The correlation analysis between anthropometric, hematologic and hemodynamic variables in patients with PE indicated that erythrocytes with lower volumes and lower levels of hemoglobin favor the occurrence of a better gestational outcome, because they are more stable and because they are associated with a decrease in the hemodynamic changes present in the disease. This should mean that the tendency to microcytosis, probably due to a mechanism of compensatory mechanical selection, is a desirable characteristic in the disease.The objective of this study was to analyze the relationships of osmotic and mechanical stability of erythrocytes with anthropometric, biochemical, hematologic and hemodynamic variables in pregnant women with preeclampsia (PE). The studied population consisted of 20 normotensive patients and 16 patients with PE. Patients with PE presented worse gestational outcome, greater hematologic impairment, erythrocytes osmotically more stable  Pre-eclampsia (PE) is a complex systemic syndrome that occurs after the 20th week of gestation  and is cThe hemodynamic profile of the Central Nervous System in pregnant women can be observed by Dopplervelocimetric analysis of the ophthalmic artery . The orbPreeclampsia (PE) is described as a hyperdynamic disease associated with diffuse endothelial lesion –15. The The erythrocytes, the most abundant cells in the bloodstream, suffer greatly from the effects of PE. The disease is associated with important changes in the erythrocyte morphology , with eaFor the good performance of its functions, the erythrocyte must remain intact. The red blood cell's ability to maintain the physical and chemical integrity of its membrane in adverse situations is called stability ,21. In tAlthough the evaluation of osmotic stability of the erythrocyte membrane is well established in the literature ,24, the The mechanical stability of erythrocytes also deserves attention –28, espeThe objective of this study was to analyze the osmotic and mechanical stability of erythrocytes and to relate stability variables to anthropometric, biochemical, hematologic and hemodynamic variables in women with preeclampsia, in order to better understand the mechanisms associated with this syndrome.The cross-sectional study presented here was previously approved by the Research Ethics Committee of the Federal University of Uberlândia and registered under number CAAE 23236614.4.000.5152. All study participants signed a Free and Informed Consent Form.This study included 36 women in the third trimester of pregnancy admitted to the Clinical Hospital of the Federal University of Uberlândia between December 2014 and June 2017. Patients without clinical and obstetric intercurrences, and without signs of labor, were included in the control or normotensive group (n = 20). Sixteen patients diagnosed with preeclampsia were included in the study group.The diagnosis of pre-eclampsia was defined according to the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy .All pregnant women included in the study made supplementation of 5 mg/day of folic acid, during the first trimester of gestation, and 200 mg/day of ferrous sulfate, a dose equivalent to 40 mg of elemental iron per day, for primary prevention of anemia caused by iron deficiency.Pregnant women with thyroid diseases, erythrocytopathies, chronic hypertension, autoimmune diseases, diabetes, kidney diseases and current use of anticonvulsants, antidepressants, tobacco, alcohol and/or drugs of abuse, and patients with gestations associated with congenital infections , twinning, fetal malformation and natimortality were excluded from the study. Patients who were on magnesium sulfate and antihypertensive drugs, except methyldopa, at the time of hospital admission were excluded from the study.3EDTA  and in one tube without anticoagulant .Blood samples (4 mL) were collected by intravenous puncture in an antecubital fossa vein, preferably from the median antecubital vein or the median cephalic vein, directly in two tubes  containing Kg  for 10 minutes. Supernatants from all tubes were removed and analyzed at 540 nm (A540) on a UV-VIS spectrophotometer  to estimate the amount of hemoglobin released in the erythrocytes lysis.A duplicate series of test mini-tubes containing 1 mL of 0.1–1.5 g/dL NaCl solution  was preincubated for 10 minutes in a thermostated bath at 37°C . After adding 20 μL of whole blood, the tubes were homogenized and again incubated at 37°C for 30 minutes. The tubes were then centrifuged at 1500 x 540 as a function of the NaCl (X) concentration were adjusted by sigmoidal nonlinear regression, according to the Boltzmann equation:max and Amin represent respectively the maximum and minimum plateaus of A540, H50 is the concentration of NaCl capable of promoting 50% hemolysis and dX represents one-fourth of the variation in NaCl concentration responsible for promoting 100% hemolysis [0, which is the saline concentration required to initiate in vitro hemolysis, and can be calculated by the formula H0 = H50 + 4dX/2. The saline concentration at the point where the in vitro lysis reaches its maximum plateau defines the variable H100, which represents the saline concentration necessary to promote total lysis of the red blood cells, being calculated by the formula H100 = H50-4dX/2 [The graphs of Aemolysis ,24. The 50-4dX/2 .g for 10 minutes in a Hitachi Koki centrifuge , the supernatants were subjected to absorbance readings at 540 nm (A540) on a UV-VIS spectrophotometer  for estimation of the amount of hemoglobin released in the mechanical lysis of erythrocytes.Volumes of 15 mL of the suspension consisting of the mixture of 250 μL of whole blood and 49.75 mL of 0.9 g/dL NaCl solution were inserted into the equipment analysis cell and subjected to mechanical aggression promoted by a propeller under 8000 rpm for 6 minutes at room temperature. Every 30 seconds of stirring, duplicated aliquots of 1 mL suspension were removed and added to minitubes. After centrifugation at 1600 x 540 (A) versus time (t) was adjusted to the hyperbola given by Michaelis-Menten equation [mmax is the maximum plateau of A540, which represents the maximum amount of hemoglobin released in the lysis of the entire erythrocyte population, and t1/2 is the time interval necessary for promotion of 50% lysis of erythrocytes (Ammax/2).The graph of the absorbance at Aequation :A=AmmaxThe Doppler ultrasound of the ophthalmic artery (OA) was performed in Medison  equipment, by a single examiner with over 10 years of experience. The AO was insonated in the medial region of the optic nerve with linear transducer at 7–10 MHz frequency, 50 Hz filter, 5 kHz pulse repetition frequency and 7 mm sample volume . Only onAn automated system  was used to obtain the hematologic parameters: red blood cell (RBC) and platelet (Plt) counts, mean platelet volume (MPV), reticulocytes index (Rtc), hematocrit (Ht), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW).+), potassium (K+), indirect bilirubin (i-B), total bilirubin (t-B), serum iron (Fe) and ferritin (Ferritin).An automated analyzer  was used to determine the following biochemical parameters: total cholesterol (t-C), triglycerides (TGC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea (U), creatinine (Cn), uric acid (UA), human serum albumin (HSA), sodium  were used to evaluate proteinuria.6 cells/mm3; Hb, 9.5–15.0 g/dL; Ht, 28.0-40.0%; MCV, 81–99 fL; MCH, 29–32 pg/cell; MCHC, 31–36 g%; RDW, 12.7–15.3%; Rtc, 0,5–2%; Plt, 146–429 x 103 cells/mm3; MPV, 8.2–10.4 fL; t-C, 219–349 mg/dL; HDL-C, 48–87 mg/dL; LDL-C, 101–224 mg/dL; VLDL-C, 21–36 mg/dL; TGC, 131–453 mg/dL; U, 3–11 mg/dL; Cn, 0.4–0.9 mg/dL; UA, 3.1–6.3 mg/dL; AST, 4–32 U/L; ALT, 2–25 U/L; Na+, 130–148 mEq/L; K+, 3.3–5.1 mEq/L; LDH, 82–524 U/L; i-B, 0.1–0.5 mg/dL; t-B, < 0.1–1.1 mg/dL; Fe, 30-193 μg/dL; Ferritin, 0–116 ng/mL; HAS, 2.3–4.2 g/dL.Reference values described for the third trimester of gestation  were useCategorical variables were compared with the use of the chi-square test. The normality of the data was evaluated by the Shapiro-Wilk test. The Student's t-test and the Mann-Whitney test were used to compare between groups the results with normal and non-normal distribution, respectively. Most of the variables did not present normal distribution and therefore the Spearman correlation analysis was used to determine the associations between the anthropometric, hemodynamic, hematologic, and biochemical variables in the group of volunteers with preeclampsia. Correlations with values of p <0.05 were considered significant. All analyzes were performed using Origin 8.5  and SPSS 15.0 .Fig 1 shows a typical sigmoid curve obtained in the determination of erythrocyte membrane stability variables. A blood isotonicity condition occurs in the region to the right of the curve, where the value on the ordinate of the lower plateau of the curve defines the variable Amin, which represents the amount of basal hemolysis present in the blood sample of each volunteer in the study. The higher this Amin value, the lower the erythrocyte stability under osmotic conditions similar to those observed in vivo. Therefore, Amin is the osmotic stability variable that most represents the stability of erythrocytes in vivo. Following this curve, from right to left, as it shall be seen, the salt concentration where the lysis begins to occur defines the variable H0. With the decrease in saline concentration, the lysis rate will reach 50% of the maximum lysis at the intermediate point of the curve, whose value in the abscissa defines the variable H50. When the lysis rate reaches its maximum point, which occurs when the curve reaches the upper plateau, the salt concentration where the lysis rate runs out defines the variable H100. The variables H0, H50 and H100 are proportional to the osmotic fragility of the erythrocytes. Therefore, the use of their inverse forms, 1/H0, 1/H50 and 1/H100 is that it effectively represents the osmotic stability of those cells. The ordinate value of the upper sigmoid plateau defines the variable Amax, which represents the maximum possible rate of lysis of the erythrocytes of the analyzed blood sample and which therefore must show obvious associations with hemoglobin levels, erythrocyte counts and the hematocrit values of the donor of the analyzed blood sample. There is yet another primary variable defined by the mathematical model of statistical fit itself; this variable is dX, which represents a quarter of the variation in saline concentration required to promote 100% hemolysis. dX is effectively a variable of osmotic stability of erythrocytes and, therefore, the dX/H50 and dX/Amin ratios are directly proportional to the erythrocyte membrane stability, since Amin and H50 have inverse relationships with the stability of these cells.Fig 2 shows a mechanical lysis curve of erythrocytes. With increasing time under mechanical stress, erythrocytes undergo lysis and release hemoglobin, resulting in increased absorbance by 540nm. The data fit defines a hyperbolic curve whose upper plateau defines the Ammax variable, which represents the absorbance associated with the amount of hemoglobin released when there is 100% lysis of the erythrocyte population. The curve passes through an intermediate point, whose abscissa value (t1/2) represents the time required to promote 50% hemolysis. The t1/2 variable is directly related to the mechanical stability of erythrocytes.Fig 3 is a schematic representation of the variation in blood flow velocity in the ophthalmic artery (OA) as a function of the duration time of a cardiac cycle. At each ejection of blood from the left ventricle (systole), a pulse pressure occurs which is represented by a rapid upward curve, generating the Systolic Velocity Peak (PSV), which is followed by sudden drop and a secondary elevation of velocity, generating a second systolic peak (P2) and a notch (aortic notch) before the end of the systolic cycle. As the vascular diameter returns to normal, the accumulated energy provides a potential necessary to promote continuous flow during diastole, which is represented in the graph by a new rise in velocity that is followed by slow deceleration, ending in the peak that characterizes the end-diastolic velocity (EDV).mean), as well as the Pulsatility Index (PI), given by (PSV-EDV)/Vmean, the Resistance Index (IR), given by (PSV-EDV)/PSV, and the Peak Ratio (PR), given by P2/PSV. In pre-eclampsia, there is a specific alteration in the morphology of the wave, which acquires the shape of hump, due to the increase in amplitude and rounding of P2, indicating the presence of hyperflow in orbital territory. The elevation of PR and P2 also indicates hyperflow in orbital territory. In contrast, the decrease in IP and IR represents an increase in the flow velocity at that site [The interpretation of the graphical representation of the OA Doppler occurs by analysis of 1) the shape of the pulse velocity wave (PWV), 2) the velocity peaks and 3) the average velocity of a cardiac cycle  is a heterogeneous disorder that has an important impact on the maternal and fetal organism ,35. In tNormal erythrocytes have a typical biconcave disk shape. This cell geometry provides a larger membrane surface area per cytoplasmic volume, which provides greater deformability in small vessels and maintenance of their physicochemical integrity . Therefoin vivo. It is possible that the osmotic stability test may be useful in characterizing the onset and progression of preeclampsia. The involvement of Amin in one of these erythrocyte stability indices and the fact that the Amin value was lower in the group of pregnant women with PE  Doppler velocimetry allowed to observe the hyperflow in orbital territory in the group of patients with PE, which supports findings reported in other studies ,8. Hypermmax, absorbance at 540 nm associated with the mechanical lysis of the whole population of RBC, and the hemodynamic variable P2, second peak of systolic velocity Click here for additional data file.


