and validated readings , and wasUrines were collected during 24 hours 3 days before the end of the protocol; proteinuria and the urinary ratio protein/creatinine were measured (ABX PENTRA C400).At the end of the experiments the rats were euthanized via a lethal dose of sodium pentobarbital i.v. Rat nasorectal length was measured. The left ventricle and left kidney were weighed. Left ventricle and left kidney weight were normalized to their ratio to nasorectal length (mg/cm). Thoracic and abdominal aortas were cleaned and stored in 4 % formaldehyde.μm thick sections and mounted on Superfrost plus slides and subjected to independent tests [Arterial structure was determined and quantified in 4% formaldehyde-fixed thoracic and abdominal aortas extracted from the rats used for hemodynamic measurements. For that purpose, a piece of about 5 mm long, corresponding to the same site used for ultrasound measurements for both TA and AA, was cut and embedded in paraffin. The tissue was then extracted from individual paraffin blocks and inserted into a preformed paraffin recipient block . The finished block was then cut into 4 nt tests .Media cross-sectional areas (MCSA) and scleroproteins quantifications were performed by morphological analysis after a Sirius red and a three-color staining protocol (Masson's trichrome) as previously described . Elastinα5 integrin . This analysis was completed with an anti-FAK antibody , which recognized focal adhesion kinase [For immunohistochemical analyses of cell-matrix interactions, a fibronectin polyclonal antibody  was used. Integrins accumulation was quantified with n kinase .Heat-mediated antigen retrieval was performed in EDTA buffer pH 9 in a water bath for 30 min. Immunostaining was performed on a Dako autostainer using a peroxidase-labeled polymer-based detection system  and diaminobenzidine as a chromogen. No specific staining was observed when primary antibody was omitted from the protocol (negative control). The distribution and quantification of staining were determined by computer-directed color analysis performed with the noncommercial image processing software Mesurin® , 18.All data were expressed as the mean ± the standard error of the mean (SEM). Then each hemodynamic parameter was analyzed with a one way ANOVA of raw data followed by a Tukey post-hoc comparison first at basal blood pressure and again at matched blood pressures across the three groups. Time effect was analyzed by a one WAY ANOVA followed by a Dunnett's test. Paired Student t test was performed to compare thoracic and abdominal values, as well as the effect of clonidine in hypertensive rats.For immunochemistry analysis, two-way ANNOVA on groups and sites was performed followed by a Tukey's multiple comparison test.Differences were considered significant at values of P<0.05.A slight reduction of body weight was observed in the SHRLN group. No groups presented with renal hypertrophy as determined by no change in animal-length normalized kidney weights. This was observed despite a reduction in kidney function in the SHRLN as determined by increased total proteinuria/24h and by the increased ratio urinary protein/creatinine .Left ventricular hypertrophy was observed in both hypertensive groups as determined by length-normalized left ventricle weight. The SHR had larger left ventricles compared to those of WKY and those of SHRLN were larger than those of SHR. The data are shown in The effect of L-NAME treatment on BP and short-term BP variability was evaluated in conscious rats used specifically for these measurements (n=8 SHR and n=9 SHRLN). L-NAME treatment increased BP in SHR. During the last week, 2 telemetered SHRLN died and others began to present slight decrease in blood pressure; thus only the 4 first weeks can be statistically analyzed. In SHR, SBP, DBP, PP, and their respective BPV were not modified during the 4 weeks. In SHRLN, SBP and DBP increased simultaneously with no change in PP. SBP BPV increased from day 14 with no change in DBP BPV, leading to a strong increase of PP BPV. β-stiffness index and local PWV as well by decreased distensibility, compliance index and pulse diameter  and pulse pressure (PP) were higher in SHR versus WKY and higher in SHRLN than in the two other groups. A similar pattern was observed for mean and diastolic diameters. Aortic stiffness was higher in SHR compared to that of WKY and L-NAME treatment leading to a greater increase in stiffness in SHRLN compared to SHR. This was demonstrated by increased diameter . The AUCdiameter  and 3.Under isobaric conditions, i.e., after decreasing BP and PP to that of WKY by administration of clonidine in SHR and SHRLN, we no longer observed differences in stiffness in the thoracic aorta between our three groups, demonstrating that the stiffness increase was strongly pressure-dependent. Distension remained slightly reduced in SHRLN compared to SHR at matched blood pressures .The AA diameter was significantly smaller than the thoracic diameter in all groups. Also, all stiffness and distensibility parameters indicated significantly higher stiffness and lower compliance as expected at this more distal part of aorta.The differences observed in the three groups at basal blood pressure were similar to those observed at the thoracic site: pressures, stiffness index, and local PWV were higher in the SHR compared to the WKY and more so in the SHRLN; distensibility, compliance index, and distension were lower in SHR than in WKY and lower in SHRLN compared to SHR.However, in contrast to the thoracic aorta, after clonidine administration, the abdominal aorta of SHRLN remained stiffer under isobaric conditions : stiffneThis increase in stiffness in the SHRLN AA but not in TA under isobaric conditions was also made apparent by comparing diameter distension at both sites and both pressures .Furthermore, during clonidine administration, the higher stiffness and lower distensibility of the AA was maintained in SHRLN compared to SHR.Wave analysis, quantified by the AUC corrected for HR Tables  and 3, cAs for the other parameters, in contrast to AA, TA distension wave recovered and was no longer different from that in WKY after BP reduction. Again importantly the decrease in heart rate was similar at TA and AA levels and the AUC value corrected for heart rate.The difference observed between AA and TA is emphasized by comparing BP and distension wave in SHRLN . in vivo data .The vascular wall thickness did not significantly differ between SHR and WKY but was increased in SHRLN compared to that of WKY and SHR. These observations were similar for TA and AA. The internal diameter was comparable in the three groups for the two sites. As expected AA diameter was much lower than TA diameter , in agreement withα5-integrin were increased only in SHRLN (for both TA and AA). Fibronectin and FAK were higher in SHR than in WKY and further increased in SHRLN compared to both WKY and SHR for the two sites. While there is a tendency for the SHR to show accumulation of fibrosis in the AA compared to the TA, we showed that it was only in the SHRLN that we had a strong specific accumulation of fibronectin and collagen at the AA and that this was associated with a significant increase in isobaric stiffness  the major effects of chronic NO reduction in hypertensive rats were characterized by a greater increase in BP and aortic stiffening associated with structural changes in the aortic wall; (2) a specific pressure independent increase in AA stiffness compared to TA in the SHRLN which is associated with greater changes in fibrotic markers.Large artery stiffening is now recognized as a cardiovascular risk factor as these compliant arteries lose their capacity to dampen the pulsatile force of cardiac systolic ejection. Increased blood pressure reduces arterial