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BACKGROUND: Circulating red blood cells (RBCs) undergo aging, a fundamental physiological phenomenon that regulates their turnover. Objective: Understanding the role of Aβ in the cross talk between cell signalling pathways and modulation of the cell structural and biomechanical properties occurring in RBCs during aging. METHODS: The morphological pattern has been monitored using Atomic Force Microscopy (AFM) imaging and measuring the RBCs' plasma membrane roughness employed as a morphological parameter capable to provide information on the structure and integrity of the membrane-skeleton. RESULTS: We show that treatment with Aβ accelerates the occurrence of morphological and biochemical aging markers in human RBC and influences the cell metabolism. Biochemical data demonstrate that contemporaneously to morphological alterations, Aβ triggers: (i) metabolic alterations and (ii) a complex signaling pathway involving caspase 3, protein kinase C and nitric oxide derived metabolites. CONCLUSIONS: our study provides a comprehensive picture in which Aβ treatment of RBC induces changes in specific cell signalling events and/or metabolic pathways, in turns affecting the membrane–cytoskeleton interaction and the membrane integrity. [ABSTRACT FROM AUTHOR]

Thrombotic disorders remain the leading cause of mortality and morbidity, despite the fact that anti-platelet therapies and vascular implants are successfully used today. As life expectancy is increasing in western societies, the specific knowledge about processes leading to thrombosis in elderly is essential for an adequate therapeutic management of platelet dysfunction and for tailoring blood contacting implants. This study addresses the limited available data on platelet function in apparently healthy subjects in relation to age, particularly in view of subjects of old age (80–98 years). Apparently healthy subjects between 20 and 98 years were included in this study. Platelet function was assessed by light transmission aggregometry and comprised experiments on spontaneous as well as ristocetin-, ADP- and collagen-induced platelet aggregation. The data of this study revealed a non-linear increase in the maximum spontaneous platelet aggregation (from 3.3% ±3.3% to 10.9% ±5.9%). The maximum induced aggregation decreased with age for ristocetin (from 85.8% ±7.2% to 75.0% ±7.8%), ADP (from 88.5% ±4.6% to 64.8% ±7.3%) and collagen (from 89.5% ±3.0% to 64.0% ±4.0%) in a non-linear manner (linear regression analysis). These observations indicate that during aging, circulating platelets become increasingly activated but lose their full aggregatory potential, a phenomenon that was earlier termed "platelet exhaustion". In this study we extended the limited existing data for spontaneous and induced platelet aggregation of apparently healthy donors above the age of 75 years. The presented data indicate that the extrapolation of data from a middle age group does not necessarily predict platelet function in apparently healthy subjects of old age. It emphasizes the need for respective studies to improve our understanding of thrombotic processes in elderly humans. [ABSTRACT FROM AUTHOR]

Lipid-containing adipocytes can dedifferentiate into fibroblast-like cells under appropriate culture conditions, which are known as dedifferentiated fat (DFAT) cells. However, the relative low dedifferentiation efficiency with the established protocols limit their widespread applications. In this study, we found that adipocyte dedifferentiation could be promoted via periodic exposure to cold (10°C) in vitro. The lipid droplets in mature adipocytes were reduced by culturing the cells in periodic cooling/heating cycles (10–37°C) for one week. The periodic temperature change led to the down-regulation of the adipogenic genes (FABP4, Leptin) and up-regulation of the mitochondrial uncoupling related genes (UCP1, PGC-1α, and PRDM16). In addition, the enhanced expression of the cell proliferation marker Ki67 was observed in the dedifferentiated fibroblast-like cells after periodic exposure to cold, as compared to the cells cultured in 37°C. Our in vitro model provides a simple and effective approach to promote lipolysis and can be used to improve the dedifferentiation efficiency of adipocytes towards multipotent DFAT cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: Degloving injuries of the fingers and especially the thumb are highly demanding problems in hand surgery and replantation often is not successful because of severe soft tissue contusion. Only few cases of successfull replantation for hand degloving injuries in thumbs are reported in literature. CASE PRESENTATION: We present the case of a young right hand dominant worker experiencing an occupational accident with a circumferential avulsion of his right thumbs' soft tissue at the level of the metacarpophalangeal (MCP) joint with complete skeletization of his thumb and a deep laceration of the nail bed as he got trapped in a machine. Bony structures and tendons remained intact corresponding Urbaniak class III/Kay class IV injury. Immediate defect coverage by replantation was performed. Additionally, a deep palmar soft tissue defect to his middle finger pulp and a laceration with disruption of his eighth finger nerve on his ring finger was adressed by revision, debridement, direct coaptation of the nerve and occlusive dressing to the middle finger. The patient regained full function and excellent cosmesis without nail deformity but only protective sensibility. He is back to his former sports and occupation. CONCLUSIONS: Though sensitive outcome is poor we recommend primary attempt for defect coverage with replantation following degloving to achieve pliable skin coverage and good cosmesis. Especially in Urbaniak III cases with complete soft tissue degloving lacking fractures or tendon lacerations good functional outcome is possible but we recommend to consent the patient in advance for other reconstructive options and give them realistic exspectations in case of failure. Contrary to popular belief replantation of completely degloved fingers is more than saving nonfunctional parts as motivated patients are able to get back to previous sports and occupation after successful replantation. [ABSTRACT FROM AUTHOR]

