Sex-related aspects of the red blood cell storage lesion

BackgroundSeveral factors contribute to the manifestation of red blood cell (RBC) storage lesions, with one of the most interesting being the “donor variation effect”. Since many haematological characteristics of blood donors are sex-dependent, sex hormones and their age-dependent variation may affect the storage profile of RBCs.Materials and methodsFresh blood from 200 healthy male and female donors underwent haematological, biochemical and physiological analysis. Three selected groups of donors (men, n=8; pre-menopausal women, n=8; and post-menopausal women, n=4) exhibiting as similar as possible baseline values were recruited for blood donation in leukoreduced CPD/SAGM units. RBC indices, haemolysis and propensity for haemolysis, reactive oxygen species (ROS) and plasma antioxidant capacity were measured bi-weekly.ResultsFemale blood was characterised by lower plasma antioxidant capacity and free haemoglobin (Hb) levels in vivo, in spite of the higher RBC osmotic fragility, compared to male blood. Comparatively low Hb concentration was also measured in stored RBCs from female donors, as in vivo. Mean corpuscular Hb (MCH), mean corpuscular Hb concentration (MCHC), and plasma antioxidant capacity were also lower in female donors throughout storage, even though baseline levels were equal to those of the male group. There was no difference in propensity of stored RBCs for haemolysis between male and female units but intracellular ROS levels were significantly lower in female RBCs. Increased end-of-storage extracellular potassium and recruitment of protein stress markers (clusterin, Hb) to the RBC membrane were observed in the units of post- vs pre-menopausal female donors at mid-storage onwards.DiscussionDonor’s sex has an impact on Hb concentration and redox parameters of stored RBCs. In addition, menopause seems to promote RBC membrane remodelling, at least during prolonged storage. Our pilot study provides new insights on the different effects on RBC storage lesion according to sex.     

Evaluation of the efficacy of platelet-rich plasma on healing of clean diabetic foot ulcers: A randomized clinical trial in Tehran,Iran

Background and aimsDiabetic foot ulcers (DFUs) are among challenging hurdles both for the patient and the physician. There is a recent trend toward finding novel and clinically efficient modalities to treat this potentially hazardous complication of diabetes mellitus in a timely manner. Herein, we aim to appraise the efficacy of platelet-rich plasma (PRP) in healing of clean DFUs.Methods90 patients with clean DFUs consisting of 56 (62.2%) males and 34 (37.8%) females with mean age (±standard deviation) of 56.52 (±7.14) years were enrolled in this study between June 2017 and December 2018. They were randomly allocated into control group (47 patients who received conventional dressing along with silver sulfadiazine ointment twice daily), and case group (43 patients who received PRP gel twice weekly for 3 weeks). All the patients were followed up for 6 months.ResultsOur study showed that PRP significantly increased the healing rate of DFUs regardless of the age (p-value: 0.0), gender (p-value: 0.0), or smoking (p-value: 0.0) and blood pressure (p-value: 0.0) status of patients, but it did not have a significant impact on the need for amputation (p-value: 0.11), level of amputation (p-value: 0.16), or the need for further treatments such as graft or angioplasty (p-value: 0.52).ConclusionRegardless of the age, gender, or smoking and blood pressure status of patients, PRP can be efficiently used in diabetic patients to accelerate the healing rate of foot ulcers.     

Advanced Constitutive Modeling of the Thixotropic Elasto-Visco-Plastic Behavior of Blood: Steady-State Blood Flow in Microtubes

The present work focuses on the in-silico investigation of the steady-state blood flow in straight microtubes, incorporating advanced constitutive modeling for human blood and blood plasma. The blood constitutive model accounts for the interplay between thixotropy and elasto-visco-plasticity via a scalar variable that describes the level of the local blood structure at any instance. The constitutive model is enhanced by the non-Newtonian modeling of the plasma phase, which features bulk viscoelasticity. Incorporating microcirculation phenomena such as the cell-free layer (CFL) formation or the Fåhraeus and the Fåhraeus-Lindqvist effects is an indispensable part of the blood flow investigation. The coupling between them and the momentum balance is achieved through correlations based on experimental observations. Notably, we propose a new simplified form for the dependence of the apparent viscosity on the hematocrit that predicts the CFL thickness correctly. Our investigation focuses on the impact of the microtube diameter and the pressure-gradient on velocity profiles, normal and shear viscoelastic stresses, and thixotropic properties. We demonstrate the microstructural configuration of blood in steady-state conditions, revealing that blood is highly aggregated in narrow tubes, promoting a flat velocity profile. Additionally, the proper accounting of the CFL thickness shows that for narrow microtubes, the reduction of discharged hematocrit is significant, which in some cases is up to 70%. At high pressure-gradients, the plasmatic proteins in both regions are extended in the flow direction, developing large axial normal stresses, which are more significant in the core region. We also provide normal stress predictions at both the blood/plasma interface (INS) and the tube wall (WNS), which are difficult to measure experimentally. Both decrease with the tube radius; however, they exhibit significant differences in magnitude and type of variation. INS varies linearly from 4.5 to 2 Pa, while WNS exhibits an exponential decrease taking values from 50 mPa to zero.     