compliance but long-term high blood pressure as well as aging and chronic kidney disease induces moreover vascular wall remodeling which in turn further increases arterial wall stiffening in a vicious circle. Vascular wall remodeling involves alteration of numerous vascular wall components: increases in collagenous and fibrotic components, calcium deposition, reduction, and/or fragmentation of elastin and alteration of the vascular smooth muscle cells and is closely related to alteration of the endothelial cells and NO bioavailability. These mechanisms are complex and still not entirely understood , 20. TheOur previous study on SHR treated with the NO inhibitor L-NAME demonstrated a major role of endothelial dysfunction on the development of arterial stiffness. After just two weeks of treatment, the animals presented with increased BP, cardiac hypertrophy, renal dysfunction, increased BP variability, and severe aortic stiffening characterized by arterial remodeling. This severe hypertensive model presented similar features with both very old SHRs  and inteThis first model experienced a significant degree of morbidity; thus it seemed prudent to increase the duration and decrease the concentration of L-NAME administration to improve animal outcomes and to better evaluate its structural and mechanical effects on aorta. In the present study we reduced the dose of L-NAME and increased the duration of the treatment to five weeks. As in the short protocol, we obtained comparable increases in BP and BP variability in conscious rats. We observed end organ damage and increased heart weight  in the SHR compared to WKY and a further increase with L-NAME treatment. Proteinuria and the protein/creatinine ratio were significantly increased in SHRLN, indicating renal dysfunction.These parameters allowed us to conclude that the five-week protocol is relevant for further studies on the role of NO reduction in vascular pathology and will be useful for both investigating the development of structural versus dynamic changes in the aorta and investigating the effects of therapeutic treatments on vascular stiffness.Among the characteristics of the SHRLN model, BPV presents two further interests. First, the significant increase in BPV confirms the increase of intrinsic stiffness found in SHRLN as discussed below. Indeed, while several mechanisms may account for the BPV, the ability of the aorta to effectively buffer the pulsatile cardiac output is certainly a key component in regulating fluctuations in BP .Second, despite correlated systolic and diastolic BP elevation, systolic but not diastolic BPV was parallelly increased throughout the duration of the treatment leading to a strong increase in PP variability. A similar pattern was observed in the short protocol and seems specific to this animal model , possiblThe primary objective of this study was to, for the first time in this model, investigate the mechanostructural relationship of both the AA and TA in the same rats. We observed that the TA presented pressure-dependent stiffening, therefore disappearing when BP matched that of normotensive rats, in contrast to AA which presented both a pressure-independent and a remodeling-dependent stiffening; this is to say that arterial stiffness remained increased under normotensive isobaric conditions. This was shown via the usual parameters of compliance, distensibility and stiffness index measured at maximal systolic PP and distension. These findings are demonstrated in  in vivo difference in arterial stiffness between the two sites in SHRSP-salt was elastin disarray which was observed only in the AA. In contrast to the salt model we did not observe elastin disarray in AA in the present study but a greater increase in collagen in both sites as previously observed [We recently compared AA and TA in a different model of hypertensive rats treated with a high salt diet  and obseobserved .α5-integrin, and focal adhesions (FAK) were also present in SHRLN in the AA and TA. Nevertheless, we observed a strong specific accumulation in the AA of SHRLN which may help to account for the increase in isobaric stiffness. These findings indicate that these fibrotic tissues begin to have a major impact on intrinsic arterial stiffness when a threshold of total fibrosis is reached. Indeed, fibronectin and collagen densities in the TA of SHRLN were close to the values of AA in SHR (As in the salt model, accumulation of fibronectin, A in SHR  and not Fibrosis is generally considered as a major factor of remodeling and stiffening . The con in vivo values, at two different BP levels, with ex vivo measures and cannot be matched in vivo between aortic sites or groups. In our last publication we nevertheless calculated wall stress values but this did not offer any additional conclusions. The major interest of our technical approach is to evaluate the dynamic properties of a precise segment of vessel in living animals and we have demonstrated the relevance of using an acute decrease in BP to obtain isobaric parameters in different groups of animals in order to differentiate the effect of the operating pressure on the vascular wall and the long-term structural remodeling [Several points regarding our methodology should be addressed although they have been largely discussed in our previous publication . First tmodeling .The thoracic site used between the diaphragm and the renal artery is often included in the abdominal aorta despite having diameter and compliance properties different from those of the abdominal infrarenal aorta. This site could have been alternatively named as the suprarenal aorta and our AA site the infrarenal aorta. The diaphragm is the limit between the thorax and the abdomen and by the way is often shown in anatomic schemes, as the limit between TA and AA but there no evidence that it is the functional and structural aortic limit. The difference between TA and AA embryologic development has not been related to the diaphragm. In human the length of the suprarenal but infradiaphragm is consistent and mainly called as superior abdominal aorta or suprarenal aorta; however a reduced vasa-vasorum, high incidence of aortic aneurysms, and reduced elastin level are described specifically for the infrarenal aorta . PrevaleIn conclusion, the data presented give evidence that NO reduction, in addition to hypertension, induces fibrosis which reaches a high level in the abdominal aorta leading to a remodeling-dependent arterial stiffening.


Blood pressure and perfusion of the brain are central components of neurological health that are often influenced by heart failure. This retrospective case-control study analyzed blood pressure changes preceding the diagnosis of dementia in patients over the age of 60. Blood pressures were obtained from the date of dementia diagnosis, and then one year and five years before diagnosis. Study “controls” were age-matched patients without dementia, using the mean age of dementia diagnosis as the first data point. Over the five-year period preceding diagnosis, 67.2% with dementia showed decreasing systolic pressure compared to 46.6% of patients without dementia. Similarly, 62.7% with dementia showed a decreasing systolic pressure over the one-year period, compared to 50.0% of those without dementia. Additionally, there was a significant difference (p < 0.001) in the dementia rates between African American and Caucasian subgroups (55.0% African Americans vs. 31.0% Caucasians). Patients with dementia were more likely to have decreasing blood pressure trends than age-matched patients without dementia and appeared to have significantly lower blood pressures one year before the diagnosis. It is crucial that providers are cognizant of these trends and risk factors for dementia as they manage blood pressures in geriatric patients.