We previously reported that whole body bioelectrical impedance analysis (BIA) measurements are correlated to some hemorheologic factors, suggesting a relationship between viscosity factors and electric properties of flowing blood not only in vitro but also in vivo. Recently we reported that with segmental BIA (analyzing the body considered as composed of 5 cylinders) predictive equations for various determinants of blood viscosity were closer than for the wole body. Another widely used BIA technique uses leg-to-leg impedance measurements so that two cylinders (the two legs) are analyzed. We investigated whether impedance measured with this technique (Tanita TBF-300) is also a predictor of blood viscosity factors. From viscometric measurements performed on venous blood drawn in recreative athletes over the range of shear rates 1 to 6000 s–1 (RHEOMETRE Anton Paar CP 50-1), we found a correlation between leg-leg resistance at 50 kHz (Rx[50 kHz]) and blood viscosity at 1000 s–1 (η1000= 0.0051 Rx[50 kHz] + 1.3265; r = 0.521 p = 0.028 yielding a prediction of η1000 (Bland Altman plot: bias 0.05 [RANGE – 0.24; 0.34]. Neither plasma viscosity nor the red cell rheology index «k» of Quemada's model are correlated with Rx[50 kHz], but hematocrit (Hct) does (Hct (%) = 0.0217 Rx[50 kHz] + 33.783; r = 0.480 p = 0.044) yielding a prediction of Hct (Bland Altman plot: bias – 0.11, [range – 1.67; 1.45]. The discrepancy between actual and predicted Hct is also correlated with resistance at 50 kHz (r = 0.575 p = 0.031) as does the discrepancy between actual and predicted Hct/viscosity ratio (r = –0.651 p = 0.006). Therefore, as other previously studied methods, leg to leg BIA predicts viscosity, suggesting that blood rheology may influence the passage of an electric current in the legs. [ABSTRACT FROM AUTHOR]

Physiological modifications of blood rheology during pregnancy and their alterations in pregnant hypertensive women have been extensively studied in the 1980's. Since vascular resistance is higher in hypertensive pregnant women whose newborns are small-for gestational-age (SGA), we investigated in a personal database if growth retardation of newborns is related to the oxygen delivery index (ratio hematocrit/blood viscosity) and to the difference between hematocrit (Hct) and the prediction of its optimal valued based on Quemada's equation. A sample of 38 hypertensive pregnant women (age 29 yr±1) was compared with 64 controls matched for age and gestational age, studied at 35±1 weeks gestation, extracted from a larger series of 162 pregnant women. On the whole the hypertensive group gave birth to smaller children (p = 0.014). Plasma viscosity correlated with blood pressure (BP) only in hypertensive women (r = 0.403 p < 0.05). The bell-shaped curve of predicted optimal Hct of non hypertensive pregnant women was similar to that of non-pregnant women, but in hypertensive women it was shifted toward higher values (p = 0.07), and the predicted optimal Hct (but not the actual one) was correlated with systolic blood pressure (SBP) (r = 0.349 p < 0.001) and diastolic blood pressure (DBP) (r = 0.218 p < 0.05). The predicted optimal Hct/viscosity (h/η) ratio was higher in hypertensive women whose newborns exhibited a low birth weight (p = 0.03), resulting in a higher discrepancy between actual and model-predicted «ideal» values of h/η ratio (p = 0.03) and Hct (p = 0.02) compared with the subgroup with no growth retardation. Therefore, in hypertensive women whose newborns exhibited a low birth weight, hemorheological parameters predicting oxygen supply are shifted to lower values than predicted by the model. [ABSTRACT FROM AUTHOR]

The ideal hematocrit is the hematocrit (Hct) value resulting in the highest value of Hct/viscosity (h/η) ratio and can thus be predicted from viscometric measurements with the use of equations such as Quemada's one which yield the determination of the bell-shaped curve of h/η as a function of Hct. In a series of recent papers we applied this approach to various populations, using viscometry at high shear rate (1000 s–1). However the shape of this curve has been reported to be dependent on the shear rate, resulting in a right-shift in this top value when Hct increase. We present here in 11 young recreative athletes the evolution of the predicted top of the h/η curve and optimal theoretical Hct and the discrepancy between theoretical and optimal values over the range of shear rates 1 to 6000 s–1. Results show that the predicted optimal value of both h/η and Hct increases when shear rate increases and that the discrepancy between predicted laquooptimalraquo and actual values decreases and becomes almost asymptotic at very high shear (500 s–1). It is minimal at 2720 s–1. The correlation between predicted laquooptimalraquo and actual values of both parameters describes the same evolution. Therefore, it is better for assessing h/η and its agreement with theoretical values, and for determining the theoretical ideal hematocrit, to measure blood viscosity at shear rates equal or superior to 500 s–1. [ABSTRACT FROM AUTHOR]

While fractional flow reserve (FFR) is a good diagnostic index to assess the myocardial ischemia, coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) can be used to address microvascular status without any significant epicardial disease. The independent predictors for FFR and IMR are totally different and acts differently on the macro- and micro-vascular dysfunction. In high FFR patients, low CFR and high IMR which indicates the presence of overt microvascular disease demonstrated poor prognosis. Thus, comprehensive physiological assessments using FFR, CFR and IMR could improve the ability to discriminate patients at high risk of future events. [ABSTRACT FROM AUTHOR]