To investigate the genetic contribution of adenosine A3 receptor (ADORA3) gene polymorphisms in the pathogenesis of chronic heart failure (CHF). Firstly, a case-control study was performed to investigate the association of ADORA3 polymorphisms with CHF risk. Three hundred northern Chinese Han CHF patients and 400 ethnicity-matched healthy controls were included. Four polymorphisms were genotyped. This case-control study was also replicated in 304 CHF patients and 402 controls from southern China. Finally, the functional variability of positive polymorphism was analyzed using luciferase reporter assay and real-time PCR.P = 0.046, OR = 1.662, 95% CI = 1.009–2.738). But it did not affect disease severity. These results were also consistent in replicated population. In addition, the transcriptional activity for promoter with the A allele was lower than that with the G allele  and ADORA3 mRNA levels were significantly higher in GG homozygotes than subjects carrying GA  or AA genotypes . Overall, the rs1544223 was significantly associated with CHF risk under the dominant model ( Should the findings be validated by further studies with larger patient samples and in different ethnicities, they may provide novel insight into the pathogenesis of CHF. Chronic heart failure (CHF) has a high prevalence in older individuals and is a major cause of morbidity, mortality, hospitalizations, and disability . DespiteNumerous physiological processes are modulated by adenosine (Ado), which is an endogenous and cardioprotective nucleoside , 6. Ther1, A2A, A2B, and A3. Some studies have demonstrated the role of the Ado A3 receptor (ADORA3) on the heart. It is thought that ADORA3 signaling protects cardiomyocytes against the damage caused by ischemia via short-term preservation by ATP, as well as protecting them from contractile dysfunction and energy depletion by normalizing intracellular Ca2+. This cardioprotective effect has been observed after induced ischemia in experimental mouse and rabbit animal models [ ADORA3 activation also induces myocardial cells apoptosis [ ADORA3 mRNA expression in the left ventricle of failing minipig hearts was significantly higher than that in control healthy minipig hearts [Ado mediates its various cardiovascular actions via four known receptor subtypes: Al models –17, and l models . Ashton l models . In addipoptosis . Del et g hearts . ADORA3 is an important factor that affects the cardioprotective properties of Ado. The activity of ADORA3 in vivo could be affected by gene polymorphisms. It is thus reasonable to hypothesize that single nucleotide polymorphisms (SNPs) in the gene encoding ADORA3 influence its activity and further affect CHF susceptibility and progress—to the best of our knowledge this issue has not been investigated previously. This hypothesis was tested by establishing the relationship between certain tag-SNPs of ADORA3 and susceptibility to CHF among a Chinese Han population and demonstrating the functional contribution of genetic polymorphisms of the ADORA3 gene, to provide insights into the prevention and individualized treatment of CHF.The activity ofChinese CHF patients (age > 18 years old) were recruited from the First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University (between 2013 and 2014), and the Kunming General Hospital of Chengdu Military Region (from 2012 to 2014). The inclusion criterion was diagnosis of heart failure according to the Guidelines for Diagnosis and Treatment of Heart Failure in China (2013). The cause of heart failure was determined in each patient by clinical assessment and echocardiography. The patient exclusion criteria included the following: presence of severe hepatic or renal insufficiency, tumors or malignant disease, acute attack of CHF, severe acute infection, metabolic disorders, and acute myocardial infarction (MI) without revascularization within 2 weeks. All sample collection was completed according to strict inclusion criteria by two visiting staffs and were reviewed by the Chief Physician of Cardiology. Ultimately, 300 patients from Xi'an and 304 patients from Kunming were eligible for inclusion in this study.The control group comprised sex- and ethnicity-matched healthy volunteers from the Medical Examination Center of the same hospital (age > 18 years) who had no known personal or family history of cardiovascular disease. A detailed interview was used to obtain information about personal and familial history in the framework of a physical examination by expert physicians to identify symptom-free subjects and to exclude those who were suspected of having any form of vascular disease. Finally, 400 controls from Xi'an and 402 controls from Kunming were included in this study.Demographic and clinical characteristics  were obtained from interviewer-administered health-risk questionnaires. The subjects were considered to have hypertension according to the Guidelines for Prevention and Treatment of Hypertension in China (2013) or if they were taking antihypertensive drugs. Dyslipidemia was defined according to the Guidelines on Prevention and Treatment of Blood Lipid Abnormality in Chinese Adults (2007), and diabetes was defined in agreement with the Guidelines for Prevention and Treatment of Diabetes in China (2013). Information regarding smoking status was self-reported. Individuals were designated “smokers” if they have reported that they had smoked at least five cigarettes daily for at least the past 12 months . ADORA3 according to Chinese Han population data from HapMap (http://www.hapmap.org), and one SNP (rs35511654) that was yielded by literature searched were selected for the present study. Sequenom MassARRAY Assay Design 3.0 Software was used to design Multiplexed SNP MassEXTEND assay [The blood samples were collected into tubes containing ethylenediaminetetraacetic acid. After centrifugation, the samples were stored at −80°C until analysis. The standard phenol–chloroform extraction method was used to extract genomic DNA from whole blood. DNA concentration was measured by spectrometry . Three tag-SNPs , which captured the majority of known common variations ofND assay . SNP genND assay . renilla (Promega) luciferase vector as a normalization control. We constructed HEK293T cells (5 × 105 per Petri dish) which were cotransfected with 1.8 μg pGM-Lu-SNP (firefly luciferase) and 0.2 μg pRL-TK (renilla luciferase) (Promega) plasmid using 5 μl Lipofectamine™ 2000. After transfection, cells were lysed 72 h in 250 μl 1x Passive Lysis Buffer and luciferase activity was measured with fluorescence microscope (Olympus) according to Dual Luciferase Reporter Gene Assay Kit (Promega). Relative luciferase activity of ADORA3 reporter constructs was calculated as the ratio of firefly luciferase activity to renilla luciferase. Reporter assays shown were the average of three parallel test results.The rs1544223 allelic differences in promoter activity in the human HEK293T line were confirmed using the pGM-Lu vector. Cells were transfected with these reporter constructs and with pRL-TKBlood samples were collected by Mr. Wang, the director of Medical Examination Center, from 107 healthy volunteers. The rs1544223 genotypes of these samples were performed with the method mentioned above. β-actin was used as an internal control.Total RNA was extracted from blood samples using blood total RNA extraction kit (Biotek). After genotyping, the total RNAs were grouped, and every group contained a GG genotype, an AG-genotype, and an AA genotype samples randomly to avoid the instrumental and artificial errors. Real-time PCR was performed for every group according to the PrimeScript™ RT Master Mix  (TaKaRa) and SYBR Premix Ex Taq II (TaKaRa). The primer sequences and product lengths are listed in Supplementary The study protocol was drawn up in compliance with the principles of the Helsinki Accord and was reviewed and approved by the local Ethical Committee for both Xi'an and Kunming populations. Statement of informed consent was obtained from all participants after a full explanation of the procedure.χ2-test, which was also used to assess differences in genotype and allele frequencies between study groups. Logistic regression analyses with dominant, recessive, and additive genetic models and allele contrast were used to assess the associations between ADORA3 SNPs and CHF.SPSS 18.0 for Windows  was used for statistical analyses. Deviation of genotype distributions from the Hardy-Weinberg equilibrium (HWE) was checked for using the χ2-test.Differences in parameters related to the severity of CHF, such as left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD), were evaluated among patients stratified according to the three different genotypes by analysis of variance, and significant differences among pairs of means were tested using Dunnett's test. Differences in genotype distribution and allele frequency for the significant SNP according to functional New York Heart Association (NYHA) class were also analyzed by t-test. Additionally, Dunnett's test was used to determine the differences of ADORA3 mRNA expression among the three genotype individuals, with wild type population as the reference group. The cutoff for statistical significance was set at P < 0.05 (two-sided).Differences in luciferase activity of allelic reporter constructs were assessed by Student's P < 0.05). The main etiologies of CHF are coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (ICDM). Most of CHF patients show poor cardiac function with low LVEF value.P < 0.01) except dyslipidemia. The main etiologies of CHF are still CAD and ICDM, and the cardiac function and LVEF for most of CHF patients are poor.In the Kunming replication population, cases and controls were of similar age and sex ratio. The prevalence of all traditional cardiovascular risk factors was significantly higher in CHF patients in comparison with that observed in the control group  and their associations with the risk of chronic heart failure under different statistical models were shown in supplementary Tables We then performed a meta-analysis to integrate data of the two populations. The results were shown in Then, the genotype distributions of rs1544223 were explored in relation to different CHF clinical subsets. In the Xi'an population, there was no difference in genotype distribution and allele frequency for the rs1544223 SNP according to functional NYHA class. Similarly, there was no difference in genotype distribution and allele frequency for this SNP between subsets of CHF patients . In addiIn the Kunming population, the similar results were found. Rs1544223 was not associated with the clinicopathological parameters of CHF patients  or AA genotypes  influenced the individual's predisposition for heart failure, indirectly verifying that fact.CHF is associated with increased systemic (plasma) and reduced local  Ado levels and the final biological action of Ado in a particular organ or cell population may depend upon the relative degree of expression and signaling efficiency of individual Ado receptor subtypes. The main cardioprotective role has been allocated to the most-studied Ado receptors. For example, pathway , 27–30. [ ADORA3 . One stuytokines . In addi effects . Auchampocardium . MoreoveMRS 1191 , 33. YosMRS 1191 . Thus, APromoter regions containing different allele showed different transcript activity, and the mRNA level of ADORA3 among the three genotypes also showed statistical differences. All of these suggested that rs1544223 might affect the gene expression level by influencing the promoter activity. Actually, rs1544223 was located in the 