bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between the spectral photon flux density distributions of light during growth and for measurements in net photosynthetic rates of cucumber leaves
Authors: Murakami Keach , Matsuda Ryo , Fujiwara Kazuhiro
Published: January 2016

The net photosynthetic rate of a leaf becomes acclimated to the plant's environment during growth. These rates are often measured, evaluated and compared among leaves of plants grown under different light conditions. In this study, we compared net photosynthetic rates of cucumber leaves grown under white light‐emitting diode (LED) light without and with supplemental far‐red (FR) LED light (W‐ and WFR‐leaves, respectively) under three different measuring light (ML) conditions: their respective growth light (GL), artificial sunlight (AS) and blue and red (BR) light. The difference in the measured photosynthetic rates between W‐ and WFR‐leaves was greater under BR than under GL and AS. In other words, an interaction between supplemental FR light during growth and the spectral photon flux density distribution (SPD) of ML affected the measured net photosynthetic rates. We showed that the comparison and evaluation of leaf photosynthetic rates and characteristics can be biased depending on the SPD of ML, especially for plants grown under different photon flux densities in the FR waveband. We also investigated the mechanism of the interaction. We confirmed that the distribution of excitation energy between the two photosystems (PSs) changed in response to the SPD of GL, and that this change resulted in the interaction, as suggested in previous reports. However, changes in PS stoichiometry could not completely explain the adjustment in excitation energy distribution observed in this study, suggesting that other mechanisms may be involved in the interaction.
Interspecific variation in localization of hypericins and phloroglucinols in the genus Hypericum as revealed by desorption electrospray ionization mass spectrometry imaging
Authors: Kucharíková Andrea , Kimáková Katarína , Janfelt Christian , Čellárová Eva
Published: January 2016

Plants of the genus Hypericum are widely known for their therapeutic properties. The most biologically active compounds of this genus are naphtodianthrones and phloroglucinols. Indirect desorption electrospray ionization mass spectrometry (DESI‐MS) imaging allows visualization and localization of secondary metabolites in different plant tissues. This study is focused on localization of major secondary compounds in the leaves of 17 different in vitro cultured Hypericum species classified in 11 sections. Generally, all identified naphtodianthrones, protohypericin, hypericin, protopseudohypericin and pseudohypericin were co‐localized in the dark glands of eight hypericin producing species at the site of their accumulation. The known phloroglucinols, hyperforin, adhyperforin, hyperfirin and some new phloroglucinols with m/z [M − H]− 495 and 569 were localized in the translucent and pale cavities within the leaf in the majority of studied species. The comparison of different Hypericum species revealed an interspecific variation in the distribution of the dark and translucent glands corresponding with the localization of hypericins and phloroglucinols. Moreover, similarities in the localization and composition of the phloroglucinols were observed in the species belonging to the same section. Adding to various quantitative studies focused on the detection of secondary metabolites, this work using indirect DESI‐MSI offers additional valuable information about localization of the above‐mentioned compounds.
Healthcare Facility Choice and User Fee Abolition: Regression Discontinuity in a Multinomial Choice Setting
Authors: Koch Steven F. , Racine Jeffrey S.
Published: January 2016

We apply parametric and non-parametric regression discontinuity methodology within a multinomial choice setting to examine the effect of public healthcare user fee abolition on health facility choice by using data from South Africa. The non-parametric model is found to outperform the parametric model both in and out of sample, while also delivering more plausible estimates of the effect of user fee abolition (i.e. the ‘treatment effect’). In the parametric framework, treatment effects were relatively constant—around 10%—and that increase was drawn equally from home care and private care. In contrast, in the non-parametric framework treatment effects were largest for large (and poor) families located further from health facilities—approximately 5%. More plausibly, the positive treatment effect was drawn primarily from home care, suggesting that the policy favoured children living in poorer conditions, as those children received at least some minimum level of professional healthcare after the policy was implemented.
Variable Selection via Additive Conditional Independence
Authors: Lee Kuang-Yao , Li Bing , Zhao Hongyu
Published: January 2016