Finally, the multivariate logistic regression revealed that only five variables significantly contributed to the model, including: lifetime history of psychotic symptoms (the variable that contributed the most to the model), followed by the Hamilton Depression total score, and cognitive performance . (4) Conclusions: treatments to ensure a good functional outcome in BD should specially prevent psychosis, target subthreshold depressive symptoms and enhance cognition, more specifically executive functions and verbal memory. (1) Background: bipolar disorder (BD) is a chronic disease that often leads to functional impairment. The objective of this study is to elucidate which variables are associated with better functional outcomes in a sample of euthymic patients with BD. (2) Methods: patients were recruited at the Hospital Clinic of Barcelona and they underwent a clinical interview, a functional assessment, and a comprehensive neuropsychological evaluation. After that, patients were divided into two groups according to the Functioning Assessment Short Test total score: functionally remitted vs. functionally impaired. Following this, a multivariate logistic regression was run in order to identify clinical, demographic and cognitive factors associated with functional remission. (3) Results: a total of 420 euthymic patients with BD were assessed for this study, distributed as follows: functionally remitted ( Bipolar disorder (BD) is a lifelong illness that often results in functional impairment ,2. CliniParticipants with BD were recruited at the Bipolar Disorders and Depression Unit from the Hospital Clinic of Barcelona. This hospital-based program provides integrated care for difficult-to-treat patients with BD from across Catalonia, as well as care to patients with BD from a specific catchment area in Barcelona ,10. The This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and Good Clinical Practice and the study protocol was approved by the ethics committee of the Hospital Clinic. All participants received extensive information on the study and provided written informed consent prior to enrolment.After providing written informed consent, all participants went through a structured clinical interview of the Program’s protocol based on the Structured Clinical Interview for DSM-IV-TR . VariablAfter collecting these data, patients were assessed with several clinical scales: first, the HAM-D and the YMRS were administered to ensure that patients met criteria for euthymia at the time of the assessment. Psychosocial functioning was assessed by means of the FAST . As explParticipants were assessed using a comprehensive neuropsychological battery. This assessment involved different tests described as follows: estimated IQ was evaluated with the Wechsler Adult Intelligence Scale (WAIS-III) , vocabult tests for continuous variables. These analyses included demographic, clinical and neuropsychological variables. The raw scores from the neurocognitive variables were converted into z-scores for a better comparison in the different tests applied. Since there is no control group, z scores were performed taking into account the mean and the standard deviation of the whole sample of patients with BD. The first step of these analyses was to calculate the total global score of the FAST for each participant in the study. After that, they were classified as functionally remitted (whenever the score was twenty or below) or as functionally impaired (when the participant scored twenty-one or above). Then, descriptive analyses of the two groups were performed using Chi-square tests for categorical variables and Student p < 0.05 in the univariate analysis was met . Data were analyzed using SPSS v.23 for Windows . All analyses were two-tailed with alpha set at p < 0.05. After the descriptive analyses, the multivariate logistic regression model was performed. Logistic regression was used to estimate the effects of the risk factors associated with functional impairment. Variables were selected for inclusion in logistic regression when significance at n = 221) vs. the functionally impaired group (n = 199). As shown in A total of 420 participants were recruited for this study. According to the severity criteria they were classified in the functionally remitted group  and SCWT interference , where patients in both groups performed similarly. In general, the neuropsychological performance of the patients in the functionally impaired group was significantly lower compared to those with no functional impairment, except for two variables: the CVLT delay free recall  in demographic and clinical variables see  and in tR-squared) of the variance in functional impairment. The model correctly classified 77.5% of the cases. As shown in p < 0.01; OR = 1.48), lifetime psychotic symptoms , working memory IQ , Wisconsin Card Sorting Test (WCST) number of categories  and CVLT short cued recall . After running the logistic regression with all these variables, it was found that the final model included only five significant variables explaining between 35.6% (Cox and Snell R square) and 47.6%  and in verbal memory  are less likely to achieve functional recovery.Lifetime psychosis appears as the most determinant variable in the model. In the present study, patients with lifetime psychosis symptoms were less likely to achieve a good functional outcome when compared to patients who had not experienced these symptoms. Psychosis occurs frequently in BD, approximately between 60–90% of patients have a lifetime history of psychotic symptoms ,24, whicAnother clinical significant variable contributing to the model includes subthreshold depressive symptoms, which is probably the most consistently reported variable across literature as a key factor that influences functional outcome ,51,52,53In relation to the neuropsychological performance, a total of three variables were found to significantly contribute to the logistic regression: two variables related with executive functions (working memory IQ and WCST number of categories) and another one related with verbal memory . In BD, neurocognitive impairment can appear practically in all cognitive domains and in a large proportion of patients with effect sizes ranging from small to medium effects ; moreoveThe lack of consistency across different studies when reporting which neurocognitive variables influence functional outcome could be in part attributed to the tools used to evaluate both neurocognitive performance and functional outcome. In this regard, the standardization of the tools to assess these different features of BD is urgently needed. In 2010, Yatham and colleagues already proposed a preliminary battery of cognitive tests to be used in research. Among the recommended tests, they included the CVLT to assess verbal learning and memory, or the use of the SCWT and WCST to assess executive functions . More reOf note is that in the present study no demographic variable has been linked with functional recovery. Gender and age were significantly different between the two groups in the univariate analysis and in line with previous literature male gender and older age were associated with poorer functional outcome ; howeverThe results derived from the present study should be interpreted with caution in light of several limitations. First, the cross-sectional nature of the study does not allow establishing causal relationships between the independent and dependent variables. In contrast, and to the best of our knowledge, this is one of the largest studies assessing a broad range of variables that could influence functional outcome in a sample of euthymic patients with BD and the present results might be taken into account to design future studies and interventions. Another limitation is that pharmacotherapy was not controlled for; hence, treatment effects on cognition and functioning have not been studied. Third, the evaluators who performed the functional assessment were blind to the neuropsychological outcome for the vast majority of patients comprising this sample; unfortunately, we cannot ensure that this condition was accomplished for all the participants assessed in this study. Finally, it is worth mentioning that the FAST scale is not a performance-based tool, like the UPSA-B. Instead, the FAST could be classified as a semi-objective scale since it is interviewer-administered and the scores are partially based on patients’ reports but also takes into account relevant information about psychosocial functioning reported by relatives, the clinician and/or clinical reports .Despite these limitations, we might conclude that long-term therapeutic interventions to enhance psychosocial functioning should focus on two targets: the clinical course and the preservation of cognition. As regards to the clinical course, avoiding psychotic symptoms appears to be the most important factor to prevent functional decline. Given that these symptoms occur during mood episodes, it might be suggested that the prevention of relapses is crucial to guarantee good functional outcomes. Lithium, together with specific adjunctive psychological treatments such as psychoeducation appear to be the most effective strategy to prevent relapses and ensure good functional outcomes ,41,42. A