Non-swelling hydrophobic poly(n-butyl acrylate) network (cPnBA) is a candidate material for synthetic vascular grafts owing to its low toxicity and tailorable mechanical properties. Mesenchymal stem cells (MSCs) are an attractive cell type for accelerating endothelialization because of their superior anti-thrombosis and immune modulatory function. Further, they can differentiate into smooth muscle cells or endothelial-like cells and secret pro-angiogenic factors such as vascular endothelial growth factor (VEGF). MSCs are sensitive to the substrate mechanical properties, with the alteration of their major cellular behavior and functions as a response to substrate elasticity. Here, we cultured human adipose-derived mesenchymal stem cells (hADSCs) on cPnBAs with different mechanical properties (cPnBA250, Young's modulus (E) = 250 kPa; cPnBA1100, E = 1100 kPa) matching the elasticity of native arteries, and investigated their cellular response to the materials including cell attachment, proliferation, viability, apoptosis, senescence and secretion. The cPnBA allowed high cell attachment and showed negligible cytotoxicity. F-actin assembly of hADSCs decreased on cPnBA films compared to classical tissue culture plate. The difference of cPnBA elasticity did not show dramatic effects on cell attachment, morphology, cytoskeleton assembly, apoptosis and senescence. Cells on cPnBA250, with lower proliferation rate, had significantly higher VEGF secretion activity. These results demonstrated that tuning polymer elasticity to regulate human stem cells might be a potential strategy for constructing stem cell-based artificial blood vessels. [ABSTRACT FROM AUTHOR]

AIM: To assess the influence of difficult examination conditions onto the diagnostic performance of CEUS (contrast-enhanced ultrasound) in focal liver lesions (FLL). METHODS: 77 liver CEUS examinations of 75 patients were analysed retrospectively. CEUS was performed as the first diagnostic procedure by one experienced sonographer after bolus injection of 1.0 up to 2.4 ml sulphur hexafluoride microbubbles using a high-end ultrasound device with a high resolution multifrequency probe (1–6 MHz). The combination of complementary imaging (CT or MRI), histology and CEUS follow up of at least 6 months was considered. Cross tables were used to define the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy. Chi-Square Test analysed categorical data. RESULTS: The patients were between 18 and 84 years old (mean 62±11 years). 26 patients suffered from liver cirrhosis (33.8%). 52 patients (67.5%) received therapy for an oncological disease. The final diagnosis showed 52 malignant FLLs including 24 hepatocellular carcinomas (HCCs), 9 cholangiocellular carcinomas (CCCs) and 19 metastases from different primary tumors. In the other 25 patients no malignant lesions could be detected, three of them presenting however liver haemangioma and two of them liver cysts. The overall lesions' size according to the CEUS findings ranged from 7 to 100 mm (mean 31.1±22.6 mm). Under good examination conditions the malignant potential of a tumor was diagnosed correctly by CEUS in 98.0% of cases (Sensitivity 97.1%, Specificity 100%, PPV 100%, NPV 94.1%, diagnostic accuracy 98.0%). Limited examination conditions (e.g. obesity, meteorism) were present in 35.1% of cases with a decrease of the diagnostic accuracy to 92.6% (Sensitivity 100%, Specificity 77.8%, PPV 90.0%, NPV 100%). CONCLUSION: Despite the influence of difficult examination conditions, CEUS is – in the hands of an experienced sonographer – an excellent diagnostic procedure for the assessment of liver lesions. [ABSTRACT FROM AUTHOR]

The analysis of platelet aggregation and thrombosis kinetics has significantly advanced with progress in microfluidic technology. However, the results of platelet aggregation tests do not fully reflect the observed clinical outcomes. To address the present unmet clinical needs, the basic but essential biology of platelets should be reconsidered in relation to the characteristics of microfluidic systems employed for platelet tests. To this end, the present article provides an overview of commercially available point of care devices and focuses on recent microfluidic studies, describing their measurement principles. We critically discuss the characteristics of the microfluidics systems used to evaluate the complex processes underlying platelet aggregation, and that are specifically designed to mimic the pathophysiological environment of blood vessels, including hemodynamic factors as well as blood vessel injury. To this end, we summarize unsolved issues related to the application of platelet function tests based on microfluidics. Overall, we confirm that platelet function tests based on microfluidics provide a versatile platform that encompasses a variety of basic research, as well as clinical diagnostic applications. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Objective of the study was to assess the performance of ultrasound strain elastography combined with conventional B-mode ultrasound to diagnose suspicious breast lesions (BI-RADS 4 and 5). METHODS: Between January 2015 and December 2017, a total of 86 patients (55±17.9 years) with solid or unclear, non-cystic breast lesions were enrolled in the study. The breast lesions were evaluated by B-mode ultrasound and subsequent ultrasound strain elastography. Ultrasound features including echo pattern, lesion shape, marginal characteristics, calcifications, orientation and posterior features are useful for differentiating benign breast lesions from malignant ones. Malignant ultrasound features are irregular shape, hypoechoic pattern, spiculated margin, nonparallel orientation and posterior shadowing. Lesions with benign features such a circumscribed margin were classified as low conspicuous. In patients with highly conspicuous malignant masses ultrasound-guided core needle biopsy or surgical excision was performed. RESULTS: Among the 86 patients, 60 masses were histologically proven and 36 of these were malignant. Of the malignant lesions 26 invasive carcinomas were of no special type (NST), 1 invasive lobular carcinoma, 3 ductal carcinomas in situ and 6 metastases. 20 of these patients had breast density classified as ACR 3 or 4. The mean size of the masses was 1.2 cm (range: 0.5–5 cm). Based on ultrasound B-mode imaging, the lesions were classified as BI-RADS category 4 (n = 20; three 4a, nine 4b and eight 4c) and BI-RADS category 5 (n = 16). One patient had to be reclassified after strain elastographxy to BI-RADS 3. The sensitivity of ultrasound with strain elastography and additional B-Mode ultrasound for the characterization of solid breast lesions was 97%, for conventional B-mode alone 92%; the respective specificities were 82% and 73%, respectively. CONCLUSION: Ultrasound elastography can be a supplementary approach to conventional ultrasound to improve the diagnostic accuracy of malignant breast lesions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pathomechanism and optimal renoprotective protocol for remote ischemic preconditioning (RIPC) have not been completely revealed yet. OBJECTIVE: To investigate micro-rheological effects of early and delayed RIPC in renal ischemia-reperfusion (I/R) in the rat. METHODS: In Control group the left femoral artery was cannulated and the left kidney was gently exposed. In the I/R group 45-minute renal ischemia with 120-minute reperfusion period was monitored. In the RIPC groups a 3×10-minute protocol was applied using tourniquet around the right hind-limb 1 hour (RIPC-1) or 24 hours (RIPC-24) prior to the I/R. Blood samples were taken for testing blood gas, acid-base, metabolic and hemorheological parameters. RESULTS: Lactate and potassium concentration significantly increased in I/R that could be reduced by RIPC, especially in RIPC-24. Creatinine concentration increased further in RIPC groups. I/R and RIPC-1 decreased the pH, RIPC-24 increased. RIPC-24 reduced the drop in base excess. Erythrocyte deformability worsened by renal I/R. In RIPC groups deformability decreased additively. However, RIPC-1 could improve the condition. RIPC-24 showed the highest erythrocyte aggregation values during reperfusion. CONCLUSIONS: Renal I/R worsened metabolic and micro-rheological parameters that could be modulated by RIPC protocols. However, it could not be decided whether the early or the delayed protocol is better. [ABSTRACT FROM AUTHOR]