The Oxidation Behavior of ZrB2-SiC Ceramic Composites Fabricated by Plasma Spray Process

Our goal is to develop a structural ceramic for high-temperature applications in which silicon carbide-based materials (SiCs) are used as matrix composites. The potential of SiCs to deposit a mixture of SiC and zirconium diboride (ZrB₂) plasma spray coating is analyzed. To deposit thermal barrier layers containing up to 50 vol.% SiC, a high-pressure plasma spray (HPPS) process was used. Although the SiC cannot be deposited by thermal spray, a mixture of SiC and zirconium diboride (ZrB₂) was deposited because these two compounds form a eutectic phase at a temperature below SiC decomposition. The preference was two different forms, 3 mm and 1 mm, of graphite substrates with different thickness values. A comparison of the morphology of SiC-ZrB₂ coatings before and after thermal treatment was performed by applying heat to the surface of a gas torch and traditional furnace between 800 °C and 1200 °C. The growth of the oxide scale was calculated with X-ray diffraction (XRD), scanning electron microscopy (SEM)/energy dispersive X-ray analysis (EDX), transmission electron microscopy (TEM), and density. The oxide scale consists of a SiO₂ layer with ZrO₂ groups. The findings indicate a greater potential for the studied material in protecting against high-temperature oxidation and in a wide variety of aerospace applications.     

Effect of Non-Thermal Atmospheric Plasma on Micro-Tensile Bond Strength at Adhesive/Dentin Interface: A Systematic Review

Objective: The objective of this review was to evaluate the effect of non-thermal atmospheric plasma (NTAP) on adhesives resin–dentin micro-tensile bond strength (μTBS) in previously published studies. Methods: Electronic search was conducted using the Medline, Cochrane library, and Scopus databases. The included studies were laboratory studies that investigated the effect of NTAP on adhesives μTBS to coronal dentin. Studies that evaluated the effect of NTAP on bond strength to indirect substrates, enamel or root dentin, were excluded. The methodological quality of included studies was assessed. Results: Thirteen studies were included in this systematic review. All the included studies were considered to have a medium risk of bias. NTAP significantly improved μTBS at 24 h or after short-term aging in five studies (38.5%) and both immediate and after long-term aging in 5 studies (38.5%). In two studies (15.4%), NTAP resulted in a short-term material-dependent effect that was not stable after long-term aging. Interestingly, in one study (7.7%), NTAP had a positive effect only in the etch-and-rinse (ER) mode after long-term aging. Conclusion: Within the limitations of this systematic review, NTAP application could enhance resin–dentin μTBS of ER adhesives or universal adhesives (UAs) applied in the ER mode. In the ER mode, the rewetting step after NTAP seems to be unnecessary. Because of the limited information currently available in the literature, further studies are required to evaluate the effect of the NTAP application on self-etch (SE) adhesives or UAs applied in the SE mode.     

Peripheral Blood Immune Profiling of Convalescent Plasma Donors Reveals Alterations in Specific Immune Subpopulations Even at 2 Months Post SARS-CoV-2 Infection

Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e.g., lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes. Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects were analyzed by multiparametric flow cytometry, allowing the identification of a wide panel of immune cells, comprising lymphocytes (T, B, natural killer (NK) and NKT cells), monocytes, granulocytes, and their subsets. Compared to active COVID-19 patients, our results revealed that the immune profile of recovered donors was restored for most subpopulations. Nevertheless, even 2 months after recovery, CP donors still had reduced levels of CD4⁺ T and B cells, as well as granulocytes. CP donors with non-detectable levels of anti-SARS-CoV-2-specific antibodies in their serum were characterized by higher Th9 and Th17 cells, which were possibly expanded at the expense of Th2 humoral immunity. The most noticeable alterations were identified in previously hospitalized CP donors, who presented the lowest levels of CD8⁺ regulatory T cells, the highest levels of CD56⁺CD16⁻ NKT cells, and a promotion of a Th17-type phenotype, which might be associated with a prolonged pro-inflammatory response. A longer follow-up of CP donors will eventually reveal the time needed for full recovery of their immune system competence.     