In addition, weight, waist circumference (WC), and blood pressure (BP) were measured. Diet and Wellness Plus was used to compute participant diet records. Regression analysis and a recursive decision tree were made to predict MetS using RStudio (V.1.1.463). BP decision tree predicted high risk of elevated blood pressure with a recall rate of 93.7%. For males; exercise, empty calories, dairy, and protein were main predictors. For females, vegetable and empty calorie consumption were primary determinants. HDL-C decision tree had a recall rate of 91.8% and showed that the main low HDL-C risk determinants for males were; exercise and grain consumption. Conversely, for females; empty calories, grain, and vegetable consumption were the key factors determining low HDL-C risk. This study shows that MyPlate recommendations are valuable to achieve adequate HDL-C and blood pressure and provides insight into the importance of tailoring food intake guidance based on gender.MyPlate is a guidance system for healthier eating choices. In this cross-sectional study, we investigated the influence of MyPlate food group consumption and exercise on metabolic syndrome (MetS) parameters in college students. Participant ( Metabolic syndrome (MetS) is a co-occurrence of factors that are associated with increased risk for chronic disease. According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria the presence of three or more of the following parameters is indicative of MetS: high waist circumference, elevated serum triglycerides, reduced high-density lipoprotein cholesterol, elevated fasting blood glucose, and hypertension . The meaIt is estimated by the National Health and Nutrition Examination Survey (NHANES), that in 2006, approximately 25.0% of the United States adult population had MetS [Short term complications of MetS can include atherosclerosis, insulin resistance, kidney disease, etc. . The proMyPlate is an online dietary recommendation platform to promote healthy eating and reduce the risk of diet-related diseases. It is published by the USDA Center for Nutrition Policy and Promotion and is a widely used tool by registered dietitian nutritionist to provide nutrition advice . This toPrevious studies have shown that men and women have distinctly different food preferences. In general, women tend to prefer fiber-rich food groups (vegetables and fruit), and high-calorie food items more than men do, while men are more inclined to consume high fat and high protein food groups ,13,14. PThe main purpose of this study was to identify food group(s) that are most determinant in the development of metabolic syndrome that are specific for gender. Furthermore, we aimed to create a model that predicts the statistical likeliness of metabolic syndrome based on such factors, establishing a framework to promote more gender-specific recommendations.This cross-sectional study (IRB# 16-ED-062) includes tests and records gathered from Weber State University students, collected between 2015 and 2018. Participants were part of an introductory nutrition course and volunteered to take part in the study. Among the 462 subjects, the study included 153 men and 309 women. Sample age ranged from 18 to 65 years, with the average age being 24 years. A two-day diet record was submitted by each participant. Subjects also participated in anthropometric and blood testing to gather measurements for MetS parameters. Parameter measurements for height, weight, waist circumference (WC), BMI, blood pressure, blood glucose, serum triglycerides, and HDL-cholesterol were collected and used for data analysis. All tests were collected in Weber State’s Human Biochemistry Laboratory.2). Blood pressure was measured using an automatic digital sphygmomanometer on the left arm at the beginning of the examination, and again after 5–10 min of seated rest to ensure accurate results. Both systolic and diastolic BP were recorded in standard units of mmHg.To the nearest centimeter, height was measured with a standardized stadiometer while the participant was facing straight forward, with good posture, and no shoes on. Weight was recorded at the nearest 0.1 kg, using a weight beam scale. Both height and weight measurements were used in the Quetelet index equation to calculate body mass index  using a one-use finger stick needle and a capillary assay tube. The finger stick procedure was completed by a standard approved protocol. The tip of the finger was held under warm water for 10–15 s to promote enhanced blood circulation. The finger was then disinfected with an alcohol wipe, dried with a lint-free cotton pad, and pricked with a finger stick. A total of 40 µg of blood was collected from each participant. The blood was placed into a Lipid Profile Alere Cholestech LDX cassette. Total cholesterol, HDL-C, TG, and blood glucose were measured by a whole blood enzymatic spectrophotometric method, using an Alere Cholestech LDX machine. Plasma LDL-C was estimated using Friedewald equation on the basis that TG > 400 mg/dL.After each blood sample was collected, the excess blood was absorbed into a separate cotton pad. All used gloves, wipes, and pads were placed into a secure biohazard trash receptacle. Used needles were placed into a closed sharps container for further disposal.Analyses were performed with the R-studio program for statistical computing and graphics © 2009–2018 RStudio (V.1.1.463), Inc. . The packages: “naniar” (V. 0.4.2), “caret” (V.6.0-84), “leaps” (V.3.0), “rpart”(V. 4.1-15), “rattle” (V.5.2.0), “rpart.plot”(V. 3.0.8), “RColorBrewer” (V.1.1-2), and “plyr” (V. 1.8.4) were used in the statistical analysis including the creation of the decision trees. NCEP ATP III MetS criteria was used to categorize participants meeting MetS parameters. The data set was split into a training and testing data set with 70% of the data set used for training and 30% for testing. The validity of the models are created with training and evaluated on testing data sets using 10-fold cross-validation.Statistical decision trees were created to predict MetS parameters. Missing data for any of the variables resulted in the observation being dropped from the data set. The decision trees were pruned to both prevent statistical overfitting and to allow for the decision tree to provide more practical recommendations to individuals. The average precision, recall, and accuracy were calculated from the 10-fold cross-validation on the testing data set. The accuracy of the model refers to the probability that the decision tree makes a correct prediction. The error of the model refers to the probability that the decision tree makes an incorrect decision. The recall of the model refers to the ability of the decision tree to make a positive diagnosis among individuals who suffer from the symptom. The precision of the model is the likelihood of the decision tree to make a true positive prediction among all positive predictions.Decisions trees work by branching the data into distinct non-overlapping regions. The tree building process is referred to as ‘top down greedy’ because each successive split which consists of choosing a variable and a node leads to the greatest possible reduction in error. These choices are a result of this statistical procedure, and are chosen by this process, not by the researchers. We input the variables of food group consumption, gender, and exercise for the model to obtain these predictions. This analysis provides a visual and hierarchical representation of the most important inputs for prediction. In this way, the decision trees provide different ways to decrease risk of meeting MetS parameters. Each cut point is associated with a probability that can be used for clinical implications based on the sample data. Decision trees have several