BACKGROUND: L-Arginine, the precursor of NO might be involved in improving the cardiovascular disorders via regulation of functional properties of erythrocytes. OBJECTIVE: This study investigated the effects of L-Arginine supplementation on responses of red blood cell (RBC) properties to high intensity interval exercise (HIIE). METHODS: Ten overweight healthy men participated voluntarily in the study and performed two HIIE trials with and without L-Arginine in two separate weeks. The HIIE protocol included 12 intervals of 3-min encompassed 1-min running at 100% of vVO2max and 2-min active recovery at 40% of vVO2max. Three blood samples were taken before and after supplementation, and immediately after exercise; and were used to measure red blood cell properties. RESULTS: The HIIE protocol increased hematocrit, hemoglobin and lactate significantly (P < 0.05), but had no significant effect on RBC aggregation, RBC deformability, and fibrinogen concentration. When data were compared for two trials no significant differences between the responses of RBC properties to two HIIE protocols were detected (P > 0.05), whereas the increases in lactate concentration following HIIE was significantly lower in L-Arginine than placebo trial (P < 0.05). CONCLUSIONS: It is concluded that L-Arginine consumption prior to HIIE does not lead to any improvement in RBC properties during HIIE in overweight healthy men. [ABSTRACT FROM AUTHOR]

BACKGROUND: Red blood cells (RBC) are exposed to varying shear stress while traversing the circulatory system; this shear initiates RBC-derived nitric oxide (NO) production. OBJECTIVE: The current study investigated the effect of varying shear stress dose on RBC-derived NO production. METHODS: Separated RBC were prepared with the molecular probe, diamino-fluoreoscein diacetate, for fluorometric detection of NO. Prepared RBC were exposed to discrete magnitudes of shear stress (1–100 Pa), and intracellular and extracellular fluorescence was quantified via fluorescence microscopy at baseline (0 min) and discrete time-points (1–30 min). RESULTS: Intracellular RBC-derived NO fluorescence was significantly increased (p < 0.05) following shear stress exposure when compared to baseline at: i) 1 min–100 Pa; ii) 5 min–1, 5 Pa; iii) 15 min–1, 5, 35 Pa; iv) 30 min–35 Pa. Extracellular RBC-derived NO fluorescence was significantly increased (p < 0.05) following shear stress exposure when compared to baseline at: i) 5 min – 100 Pa; ii) 15 min–100 Pa; iii) 30 min–40, 100 Pa. CONCLUSIONS: These data indicate that: i) a dose-response exists for the RBC-derived production of NO via shear stress; and ii) exposure to supra-physiological shear stress allows for the leakage of RBC intracellular contents (e.g., RBC-derived NO). [ABSTRACT FROM AUTHOR]

BACKGROUND: While complication rates in free tissue transfers have continuously decreased over time due to improved techniques, the intraoperative use of vasopressors and their negative effects on flap microcirculation and patency of the anastomoses remains controversial. To further elucidate this matter, this retrospective study examines the effect of intraoperative vasopressors on free gracilis muscle and free fasciocutaneous anterolateral thigh (ALT) flaps for lower extremity reconstruction. METHODS: A total of 425 patients underwent 437 free flaps for lower limb reconstruction. The series was divided into two groups: use of intraoperative vasopressors (V, n = 318) or no use (NV, n = 119). The data were retrospectively screened for patients' demographics, perioperative details, and surgical complications. RESULTS: The two groups were comparable regarding patient comorbidities. Independently of flap type, there were no significant difference between the groups regarding major complications, i.e. total flap loss (V: 5.35% versus NV: 5.04%, p = 0.899) or revision rate (V: 18.87% versus NV: 12.61%; p = 0.122), or minor complications, i.e. partial flap loss (V: 6.29% versus NV: 5.88%, p = 0.875). CONCLUSION: This study confirms that the usage of intraoperative vasopressors has no influence on free flap survival rate in lower extremity reconstruction. It seems to be no difference between free muscle or fasciocutaneous flaps. [ABSTRACT FROM AUTHOR]