We propose a non-parametric variable selection method which does not rely on any regression model or predictor distribution. The method is based on a new statistical relationship, called additive conditional independence, that has been introduced recently for graphical models. Unlike most existing variable selection methods, which target the mean of the response, the method proposed targets a set of attributes of the response, such as its mean, variance or entire distribution. In addition, the additive nature of this approach offers non-parametric flexibility without employing multi-dimensional kernels. As a result it retains high accuracy for high dimensional predictors. We establish estimation consistency, convergence rate and variable selection consistency of the method proposed. Through simulation comparisons we demonstrate that the method proposed performs better than existing methods when the predictor affects several attributes of the response, and it performs competently in the classical setting where the predictors affect the mean only. We apply the new method to a data set concerning how gene expression levels affect the weight of mice.
Is Personalization the Right Plan at the Wrong Time? Re‐thinking Cash‐for‐Care in an Age of Austerity
Authors: Pearson Charlotte , Ridley Julie
Published: January 2016

As personalization has dominated the policy agenda for reform in social care, its roll‐out as a mainstream option has coincided with global programmes of austerity which have targeted services for disabled people. Was this simply bad timing or was its implementation always part of the agenda for reform? Whilst the principle of cash‐for‐care schemes drew strongly on promoting the independence and autonomy of disabled people, early incarnations of direct payments policy in the UK were initially at least in part rolled out in light of potential cost savings to social care budgets. This article explores these and other issues in light of evaluations of the Scottish government's self‐directed support (SDS) test sites (2009–11) and implementation of subsequent legislation enforcing models of SDS in Scotland from April 2014. Discussion draws on the authors’ recent book (Pearson et al. 2014) to reflect on what the evidence can tell us about radically transforming social care at a time of global austerity.
Gastrointestinal dysmotility disorders in critically ill dogs and cats
Authors: Whitehead KimMi , Cortes Yonaira , Eirmann Laura
Published: January 2016

Objective

To review the human and veterinary literature regarding gastrointestinal (GI) dysmotility disorders in respect to pathogenesis, patient risk factors, and treatment options in critically ill dogs and cats.

Etiology

GI dysmotility is a common sequela of critical illness in people and small animals. The most common GI motility disorders in critically ill people and small animals include esophageal dysmotility, delayed gastric emptying, functional intestinal obstruction (ie, ileus), and colonic motility abnormalities. Medical conditions associated with the highest risk of GI dysmotility include mechanical ventilation, sepsis, shock, trauma, systemic inflammatory response syndrome, and multiple organ failure. The incidence and pathophysiology of GI dysmotility in critically ill small animals is incompletely understood.

Diagnosis

A presumptive diagnosis of GI dysmotility is often made in high‐risk patient populations following detection of persistent regurgitation, vomiting, lack of tolerance of enteral nutrition, abdominal pain, and constipation. Definitive diagnosis is established via radioscintigraphy; however, this diagnostic tool is not readily available and is difficult to perform on small animals. Other diagnostic modalities that have been evaluated include abdominal ultrasonography, radiographic contrast, and tracer studies.

Therapy

Therapy is centered at optimizing GI perfusion, enhancement of GI motility, and early enteral nutrition. Pharmacological interventions are instituted to promote gastric emptying and effective intestinal motility and prevention of complications. Promotility agents, including ranitidine/nizatidine, metoclopramide, erythromycin, and cisapride are the mainstays of therapy in small animals.

Prognosis

The development of complications related to GI dysmotility (eg, gastroesophageal reflux and aspiration) have been associated with increased mortality risk. Institution of prophylaxic therapy is recommended in high‐risk patients, however, no consensus exists regarding optimal timing of initiating prophylaxic measures, preference of treatment, or duration of therapy. The prognosis for affected small animal patients remains unknown.
Red blood cell microvesicles: a storage lesion or a possible salvage mechanism
Authors: Delobel J. , Barelli S. , Canellini G. , Prudent M. , Lion N. , Tissot J.‐D.
Published: January 2016