advantages: when there is a non-linear or complex relationship between the input variables and the response variable decision trees generally outperform linear regression for the given input variables. Decision trees closely mirror human decision making process, and are easier to explain than linear regression.The multiple regression models are restricted to the male population resulting in 135 observations once data with missing variables were removed. We selected our multiple regression models using the best subsets method considering all variables. We evaluated the models on the testing data set using 10-fold cross-validation on the average mean squared error, proportion of variance explained by the model, and mean absolute error. The best regression models were waist circumference and diastolic blood pressure.To analyze the effects of Food Group consumption on MetS parameters, participants were divided by gender. Our sample included 153 males between the ages of 18 and 65 years, with an average age of 23 ± 1.4 years, and 309 females between the ages of 18 and 49 years, with an average age of 25 ± 0.7 years .Approximately 16.7% of the participants met the requirements for MetS . SpecifiResults stratified by gender of exercise, fruit, vegetable, grain, protein, and empty calorie consumption can be found in Approximately 54.3% of the male participants, and 37.9% of the female participants had elevated blood pressure over the MetS indicating threshold of 130/85 mmHg  Table 1Table 1. This decision tree begins predicting whether the participant has elevated blood pressure based on gender, dietary factors, and physical activity levels. The variables used to predict elevated blood pressure were gender, exercise, empty calorie percentage (EmptyP), empty calorie amount (EmptyA), grain calorie percentage (GrainP), grain calorie amount (GrainA), vegetable calorie percentage (VegP), vegetable calorie amount (VegA), fruit calorie percentage (FruitA), fruit calorie amount (FruitP), protein calorie percentage (ProtP), protein calorie amount (ProtA), dairy calorie percentage (DairyP), and dairy calorie amount (DairyA) . Data foIf the participant is male, predictions for the presence of elevated blood pressure can be viewed on the top half of the decision tree in For male participants who exercise more than 2.5 times per week, the tree then further directs its decision calculators on the amount of dairy that the participant consumes each day. If the male exercises more than 2.5 times per day and consumes greater than or equal to 0.9 cups (c) (212 g) of dairy each day, the tree predicts that he has a low risk for elevated blood pressure, with a true prediction rate of 89%. If he consumes less than 0.9 c (212 g) of dairy each day, then the tree is concerned with the amount of dietary protein consumed daily. If males exercise more than 2.5 times per day, consume less than 0.9 c (212 g) of dairy each day, and consume more than 9.8 oz (277 g) of protein each day than it is predicted he has a low risk for elevated blood pressure with a true prediction rate of 80%. However, in the same circumstances, our tree predicts that males do have a high risk for elevated blood pressure if they eat less than 9.8 oz (277 g) of protein per day with a true prediction rate of 90%.For males who exercise less than 2.5 days, the tree queries if the male consumes an empty calorie % ≥ 338%. If the male has levels greater than 338% the tree predicts that he does not have a high risk of elevated blood pressure with a true prediction rate of 100%. If the male has an empty calorie percentage less than 338%, then the tree predicts that he has a high risk of elevated blood pressure, with a true prediction rate of 79%.If the participant is female, predictions for the presence of elevated blood pressure can be viewed on the bottom half of the decision tree in In a 10-fold cross-validation, we found that the predictions about blood pressure, made by the decision tree in Roughly 50.3% of male participants and 43.4% of females participants had low HDL-C, below the threshold of 40 mg/dL for males, and 50 mg/dL for females  Table 1Table 1. The variables used to predict decreased HDL-C were gender, exercise, empty calorie percentage (EmptyP), empty calorie amount (EmptyA), grain calorie percentage (GrainP), grain calorie amount (GrainA), vegetable calorie percentage (VegP), vegetable calorie amount (VegA), fruit calorie percentage (FruitA), fruit calorie amount (FruitP), protein calorie percentage (ProtP), protein calorie amount (ProtA), dairy calorie percentage (DairyP), and dairy calorie amount (DairyA) .The results for the predictions of low HDL-C for males can be viewed on the top section of the tree in If males exercise more than 3 days, the tree then focuses on percentage of the recommended amount of grains consumed. If consumption is greater than 132% of the grain recommendation, then the tree predicts that this male does not have high risk of low HDL-C, with a true prediction rate of 80%. If the male gets less than 132% of his grain recommendation, then the tree predicts that this male will have a high risk of low HDL-C with a true prediction rate of 78%.For female participants, predictions for the presence of low HDL-C can be viewed on the bottom section of the tree in In a 10-fold cross-validation, we found that the predictions regarding HDL-C, made by the decision tree in We modeled waist circumference in males. Our best model was constructed using five variables (Diastolic blood pressure (DBP), triglyceride, glucose, exercise, and empty calorie percentage). Our model is of the form:Predicted Waist Circumference = 15.84 + 0.594 × DBP + 0.041 × Triglyceride + 0.302 × Glucose − 2.096 × Exercise − 0.022 × Empty Calorie Percentage. p = 1.31 × 10−5). A one-unit increase in triglyceride (mg/dL), ceteris paribus, is associated with a 0.041 cm increase in waist circumference (p = 0.000218). A one-unit increase in glucose, ceteris paribus, is associated with a 0.302 cm increase in waist circumference (p = 0.0159). One unit increase in the exercise variable, ceteris paribus, is associated with a 2.096 cm decrease in waist circumference (p = 0.0166). Note that the exercise variable is defined frequency of exercise where 1 = never, 2 = 1–2 days, 3 = 3–4 days, 4 = 5–6 days, 5 = every day. A one-unit increase in the empty calorie % of goal, ceteris paribus, is associated with a 0.022 cm decrease in waist circumference (p = 0.0096).The model had an adjusted R-squared = 0.5833, meaning our five variable model can explain 58.33% of the variation in male waist circumference. According to our model one unit (mmHg) increase in DBP, ceteris paribus, is associated with a 0.594 cm increase in waist circumference . Our model is of the form:Predicted DBP = 44.67 + 0.385* (Waist Circumference) + 0.041* −0.049* − (0.026) ×  + 0.005. p = 2.56 × 10−11). One unit increase in total cholesterol (mg/dL), ceteris paribus, is associated with a 0.041 increase in DBP (p = 0.0181). One unit increase in vegetable % of goal, ceteris paribus, is associated with a 0.049 decrease in DBP (p = 0.0254). A one-unit increase in dairy % of goal, ceteris paribus, is associated with a 0.026 decrease in DBP (p = 0.0386). A one-unit increase in protein % of goal, ceteris paribus, is associated with a 0.005 increase in DBP (p = 0.0214).The model had an adjusted R-squared = 0.5042, meaning our five variable model can explain 50.42% of the variation in male diastolic blood pressure. One cm increase in waist circumference, ceteris paribus, is associated with a 0.385 increase in DBP  was lower, and we found that the practical advice from the tree was not intuitive and harder to follow due to the size/depth of the tree.We studied the effects of exercise, empty calories, vegetables, fruits, grains, dairy, and protein consumption on MetS parameters. Our model suggests that female blood pressure was most affected by vegetable consumption, empty calorie intake, and/or a combination of the two; while male blood pressure seemed more dependent on exercise, dairy consumption, empty calories, protein intake, and/or a combination of these factors. Next, our model proposes that a female’s HDL-C was most influenced by the number of empty calories, grains, and/or vegetables consumed. Alternatively, exercise, grain consumption, and/or a combination of the two, tended to affect male’s HDL-C levels more than other measured factors.Differences in lifestyle and dietary patterns may be responsible for the variance of determinants on