Known epigenetic biomarkers for prostate cancer detection and management: exploring the potential of blood-based liquid biopsies

Introduction: Although prostate cancer (PCa) stands as an important cause of cancer-related deaths, a sizeable proportion of diagnosed cases are clinically insignificant. Hence, novel and more specific biomarkers to identify clinically significant PCa are needed. Liquid biopsies offer the potential to accurately identify cancer markers, including PCa. Epigenetic biomarkers such as cell-free DNA and circulating RNAs have emerged as minimally invasive cancer markers.

Areas covered: Herein, we provide an overview of epigenetic biomarkers current state based on a comprehensive review of the relevant literature in blood-based liquid biopsies and challenges/limitations of this new and growing field of cancer biomarkers.

Expert opinion: The epigenetic-based biomarkers characteristics make them attractive to the clinics and their minimally invasive assessment are a promising opportunity for PCa detection/management. The main limitations are the lack of robust validation studies and integrated approaches. Future studies would benefit from a change in focus to a ‘selected PCa detection’.     

癌相关抗原125对慢性肝病合并腹水的诊断价值

检测慢性肝病合并腹水形成患者血浆及腹水中CA12 5水平 ,探讨其临床意义。采用ELISA法检测 141例慢性肝病患者血浆CA12 5值 ,对 40例合并腹水的慢性肝病同时测腹水CA12 5值。结果显示 ( 1)慢性肝病合并腹水形成者血浆CA12 5值显著高于无腹水形成者 (P <0 0 1) ;( 2 )腹水中CA12 5值显著高于血浆中值 (P <0 0 1) ,且二者呈正相关 (r=0 965 ,P <0 0 1) ;( 3 )大量放腹水后 ,血浆中及腹水中CA12 5值显著下降 ,且腹水CA12 5值下降的幅度大于血浆CA12 5值下降的幅度 (P <0 0 1)。提示CA12 5是诊断慢性肝病合并腹水形成的一项敏感指标     

血浆置换对重型乙型病毒性肝炎HBV DNA含量的影响及与预后的关系

探讨经血浆置换（PE）治疗重型乙型病毒性肝炎后,患者血清中HBV DNA含量的变化对预后的影响。随机选取60例乙型肝炎病毒标志物阳性患者,20例为对照组,40例在内科治疗的基础上加PE治疗。观察治疗前后血清HBV DNA含量变化。40例经PE治疗的患者血清HBV DNA含量下降,PE治疗有效组比PE治疗无效组和对照组降低更明显,且肝功能指标改善也更明显。PE治疗可以有效的去除重型肝炎患者血清HBV DNA,改善肝功能及预后,提高患者的存活率。     

Physiological role of cholecystokinin on postprandial insulin secretion and gastric meal emptying in man. Studies with the cholecystokinin receptor antagonist loxiglumide

Summary Cholecystokinin was previously proposed to play an important role in the regulation of postprandial insulin secretion either indirectly, by inhibiting gastric meal emptying, or directly, by acting as an incretin promoting the release of insulin. The aim of this investigation was therefore to clarify the role of endogenous cholecystokinin in the regulation of insulin release and gastric emptying applying the highly potent and specific cholecystokinin receptor antagonist loxiglumide. Five healthy volunteers were examined after an overnight fast. Gastric meal emptying was measured by the double indicator technique using a multiple lumen tube in the duodenum and ^99mTc-diethylenetriamine pentaacetate as a meal marker and polyethylene glycol 4000 as a duodenal perfusion marker. Postprandial insulin, C-peptide, cholecystokinin and glucose levels were measured after ingestion of two isocaloric meals of a) Ensure (containing fat, protein and glucose), and b) a pure glucose meal (1.11 mol/l). The meals were given either with an intravenous infusion of loxiglumide (22 mol·kg^–1·h^–1) or placebo. The infusion of loxiglumide markedly accelerated the gastric emptying of the mixed meal (area under curve, 5576±352 min vs 3498±109 min; p<0.001) and the pure glucose meal (area under curve 5662±537 min vs 3551±534 min; p<0.05). Simultaneously, loxiglumide induced a more rapid rise in postprandial insulin levels after both meals resulting in significantly higher (p<0.05) insulin levels during the first postprandial hour, but similar insulin levels in the second postprandial hour. Accordingly, we found a close correlation between meal emptying and insulin release (r=0.748, p<0.01). Integrated insulin and C-peptide levels for the whole 2-h experimental period tended to be higher during loxiglumide infusion, but the difference did not reach statistical significance. Similar plasma glucose levels at all time periods were observed with and without loxiglumide infusion. Higher cholecystokinin levels were measured during loxiglumide infusion after the mixed (p<0.01) and the pure dextrose (p<0.05) meals. We conclude that postprandially released cholecystokinin exerts an important role in the regulation of gastric meal emptying and consecutively the postprandial pattern of insulin release. In contrast, no evidence was found for an insulinotropic role for cholecystokinin in man.