Erythrocyte concentrates are the major labile blood products used for transfusion worldwide. Erythrocyte concentrates are stored at 4°C for up to 42–49 days in additive solutions. This storage induces cellular lesions, which include alterations in red blood cell (RBC) metabolism, protein content and rheological properties. The impact of these storage lesions is intensely debated, because transfusion‐related clinical adverse outcomes have been associated with the age of erythrocyte concentrates. Although altered red blood cell metabolism and early rheological changes are reversible with one transfused, oxidized proteins cannot be repaired. Thus, some irreversible damage might affect the quality of the blood product and the efficiency of the transfusion. In vivo, red blood cells are constantly exposed to oxygen fluxes but are well equipped to deal with oxidative challenges. Moreover, erythrocytes can eliminate oxidized proteins by capturing them in microvesicles, which are subsequently shed into the medium. This review discusses some biochemical aspects of RBC storage and microvesiculation.
Handling low haemoglobin and iron deficiency in a blood donor population
Authors: Magnussen K. , Ladelund S.
Published: January 2016

Background

Blood donors with low haemoglobin concentration (Hb) and iron deficiency are well‐known challenges in any blood bank setting. The handling of such donors is complex, and although iron deficiency is a frequent cause of anaemia, there are differential diagnoses.

Aims

The primary aims were to standardize and optimize the handling of blood donors with Hb below the limit for donation. Secondary aims were to deal with all issues related to high or low either Hb or ferritin in blood donors.

Methods

The problem was approached by centralizing measurement of Hb, initiating ferritin measurements and establishing Centre for Donor Haemoglobin and Iron. An algorithm was created, taking Hb and ferritin into account. The donors were mainly contacted by post, but when Hb was low or when there was insufficient effect of previously given iron supplementation, the donors were contacted by phone to improve compliance. Hb was measured on Sysmex‐XE2100D at every donation. Ferritin was measured once in all donors, at every 10th donation and repeated when outside 60–300 μg/l or Hb low at the previous donation.

Results

February 1st 2012–February 1st 2015, 71 450 donors (53·5%women/46·5%men) donated 281 814 units of whole blood. Due to changes in calibration, Hb changes could only be monitored over the first 24 months. Mean Hb increased in the female and male donors (P < 0·0001). Percentage of donors with low Hb decreased (women OR/month = 0·98; P < 0·0001; men OR/month = 0·97; P < 0·0001).

Summary/conclusions

The program of iron supplementation restricted only to those that would benefit has led to an increase in Hb and a reduction in the number of donors with low Hb.
New additive solutions for red cells
Authors: de Korte D.
Published: January 2016

Shortly after the introduction of component therapy in the 1960s, the first additives for red cell concentrates (RCC) were introduced. This development resulted in prolongation of RCC shelf life from 21 to 35 or 42 days. Over the years, some new solutions were developed, but still SAGM (Europe) and AS‐1 (United States) are the standard, nearly exclusive in combination with CPD as anticoagulant. Most of these new solutions were minor variations on SAGM or AS‐1, with limited improvement of in vitro quality of erythrocytes. Development of new concepts, resulting in improved quality of RCC, was in first instance focused on achieving longer storage time. However, as a result from the concern about possible negative side effects caused by transfusion of older units, the research on new additive solutions is more focused on having a better quality during the currently accepted maximum storage time of 35–42 days. Around 1990, Meryman developed the concept of the so‐called chloride shift. Through replacement of chloride by impermeable solutes, it is possible to manipulate the intracellular pH of erythrocytes, resulting in high 2,3‐DPG and/or ATP values throughout storage. During the past 15–20 years, several research groups, with the group of Greenwalt and Hess as pioneers, developed new additive solutions based on the Meryman concept. Recently, the first commercial product from these studies was launched, with an improved in vitro quality parameter profile and improved in vivo recovery data. Finally, some recent developments are discussed with respect to alkaline additive solutions and anaerobic storage of erythrocyte concentrates.
The air they breathe
Authors: Dzik W.
Published: January 2016

Background

While all living creatures share Earth's atmosphere, they have adapted respiration to unique environments with the capacity to outperform anything humanly possible.

Aims

To describe tissue oxygenation strategies used by different animal species.

Methods

Published research on the respiratory physiology of deep‐diving mammals and high‐flying migratory birds.