MetS parameters between male and female populations. For instance, the consumption of vegetables seems to have a major impact on female blood pressure, however, this does not connote that male blood pressure is unaffected by vegetable consumption . Male blFurthermore, factors affecting HDL-C concentrations also differ between males and females. For example, our decision tree displays that exercise is an important determinant factor of HDL-C status among males but is not represented in the decision tree among the female participants . While pOur model suggests that exercise is an important factor in male blood pressure. The tree predicted that males would not have high blood pressure if they participated in physical activity more than 2.5 times per week, in conjunction with either meeting a specific dairy intake or a specific protein intake. Exercise is associated with a decrease in post-activity systolic blood pressure . SpecifiMales were predicted by our model to have adequate blood pressure if they consumed greater than or equal to 0.9 c (212 g) of dairy each day in combination with exercising at least 2.5 times per week. Several studies have also reported an inverse relationship with dairy consumption and blood pressure ,34,35. TMales who participated in physical activity at least 2.5 times per day, consumed lower than 0.9 c (212 g) of dairy, and consumed more than or equal to 9.8 oz (277 g) of protein per day, were predicted to have adequate blood pressure. Our findings were similar to other conducted research about total protein intake and blood pressure ,38,39,40Our model shows that males that exercise more than 2.5 days a week and consumed more than 328% of empty-calorie recommendations have low risk of having high blood pressure. Our observation contradicts many studies on the effect of empty calories in blood pressure ,24. It iWomen who consumed greater than 22% of their recommended intake, were predicted by our tree to have adequate blood pressure. It is well known that vegetables are typically low in sodium, and rich in potassium. Several studies report that diets high in vegetables, low in sodium, and/or high in potassium protect against hypertension ,46,47. TOur tree predicted that women would have high blood pressure if their vegetable consumption was less than 22% and empty calorie consumption was greater than 788 kcal. Low vegetable consumption could contribute to high blood pressure by reasons previously discussed. Additionally, increased empty calorie intake , may have several consequential effects that could increase one’s blood pressure. First, increased consumption of empty calorie saturated fats is linked to an increased risk of plaque formations and atherosclerosis. An increased presence of arterial fatty plaques may decrease and/or inhibit the bioavailability of nitric oxide. Thus, decreasing nitric oxides vasodilating effects on blood vessels, and increasing blood pressure ,52. FoodOur model predicts that men who do not exercise at least 3 times per week will have low HDL-C. However, when they exercise more than 3 days per week and consume a higher amount of grains, they are predicted to have normal HDL-C. Additional studies have also found that exercise is extremely beneficial in raising HDL-C concentrations ,56. DyslSimilar to female participants who consumed adequate grains, males who consumed greater than 132% of their recommended GrainP, were predicted by our model to have normal HDL-C. High fiber, low glycemic index, low glycemic load grains may be responsible for this finding ,58,59.We observed in our model that females who typically consume more than 443% of their empty calorie recommendation have a decreased risk for low HDL-C. Although there are multiple empty calorie food sources associated with increased HDL-C such as eggs , dairy , and unpFemales who typically consume less than 443% of their empty calorie recommendation, and less than 5.8 oz (164 g) of grains per day, were predicted to have normal HDL-C levels according to our decision tree. Similarly, The American Heart Association advocates increasing HDL-C by incorporating a diet that is low in empty calories such as saturated fat, trans fat, and added sugars, while including adequate grain consumption from mostly whole grain and fiber-rich foods ,58. WhenOur model predicted that females would have normal HDL-C if they consume at least 0.05 c (12 g) Vegetables, in conjunction with getting adequate grains and lower empty calories. A diet high in whole grains and vegetables will be high in soluble fiber. Soluble fiber is known to lower blood lipid levels, and improve total cholesterol to HDL cholesterol levels ,64, whicIt has been observed that elevated waist circumference is linked to an increased prevalence of hypertension, hyperglycemia, and dyslipidemia . This coOur MLR diastolic blood pressure determinants are in accordance with the BP decision tree  previousMetS is growing in younger populations. Prevention at early life stages maybe beneficial to decrease the progression of the symptoms. It was observed that many individual parameters have higher rates of prevalence even in this younger population, Our decision tree analysis showed that the MyPlate food guidance system is a useful tool to prevent low HDL-C prevalence and high blood pressure. Nonetheless, food recommendations seem to be more valuable when stratified by gender. This is unlikely to be due to the different effect of food in male and female physiology but rather on the food preferences by gender. Our study provides insight into the importance of tailoring recommendations to food items that are likely to be part of an individual diet rather than foods that are unlikely to be consumed by such individuals. Additionally, this analysis provides practical advice on specific requirements of MyPlate food group consumption to reduce risk of elevated BP, WC, and low HDL-C . We foun


The term “lacunar infarction” referred to small infarctions in the basal ganglia, internal capsule, thalamus, and brainstem, due to hypertensive small vessel disease. However, it has become common to refer to all small infarctions as lacunar. It is important to understand that true lacunes occur in a phylogenetically ancient part of the brain, the “vascular centrencephalon”, where short straight arteries with few branches transmit high blood pressure straight through to end-arterioles. The cortex is supplied by long arteries with many branches, so there is a very large blood pressure gradient in the brain. When blood pressure in the brachial artery is 117/75 mmHg, the pressure in the lenticulostriate artery would be 113/73, and the pressure in small parietal arterioles would be only 59/38 mmHg. Recent studies have reported that patients with a pulse pressure >60 mmHg and diastolic pressure <60 mmHg have a doubling of coronary risk and a 5.85-fold increase in stroke risk. This means that new low systolic targets being proposed will probably decrease the incidence of true lacunes, but increase small subcortical infarctions in the hemispheres. The pathogenesis of small vessel disease should be interpreted in the light of these blood pressure gradients. There is a widespread tendency to assume that small vessel disease in the brain  is one single condition, but it is apparent that there are several different kinds of small vessel diseases. The purpose of this review is to focus on an aspect of small vessel disease that is seldom considered: Blood pressure gradients in the brain. Apart from vasculitis and rare conditions such as Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), it appears likely that there are at least three different kinds of small vessel disease, found in different regions of the brain: Deep/hypertensive, lobar/hypotensive, and periventricular/venous.It is clear that a stroke is a major contributor to dementia. This is particularly the case for the kinds of strokes associated with small vessel disease. The association goes in both directions: Strokes aggravate dementia, and amyloid (which is associated with Alzheimer disease) aggravates strokes.In the Nun Study , a prospWhen C. Miller Fisher initially described the lacunar syndromes in relation to hypertensive small vessel disease ,5,6, theThat region of the brain was named by Hachinski the “Vascular Centrencephalon” ; the phySince the advent of magnetic resonance imaging  it has become clear that small white matter intensities are highly predictive of cognitive decline. It has become increasingly common to refer to