5′untranslated region (5′UTR) of the A DORA3 gene. The regulation of mRNA translation initiation in eukaryotic cells is achieved mainly through a highly structured 5′UTR , 36. In  ADORA3 enhances cardioprotection with no adverse effects, but a six fold overexpression in mice could result in dilated cardiomyopathy [ ADORA3 is expressed in the heart at a very low level. Hence, this receptor is either very efficiently coupled to the signaling pathways protecting the heart or its cardioprotective effects are also induced by activation of the ADORA3 in cells outside cardiac tissues [ ADORA3 is highly complex, and they have yet to be fully elucidated. Further related studies are needed.The role of rs1544223 on ADORA3 expression may exert some effect on the cardioprotection of this receptor. Studies in murine models have revealed that slight overexpression ofmyopathy . Jacobso tissues . All of  ADORA3 in rheumatoid synovial tissue, and the influence of methotrexate (MTX) exposure on this expression. They also investigated whether polymorphisms within ADORA3 were associated with response and/or adverse effects associated with MTX. They found no association between the rs1544224 SNP and the disease activity or MTX-associated adverse effects in rheumatoid arthritis. Furthermore, since rs1544223 was found to be in incomplete linkage disequilibrium with rs1544224, there was also no association between rs1544223 and either the disease activity or MTX-associated adverse effects in rheumatoid arthritis [The roles of rs1544223 in other diseases have been explored in many studies. Campbell et al. evaluated its effect on autism spectrum disorder, but did not find any significant associations . Stamp erthritis . In addiAnother widely studied SNP of the ADORA3 gene was rs35511654, which changes isoleucine to leucine at position 248 of the receptor; this amino acid is located in the sixth transmembrane domain of the receptor. It has been shown that nearby amino acids are involved in the recognition of agonists and antagonists as well as signal transduction and receptor activation . One stu ADORA3 locus on disease severity, as no difference in allele frequency or genotype distribution was observed according to NYHA class, LVEF, LVEDD, and LVESD. These data possibly strengthen the observation that the ADORA3 locus could be involved in protection against CHF, but not in its progression. In addition, the associations between ADORA3 SNPs and hypertension CHF, dyslipidemia CHF, diabetes CHF, or smoking habit CHF were not found, which suggested that ADORA3 activity might not affect hypertension, dyslipidemia, diabetes, or smoking habit phenotypes.This is the first demonstration of rs1544223 being associated with susceptibility to CHF. This susceptibility suggests that genotype testing is important for identifying carriers of the risk genotypes that would increase their susceptibility to CHF. Any such people identified will be able to take the necessary protective measures, which are particularly important in those with traditional cardiovascular risk factors. The present findings did not demonstrate an influence of theSubstantial differences in geographical conditions and dietary habits exist between those residing in northern and southern China. In this study, we collected data on both northern Chinese population and southern Chinese population, reducing the bias from region or population. The main limitation of this study is that we only studied the role of rs1544223 on gene expression, and its deep function mechanism, such as its effect on transcription factors and microRNA combination, needed to be explored further.This preliminary study has revealed an association between the ADORA3 gene and CHF thus provides new insights for investigating the contribution of Ado to heart function. The findings of the present study are intriguing because of their novelty. Nevertheless, because of the limited sample size, further studies performed in larger populations are required to better define the role of the rs1544223 SNP in influencing not only CHF susceptibility but also the severity of the disease.


Three-dimensional color flow Doppler (3DCF) is a new convenient technique for cardiac output (CO) measurement. However, to date, no one has evaluated the accuracy of 3DCF echocardiography for CO measurement after cardiac surgery. Therefore, this single-center, prospective study was designed to evaluate the reliability of three-dimensional color flow and two-dimensional pulse wave Doppler (2D-PWD) transthoracic echocardiography for estimating cardiac output after cardiac surgery.Post-cardiac surgical patients with a good acoustic window and a low dose or no dose of vasoactive drugs (norepinephrine < 0.05 μg/kg/min) were enrolled for CO estimation. Three different methods  were used to estimate CO before and after interventions .A total of 20 patients were enrolled in this study, and 59 pairs of CO measurements were collected (one pair was not included because of increasing drainage after the dobutamine test). Pearson’s coefficients were 0.260 between the CO-FT/V and CO-PWD measurements and 0.729 between the CO-FT/V and CO-3DCF measurements. Bland-Altman analysis showed the bias between the absolute values of CO-FT/V and CO-PWD measurements was − 0.6 L/min with limits of agreement between − 3.3 L/min and 2.2 L/min, with a percentage error (PE) of 61.3%. The bias between CO-FT/V and CO-3DCF was − 0.14 L/min with limits of agreement between − 1.42 L /min and 1.14 L/min, with a PE of 29.9%. Four-quadrant plot analysis showed the concordance rate between ΔCO-PWD and ΔCO-3FT/V was 93.3%.In a comparison with the FT/V system, 3DCF transthoracic echocardiography could accurately estimate CO in post-cardiac surgical patients, and the two methods could be considered interchangeable. Although 2D-PWD echocardiography was not as accurate as the 3D technique, its ability to track directional changes was reliable. Hemodynamic optimization has been shown to improve postoperative outcomes for moderate- and high-risk patients  and for Echocardiography is a noninvasive, convenient platform for measuring CO.  It is veThis study was approved by the Ethics Committee of Zhongshan Hospital , which is affiliated with Fudan University (No. B2017–139). Informed consent was obtained from all study participants.This single center, prospective study was conducted in adult cardiac surgical patients at the Zhongshan Hospital of Fudan University from 1 May to 31 May, 2018. In our hospital, all cardiac surgical patients were routinely transferred to the cardiac surgical intensive care unit with tracheal intubation after surgery. After admission, research personnel screened all patients for enrollment. The inclusion criteria were: 1) cardiac surgical patient; 2) good acoustic window; and 3) low dose or no dose of vasoactive drugs. The exclusion criteria were: 1) age < 18 and > 80 years; 2) aortic valve disease; 3) arrhythmias, extrasystole included; and 4) preoperative ejection fraction < 0.4.2O; respiratory rate: 12–16 breaths/minute; fraction of inspired oxygen 50–100%. These parameters were adjusted to meet the goal of PaCO2 ≤ 45 mmHg and oxygen saturation (SaO2) > 96%. Both the dose of sedatives and the parameters of ventilation were unchanged in the duration of this study.Enrolled patients were sedated via propofol and remifentanil for the duration of CO measurements. No inspiratory efforts were observed and no muscular blocking agents were used in this study. Patients were ventilated using intermittent positive pressure ventilation. The ventilatory parameters were set up as follows: tidal volume: 6–8 mL/kg predicted body weight; positive end-expiratory pressure: 5 cmHAfter the intensivists and echocardiography experts confirmed the enrollment, the FloTrac pressure transducer was connected to the radial artery catheter of each patient and the Vigileo™ monitor (third version). 2D images were acquired using the Siemens Acuson SC2000™ Prime ultrasound system with a 4V1c transducer (1.25–4.5 MHz), as shown in Fig. 3D color flow Doppler images were acquired using the Siemens Acuson SC2000™ Prime ultrasound system with a 4Z1c (1.5–3.5 MHz) volume imaging transducer, as shown in Fig. The echocardiograph experts were blinded to the hemodynamic variables recorded by the FloTrac/Vigileo™ system (these were collected by the intensivist). Systolic, diastolic, and mean arterial pressures and HR were recorded by the real-time bedside monitor. Central venous pressure was recorded through the jugular vein catheter.2, HCO3−, pO2, lactate, and hemoglobulin); (5) preoperative echocardiographic parameters (left ventricular ejection fraction [LVEF]); and (6) hemodynamic data at baseline , after volume loading  and after dobutamine testing . The hemodynamic data collected in this study included: HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), central venous pressure (CVP), cardiac index (CI), stroke volume (SV), stroke volume variation (SVV), and CO. (7) echocardiography related data at different time points: CO, SV, VTI and LVEF.The following data were recorded for each patient: (1) baseline demographic data ; (2) patient’s degree of disease severity ; (3) type of surgery ; (4) blood gas parameters before enrollment  were each compared with that from FloTrac using a correlation analysis and by calculating Pearson’s coefficient, expressed as the r value. Agreements of CO measured by the different methods were determined by Bland-Altman analysis, with assessment of the bias as the mean difference between methods. The limits of agreement (LoA) were calculated as the mean ± 1.96 SD from the bias, defining the range in which 95% of the values were expected to fall [p value < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS 22.0 software , GraphPad Prism 5.0, and MedCalc 15.6.1.0 software .Normality was assessed using the Kolmogorov-Smirnov test for all data. Continuous variables are given as means ± SD while categorical variables are reported as adjusted proportions. Comparisons of hemodynamic variables (continuous variables) between different time points were performed by paired Student’s  to fall . The per to fall . Trendin to fall . For all2. The mean APACHE II score was 7 ± 2, while the mean EuroSCORE was 4 ± 2. The mean LVEF before surgery was 61% ± 10%. The most common surgical treatment in this study was mitral/tricuspid valve surgery ; other surgical treatments included coronary artery bypass graft , resection of a cardiac tumor , and repair of an atrial septal defect . All patients were in sinus rhythm and had no severe metabolic abnormalities that had an influence on blood pressure or hemorrhage after surgery.Demographic and clinical characteristics were summarized in Table Hemodynamic parameters at different time points were summarized in Table n = 59), Pearson’s coefficients were 0.260 between CO-FT/V and CO-PWD and 0.729 between CO-FT/V and CO-3DCF. Bland-Altman analysis showed the bias between the absolute values of CO-FT/V and CO-PWD was − 0.6 L/min with limits of agreement between − 3.3 L/min and 2.2 L/min, with a PE of 61.3%. The bias between CO-FT/V and CO-3DCF was − 0.14 L/min with limits of agreement between − 1.42 L /min and 1.14 L/min, with a PE of 29.9%. The comparisons between CO-FT/V and CO-PWD, CO-FT/V and CO-3DCF are summarized in Fig. Considering all pairs of measurements performed in this study , 30 pairs exhibited a more than 15% change. The concordance rate between ΔCO-PWD and ΔCO-3DCF was 93.3%.The results of the four quadrant-plot analysis are shown in Fig. In this prospective study evaluating the reliability of CO measured by 3DCF and 2D-PWD transthoracic echocardiography in post-cardiac surgical, hemodynamically stable patients, we found that CO values measured by 3DCF echocardiography and FT/V could be considered interchangeable with a PE of 29.9%. Although the precision of 2D-PWD echocardiography in measuring CO was not as good as that of the 3DCF technique, its ability to track changes in CO in different clinical settings was reliable. To the best of our knowledge, this is the first study to evaluate the accuracy of the 3DCF technique in measuring CO after cardiac surgery.Hemodynamic instability is very common in the early period after cardiac surgery, either because of preoperative status or intraoperative events such as cardiopulmonary bypass , 21. TodIn this study, the comparison between the absolute values of CO-FT/V and CO-PWD showed a low bias, but with an unacceptably high LoA and PE (61.3%). This may be due to the inherent limitations of the pulse wave Doppler technique , 25. FirThe percentage error between CO-3DCF and CO-FT/V was 29.9%, which meant that the two methods could be used interchangeably according to Critchley et al.  