Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity

Transfusion of red cell concentrates (RCCs) is associated with increased risk of adverse outcomes that may be affected by different blood manufacturing methods and the presence of extracellular vesicles (EVs). We investigated the effect of different manufacturing methods on hemolysis, residual cells, cell-derived EVs, and immunomodulatory effects on monocyte activity. Thirty-two RCC units produced using whole blood filtration (WBF), red cell filtration (RCF), apheresis-derived (AD), and whole blood-derived (WBD) methods were examined (n = 8 per method). Residual platelet and white blood cells (WBCs) and the concentration, cell of origin, and characterization of EVs in RCC supernatants were assessed in fresh and stored supernatants. Immunomodulatory activity of RCC supernatants was assessed by quantifying monocyte cytokine production capacity in an in vitro transfusion model. RCF units yielded the lowest number of platelet and WBC-derived EVs, whereas the highest number of platelet EVs was in AD (day 5) and in WBD (day 42). The number of small EVs (<200 nm) was greater than large EVs (≥200 nm) in all tested supernatants, and the highest level of small EVs were in AD units. Immunomodulatory activity was mixed, with evidence of both inflammatory and immunosuppressive effects. Monocytes produced more inflammatory interleukin-8 after exposure to fresh WBF or expired WBD supernatants. Exposure to supernatants from AD and WBD RCC suppressed monocyte lipopolysaccharide-induced cytokine production. Manufacturing methods significantly affect RCC unit EV characteristics and are associated with an immunomodulatory effect of RCC supernatants, which may affect the quality and safety of RCCs

Effect of a single Dialysis session on plasma Lp(a) levels in patients on Maintenance haemodialysis

Background: &#xd;&#xa;Cardiovascular disease (CVD) is a major cause of mortality in End stage renal disease (ESRD) patients on Maintenance haemodialysis (MHD). Lp (a), is a specialized form of glycoprotein-LDL-cholesterol complex and is an independent risk factor for myocardial infarction. The risk is related to its atherogenic and thrombogenic properties. The present study was taken up to evaluate changes in Lp(a) and Lipid profile in patients undergoing hemodialysis session. &#xd;&#xa;&#xd;&#xa;Methodology: &#xd;&#xa;Twenty seven patients with end stage renal disease who were on maintenance hemodialysis were included. Plasma samples were collected hourly during a dialysis session with polysulfone membrane using bicarbonate dialysate. Plasma cholesterol, triglycerides, and Lp(a) were estimated on Beckmann CX9 Fully Automated Analyzer using commercial kits. Statistical analysis was performed using SPSS for windows version 11.5.&#xd;&#xa;&#xd;&#xa;Results: &#xd;&#xa;Results of analysis of variance for repeated measures after correction for hemoconcentration where necessary revealed a decrease in Lp(a) (p=0.022) and triglycerides (p=0.001) levels and no change in cholesterol (p=0.48) levels.&#xd;&#xa;&#xd;&#xa;Conclusion: &#xd;&#xa;Maintenance dialysis program is known to produce Dyslipidemia. Study of Lp(a) in dialysis patients is important as this is an independent risk marker. However there are very few reports on changes in Lp(a) due to the dialysis session. Our findings will be discussed in comparison with other reports.&#xd;&#xa

Droplet-like Fermi surfaces in the anti-ferromagnetic phase of EuFe2_2As2_2, an Fe-pnictide superconductor parent compound

Using angle resolved photoemission it is shown that the low lying electronic states of the iron pnictide parent compound EuFe$_2$As$_2$ are strongly modified in the magnetically ordered, low temperature, orthorhombic state compared to the tetragonal, paramagnetic case above the spin density wave transition temperature. Back-folded bands, reflected in the orthorhombic/ anti-ferromagnetic Brillouin zone boundary hybridize strongly with the non-folded states, leading to the opening of energy gaps. As a direct consequence, the large Fermi surfaces of the tetragonal phase fragment, the low temperature Fermi surface being comprised of small droplets, built up of electron and hole-like sections. These high resolution ARPES data are therefore in keeping with quantum oscillation and optical data from other undoped pnictide parent compounds.Comment: 4 figures, 6 page