Circulating blood cells are prone to varying flow conditions when contacting cardiovascular devices. For a profound understanding of the complex interplay between the blood components/cells and cardiovascular implant surfaces, testing under varying shear conditions is required. Here, we study the influence of arterial and venous shear conditions on the in vitro evaluation of the thrombogenicity of polymer-based implant materials. Medical grade poly(dimethyl siloxane) (PDMS), polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) films were included as reference materials. The polymers were exposed to whole blood from healthy humans. Blood was agitated orbitally at low (venous shear stress: 2.8 dyne · cm–2) and high (arterial shear stress: 22.2 dyne · cm–2) agitation speeds in a well-plate based test system. Numbers of non-adherent platelets, platelet activation (P-Selectin positive platelets), platelet function (PFA100 closure times) and platelet adhesion (laser scanning microscopy (LSM)) were determined. Microscopic data and counting of the circulating cells revealed increasing numbers of material-surface adherent platelets with increasing agitation speed. Also, activation of the platelets was substantially increased when tested under the high shear conditions (P-Selectin levels, PFA-100 closure times). At low agitation speed, the platelet densities did not differ between the three materials. Tested at the high agitation speed, lowest platelet densities were observed on PDMS, intermediate levels on PET and highest on PTFE. While activation of the circulating platelets was affected by the implant surfaces in a similar manner, PFA closure times did not reflect this trend. Differences in the thrombogenicity of the studied polymers were more pronounced when tested at high agitation speed due to the induced shear stresses. Testing under varying shear stresses, thus, led to a different evaluation of the implant thrombogenicity, which emphasizes the need for testing under various flow conditions. Our data further confirmed earlier findings where the same reference implants were tested under static (and not dynamic) conditions and with fresh human platelet rich plasma instead of whole blood. This supports that the application of common reference materials may improve inter-study comparisons, even under varying test conditions. [ABSTRACT FROM AUTHOR]

Polymers are often contaminated with lipopolysaccharides also known as endotoxins. Even small amounts of endotoxins can have strong effects on endothelial cell function so that the endothelialisation of cardiovascular implants might be hampered. An open question is how endothelial cells seeded on a body foreign substrate respond to shear load after adding Lipid A (LPA), the domain, which is responsible for much of the toxicity of gram-negative bacteria, and whether morphological changes of endothelial cells occur. LPA supplementation to the culture medium in increasing concentrations (5, 25 and 50μg/ml) resulted in progressive reductions of the density of adherent HUVEC after shear load (p < 0.001). 48% of the HUVEC in control cultures (0μg/ml LPA) were still adherent after 2 hours of shearing at 6 dyne/cm2, while 80 minutes after addition of 50μg/ml LPA, 88% of the HUVEC had already detached from the substrate and after 100 minutes no more HUVEC were attached. The results demonstrate that endotoxins are of extreme importance for the behavior of HUVEC and that in vivo pathologies can be increasingly simulated in vitro. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We aimed to evaluate whether PIRADS 3 lesions in multiparametric MRI (mpMRI) represent a significant risk of prostate cancer (PCa) in a real-world setting of different referring radiologic institutes. MATERIALS AND METHODS: Between May 2015 and October 2017, a total of 408 patients were referred to our clinic for MRI-ultrasound fusion targeted biopsy of the prostate (FusPbx) due to suspected prostate cancer. In all patients, preoperatively an mpMRI of the prostate was performed by altogether 62 different radiologic institutes. Prostate lesions were classified according to the PIRADS system. A PIRADS 3 lesion was diagnosed in 41 patients. FusPbx was performed transrectally using a Philips EPIQ 7 (Philips Medical Systems, Bothell, WA) scanner with plane wise fusion of ultrasound and MRI image data. In addition to FusPbx in each patient a randomized 12-core transrectal ultrasound guided biopsy (USPbx) was performed. RESULTS: Mean PSA Level was 9.5 ng/ml (range: 1– 26 ng/ml), mean patients age was 66.1 years (48.6– 80.4). In 11/41 patients (26.8%) prostate cancer was diagnosed by FusPbx of the PIRADS 3 lesion. In the target lesion PCa was classified as Gleason Score 3+3 in 5 patients, as 3+4 in 3, 4+3 in 1, 4+4 in 1 and 4+5 in 1 patient. In patients with negative FusPbx USPbx revealed PCa in another 7 patients (17.1%). In 5 of these GS 3+3 PCa was found, in another 2 patients GS 3+4 PCa. CONCLUSIONS: PIRADS 3 lesion indicates an equivocal likelihood of significant prostate cancer. In our series the overall PCa detection rate was 26.8% and 14.6% for clinically significant cancer in PIRADS 3 lesions. This evokes the question, if PIRADS 3 lesions could be surveilled only. The findings should be confirmed in a larger series. [ABSTRACT FROM AUTHOR]