CO was sThere were several limitations of this study. First, its sample size was small, and patients were enrolled because of their good acoustic windows. But not all post-cardiac surgical patients have good acoustic windows, which limits the usefulness of the conclusions in post-cardiac surgical patients. Second, we used a FloTrac/Vigileo™ (third generation) system as the reference method, not the gold standard thermodilution method. Although the patients enrolled were all in good condition and CO measured by the FT/V technique should be accurate in these patients as discussed before, there might still be some discrepancy from the true values. Third, the patients enrolled in this study only represented a subset of ICU patients after cardiac surgery, whether the 3D echocardiography technique adopted would have the same accuracy in all cardiac surgical patients needs further confirmation. Last, this was a single-center study and is subject to intrinsic limitations; a further multicenter study is needed to confirm our findings.3DCF transthoracic echocardiography could accurately estimate CO in post-cardiac surgical patients compared with a FT/V system; the two methods could be considered interchangeable. Although 2D-PWD echocardiography was not as accurate as the 3DCF technique, its ability to track directional changes was reliable.


Changes to the retinal vasculature are known to be associated with hypertension independently of traditional risk factors. We investigated whether measurements of retinal vascular calibre from ultra-widefield fundus imaging were associated with hypertensive status.We retrospectively collected and semiautomatically measured ultra-widefield retinal fundus images from a subset of participants enrolled in an ongoing population study of ageing, categorised as normotensive or hypertensive according to thresholds on systolic/diastolic blood pressure (140/90 mm Hg) measured in a clinical setting. Vascular calibre in the peripheral retina was measured to calculate the nasal–annular arteriole:venule ratio (NA-AVR), a novel combined parameter.Left and right eyes were analysed from 440 participants , including 151 (34.3%) categorised as hypertensive. Arterioles were thinner and the NA-AVR was smaller in people with hypertension. The area under the receiver operating characteristic curve of NA-AVR for hypertensive status was 0.73 (95% CI 0.68 to 0.78) using measurements from left eyes, while for right eyes, it was 0.64 (95% CI 0.59 to 0.70), representing evidence of a statistically significant difference between the eyes (p=0.020).Semiautomated measurements of NA-AVR in ultra-widefield fundus imaging were associated with hypertension. With further development, this may help screen people attending routine eye health check-ups for high blood pressure. These individuals may then follow a care pathway for suspected hypertension. Our results showed differences between left and right eyes, highlighting the importance of investigating both eyes of a patient. Changes to the retinal vasculature are associated with hypertension independently of traditional risk factors.Semiautomated measurements of nasal–annular arteriole:venule ratio in ultra-widefield fundus imaging were associated with hypertension.Our results also showed differences between left and right eyes, highlighting the importance of investigating both eyes in a given patient.With further development, this tool may help screen people attending routine eye health check-ups for high blood pressure. These individuals may then follow a care pathway for suspected hypertension. This could bring health benefits to the individual and economic benefits to society.Hypertension is a common, generally asymptomatic condition that is a leading risk factor of death and disability worldwide.An image of the retina taken by a fundus camera or a scanning laser ophthalmoscope reveals a detailed view of the body’s microcirculation through non-invasive examination. Quantitative features derived from the retina, such as measurements of vascular calibre  near the optic disc, have been associated with increasing blood pressureAnalyses of the retina have been limited in part by the viewing field of imaging systems. For a 45° fundus camera, this is typically a circular area extending approximately 4 mmIn this study, we assessed measurements of retinal vessels in ultra-widefield imaging for association with hypertension.The Northern Ireland Cohort for the Longitudinal Study of AgeingThe ultra-widefield scanning laser ophthalmoscope generates simultaneous red and green images that are combined to give a pseudo-colour image of the retina . Green lImages and clinical data were extracted from the NICOLA study database. Inclusion criteria were people in the age range of 50–59 years, availability of scanning laser ophthalmoscope images in both eyes and availability of blood pressure readings. All participants who met these criteria at the time of database interrogation were included in the sample. Clinical systolic and diastolic blood pressure were derived from the average of two sitting measurements taken at rest in a quiet place, from the same arm, 1 min apart, using an automatic digital blood pressure monitor (Omron M10-IT) and arm cuff. Hypertension was defined as systolic blood pressure of ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg.The nasal–annular arteriole:venule ratio (NA-AVR) is a novel morphometric parameter which extends the conventional definition of arteriole:venule ratioThe optic disc location, its approximate outline and the fovea location were manually annotated by a trained operator . These landmarks were used to establish the zone of measurement as an annular segment subtending 180° nasal to the optic disc and fixed on a line passing through the centre of the fovea and optic disc. It extended from 6.5 to 8.5 optic disc radii from the optic disc centre . If the Next, automatic segmentation of the retinal vessels was performed using a validated computer algorithm described elsewhere.The retinal vessels detected in the zone of measurement were overlaid on the original image. The operator modified the detected vasculature to correct for false-positive and false-negative detections and labelled each vessel segment as arteriole or venule according to their appearance and connectivity.The calibre (in microns) for each vessel segment in the measurement zone was estimated as the average distance between parallel splines automatically fitted to the detected vessel edges.Finally, NA-AVR was calculated as the ratio of the average calibre of the three widest arterioles and the average of the three widest venules. Fewer arteriole and venule segments were used when less than three were available.Intraobserver measurement repeatability for NA-AVR was assessed for the left and right eyes in a random subset (n=46) of the study cohort. Each operator interaction (above-mentioned steps 1 and 3) was repeated to generate a second set of NA-AVR measurements. To mitigate potential bias in the treatment of left and right eyes, 50% of the eyes chosen for reanalysis were mirrored in the vertical axis to simulate the appearance of the opposing eye. The operator was blinded to previous measurements, and the images were presented in a different order.The operator was blind to all clinical information, such as sex and hypertensive status, during the stages of image measurement to mitigate for observer bias.2, and a paired Student t-test were used to compare measures between eye pairs and in the repeatability analysis. The F-statistic was used to test significance for the relationship of NA-AVR with systolic and diastolic blood pressures. All CIs were evaluated at the 95% level.Two-tailed Student t-tests and the area under the receiver operating characteristic curve (AUC) were used to assess NA-AVR as a predictor for hypertensive status. Pearson’s linear correlation coefficient, RImage processing and statistical analysis were undertaken using MATLAB .In total, 460 participants in the NICOLA study  met the inclusion criteria. Of these, 20 (4.3%) were excluded due to the retina being obscured in the measurement zone, leaving 440 available for analysis. The number of participants categorised as hypertensive from their clinical blood pressure measurements was 151 (34.3%), of which 57 (37.7%) were female.2=0.118, p<0.005) and diastolic  blood pressures.A linear relationship between NA-AVR and blood pressure, both systolic and diastolic, was observed . There w10.1136/openhrt-2019-001124.supp1Supplementary dataNA-AVR was lower in hypertension compared with normotension when stratified by both eye and sex . There w2=0.50 (95% CI 0.43 to 0.57) and 0.31 (95% CI 0.22 to 0.39) for arterioles and venules, respectively. NA-AVR measured in the left eye was smaller than that in the right eye, with a difference of −0.03  was observed between measurements of venular calibre see .10.1136/openhrt-2019-001124.supp2Supplementary dataNA-AVR and arteriolar calibre were reduced in hypertension compared with normotension, and there was a trend of decreasing NA-AVR with increasing systolic and diastolic blood pressures, which is consistent with previous literature.Differences were observed in arteriolar calibre and NA-AVR between left and right eye pairs in both normotension and hypertension. This differs from conclusions drawn in previous studies that measured vascular calibre closer to the optic disc. In the Rotterdam study, a subset of 100 subjects found no differences between eyes for arteriolar or venular calibre,NA-AVR for detection of hypertensive status differed between left and right eye pairs for men but not for women, where lower arteriole:venule ratios were found in men. The disparity between left and right eye performances with sex is a potentially interesting area for a future study. We do not currently know of any physiological reason for this effect.This study had the following limitations. Blood pressure measurements taken in a clinical setting can suffer from the so-called ‘white-coat effect’ (at a rate of 9.4%–24.2%) where elevated measurements are recorded, resulting in overdiagnosis of hypertension, and masked hypertension (8.6%–17.0%) where lower measurements are recorded, resulting in underdiagnosis.The clinical utility of the proposed system might be improved with further automation. For example, automatic arteriole–venule classification could be achieved by machine learning techniques.