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

Comparative study of pre-operative CT scan and per-operative findings in carcinoma ovary

Background: Initial therapy for ovarian carcinoma involves aggressive surgery to remove as much tumor as possible. However, this procedure is not beneficial for patients unless tumor is optimally debulked. This study was performed to compare the CT scan findings and per-operative findings and to determine whether CT can be used to predict the success of debulking surgery.Methods: A retrospective and prospective   study was conducted from 2011 to 2013 comparing pre operative CT scan findings and per operative findings of patients diagnosed with carcinoma ovary. 59 patients met the inclusion criteria. Five radiographic features were analysed and a  score of 0 to 2 was assigned to each. These scores were added and compared to the surgical results.Results: We found that CT was highly sensitive in the diagnosis of retroperitoneal lymph node, ascites and omental involvement with sensitivity of 85.7%, 100% and 73.6% respectively. Sensitivity to detect peritoneal deposits and sub diaphragm deposits was 60% and 16.6% respectively. Specificity was uniformly greater than 85% for all parameters except ascites and retro peritoneal lymph nodes which was 71.4% and 54.8%. On a 10-point preoperative CT scoring system, a score of ≥3 identified patients whose tumors were not successfully debulked with a sensitivity of 79% and a specificity of 93%.Conclusions: CT scan is highly sensitive and specific in identifying metastatic disease and can be used as a pre-operative tool in advanced carcinoma ovary to guide further management

Pressure effects on the electron-doped high Tc superconductor BaFe(2-x)Co(x)As(2)

Application of pressures or electron-doping through Co substitution into Fe sites transforms the itinerant antiferromagnet BaFe(2)As(2) into a superconductor with the Tc exceeding 20K. We carried out systematic transport measurements of BaFe(2-x)Co(x)As(2) superconductors in pressures up to 2.5GPa, and elucidate the interplay between the effects of electron-doping and pressures. For the underdoped sample with nominal composition x = 0.08, application of pressure strongly suppresses a magnetic instability while enhancing Tc by nearly a factor of two from 11K to 21K. In contrast, the optimally doped x=0.20 sample shows very little enhancement of Tc=22K under applied pressure. Our results strongly suggest that the proximity to a magnetic instability is the key to the mechanism of superconductivity in iron-pnictides.Comment: 5 figure

Point-contact spectroscopic studies on normal and superconducting AFe_2As_2-type iron-pnictide single crystals

Point-contact Andreev reflection spectroscopy (PCARS) is applied to investigate the gap structure in iron pnictide single crystal superconductors of the AFe_2As_2 (A=Ba, Sr) family ("Fe-122"). The observed point-contact junction conductance curves, G(V), can be divided into two categories: one where Andreev reflection is present for both (Ba_{0.6}K_{0.4})Fe_2As_2 and Ba(Fe_{0.9}Co_{0.1})_2As_2, and the other with a V^{2/3} background conductance universally observed extending even up to 100 meV for Sr_{0.6}Na_{0.4}Fe_2As_2 and Sr(Fe_{0.9}Co_{0.1})_2As_2. The latter is also observed in point-contact junctions on the nonsuperconducting parent compound BaFe_2As_2. Mesoscopic phase-separated coexistence of magnetic and superconducting orders is considered to explain distinct behaviors in the superconducting samples. For Ba_{0.6}K_{0.4}Fe_2As_2, double peaks due to Andreev reflection with strongly-sloping background are frequently observed for point-contacts on freshly-cleaved c-axis surfaces. If normalized by a background baseline and analyzed by the Blonder-Tinkham-Klapwijk model, the data show a gap size ~3.0-4.0 meV with 2\Delta_0/k_BT_c ~ 2.0-2.6, consistent with the smaller gap size reported in the LnFeAsO family ("Fe-1111"). For the Ba(Fe_{0.9}Co_{0.1})_2As_2, G(V) curves typically display a zero-bias conductance peak.Comment: 12 pages, 6 figure