Results

The oxygen‐binding characteristics of haemoglobin are relatively constant across broad species of animals on Earth, but available oxygen is remarkably different in different environments. Deep‐diving marine mammals reach depths of 1 mile where pressures are 200 times greater than at sea level and can hold their breath for up to 1 h. They oxygenate muscles using wilful control of heart rate and blood flow collectively. They avoid nitrogen narcosis by emptying their lungs of air prior to dives. Myoglobin plays an important role in tissue oxygenation. Deep‐diving mammals are the finest anaerobic athletes on the planet. In contrast, birds breathe in a manner entirely different from mammals and oxygenate their blood during both inspiration and expiration. This remarkable process results in a far more efficient method of blood oxygenation than can be achieved in mammals (including humans), making birds the finest aerobic athletes on Earth.

From the perspective of oxygen delivery to tissues, athletic capacity and adaptation to environmental stress, certain non‐human species demonstrate superior performance. A better understanding of the how other creatures use the same air that we breathe may lead to greater respect for species diversity and animal life.
Recombinant blood group proteins in clinical practice – from puzzling to binary antibody testing
Authors: Seltsam A. , Blasczyk R.
Published: January 2016

The main drawback of red blood cell (RBC)‐based antibody detection assays is that a positive reaction between serum and test cells does not identify the specificity of a given red blood cell antibody. When antibody mixtures or rare RBC antibodies are present, this indirect method reaches its limits. Recently, CE‐marked recombinant blood group proteins (rBGPs) have become available in sufficient quantity and quality. The advantage of rBGPs over RBCs is that proteins carrying a single antigen can be used in the antibody identification assay, so a positive test directly indicates the presence and specificity of the target antibody. The use of soluble rBGPs in addition to RBCs has been shown to increase the sensitivity and specificity of antibody detection and identification in cases with difficult‐to‐identify antibodies, resulting in increased efficiency in providing blood to immunized patients. The rBGPs have been successfully used in a wide range of solid‐phase assays (ELISA, microspheres, microarrays). Although all relevant antigen specificities have not yet been established, rBGPs have a diagnostic potential that could already be useful in antibody detection assays combining RBC‐derived antigens and recombinantly expressed antigens. Such combined assays would benefit from the potential of rBGPs for single‐step, direct antibody detection and identification, which could greatly facilitate and accelerate the identification of common and rare RBC antibodies. The clinical use of rBGPs in pretransfusion antibody screening would introduce a paradigm shift that could help to reduce the risk of haemolytic transfusion reaction, one of the leading causes of transfusion‐related death.
The emerging role for red blood cells in haemostasis: opportunity for intervention
Authors: Villa C. H. , Muzykantov V. R. , Cines D. B.
Published: January 2016

Red blood cells (RBCs) participate in haemostasis and thrombosis through their biochemical properties, biomechanical and rheological properties, intercellular interactions, assembly of coagulation factors, release of procoagulant signaling compounds, and composition of the fibrin clot. Targeting anti‐thrombotic and anti‐inflammatory drugs to RBCs provides a new approach to mitigate thrombosis and other intravascular pathologies.
Current concepts in TRALI pathogenesis
Authors: Looney M. R.
Published: January 2016

Transfusion‐related acute lung injury (TRALI) is the leading cause of mortality from blood product transfusions. Clinical and experimental studies support a multievent model of injury in which a variety of risk factors (‘first hit’) render the transfusion recipient susceptible to lung injury when transfused with a blood product containing antibody and non‐antibody mediators that provide the ‘second hit’ in the model. Our understanding of the mechanisms of antibody‐based TRALI has been advanced by the major histocompatibility complex (MHC) Class I monoclonal antibody model of TRALI in mice. Challenge of lipopolysaccharide (LPS)‐primed BALB/c mice with cognate MHC Class I antibody produces severe protein‐rich pulmonary oedema, and the lung injury response is critically dependent on the involvement of neutrophils and platelets. In the lung microcirculation, neutrophils and platelets spatially interact forming heterotypic aggregates that can be blocked with aspirin, which also reduces lung injury and mortality in a lipoxin‐dependent pathway. Activated platelets also trigger the formation of neutrophil extracellular traps (NETs), which can be found in the lungs and blood of experimental and clinical cases of TRALI. Several lines of evidence point to the pathogenicity of NETs in TRALI. Inhibiting the formation of NETs by targeting platelet activation (aspirin) ameliorates lung injury. Dismantling the NET structure using deoxyribonuclease 1 (DNase1) or inhibiting extracellular histones, a key component of NETs, also robustly protects from lung injury. In summary, experimental modelling of TRALI has identified a novel pathophysiologic cascade involving neutrophils, platelets and NETs and has in turn illuminated rational therapeutic approaches for the prevention or treatment of TRALI.
Assessing the risk of transfusion‐transmitted emerging infections
Authors: Domanović D.
Published: January 2016