all small infarctions  as “lacunar”, but this mis-nomerization has led to confusion about the pathogenesis of small vessel disease. This is important because it may confuse efforts in the prevention of dementia via the prevention of stroke. It is clear that treating hypertension is one way to prevent/delay dementia; this is no doubt due to the prevention of hypertensive small vessel disease. Recent guidelines have recommended lowering the definition of hypertension to a systolic pressure <130 mmHg; however, with even lower blood pressure targets such as 120 mmHg being contemplated in the wake of the Systolic Pressure Intervention Trial (SPRINT),  there isThe human cortex is perfused by long arteries with many branches, resulting in a marked decrease in blood pressure between the vascular centrencephalon and the small arterioles perfusing subcortical regions over the convexity. Blood pressure drops as flow is divided among branches, so at the distal end of the long arteries with many branches, blood pressure is much lower than in the parent artery. Blanco et al.  calculatThere is a particular sub-group of patients who would be at risk from a systolic blood pressure target of 120 mmHg: Those with stiff arteries, causing a wide pulse pressure. Two important papers have shown a marked diastolic J curve in patients with a pulse pressure >60 mmHg and a diastolic pressure <60 mmHg. McEvoy et al.  reported> 60 with diastolic blood pressures >100 mmHg, but no hypertensive end-organ disease, half had a cuff blood pressure in the brachial artery, that was >30 mmHg higher than the intra-arterial pressure measured in the distal brachial artery. This happens because the cuff must squeeze harder to collapse stiff arteries. Osler commented on this, and Messerli studied the Osler Maneuver  in relation to cuff artefact. In 1985 our group reported that patients with stiff arteries, identified by a high pulse-wave velocity, were more likely to have a large cuff artefact [Spence reported in 1978  that amoartefact . Thus paThe problem will be aggravated by beta-blockers and perhaps diltiazem, because bradycardia results in an increased stroke volume, which widens pulse pressure in patients with stiff arteries. The distribution of deep versus lobar white matter intensities (WMI), and their relationship to hypertension and pulse pressure, are illustrated in a paper from the group of Warlaw in Edinburgh . SymptomA special form of this problem occurs with CADASIL, with “impaired vascular reactivity in sub-cortical vessels, in part due to arterial changes of thickened hyalinized walls, smooth muscle degeneration, and accumulation of granular osmiophilic material (GOM). This “earthen pipe” state of vessels impairs auto-regulation, with dependence on systemic blood pressure for perfusion of sub-cortical regions.” Chronic hypo-perfusion can accelerate cognitive decline in patients with CADASIL.  Acute hyPatients with longstanding hypertension have a thickening of their cerebral arterioles, due to hypertrophy of the muscle layer, the result of constricting against higher pressure. They therefore, have a shift of their cerebral blood flow auto-regulation to higher pressures, so they are more likely to have strokes if blood pressure is suddenly dropped, for example with such therapies as “sub-lingual” nifedipine, or intra-muscular hydralazine . Figure. The othA further complication in the understanding of small vessel disease, is that white matter intensities in the periventricular region, are probably due, not to arterial or arteriolar disease, but to venous disease. A close association has been observed between venous collagenosis and periventricular leukoaraiosis, both in Alzheimer disease and in elderly patients ,26. It iResearch is needed to assess differences among small vessels leading to small infarctions in the vascular centrencephalon, periventricular regions, and in lobar regions . Histological analyses with staining for amyloid, inflammatory markers, chemokines, and cytokines would be of interest. It would also be interesting to carry out imaging of amyloid and tau with positron emission tomography (PET),  and PET Besides rare forms of small vessel disease such as vasculitits and CADASIL, there are probably three main forms of small vessel disease, that might be classified as deep/hypertensive, lobar/hypotensive, and periventricular/venous.In considering the pathogenesis of cerebral small vessel disease, it is important to understand the very large pressure gradients in the brain. Understanding these differences should improve strategies for the prevention of cognitive decline by preventing stroke.


The ratio of arterial oxygen partial pressure to inspired oxygen fraction (P/F ratio), systolic and diastolic echocardiographic parameters were measured at 20 min after the first, second, and third PEEP. P/F ratio at PEEP_5 was significantly higher compared to PEEP_0 (p = 0.014), whereas the P/F ratio at PEEP_10 did not show significant differences compared to PEEP_0 or PEEP_5. Left ventricular ejection fraction (LV EF) and right ventricular fractional area change (RV FAC) at PEEP_10  were significantly lower compared to PEEP_0 or PEEP_5. RV E/E’ (p = 0.048) and RV myocardial performance index (p < 0.001) at PEEP_10 were significantly higher than those at PEEP_0 or PEEP_5. In conclusion, increasing PEEP to 10 cmH2O decreased biventricular function, especially on RV function, with no further improvement on oxygenation compared to PEEP 5 cmH2O during OLV.Although the application of positive end-expiratory pressure (PEEP) can alter cardiopulmonary physiology during one-lung ventilation (OLV), these changes have not been clearly elucidated. This study assessed the effects of different levels of PEEP on biventricular function, as well as pulmonary oxygenation during OLV. Thirty-six lung cancer patients received one PEEP combination of six sequences, consisting of 0 (PEEP_0), 5 (PEEP_5), and 10 cmH One-lung ventilation (OLV), which is essential in thoracic surgery, induces ventilation/perfusion ratio (V/Q) mismatch by increasing intra-pulmonary shunts and dead space . Histori2O improved pulmonary oxygenation during OLV [2O can restrict venous return and elevate right ventricular (RV) afterload, leading to limited left ventricular (LV) diastolic filling and decreased cardiac output [Application of positive-end expiratory pressure (PEEP) is an important factor in optimal OLV strategy, and several studies have investigated the amounts of PEEP that are beneficial during OLV. A recent study showed that an “individualized” PEEP level measuring around 10 cmHring OLV . Howeverc output .No existing prospective study has yet evaluated the effect of PEEP on pulmonary oxygenation and biventricular function simultaneously during OLV. The primary purpose of this study was to compare the effects of different levels of PEEP on pulmonary oxygenation and biventricular function in patients undergoing thoracic surgery under OLV.clinicaltrials.gov (NCT02483806). This study was approved by the institutional review board of Yonsei University Health System (IRB # 4-2015-0325) in Seoul, South Korea, and written informed consent was obtained from all patients before participating in the study. The trial was registered prior to patient enrollment at For this study, we enrolled lung cancer patients who were scheduled for single lobe lobectomy with video-assisted thoracoscopic surgery (VATS) from September 2015 to April 2016. The inclusion criteria were patients aged from 40 to 80 years and patients with American Society of Anesthesiologists physical status classification score of II–III. The exclusion criteria were patients with any kind of arrhythmia; New York Heart Association functional classification of III–IV; end-stage liver or kidney diseases; esophageal varices; and those who had either severe obstructive or restrictive lung diseases. 