The impact of contrast-induced acute kidney injury (CI-AKI) on patients with chronic renal disease is well-known. Remote ischemic preconditioning (RIPC) is a non-invasive method that can reduce the risk of CI-AKI, but studies on RIPC have had different results. The aim of the present study was to assess the potential impact of RIPC on CI-AKI.2) who underwent coronary angiography or angioplasty received adequate hydration. RIPC was performed in 66 patients by applying an upper arm blood pressure cuff. The cuff was inflated four times for 5 min to 50 mmHg above the systolic blood pressure, followed by deflation for 5 min. In the control group, the blood pressure cuff was inflated only to 10 mmHg below the patient’s diastolic blood pressure. The primary endpoint was an increase in serum cystatin C ≥ 10% from baseline to 48–72 h after exposure to the contrast.In a randomized, double blinded, controlled trial, 132 patients with chronic renal dysfunction (glomerular filtration rate < 60 mL/min/mP = 1). In addition, when the results were analyzed based on the Mehran risk score for subgroups of patients, RIPC did not reduce the occurrence of the primary endpoint (P = 0.97).The primary endpoint was achieved in 48 (36.4%) patients (24 in each group). RIPC did not show any significant effect on the occurrence of the primary endpoint .The clinical trial was registered on (Identification number  Diagnostic coronary angiography (CA) and percutaneous coronary intervention (PCI) are routinely performed in patients with coronary artery disease (CAD). Contrast-induced acute kidney injury (CI-AKI) increases mortality and morbidity, and it is one of the most important adverse effects of contrast medium (CM), particularly in patients with pre-existing renal dysfunction , 2. BaseGiven the lack of enough data regarding the protective effects of RIPC in patients at moderate-to-high risk of developing CIN and the different effects of RIPC on serum creatinine and cystatin C levels in various reports, we performed a double-blind, randomized, controlled trial to assess the impact of RIPC after CM administration to protect renal function.http://www.irct.ir/ IRCT2016050222935N2.We performed a prospective, randomized, single-center, double-blinded, sham-controlled trial between December 2016 and August 2017 at Mazandaran Heart Center, Mazandaran University of Medical Sciences, Sari, Iran. All patients gave written informed consent and the study is registered at 2, according to the Modification of Diet in Renal Disease formula  in the control group and 16 [24.2%] in the RIPC group) were readmitted to the hospital  who underwent coronary or peripheral procedures and showed that a cystatin C increase ≥10% compared with baseline was the best cut-off value to identify patients at risk of developing CIN [Excretion of creatinine in urine is the result of glomerular filtration and tubular secretion . Thus, iping CIN . In the Our study’s results are similar to and different from those of previous randomized trials involving RIPC to prevent CIN. First of all, similar to the study by Menting et al.   should be performed to assess the effect of RIPC as an adjunct to hydration to provide additional protection in this high risk group.


In obese patients, high closing capacity and low functional residual capacity increase the risk for expiratory alveolar collapse. Constant expiratory flow, as provided by the new flow-controlled ventilation (FCV) mode, was shown to improve lung recruitment. We hypothesized that lung aeration and respiratory mechanics improve in obese patients during FCV.We compared FCV and volume-controlled (VCV) ventilation in 23 obese patients in a randomized crossover setting. Starting with baseline measurements, ventilation settings were kept identical except for the ventilation mode related differences . Primary endpoint of the study was the change of end-expiratory lung volume compared to baseline ventilation. Secondary endpoints were the change of mean lung volume, respiratory mechanics and hemodynamic variables.p < 0.001, mean lung volume: FCV, − 108.2 ± 198.6 ml; VCV, − 315.8 ± 252.1 ml; p < 0.001) and at comparable plateau pressure , mean tracheal pressure was higher . All other respiratory and hemodynamic variables were comparable between the ventilation modes.The loss of end-expiratory lung volume and mean lung volume compared to baseline was lower during FCV compared to VCV (end-expiratory lung volume: FCV, − 126 ± 207 ml; VCV, − 316 ± 254 ml; Plat and ventilation frequency. The increase in end-expiratory lung volume during FCV was probably caused by the increased mean tracheal pressure which can be attributed to the linearized expiratory pressure decline.This study demonstrates that, compared to VCV, FCV improves regional ventilation distribution of the lung at comparable PEEP, tidal volume, PDRKS00014925. Registered 12 July 2018.German Clinical Trials Register:  In obese patients, the excessive adipose tissue around the thorax and the visceral organs reduce the functional residual capacity and expiratory reserve volume . ObesityAn emerging ventilation technique to linearize expiratory flow is flow-controlled ventilation (FCV), provided by the new ventilator Evone . This device provides a constant positive flow during inspiration and a constant negative flow during expiration. Thereby pressure increases linearly during inspiration [comparable to volume-controlled ventilation (VCV)] and decreases linearly during expiration. Recently, we demonstrated that linearizing the expiratory flow improved lung recruitment, the homogeneity of lung aeration , 7, gas We hypothesized that FCV improves regional ventilation distribution of the lung and respiratory system mechanics in obese patients. Therefore, we compared regional ventilation using electrical impedance tomography (EIT) and respiratory system mechanics during FCV and VCV in obese patients in a randomized controlled crossover trial.The study was approved by the Ethics Committee of the University Medical Center of Freiburg  on 29th March 2018 (Chairperson Prof. Dr. R. Korinthenberg) and registered at the German Register for Clinical Trials (DRKS00014925). Please note that this study adheres to the CONSORT guidelines.− 2. Patients eligible for enrolment were patients with physical status ASA ≤ III undergoing elective bariatric surgery. Exclusion criteria were ASA physical status >III, age < 18 years, pregnancy, emergency procedure, cardiac pacemaker and other active implants, chronic obstructive pulmonary disease classified as GOLD stage > II or refusal to participate. The trial was conducted at the University Medical Center Freiburg, Germany. Participants were enrolled and assigned by a study related anesthesiologist. Data were collected at the University Medical Center of Freiburg, Germany.In order to cope with potential interindividual variability, the study was designed as a randomized controlled interventional crossover trial. After obtaining written informed consent, we studied twenty-three obese patients with body mass index (BMI) ≥ 30 kg∙m2, noninvasive blood pressure measurement; Infinity Delta XL, Dräger Medical, Lübeck, Germany) and a 18–20-G intravenous catheter was established. After preoxygenation to an fraction of expired oxygen of 0.8, anesthesia was induced with 0.3–0.5 μg∙kg− 1 predicted body weight [− 1 actual body weight iv propofol . Tracheal intubation was facilitated with 0.6 mg∙kg− 1 predicted body weight iv rocuronium (Fresenius Kabi). If the patient required a rapid sequence induction, neuromuscular blockage was performed by the administration of 1.0 mg∙kg− 1 predicted body weight iv rocuronium. Neuromuscular blockage was monitored with a mechanomyograph . For tracheal intubation, we used tracheal tubes with low pressure cuffs . After adequate placement of the tracheal tube, iv propofol was administered continuously (110–150 μg∙kg− 1∙min− 1). Potential hypotension  was treated with a continuous infusion of iv noradrenaline (0.03–0.2 μg∙kg− 1∙min− 1). Perioperative volume requirements were addressed with a crystalloid solution . According to our local standard, mechanical ventilation was started as volume-controlled baseline ventilation  with a tidal volume of 7 ml∙kg− 1 predicted body weight, inspiration-to-expiration ratio of 1:2, a positive end-expiratory-pressure (PEEP) of 9 cmH2O and ventilation frequency set to maintain an end-tidal carbon dioxide partial pressure between 4.7 and 5.1 kPa. These ventilation settings were based on our study protocol and in accordance with our clinical routine in obese patients. After 7 min of baseline ventilation, all patients were randomly allocated to one of two crossover groups to receive ventilation sequences either VCV-FCV or FCV-VCV for 7 min per ventilation mode. To avoid irritations due to the surgical procedure , our study was performed prior to the surgical intervention. For adequate allocation, a computer generated randomization in blocks was used. Disclosure of the randomization was requested right after induction of anesthesia. A study related anesthesiologist conducted the randomization in blocks, enrolled participants and assigned participants to the interventions. During the study protocol, ventilation variables were kept constant as set during the baseline measurements. To prevent from the risks of extubation and reintubation, FCV was performed by introducing the narrow-bore tracheal tube  into the standard tracheal tube. Blocking the cuff of the Tritube in the lumen of the tracheal tube provided a sufficient seal. By controlling both tube’s markings, placement of the Tritube’s tip exceeding that of the standard tracheal tube by 2–5 mm was ensured, and the potential risk of bronchial intubation was avoided. Respiratory data were collected from both ventilators via the respective serial communication interface and analyzed offline. Electrical impedance tomography (EIT) was performed with PulmoVista 500  in all patients to measure regional ventilation, changes in relative thoracic electrical impedance during the different ventilation phases, relative end-expiratory lung volume (ΔEELV) and to compare the expiratory decrease in intrapulmonary air [After obtaining written informed consent, 23 patients were included in the study. After primary recruitment and preoperative evaluation, the patients received routine monitoring , mean tracheal pressure (Pmean), mean tracheal pressure during expiration (Pmean expiration), peripheral oxygen saturation (SpO2), fraction of inspired oxygen (FiO2) and quasi-static respiratory system compliance (CRS). To calculate CRS during FCV, the plateau pressure was determined from a short (approximately 0.1 s) end-inspiratory pause. This pause is performed automatically by the Evone ventilator  with every ten breaths and used to calculate CRS. Non-invasively collected hemodynamic variables included mean systolic blood pressure, mean diastolic blood pressure, mean arterial pressure and heart rate. To compare relative intrapulmonary air distribution, baseline tidal impedance curves for ventral and dorsal lung areas were determined and compared as described before [25, ΔEI50, ΔEI75 and ΔEI100), then matched with the correlating decrease in tidal volume and compared successively.