Arthritis often presents with serious pain of the affected joints. The pain results mainly from underlying inflammatory processes initiated by the immune response to the degenerative structural changes within the joints and is associated with microvascular vasodilation that increases articular blood flow. Laser Doppler-based methods facilitate reliable quantification of microvascular perfusion. We hypothesize that laser Doppler-based measurements of periarticular blood flux can be utilized for assessment of arthritis pain in patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Renal cell carcinomas (RCC) represent a heterogeneous group of hypo- and hypervascularized malignancies. Using contrast-enhanced ultrasound (CEUS) specific imaging features of clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC) subtypes have been demonstrated. However, some RCCs show atypical imaging features making it difficult to distinguish between the subtypes. OBJECTIVE: This study was performed to evaluate the observed enhancement features of pRCC in CEUS and to assess the sensitivity in the diagnosis of suspected renal malignancies in a 10 year retrospective analysis at our institution. METHODS: The study population consisted of 60 patients with histologically confirmed pRCC. All patients underwent CEUS imaging between 2005 and 2015 as part of their diagnostic workup. RESULTS: In 45 out of 60 (75%) cases the examined pRCC showed typical hypoenhancement and wash-out. 15 out of 60 (25%) pRCC showed atypical enhancement features; in 14 cases the contrast enhancement indicated a ccRCC. 1 complex cyst was falsely reported as IIF lesion. 59 out of 60 malignancies were reported as malignant using CEUS resulting in a sensitivity of 98.4%. CONCLUSIONS: CEUS is an eligible imaging technique to visualize the contrast enhancement features of pRCC. However, up to 25% of pRCCs show an atypical enhancement pattern making it difficult to distinguish it from other renal lesions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Radiologic imaging, especially ultrasound has an important role in the assessment of gallbladder alteration. Contrast-enhanced ultrasound (CEUS) is an easy and fast imaging technique that overcomes the limitations of greyscale ultrasonography. It is a safe tool that can be used as an additional imaging modality in order to elucidate and differentiate gallbladder pathological findings. OBJECTIVE: The aim of this retrospective study analysis is to assess the diagnostic performance of CEUS in gallbladder alterations and compare the results to the histopathological findings. METHODS: A total of 17 patients between 2009 and 2017 with uncertain gallbladder appearance were retrospectively analysed. A single experienced physician with more than fifteen years' experience performed CEUS examinations by applying a second-generation blood pool agent (SonoVue®, Bracco, Milan, Italy). Archived images were interpreted by the same physician and compared to the histopathological findings. RESULTS: CEUS results, when correlated to the respectively pathologic findings, presented a sensitivity of 100%, a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%. All patients were successfully examined without any adverse reaction. CONCLUSION: In conclusion, the excellent results in this study acknowledged that CEUS is a feasible alternative tool to differentiate gallbladder pathologic alterations. [ABSTRACT FROM AUTHOR]

BACKGROUND: The first method of choice for gallbladder alteration detection is the conventional ultrasound. Due to some imaging limitations, contrast-enhanced ultrasound (CEUS) has been widely used in the last years. CEUS is an additional modality that is able to depict microvessels flow and elucidate suspicious findings. OBJECTIVE: The aim of this retrospective mono-center analysis study is to evaluate the performance of CEUS in gallbladder diseases and compare it to cross-sectional imaging modalities and histopathological results as gold standard. METHODS: The retrospective study analysed 37 patients with gallbladder diseases between 2009 and 2017. All patients underwent CEUS examinations and additional cross-sectional imaging was also performed: CT imaging on 24 (64.9%) patients, MRI imaging on 18 (48.6%) patients, CT and MRI imaging on (28.7%). CEUS images were performed and interpreted by a single physician. RESULTS: CEUS imaging results of the gallbladder showed a sensitivity and specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%. CT imaging of the gallbladder showed a sensitivity of 100%, specificity of 75%, PPV of 100%, and NPV of 95%. MR imaging of the gallbladder showed a sensitivity of 100%, specificity of 93%, PPV of 75%, and NPV of 100%. CONCLUSION: Ultrasound imaging plays an essential role in the evaluation of gallbladder disease. Due to additional features of contrast-enhanced ultrasound, it is possible to differentiate gallbladder pathologic alterations by depicting its micro and macrocirculation and display important malignant features that recommends prompt management. Patients with contraindications to other cross-sectional imaging modalities benefit from this safe technique. [ABSTRACT FROM AUTHOR]

BACKGROUND: The laser Doppler fluxmetry (LDF) is a non-invasive method to assess skin blood perfusion, measuring the flow of blood cells inside a tissue volume without harming the tissue. In the diagnosis of skin circulation disorders, the results of the LDF measurement are generally used in such a way that "normal" (or non-ill) or "pathological" values are achieved by comparison with a reference sample, for example of apparently healthy subjects. MATERIAL AND METHODS: In this study, the values of LDF for the diagnosis of microcirculatory disorders in patients with coronary artery disease (n = 20) or in patients with microcirculatory disorders, already diagnosed by capillary microscopy (n = 46), were examined. RESULTS: The mean values of LD amplitudes in the four frequency windows for patients with coronary artery disease were in the reference range. However, some of the patients showed reduced LD values: in eleven of the twenty patients, one or more mean LD amplitudes were below the reference range. Four of the eleven patients had pathologically decreased capillary erythrocyte velocities of very = 0.09–0.21 [mm/s], while the other seven patients had normal blood circulation at rest. For all patients with a proven cutaneous microcirculatory disorder, the mean LD amplitude in at least one of the frequency windows FF2 to FF4 was pathologically reduced. CONCLUSION: The Laser-Doppler fluxmetry method used in the study allows the reliable diagnosis of cutaneous microcirculatory disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic venous disease (CVD) is extremely common worldwide with prevalence increasing with age. It is associated with a reduced quality of life, particularly in relation to pain, physical function and mobility. Symptomatic chronic venous insufficiency (CVI) with venous ulcer at its' endpoint, indicates interventional surgery to cure venous reflux therewith promoting wound healing and preventing recurrence. In this retrospective, single-centre, consecutive case-control study in a single patient population of a university clinic in northern Germany a holistic evaluation of varicose vein surgeries has been undertaken. Part I covered postoperative complications in relation to co-morbidities, co-medication and clinical presentation. Part II of this article presents now the hemodynamic results in relation to the perioperative evolution of CVI specific symptoms. METHODS: Records of n = 429 (467 extremities) patients from 2009-2013 treated with open surgery were analysed with regards to perioperative hemodynamics. Evolution of CVI symptomology was accessed postoperatively with the help of a questionnaire and patient records in the case of complication development. Venous hemodynamics was analysed in the whole patient population and with regards to complication subgroups: no events (NE), neglectable adverse events (NAE) and non-neglectable adverse events (NNAE). RESULTS: Postoperatively, patients' CVI-symptoms like pain (p < 0.001), swelling (p < 0.001) and itching (p = 0.003) significantly improved. The venous refill time and venous pump capacity improved significantly after open vein surgery (p < 0.05). Regardless of the development of postoperative complications there was a significant improvement of venous function at 6 weeks- and one-year postoperative in follow-up (p < 0.05). Symptom regression was strongly correlated with hemodynamic improvement. CONCLUSION: A significant improvement of patients' symptoms was achieved by means of open-surgery, regardless of postoperative complication development. This was in accordance with the improvement of venous hemodynamics. A strong correlation between symptom regression and improvement in venous hemodynamics could be proven. [ABSTRACT FROM AUTHOR]