Background and Objectives

The risk from established blood‐borne infections is not eliminated, and newly emergent pathogens in the era of mass international travel and climate change are posing a continuous threat to blood safety. This is an overview of risk assessment methodologies, frameworks used in response to threats posed by transfusion‐transmitted emerging infectious diseases (TT EIDs), and approaches and tools developed by the European Centre for Disease Prevention and Control (ECDC) aiming to provide EU Member States and the EU Commission with the best advice available concerning infectious risks of donations and human use of substances of human origin (SoHO).

Materials and Methods

Comprehensive literature searches were conducted in PubMed, Medline and EMBASE for articles published in English. In addition, the EU Commission's reports and ECDC's technical documents were used to retrieve relevant data.

Results

The risk assessment is a part of the risk management process that comprises preparatory activities, risk analysis and risk evaluation. International efforts have been taken to identify, prioritize and develop fact sheets, toolkits and frameworks for assessing the threat of emerging infections and their impact on blood safety and availability. ECDC developed a European Up‐Front Risk Assessment Tool to allow member states to assess the risk of TT EDIs. ECDC's interactive maps inform the competent authorities for blood about areas with ongoing transmission of West Nile virus to humans to support their implementation of screening and blood safety legislation. ECDC has identified and prioritized eleven arthropod‐borne diseases that may pose a threat to the safety of SoHO. A priority list was the basis for developing a comprehensive, review‐based risk assessment and defining preventive interventions of their transmission through SoHO.

Conclusion

Risk assessment determines the necessity, urgency and magnitude of response to threats posed by TT EIDs. In order to timely assess the risk, it is important to be vigilant and to identify the infectious threat to the blood safety as soon as possible. The manner in which the risk assessment is applied is dependent on uncertainties manifested by EID, a specific context of blood transfusion practice and a framework within which the risk is managed.
Recent advances in platelet processing and storage
Authors: Lozano M. , Cid J.
Published: January 2016

Platelet rich plasma (PRP) method was the first method used for platelet concentrate (PC) preparation and continues to be the only licensed method in the USA. By contrast in Europe since the eighties of the last century, the PRP method has been progressively replaced by methods based on the removal of the buffy coat (BC) layer. Initially BC were processed individually to produced a single PC but it was soon recognized that the pooling of 4–6 BC units with the addition of a plasma unit of one of the donors of the pool or a platelet additive solution (PAS), improved the efficiency of the separation and eased the transfusion process since the final product was stored as an adult transfusion dose ready to be connected to the patient. Semi‐automatic devices were developed for the separation of whole blood into red blood cells, plasma and the BC and for the separation of the BC into the PC. The introduction of PAS in combination with plasma (in general about 35% of plasma and 65% PAS) for storing PC has shown to offer advantages such as an increased availability of plasma for fractionation, a reduction of transfusion reactions to platelets and a potential reduction in the risk of transfusion related acute lung injury. While early generations of PAS were associated to a decrease in the post‐transfusion corrected platelet count in comparison to PC stored in 100% plasma, this effect has not been found with the newer generation of PAS.
Engaging ethnic minority blood donors
Authors: Charbonneau J. , Daigneault S.
Published: January 2016

Background and Objectives

Targeting ethnic minorities is consistent with the objective of ensuring better access to rare phenotypes. The number of blood donors is generally lower among these groups. This article seeks to present the solutions Héma‐Québec has developed to address this challenge.

Materials and Methods

In 2010–2011, the organization conducted 53 awareness‐raising activities targeting black communities. In 2009–2010, 83 interviews were conducted with donors and leaders of diverse ethnic groups in Montreal. Employees’ perceptions were also explored. Based on research findings, a training seminar was developed and provided to 69 front‐line managers. Its most important elements were integrated into basic training for all employees.

Results

The number of black community donors climbed from 170 in 2009 to 1582 in 2012. However, experiences with ethnic associations and donors have raised many concerns among staff. The 2‐day training helped planning services develop better recruitment strategies and bolster employees’ self‐confidence with regard to their interactions with ethnic minorities.