ΔEELV was the primary endpoint of this study. EIT recordings were analyzed using software developed in Matlab . We derived ΔEELV from adjusting end-expiratory impedance changes by tidal volume and tidal impedance changes as described before , 11. As d before , 12. ThePressure data from the Evone are based on direct tracheal pressure measurement via a dedicated lumen of the Tritube. To allow for comparability of pressure data from both ventilators and to calculate quasi-static compliance of the respiratory system, airway pressure data from the Dräger Fabius Tiro were generally converted into tracheal pressure data by calculating the flow dependent pressure drop across the respective tracheal tube and pointwise subtracting this value from airway pressure . Thus alThe datasets used and analyzed during the current study are available from the corresponding author on request. Please note that EIT data files require large memory.In regard to previous investigations on gas exchange during FCV in a porcine model of ARDS  and the https://www.jamovi.org). For each measured primary and secondary endpoint (dependent variable), the influence of the ventilation mode  and the ventilation sequence  (factors) was investigated. P < 0.05 was considered statistically significant.Values are presented as mean ± standard deviation, unless indicated otherwise. Statistical analysis was done using Matlab . Linear mixed effects model analyses were performed to check for differences between respiratory variables and variables resulting from EIT measurements during the ventilation phases using R based software (jamovi project (2018), jamovi (Version 0.9.2.3), retrieved from In total, 23 consecutive patients presenting for elective bariatric surgery were included and 19 complete data sets could be recorded. Patients were recruited from 30th July 2018 to 23rd October 2018. One patient had to be excluded due to limited size of the EIT belt, three other patients due to incomplete data collection . ΔMLV between baseline and FCV (− 108 ± 198 ml) was lower than between baseline and VCV   Fig. . Pmean a25, ΔEI50, ΔEI75 and ΔEI100 showed a more even decrease during FCV compared to VCV (Fig. 25 decreases about 45% during baseline ventilation and VCV and 25% during FCV. ΔEI50 showed no differences between the ventilation modes. ΔEI75 and ΔEI100 showed a lower decrease in global thoracic electrical impedance during baseline ventilation and VCV compared to FCV (Fig. FCV was characterized by a more even decay of impedance throughout the expiration phase Fig. . ΔEI25, VCV Fig. . ΔEI25 dFCV Fig. .Fig. 5EIn this study, we compared respiratory system mechanics and regional ventilation in obese patients during short application of FCV and VCV. The main findings of our study are that in obese patients, ΔEELV and mean lung volume decreased less during FCV than during VCV – even with identical respiratory and hemodynamic variables.These effects were comparable to the effects one would expect from a PEEP increase and/or a tidal volume increase. However, minimal and maximal airway pressure and tidal volume remained unchanged. Our results are consistent with and enlarge upon earlier findings on the implications of a linearized expiratory pressure decrease in lung-healthy patients, lung healthy pigs and a porcine lung-injury model –9.We observed the changes of respiratory mechanics during the VCV and FCV phases. Since baseline measurements were performed prior to the following ventilation sequence, we attribute the observed differences between baseline and VCV to the general tendency of the respiratory system to continued derecruitment during mechanical ventilation  which maThe mechanisms behind this recruiting effects may be time dependent: when the lung volume falls below the closing capacity airway closure can occur within the expiration , 23. In Theoretical and clinical observations predict that the linearized decrease in expiratory airway pressure has a beneficial impact on the intrapulmonary inhomogeneity , 17, 24.RS did not differ significantly between the investigated ventilation conditions. Reduced CRS in obese patients may be caused mainly by excess adipose tissue around the chest wall and poor posture caused by thoracic kyphosis and lumbar hyperlordosis, aggravated through excessive abdominal fat tissue [RS only to a minor extent. This hypothesis is supported by earlier investigations that demonstrated that the intratidal recruitment state might differ without affecting CRS [. To investigate potential effects of FCV on the CRS in obese patients, longer application of FCV may be necessary.Ct tissue . Under tting CRS , 27. To 2 elimination. However, in contrast to other centers, placing an arterial line is not part of our standard treatment in this patient group. Therefore, we felt that such invasive approach was not justified for our study. Further, it should be stated that duration of ventilation of 7 min in each ventilation mode is too short to fully evaluate the effects of FCV on regional ventilation. It follows that further studies are required to investigate the long-term effects of FCV on measurements of regional ventilation, respiratory and hemodynamic variables in obese patients.We did not perform arterial blood gas analyses to examine the effects of FCV on gas exchange in our patients. In preclinical  and clinPlat and PEEP, compared to VCV. The recruiting effect caused by the linearized expiratory air flow and the elevated Pmean during FCV may help prevent atelectasis and hypoxemia during mechanical ventilation in obese patients.This is the first study to investigate the influence of FCV on respiratory mechanics and regional ventilation and in obese and morbidly obese patients. Utilizing measurement of regional ventilation, we could demonstrate that the linearized expiratory flow during FCV provided better maintenance of lung aeration with comparable tidal volume, P


Fragmented QRS (fQRS) is a sign of adverse cardiovascular events in variouscardiovascular diseases. It is also associated with increased blood pressureand non-dipping in hypertensive patients. However, no study has investigatedthe importance of fQRS in prehypertensive patients.The aim of our study is to investigate the relationship between fQRS andnon-dipper status in prehypertensive patients.Two hundred and sixteen eligible, newly diagnosed prehypertensive patientswho underwent 24-hour ambulatory blood pressure monitoring (ABPM) forfurther evaluation of blood pressure between June 2015 and July 2016 wereincluded into the study. Patients were divided into three groups accordingto ABPM results: normotensives, dipper prehypertensives, and non-dipperprehypertensives. Groups were compared regarding presence of fQRS onelectrocardiography. Additionally, multinomial logistic regression analysiswas used to determine the relationship between fQRS and blood pressurepattern in prehypertensive patients.According to ABPM recordings, 61 patients had normotensive blood pressurepattern (systolic blood pressure < 120 mmHg and diastolic blood pressure< 80 mmHg). Of the remaining 155 prehypertensive patients, 83 weredippers and 72 were non-dippers. Non-dipper prehypertensives had asignificantly higher frequency of fQRS compared to normotensives (p =0.048). Furthermore, multinomial logistic regression analysis revealed thatfQRS is an independent predictor of non-dipping blood pressure pattern inprehypertensive patients .We found that fQRS is a predictor of non-dipping in prehypertensives. As amarker of fibrosis and higher fibrotic burden within myocardium, fQRS may beuseful in identifying high-risk prehypertensive patients before thedevelopment of hypertension. Because of the difficulties involved in diagnosingprehypertension, the definition of prehypertension remains controversial.Prehypertension is not a benign condition; it indicates future hypertension andadverse cardiovascular events and is generally defined as systolic blood pressure(SBP) of 120-139 mmHg and/or diastolic blood pressure (DBP) of 80-89 mmHg.5-7 It is defined by the presence of notches in the R or S wave intwo contiguous leads in one of the major coronary artery territories without atypical bundle branch block and with a QRS duration of < 120milliseconds.8 Importantly,increased blood pressure is associated with presence of fQRS on ECG.9 Furthermore, non-dipper hypertensivepatients have higher frequency of fQRS on ECG compared to dippers, thus indicatingmyocardial fibrosis and higher fibrotic burden in non-dippers.10,11 However, the importance andusefulness of fQRS in prehypertensive patients is not clear. The present study aimedto investigate the relationship between prehypertensive blood pressure patterns andthe presence of fQRS on ECG to identify the myocardial fibrotic burden and riskassessment of prehypertensive subjects before the development of hypertension.A narrow fragmented QRS complex (fQRS) on electrocardiography (ECG) is a sign ofinhomogeneous and delayed ventricular conduction and is associated with myocardialscarring, fibrosis, and adverse cardiovascular events in various cardiovasculardiseases.14,12 Diabetes mellitus was definedas at least two fasting plasma glucose levels of ≥ 126 mg/dL, two-hourplasma glucose levels of ≥200 mg/dL, or treatment with antidiabeticdrugs, and smoking was defined as the regular use of cigarettes. All patientsunderwent a detailed echocardiographic examination, and LVH was defined based onelectrocardiographic modified Sokolow-Lyon index and/or an increased leftventricular mass index of > 95 g/m2 for women and >115 g/m2 for men, detected by echocardiography.12A total of 283 consecutive patients who were defined as newly diagnosedprehypertensive patients after routine cardiac examination at our outpatientclinic between June 2015 and July 2016 were screened for the study.Prehypertension was defined as SBP of 120-139 mmHg and/or a DBP of 80-89 mmHg inaccordance with the Seventh Report of the Joint National Committee onPrevention, Detection, Evaluation, and Treatment of High Blood Pressure(JNC7).The study protocol complied with the Declaration of Helsinki and was approved bythe local ethics committee.4,12Final diagnoses of blood pressure level and pattern were made based on ABPMrecordings. All measurements were taken with an oscillometric device. The cuffwas placed on the non-dominant arm and automated recordings were obtained every30 minutes during 24-hours. Recordings were made on working days and patientswere encouraged to undertake their normal daily activities. If >20% of theABPM recordings were invalid, the test was repeated. Sleep durations wereevaluated based on the information obtained from the patients, and no patientreported a change in the daily sleeping and waking periods linked to the ABPMdevice. The 24-h mean and the daytime and nighttime blood pressure values werecalculated for each patient from ABPM recordings. Dipper blood pressure patternwas described as more than 10% decline in SBP and DBP at nighttime andnon-dipper pattern was defined as less than 10% decline in SBP and DBP atnighttime.8  version22.0. Continuous variables were expressed as mean ± standarddeviation/median (25-75 percentiles) according to normality and distributioncharacteristics and were compared using one-way ANOVA, independent samplest-test, or Mann-Whitney U-test, according to group number and distributioncharacteristics. Categorical variables were expressed as number and percentage(%) and were compared using the χ2 test or the Fisher exact test.Multinomial logistic regression analysis (using normotensive patients as thereference category) was used to determine the relationship between fQRS andblood pressure pattern in prehypertensive patients. Impact significance wasreported as odds ratio (OR) and corresponding 95% confidence interval (CI). P< 0.05 was considered significant in all statistical analyses.The patients were divided into three groups