Introduction: Dandelion (Taraxacum officinale coll.), also called the common dandelion grows wild throughout Europe, Asia and the Americas. It is a perennial plant of the family of Asteraceae, having powerful healing properties. The entire plant – flowers, roots and leaves – is the medicinal raw material.

Introduction: Obesity is linked to metabolic disorders. Bariatric surgery offers a promising therapeutic effect in the treatment of obesity, but its impact on fatty acid (FA) profiles within erythrocytes and the associated clinical implications remain underexplored., Objectives: This study aimed to assess changes in erythrocyte membrane FA composition after laparoscopic sleeve gastrectomy (LSG) and to correlate these alterations with clinical parameters., Patients and Methods: A total of 61 patients with morbid obesity undergoing LSG and 32 healthy controls were enrolled. Erythrocyte membrane FA composition was analyzed using gas chromatography. Clinical parameters, including body mass index (BMI), blood pressure, and multiple biochemical markers, were evaluated. In the surgical patients, the dynamics of metabolism post‑LSG was assessed by exploring the ratios of erythrocyte FA concentrations at baseline and 6 months postsurgery, with the corresponding ratios calculated for clinical parameters., Results: Bariatric intervention resulted in reduction of median BMI (41.1 to 32 kg/m2) and median fat mass (54.1 to 35.2 kg). Other anthropometric parameters also improved significantly. Favorable changes in FA metabolism post‑LSG, potentially leading to a reduction in cardiovascular disease risk, were observed. The OMEGA‑3 Index (median, 1.8 vs 3) and the eicosapentaenoic / arachidonic FA ratio (median, 0.1 vs 0.2) increased after surgery. Linoleic acid (LA) was shown to be significantly associated with markers of obesity. The LA ratios increased along with the reduction of BMI (r = -0.32), fat mass (r = -0.39), and waist circumference (r = -0.33) proportions. A positive correlation was noted between LA concentration and excess weight loss percentage (r = 0.49), and excess BMI loss percentage (r = 0.5)., Conclusions: The study underscores distinct post‑LSG changes in erythrocyte FA profiles, potentially associated with reduced weight and BMI, improved inflammatory status, and lower cardiovascular disease risk.

Sensitive biomaterials subjected to surface modification require delicate methods to preserve their structures and key properties. These include collagen-sealed polyester vascular prostheses. For their functionalization, coating with polycatecholamines (PCAs) can be used. PCAs change some important biological properties of biomaterials, e.g., hydrophilicity, bioactivity, antibacterial activity, and drug binding. The coating process can be stimulated by oxidants, organic solvents, or process conditions. However, these factors may change the properties of the PCA layer and the matrix itself. In this work, collagen-sealed vascular grafts were functionalized with a poly(l-DOPA) (PLD) layer using novel seawater-inspired ion combination as an accelerator, compared to the sodium periodate, Cu 2+ /H 2 O 2 mixture, and accelerator-free reference methods. Then, poly(l-DOPA) was used as the interface for antibiotic binding. The coated prostheses were characterized (SEM, FIB-SEM, FTIR, UV/vis), and their important functional parameters (mechanical, antioxidant, hemolytic, and prothrombotic properties, bioactivity, stability in human blood and simulated body fluid (SBF), antibiotic binding, release, and antibacterial activity) were compared. It was found that although sodium periodate increased the strength and drug-binding capacity of the prosthesis, it also increased the blood hemolysis risk. Cu 2+ /H 2 O 2 destabilized the mechanical properties of the coating and the graft. The seawater-inspired ion-accelerated method was efficient, stable, and matrix- and human blood-friendly, and it stimulated hydroxyapatite formation on the prosthesis surface. The results lead to the conclusion that selection of the PCA formation accelerator should be based on a careful analysis of the biological properties of medical devices. They also suggest that the ion-accelerated method of PLD coating on medical devices may be highly effective and safer than the oxidant-accelerated coating method.

Fungi are a unique natural resource rich in polysaccharides, proteins, and other components. Polysaccharides are considered one of the most important bioactive components in fungi. Increasing numbers of studies have confirmed that fungal polysaccharides have various biological activities. Given these facts, the main aim of this investigation was to carry out isolation, identification, and structural characterisation of a new polysaccharide (EPS) derived from laboratory-cultured vegetative mycelium of a new Spongipellis borealis strain isolated from the environment. The examination of monosaccharides in the EPS demonstrated that the isolated biopolymer was composed mainly of glucose, galactose, and mannose monomers. The analysis of the methylation of the studied polymer indicated that it contained mainly terminal, →3)-linked, →4)-linked, and →2,4)-linked hexoses. The effect of fungal polysaccharides on S. borealis proteolytic enzymes (pepsin, trypsin, and pycnoporopepsin) and laccase activity was determined for the first time. Incubation of the enzyme preparation and EPS showed an influence of EPS on the stability of these enzymes, compared to the control values (without EPS).