Evidence for Dirac nodes from quantum oscillations in SrFe2As2

We present a detailed study of quantum oscillations in the antiferromagnetically ordered pnictide compound SrFe2As2 as the angle between the applied magnetic field and crystalline axes is varied. Our measurements were performed on high-quality single crystals in a superconducting magnet, and in pulsed magnetic fields up to 60 T, allowing us to observe orbits from several small Fermi-surface pockets. We extract the cyclotron effective mass m☆ and frequency F for these orbits and track their values as the field is rotated away from the c axis. While a constant ratio of m☆/F is expected for a parabolic band, we observe deviations from this behavior. We conclude that this observation points to orbits derived from a band with Dirac dispersion near the Fermi level

A rare case of arteriovenous malformation following hysterectomy in a case of choriocarcinoma

A uterine arteriovenous malformation (AVM) is a rare cause of uterine bleeding. It may have varied presentations ranging from being completely asymptomatic; to features of congestive heart failure, to vaginal bleeding which may at times life be threatening. Clinical findings in such cases are often un-reliable; requiring a high index of suspicion to make the diagnosis. We report a case of a 46-year-old lady who presented with heavy vaginal bleeding. She has undergone hysterectomy with a histopathology of choriocarcinoma one and half months back. She has received chemotherapy and 8 fractions of radiotherapy for the same. AVM was diagnosed following a CT angiogram and was managed by embolization. We also discuss in brief about this uncommon but serious condition which the radiologist/gynaecologist may encounter in their practice. AV Malformation is a rare but potentially life-threatening cause of vaginal bleeding which must be kept in the differential diagnosis of sudden and massive vaginal bleeding. It requires a high index of clinical suspicion. Despite its rarity, early recognition of an AVM is imperative to enable timely diagnosis and intervention

The Gut-Brain Axis in Multiple Sclerosis: A Systematic Review of Microbiome Modulation and Neurological Outcomes

Background: The disease multiple sclerosis (MS) is an autoimmune chronic disorder that afflicts the central nervous system with demyelination and is associated with a variety of neurological symptoms. Increasing research interest is focused on the gut-brain axis, which constitutes a communication network between the gastrointestinal tract and the central nervous system, especially regarding the modulation of immune responses and the influence on neurological health.Objective: The current systematic review looks to establish whether alterations in the human microbiome due to dietary change, probiotics, and prebiotics relate to neurological effects in patients with multiple sclerosis via the gut-brain axis.Methods: The inclusion criteria will be original research articles that include randomized controlled trials, cohort studies, case-control studies, and observational studies on human subjects with all types of MS. The studies should report neurological outcomes such as symptoms, disease progression, and biomarkers of neuroinflammation. Articles published within the last ten years will be included, while animal studies, non-pertinent neurological disorders, and those lacking relevant methodologies will be excluded.Results: The review synthesized the effects of microbiome modulation on immune responses, focusing on cytokine production and inflammatory cell activation. Preliminary findings suggest that dysbiosis exacerbates neuroinflammation and contributes to disease progression. Therapies targeting the gut microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, show potential for improving clinical outcomes, although results remain variable. The variability of individual microbiota, lack of robust clinical trials specifically for MS, and concerns regarding safety and efficacy of these interventions present significant challenges. Membrane technology enhances the study of the gut-brain axis in multiple sclerosis (MS) by enabling the isolation of gut-derived biomolecules, which influence immune responses and neuroinflammation. This integration offers insights into microbial signatures and potential therapeutic interventions, paving the way for innovative treatments targeting gut health to improve MS outcomes. Understanding the interplay between gut microbiota and MS is essential for developing innovative therapeutic strategies. This review aims to provide insights into the GBA\u27s role in MS, paving the way for future research and clinical applications