based on 24-hour ABPM recordings.According to ABPM recordings, 61 patients had a normotensive blood pressure pattern(SBP < 120 mmHg and DBP < 80 mmHg), and we designated these patients as thecontrol group. Of the remaining 155 prehypertensive patients, 83 had dipper bloodpressure pattern and 72 had non-dipper pattern. The mean age of the study populationwas 50.5 years, with 45.8% being female. The frequency of fQRS was 13.9%. The groupswere similar regarding cardiovascular risk factors, laboratory parameters, andclinical characteristics. The baseline characteristics, laboratory parameters, andblood pressure levels of the groups are presented in The main finding of our study was that the frequency of fQRS was significantly higherin patients with non-dipper prehypertension compared to normotensives. Furthermore,the presence of fQRS on ECG was found to be a predictor of non-dipping inprehypertensive patients. To our knowledge, this is the first study to report theimportance of fQRS in prehypertensive patients.2,13,14Similarly to hypertension, prehypertension consists of non-homogeneous patients.Therefore, early identification of high-risk prehypertensives could lead to adequateprevention. Previous studies reported that deteriorated circadian blood pressurevariability in prehypertensive patients may be associated with repolarizationabnormalities detected by ECG.15However, as a marker of depolarization abnormality, the importance of fQRS inprehypertensive patients is not clear. fQRS is a sign of inhomogenous ventricularconduction caused by myocardial scar, ischemia, or fibrosis.8 It has been shown that fQRS is apredictor of mortality and adverse cardiovascular outcomes in various cardiovasculardiseases.6-8 Additionally, fQRS is a well described fibrotic factor inhypertension.11,16It has been demonstrated that the frequency of fQRS is significantly higher inhypertensive patients than in normotensives,9 and non-dipper hypertensive patients have higher frequencyof fQRS on ECG compared to hypertensive dippers.10,11 These studies revealed that increased blood pressure levels andelevated nighttime blood pressure levels are associated with the presence of fQRS onECG in hypertensive patients, which indicates the higher fibrotic burden withinmyocardium in these patients.Prehypertension confers a high risk of progression to hypertension, and it may beassociated with increased adverse cardiovascular events, inflammation, and targetorgan damage.17-19Our study demonstrated that non-dipping blood pressure patterns are significantlyassociated with the presence of fQRS on ECG in prehypertensive patients, similarlyto in hypertensive patients. Since the presence of fQRS on ECG is an importantpredictor of fibrosis and fibrotic burden within myocardium, the results of ourstudy indicate a higher fibrotic burden in prehypertensive non-dippers compared tonormotensives. The possible underlying mechanism for the association between fQRSand non-dipper blood pressure pattern in prehypertensives might be similar inhypertensive patients. Autonomic dysfunction-related increased sympathetic activityduring nighttime, and chronic-continuous pressure overload related collagen fibersand connective tissue matrix accumulation within the myocardium might play the keyroles for higher fibrotic burden and fibrosis in these patients.4,20 Hence, definition of non-dippers is clinically important. Inaddition to being the precursor of hypertension, prehypertension includes a varietyof patients who are at high risk for adverse cardiovascular events. Therefore, ourresults suggest that fQRS may be useful in defining the deteriorated circadian bloodpressure variability which indicates high-risk prehypertensives.Non-dipping hypertension is a prognostic factor, and increased nighttime bloodpressure levels indicate worse adverse cardiovascular outcomes compared to dipperpatterns.4,21 Similarly, our study revealed thatan important proportion of prehypertensive patients were not prehypertensive after24-hour ABPM results. Since 24-hour ABPM is the gold standard for evaluation anddiagnosis of hypertension, our study includes real prehypertensives.Another aspect of our study is the importance of using 24-hour ABPM for detailedevaluation of blood pressure and final blood pressure pattern diagnosis. It is knownthat blood pressure patterns vary between ABPM and office records.Our study has some limitations. First, the study sample size is relatively small;however, the detection of prehypertensive patients is not an easy procedure inclinical practice. Second, our study included only newly diagnosed prehypertensivepatients. Third, definition of prehypertension based on ABPM records is not clear.Hence, we designated patients with non-hypertensive elevated blood pressure asprehypertensives. Finally, lack of data regarding confirmation of fibrosis withinmyocardium by magnetic resonance imaging is another limitation.Fibrosis within myocardium is an important predictor of adverse cardiovascular eventsin patients with elevated blood pressure. fQRS is a simple and easily detectable ECGfinding that indicates fibrosis within myocardium. This study revealed an importantrelationship between fQRS and non-dipper status in prehypertensive patients. Wefound that non-dipper prehypertensives have significantly higher frequency of fQRScompared to normotensives, and fQRS is an independent predictor of non-dipping inprehypertension. Our results suggest that fQRS may be useful in identifyinghigh-risk prehypertensive patients before the development of hypertension. Thisidentification may be helpful in terms of adequate prevention for futurecardiovascular events. Future studies are necessary to demonstrate the prognosticvalue of fQRS in prehypertensive patients and to understand whether a moreaggressive prehypertension treatment could normalize the ECG findings.


High bronchodilator reversibility in adult asthma is associated with distinct clinical characteristics. In this study, we aim to make a comparison with T-helper 2 (Th2)-related biomarkers, lung function and asthma control between asthmatic patients with high airway reversibility (HR) and low airway reversibility (LR).Patients with asthma diagnosed by pulmonologist according to Global Initiative for Asthma guidelines were recruited from the outpatient department of our hospital from August 2014 to July 2017. Patients were divided into HR and LR subgroups based on their response to bronchodilators of lung function (HR = Δforced expiratory volume in one second (FEV1) postbronchodilator ≥ 20%). Blood eosinophil count and serum IgE level, which are biomarkers of T-helper (Th)-2 phenotypes, were detected for patients. Asthma Control Test (ACT) was used to assess asthma control after the first-month initial treatment.A total of 265 patients with asthma were followed 1 month after initial treatment. HR group shows a higher level of Th2-high biomarkers (blood eosinophil count (10^9/L): 0.49 ± 0.28 vs 0.36 ± 0.19, P < 0.01; IgE (ng/ml): 1306 ± 842 vs 413 ± 261, P < 0.01), lower baseline lung function 25–75: 0.76 ± 0.37 vs 1.00 ± 0.67, P < 0.01; FEF25–75%pred: 21.15 ± 10.09% vs 29.06 ± 16.50%, P < 0.01), and better asthma control  than LR group. HR was associated with a decreased risk of uncontrolled asthma after the first-month initial treatment .HR is a physiologic indicator of lower lung function and severer small airway obstruction, and is more related with an increased level of Th2-biomarkers than LR. Moreover, HR may indicate controlled asthma after the first-month initial treatment. This finding may contribute to identification of asthma endotype. Airway bronchodilator reversibility is the characteristic that differentiates asthma population from patients with irreversible obstructive lung diseases . It has From August 2014 to July 2017, adult patients with asthma diagnosed by pulmonologists at the first time according to the definition of GINA , 7. The Inclusion criteria in the present study were as following: (1) age between 18 and 65 years, (2) forced expiratory volume in one second (FEV1) % predicted less than 80%, (3) reversibility in FEV1 12% (and at least 200 ml) following administration of a short-acting β-agonist, (4) no evidence of active infection, (5) no medical conditions associated with immune suppression. Patients were excluded if they had chronic obstructive pulmonary disease (COPD) or asthma-COPD overlap [Subjects were classified into high airway reversibility (HR) group and low airway reversibility (LR) group. The HR group included patients with a ≥ 20% increase in FEV1 following administration of a short-acting bronchodilator during screening and baseline pulmonary function testing. The LR group included those with reversibility below that level [t test or Chi square test. The associations between asthma control and clinical characteristics were explored with unconditional logistic regression models with LOGISTIC procedure in SAS 9.4 . The results were presented as odds ratios (OR) and 95% confidence intervals (CI). P values < 0.05 were considered to be statistically significant.Group data were expressed as the mean ± standard deviation (SD). Significant differences were evaluated using independent-samples Figure Demographics characteristics for all patients were summarized in Table Moreover, Table We further explored the association between HR and asthma control after the first-month initial treatment. Table In our study, HR was more frequently associated with a higher level of Th2-biomarkers, lower lung function in baseline, and better asthma control after the first-month initial treatment than LR. Furthermore, HR and high FEF25–75 after inhaling short-acting bronchodilator were respectively associated with better asthma control. It may contribute to identifying the endotype of asthma by further clarifying the relationship between airway bronchodilator reversibility, obstruction in small airway, Th2-biomarkers and disease control after initial treatment.In the present study, asthmatic patients with HR were showed a higher level of Th2-biomarkers than LR group. That finding was similar with previous report . MoreoveInterestingly, it didn’t find an association between Th2 biomarker and asthma control after the first-month initial treatment in our study. Previous study found that asthmatic patients with higher blood eosinophil counts fared poorer asthma control . HoweverFEF50, FEF75 and FEF25–75 in baseline of patients with HR were less than those with LR in our study. FEF75 and FEF25–75 could accurately reflect flow at low lung volumes, which is helpful to showing small airway obstruction in early stage of obstructive lung disease , 12. ParFurthermore, the present study showed that HR was associated with a decreased risk of poor asthma control after the first-month initial treatment. In contrast, previous study found that patients with higher airway reversibility were showed worse controll of asthma at 12 month-follow-up . These fWe acknowledge that our study has limitations. The patients were followed only 1 month after initial treatment. Although we can’t explore asthma control of HR group in a long-term, previous study reported different findings on asthma control in patients with HR for a long-term from a short-term . Those iIn conclusion, HR is a physiologic indicator of lower lung function, particularly small airway obstruction, and is more related with an increased level of Th2-biomarkers than LR. Moreover, HR indicates well asthma control after the first-month initial treatment. Those findings may be help to identify the endotype of asthma.