2O of pressure for 30 seconds. During the induction period, 5 mL/kg of Hartmann’s solution was given to each patient to minimize preload reduction by PEEP application. No premedication was given to any of the patients. Anesthesia was induced using propofol (1.0–2.0 mg/kg), remifentanil (0.5–1.0 μg/kg), and 0.9 mg/kg of rocuronium. All patients were intubated with left-sided double-lumen tubes , and correct positioning was confirmed using a fiber-optic bronchoscope. Patients’ arterial blood pressure and central venous pressure levels were monitored using standard monitoring devices. A central vein catheter was inserted at the right internal jugular vein. Multiplane transesophageal echocardiography probes  were inserted, and lung alveolar recruitment was performed with maximal 30 cmH−1·min−1 of remifentanil targeted at Bispectral index  between 40 and 60. Autoflow pressure-controlled ventilation mode  was applied to all patients. Ventilation was initiated using a tidal volume of 6 mL/kg of the predicted body weight with 1:2 inspiratory-to-expiratory ratio, an inspired oxygen fraction (FiO2) of 0.6, and 5 cmH2O of PEEP. All patients had an initial PEEP level of 5 cmH2O during TLV. Respiratory rate was adjusted to maintain an end-tidal carbon dioxide (EtCO2) at approximately 40 mmHg. When the patient’s oxygen saturation measured by pulse oximetry decreased to less than 90% during OLV, FiO2 was incrementally increased to 0.8 and 1.0.Anesthesia was maintained with 1.0–2.0 vol % sevoflurane and 0.05–0.1 μg·kg2O, 5 cmH2O, and 10 cmH2O; and the measurements of each PEEP application was designated as PEEP_0, PEEP_5, and PEEP_10, respectively, for statistical analysis. The study had a crossover design with patients randomly assigned to one of six PEEP sequence combinations of 0, 5, and 10 cmH2O. The baseline hemodynamic, echocardiographic, and respiratory variables were measured at 10 min after the recruitment maneuver during TLV in a supine position. The patient was then placed in the lateral decubitus position. When hemodynamic parameters were stabilized, OLV was initiated and variables were measured again at 20 min after the first, second, and third PEEP applications. Since vascular clamping can alter perfusion of the non-dependent lung, patients were excluded if the pulmonary vessel was clamped for lobectomy during the experimental period.PEEP was applied at three different levels of 0 cmH2, EtCO2, ratio of arterial oxygen partial pressure (PaO2) to FiO2 (P/F ratio), peak airway pressure (Ppeak), dynamic compliance, and dead space ventilation . Dynamic compliance was calculated as VT/(Ppeak−PEEP). VD/VT was calculated in accordance to Hardman and Aitkenhead equation [2 and arterial carbon dioxide partial pressure (PaCO2) as VD/VT = 1.14 × (PaCO2−EtCO2)/PaCO2−0.005.Arterial blood gas analyses were performed at every experimental step, and the respiratory variables included FiOequation  using thHemodynamic variables obtained were the heart rate, mean arterial pressure, and central venous pressure. The echocardiographic assessment was conducted by a single anesthesiologist blinded to the experimental conditions using a single echocardiography system  from mid-esophageal four-chamber view at the end of expiration. This assessment included the measurement of LV ejection fraction (LV EF), RV fractional area change (RV FAC), peak early diastolic velocities of septal mitral annulus and lateral tricuspid annulus , late diastolic velocities of MV and TV , peak systolic velocities (MV S′ and TV S′), and tricuspid annular plane systolic excursion (TAPSE). Peak early diastolic transvalvular inflow velocities (E) of MV and TV were also measured to calculate E/E′ for both ventricles. To measure the overall biventricular function, myocardial performance index (MPI) was obtained for the left ventricle and right ventricle from tissue Doppler indices of the mitral valve (MV) and tricuspid valve (TV) using the following formula: MPI = (isovolumic contraction time + isovolumic relaxation time)/ejection time . p value < 0.05 was considered statistically significant.Based on the results from previous studies ,9 and taOf the 40 patients who were screened for the study, four were excluded; therefore, data were collected and analyzed from 36 patients . VATS lo2 values (p = 0.015) and P/F ratios (p = 0.014) were significantly different between PEEP_0 and PEEP_5, whereas there was no difference between PEEP_0 and PEEP_10  or between PEEP_5 and PEEP_10  (p < 0.001), whereas there was no statistical difference in VD/VT among the three groups (PaO> 0.999) . There we groups .p < 0.001, FAC; p = 0.001, respectively) and PEEP_5  (p = 0.044). The results of TAPSE were comparable among the different PEEP levels.Hemodynamic variables and tissue Doppler echocardiographic parameters measured at different PEEP levels during OLV are shown in ctively) . There wp < 0.001) and PEEP_5   was significantly higher than those for PEEP_0  .The ICCs for the agreement of echocardiographic parameters are given in 2O of PEEP, cardiac function changed at 10 cmH2O of PEEP in both systolic and diastolic phases of left and right ventricles. There was a decreasing trend in biventricular diastolic function as PEEP increased, which was represented by the E/E’ value of both ventricles. The overall RV function decreased when PEEP was increased from 0 to 10 cmH2O, which was represented by MPI. However, pulmonary oxygenation was not different between 5 and 10 cmH2O levels of PEEP, indicating that higher PEEP level was not advantageous.The study evaluated the effects of different PEEP levels on pulmonary oxygenation and biventricular function under OLV. Compared to 5 cmHGeneral anesthesia with positive pressure ventilation impairs pulmonary gas exchange and respiratory mechanics, even in patients with healthy lungs . Such ef2O, preserved oxygenation and lung mechanics better than consistent 5 cmH2O of PEEP during OLV. Several clinical studies on thoracic surgery [2O to improve oxygenation during OLV after performing alveolar recruitment. However, other studies showed that 5 cmH2O of PEEP with a tidal volume of 6 mL/kg is enough to provide adequate gas exchange [2O in healthy lungs did not improve oxygenation compared to that with 5 cmH2O [2O of PEEP had no beneficial effect compared to 5 cmH2O of PEEP in terms of pulmonary oxygenation.There are many conflicting results regarding the effect of PEEP on oxygenation improvement during OLV ,18,19. R surgery ,21 and r surgery  have repexchange , improveexchange , and allexchange . A study 5 cmH2O . PEEP wa2O of PEEP was applied. Increasing levels of PEEP impairs biventricular function [2O of PEEP was associated with decreased preload, as well as reduced compliance of both ventricles, which was considered to contribute to the changes in diastolic ventricular filling [2O of PEEP was found to exacerbate LV diastolic relaxation abnormality during TLV in patients with pre-existing diastolic dysfunction [2O was applied to patients with acute respiratory distress syndrome (ARDS) in the intensive care unit. In OLV, increased right-ventricular afterload augmented by increased airway pressures may provide deleterious increases in shunt fraction and decrease in cardiac output and right-ventricular function [2O PEEP despite improved dynamic compliance. Moreover, the increase in mean alveolar pressure might explain the redistribution of blood flow from the over-distended dependent lung to the non-dependent lung, via increased pulmonary vascular resistance [Although the application of PEEP may lead to a reduction in LV afterload, it does not necessarily increase cardiac output, due to the predominant adverse effect on LV filling . Rather,function ,26, main filling . Even 5 function . In addifunction . Schmittfunction . This desistance .2O [The indices of tissue Doppler echocardiography are reliable and valuable parameters for estimating intra-operative cardiac functions . It is r2O , althoug2 could have been more appropriate in comparing the effect of different PEEP on pulmonary oxygenation. Indeed, there is a variation in the P/F ratio with the change of FiO2 [The present study had several limitations. First, we neither returned PEEP to baseline (zero PEEP) nor performed a recruitment procedure during the application of experimental PEEP. Nevertheless, a crossover design involving the cyclical application of different PEEP levels was used to offset the blind spot in this study, and no parameter was influenced by previous PEEP application after statistical verification. Furthermore, considering that hypoxic pulmonary vasoconstriction was settled within 10 m after initiating OLV , changes of FiO2 . However of FiO2 , but als of FiO2 . Fourth,2O of PEEP augmented oxygenation during OLV without altering biventricular function. However, increasing PEEP to 10 cmH2O decreased cardiac function, especially on RV function, without further enhancing pulmonary oxygenation. Based on these findings, physicians should note that there may not be any advantage to applying 10 cmH2O of PEEP over 5 cmH2O of PEEP during OLV.In conclusion, the results of this study demonstrated that applying 5 cmH