Objective: The study aims at assessing the relationship between blood pressure, heart geometry parameters, and the erythrocyte content of sulfur, potassium, chlorine and phosphorus, in a group of patients with ambulatory systolic and diastolic blood pressure (SBP, DBP) below 140 or 90 mm Hg, respectively, who were otherwise healthy and untreated., Methods: The study group consisted of 42 adults recruited in a primary care setting. The individuals were healthy, not undergoing any therapy and free from smoking. For each individual, data were obtained on: average 24-hour SBP and DBP, left ventricle geometry, complete blood count, lipids profile, fibrinogen, hs-CRP and the erythrocyte concentration of sulfur (S), potassium (K), chlorine (Cl) and phosphorus (P)., Results: Multivariate regression analysis showed statistically significant relationships of diastolic posterior wall thickness (PWTd) and relative wall thickness (RWT) with the concentration ratio of sulfur and potassium (S/K) in erythrocytes: PWTd and RWT increase as the S/K ratio increases. Also, SBP was found to be positively correlated with the S/K ratio., Conclusions: The increase in sulfur content in RBCs could be an indicator of the downregulation of nitric oxide (NO) erythrocyte bioavailability exerted by endogenously produced hydrogen sulfide (H2S), and, in consequence, a marker of the development of hypertension and/or adverse changes in heart geometry.

Background: The EUROACTION study (nurse‑coordinated multidisciplinary, family‑based cardiovascular disease prevention program) documented the efficacy of a nurse‑managed, comprehensive prevention program in reducing risk factors for cardiovascular disease (CVD). No information was available on survival., Aims: The aim of the study was to assess the effects of EUROACTION intervention on CVD risk factors and 12‑year survival in the Polish component of the study., Methods: Two district hospitals and 2 primary care practices were allocated randomly to intervention (INT) or usual care (UC). The primary endpoints were lifestyle and risk factors changes at 1‑year follow‑up. Differences in survival were analyzed using the multivariable Cox proportional hazards regression models., Results: The study involved 628 patients with coronary heart disease (CHD) and 711 high‑risk patients. Compared to UC, INT patients achieved healthier lifestyles and a larger reduction of risk factors at 1 year but these differences were not maintained 12 years after the intervention. Less deaths occurred in patients from the INT hospital and from INT primary practice (hazard ratio [HR], 0.58; 95% CI, 0.42-0.82 and HR, 0.53; 95% CI, 0.3-0.95, respectively). Adjustment for the covariates slightly attenuated the estimates and removed significance (HR, 0.74; 95% CI, 0.52-1.04 and HR, 0.66; 95% CI, 0.36-1.24, respectively). For combined CHD and high‑risk patient groups, compared with UC, INT patients had a 36% lower risk of death after adjustment for age, sex, and history of CHD (HR, 0.64; 95% CI, 0.48-0.86)., Conclusions: The impact of the EUROACTION intervention on lifestyle and CVD risk factors could have contributed to lower mortality in INT coronary and high‑risk patients. These results emphasize the need for sustaining the interventions to help patients maintain a healthy lifestyle.

Cellular membrane potential plays a key role in the formation and retrieval of memories in the metazoan brain, but it remains unclear whether such memory can also be encoded in simpler organisms like bacteria. Here, we show that single-cell-level memory patterns can be imprinted in bacterial biofilms by light-induced changes in the membrane potential. We demonstrate that transient optical perturbations generate a persistent and robust potassium-channel-mediated change in the membrane potential of bacteria within the biofilm. The light-exposed cells respond in an anti-phase manner, relative to unexposed cells, to both natural and induced oscillations in extracellular ion concentrations. This anti-phase response, which persists for hours following the transient optical stimulus, enables a direct single-cell resolution visualization of spatial memory patterns within the biofilm. The ability to encode robust and persistent membrane-potential-based memory patterns could enable computations within prokaryotic communities and suggests a parallel between neurons and bacteria., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bacteria exhibit cell-to-cell variability in their resilience to stress, for example, following antibiotic exposure. Higher resilience is typically ascribed to "dormant" non-growing cellular states. Here, by measuring membrane potential dynamics of Bacillus subtilis cells, we show that actively growing bacteria can cope with ribosome-targeting antibiotics through an alternative mechanism based on ion flux modulation. Specifically, we observed two types of cellular behavior: growth-defective cells exhibited a mathematically predicted transient increase in membrane potential (hyperpolarization), followed by cell death, whereas growing cells lacked hyperpolarization events and showed elevated survival. Using structural perturbations of the ribosome and proteomic analysis, we uncovered that stress resilience arises from magnesium influx, which prevents hyperpolarization. Thus, ion flux modulation provides a distinct mechanism to cope with ribosomal stress. These results suggest new approaches to increase the effectiveness of ribosome-targeting antibiotics and reveal an intriguing connection between ribosomes and the membrane potential, two fundamental properties of cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Raman spectroscopy of erythrocytes provides detailed information about the structure and status of heme moiety, which can be used to provide new insights into molecular pathogenesis of several diseases. In this study, we present the first Raman spectroscopy investigations of the effect of hemoglobin oxygenation in the context of hypertensive disease. The experimental data was subjected to Logistic Regression, which indicated heme‑oxygenation status as an important risk factor alongside other clinical parameters. The 1605/1621 cm -1 band ratio was selected as an optimal Raman metric for risk assessment and along with other band ratios (1583, 1639, 1310 cm -1 ) related to heme status and when combined with clinical data via logistic regression gave an Area Under the Curve (AUC) >0.95 for prehypertension risk prediction. The work demonstrates the feasibility of Raman spectroscopy to distinguish between prehypertensive and normotensive states. Simultaneously, it is implied that the etiology of the high blood pressure progression may be connected with the changes in hemoglobin oxygenation., (Copyright © 2018. Published by Elsevier B.V.)