DREAM-GLOBAL (Diagnosing hypertension—Engaging Action and Management in Getting Lower Blood Pressure in Indigenous and low- and middle-income countries) studied a SMS text messaging–based system for blood pressure measurement and hypertension management in Canadian Aboriginal and Tanzanian communities. The use of SMS text messages is an emerging point of interest in global health care initiatives because of their scalability, customizability, transferability, and cost-effectiveness.The study aim was to assess the effect on the difference in blood pressure reduction of active hypertension management messages or passive health behavior messages. The system was designed to be implemented in remote areas with wireless availability. This study described the implementation and evaluation of technical components, including quantitative data from the transmission of blood pressure measurements and qualitative data collected on the operational aspects of the system from participants, health care providers, and community leadership.The study was implemented in six remote Indigenous Canadian and two rural Tanzanian communities. Blood pressure readings were taken by a community health worker and transmitted to a mobile phone via Bluetooth, then by wireless to a programmed central server. From the server, the readings were sent to the participant’s own phone as well. Participants also received biweekly tailored SMS text messages on their phones. Quantitative data on blood pressure reading transmissions were collected from the study central server. Qualitative data were collected by surveys, focus groups, and key informant interviews of participants, health care providers, and health leadership.In Canada, between February 2014 and February 2017, 2818 blood pressure readings from 243 patients were transmitted to the central server. In Tanzania, between October 2014 and August 2015, 1165 readings from 130 patients were transmitted to the central server. The use of Bluetooth technology enabled the secure, reliable transmission of information from participants to their health care provider. The timing and frequency were satisfactory to 137 of 187 (73.2%) of participants, supporting the process of sending weekly messages twice on Mondays and Thursdays at 11 am. A total of 97.0% (164/169) of the participants surveyed said they would recommend participation in the DREAM-GLOBAL program to a friend or relative with hypertension.In remote communities, the DREAM-GLOBAL study helped local health care providers deliver a blood pressure management program that enabled patients and community workers to feel connected. The technical components of the study were implemented as planned, and patients felt supported in their management through the SMS text messaging and mobile health program. Technological issues were solved with troubleshooting. Overall, the technical aspects of this research program enhanced clinical care and study evaluation and were well received by participants, health care workers, and community leadership.Clinicaltrials.gov NCT02111226; https://clinicaltrials.gov/ct2/show/NCT02111226. There are over 1 billion individuals living with hypertension around the world, of which two-third are in developing countries .The prevalence of cardiovascular disease, obesity, diabetes, and other related conditions is significantly higher in Indigenous populations in Canada than the rest of the population. Although the prevalence of hypertension is slightly lower, rates of hypertension awareness, treatment, and control are also lower . This isThe use of SMS text messaging in health care interventions is becoming a point of interest because of its scalability and capacity for adaptation to various populations at a low cost . StudiesThe DREAM-GLOBAL, Diagnosing hypertension—Engaging Action and Management in Getting Lower Blood Pressure in Indigenous and low- and middle-income countries, research study was a randomized controlled trial comparing only the blood pressure lowering effect of passive health behavior messages with both active blood pressure management messages and passive health behavior messages . The actThe DREAM-GLOBAL study randomized participants to either active or passive SMS text messages, and the protocol has been previously published . The stuThe details of how the communities were identified and assessed for research readiness have been previously described . The popCellular safety information was outlined to the participants before the study, including adherence to a ban on handheld devices while driving. Participants were advised not to share their phone with others if they did not want anyone to know about their participation in the study, and they were also advised not to send important personal information .Ethics approval was obtained from the Sunnybrook Health Sciences Centre Research Ethics Board  and from participating University and community ethics boards. The study was carried out according to the principles of Good Clinical Practice, the Declaration of Helsinki, and the TriCouncil Policy Statement on ethical conduct for research involving humans -13. The Before the training and study launch, usability testing was conducted within the study investigator’s clinics to confirm reliability of the technology to record and transmit the blood pressure readings to the central server  and a BlackBerry Bold (BlackBerry Inc) mobile phone, with the DREAM-GLOBAL mobile app installed. In Tanzania, an Android mobile phone was used. Blood pressure readings from the UA-767PBT blood pressure monitor were transmitted via Bluetooth to the community health worker’s mobile phone and from the mobile phone to a secure central server in Canada. The central server was programmed to assess the blood pressure readings as normal or high. The server was programmed to wait for up to 3 blood pressure readings, for an individual patient, over 5 min. The average of the 3 readings was then calculated by the central server and then transmitted to the patient’s primary health care provider by fax and to the patient’s own phone by SMS. If the blood pressure was high, an SMS text message was sent to the participant, with advice to contact their health care provider over the coming week , James Bay coast (Quebec), and the north shore of New Brunswick. In Tanzania, a preliminary portion of the study was carried out in 2 rural villages in Hai District, Kilimanjaro Region, to demonstrate that blood pressure can be measured and transmitted through the system. In Canada, a total of 2818 patient blood pressure readings from 243 patients were transmitted to the central server between February 2014 and February 2017. In Tanzania, with the pilot blood pressure measurement study, 1165 readings from 130 patients were transmitted to the central server between October 2014 and August 2015. The study server was programmed to wait for up to 3 readings and then send the mean to the participant’s own phone. This also provided a record about the participant’s blood pressure and allowed the participant to confirm that it was the measurement just taken. There were no incidents of participants finding incorrect readings transmitted from, for example, the participants who had their blood pressure measured immediately before the study. Participants overwhelmingly agreed that the program should be recommended to a friend or relative. Following the study, after presentation of the study progress, all 6 communities supported continuing the program. Only 20 of these participants did not have any blood pressure readings beyond 2 months of enrolling into the study.An evaluation form was provided with open-ended questions. The results of the Participant Evaluation Form for SMS text messages are found in On the questionnaire, 168 of 187 (89.8%) participants responded that the messages were clear and felt that they made sense. For 137 of 187 (73.2%) participants, the timing and frequency were satisfactory, supporting the process of sending messages on Mondays and Thursdays at 11 am. In response to a probe about privacy concerns about having their blood pressure readings and other health messages sent to their phones, 92 of 121 respondents (76.0%) felt that this was not a problem. Behavior changes noted by participants attributed to the SMS text messages included increased exercise, diet changes to give up sweetened beverages, more awareness of sodium and reading product labels, smoking cessation, and appreciation of the stress reduction messages. In 1 community, the mental health worker shared that their clients were more accessible and receptive if they were participating in the study. Participants also expressed that they felt supported, particularly if they were taking medications and had a greater understanding. Those not on medication noted that they would be more comfortable starting therapy if necessary. Almost one-third of participants shared the messages with family and friends and looked at the texts at their convenience.An early complaint from the mobile phone app users was the potential to keep the last participant’s name open on the app, when the next participant was ready to have their blood pressure assessed. This would lead to the next participant’s blood pressure being assigned to the previous participant, and it became apparent when the next participant did not receive a confirmatory SMS text message with the blood pressure reading. To address this, the instructions on how to use the app when measuring patients one after another were revised, and the users were updated on the new process. The most frequent complication was a failure to transmit readings by Bluetooth transmission from the monitors to the BlackBerry phones. This was found to be because of the BlackBerry operating system software in older devices, which did not update automatically. This required resetting the device. Some noted that the BlackBerry mobile phone’s version of the DREAM-GLOBAL app was not user friendly—the BlackBerry screens were small, and some parts of the app were difficult to access. In addition, occasional failure of BlackBerry function because of extreme cold or trouble with battery charge was observed. In the early months of study implementation, it was discovered that some BlackBerry devices had not been configured with the correct access point name (APN) setting for the service provider; APN settings were then reconfigured correctly through a troubleshooting process. For Tanzania, none of these problems occurred with the Android software and devices. Updates to the Android software and larger mobile phone screens made it easier to see the roster of participants. More space was allocated for participant’s names to make it easier to distinguish among participants with similar names. When a participant’s phone was replaced, the new number had to be input into the registration software on the Web to ensure the participant continued to receive SMS text messages.The community health workers were asked to provide feedback on their overall experience with the program, from site training to the use of technology. Data are summarized in The community health workers and nurses noted that they were seeing their clients participating in the study more frequently and that they became more comfortable with blood pressure measurement. In addition, participants knew their blood pressure numbers and were better able to address other health care issues, particularly related to mental health issues. They felt that the program led them to have better communication with their physicians and that they had greater confidence about the appropriate therapy for hypertension and knowing when action was needed. They also expressed appreciation for the site visits and ongoing telephone conference communication follow-up. The technological training was well received by the community health workers; in follow-up interviews after the training, almost all either agreed or strongly agreed that the training was helpful and gave them confidence in their ability to perform their role. The community health worker feedback from the site initiation and training is summarized in After completion of the study, site visits with band leadership and community health leadership and elders were conducted to assess interest and for approvals to continue the program. A total of 5 of the communities remained engaged in the research. A total of 1 community did not allow follow-up with the community leadership during the study, but it did welcome a poststudy review and supported continuing the program after the study completion.Health care providers shared that they noted that their patients participating in the study appreciated being contacted on their cell phones by the SMS text messages. They felt that their patients were more informed and engaged in their disease management and more likely to follow-up with their physicians. Many were surprised to see that their patients were calling them and making appointments, as per the instructions from their cell phone. It was noted that the white coat effect for blood pressure was identified through the community measurement of blood pressure, and more people, who would otherwise not visit, visited the health center.Overall, despite some initial issues, the technology performed as hoped in delivering the SMS text messages to patients, which garnered a positive reception from the communities involved. It also demonstrated that communities had enough technological resources to manage the study. The fact that the community health worker time to manage the study in each community was granted by the health leadership indicates the commitment and engagement of each community. All communities involved requested to have the program continue after the study’s completion.DREAM-GLOBAL was designed to increase the capacity for affordable, evidence-based, guidelines-driven hypertension management interventions at the patient, provider, and community level. This study demonstrated that information could be obtained and transmitted with fidelity from participants in remote settings. It also confirmed that patients were willing and able to participate in the program . It was Community health workers and professional health care providers found that the technology was able to enhance their communication with participants and between each other. The process assisted with participant engagement in their own health care, which has also been demonstrated . TraininThe DREAM-GLOBAL system used minimal resources, requiring only the server, devices, and bulk SMS transmission. Transmission of blood pressure data has also recently been validated . This syThe DREAM-GLOBAL study has resulted in an innovative system that has the ability to provide blood pressure screening and connect patients to health care providers in the community who can diagnose and treat hypertension. The technical platform provided a solution for hypertension management in low-resource settings, with the use of task shifting in blood pressure measurement and meaningful SMS text messages that promote health behavior change. The system has the potential to further improve patient care, as it can be easily adapted to regional needs and scaled up to include other aspects of chronic disease management.