Conclusion

New strategies are dependent on the specific characteristics of each country's ethnic diversity, the availability of empirical data on minorities, and the clearly expressed will of management in blood products supply organizations.
A randomized controlled trial comparing the outcome of critically ill adults who received fresher vs. older red cells units
Authors: Lacroix J. , Hébert P. C. , Fergusson D. A. , Tinmouth A. , Walsh T. , Stanworth S. , Campbell H. , Boyd J. , Burrows H. , Hemmatapour S. ,   the Canadian Critical Care Trials Group
Published: January 2016

Background and Objectives

Red blood cell (RBC) units are stored up to 42 days postcollection. The standard policy is to deliver the oldest units in order to limit blood wastage. The hypothesis of the ‘Age of Blood Evaluation’ (ABLE) study was that the outcomes of adults transfused in intensive care units (ICU) with RBC units stored ≤7 days will be better than controls who received the oldest RBC units.

Materials and Methods

The ABLE study is a double‐blind randomized controlled trial. The primary outcome measure was all‐cause 90‐day mortality postrandomization. Secondary outcomes included 28‐day, ICU and hospital mortality, acquired infections, length of ICU and hospital stay, and length of treatments. Statistical analyses were performed using an intention‐to‐treat approach.

Results

From 2009 to 2014, 1211 patients were allocated to the fresh arm, 1219 to the control arm (length of storage: 6·1 ± 4·9 and 22·0 ± 8·4 days, P < 0·001). There were 448 deaths (37·0%) in the fresh arm 90‐day postrandomization, and 430 (35·3%) in the control arm (absolute risk difference: 1·7%; 95% CI: −2·1% to 5·5%). A survival analysis revealed that the hazard ratio of deaths 90 days postrandomization was 1·1% in the fresh‐blood group (95% CI: 0·9% and 1·2%). The same trend against the fresh arm intervention was observed with all but one secondary outcome measure.

Conclusion

The transfusion of RBC units stored ≤7 days does not improve the outcome of critically ill adults compared to the transfusion of units stored about 3 weeks (ISRCTN44878718).
New developments in the use of apheresis to collect haematopoietic cells for cell transplantation and cell therapies
Authors: Granata A. , Drezet A. , Faucher C. , Lemarie C. , Calmels B. , Chabannon C.
Published: January 2016

Currently, there is renewed interest in apheresis as a tool to collect blood mononuclear cells. Several manufacturers have introduced a new generation of cell separators. Historical applications, that is the collection of autologous or allogeneic hematopoietic stem and progenitor cells for ‘bone marrow transplantation’, witness new developments: introduction of new agents that mobilize stem cells help deal with ‘poor mobilizers’ and streamline the collection process, algorithms based on robust measurement of circulating and collected CD34+ cells allow to tailor the collection procedure to better suit donors and recipients’ needs. Furthermore, new forms of cellular therapies are being developed, with potential applications as additions, substitutes or unrelated to conventional hematopoietic stem cell transplantation. These are mostly immune therapies that will be manufactured from blood mononuclear cells; these will be efficiently engineered only when the collected cell product meets predefined specifications that are likely to be different and more stringent than they are for the collection of minimally manipulated autologous or allogeneic blood grafts. Thus, healthcare professionals who perform or supervise apheresis will need to update and upgrade their skills and competencies in the near future.
Unravelling of the role of long noncoding RNAs in haematopoiesis
Authors: Alvarez‐Dominguez J. R. , Lodish H. F.
Published: January 2016

The formation of all blood cells requires tight coordination of highly specific yet dynamic gene expression programmes. These programmes are established by integrated networks of transcription factors, chromatin modifiers and regulatory RNAs. Recent advances have revealed that special types of RNAs, long noncoding RNAs (lncRNAs), are critical components in these networks. lncRNAs are activated in cell type‐, developmental stage‐ and context‐specific manners to coordinate gene expression via transcriptional or post‐transcriptional mechanisms. They can function via RNA–DNA, RNA–RNA and RNA–protein interactions and can thus affect the activation of genes or the splicing, stability or translation of their transcripts. As a result, distinct collections of lncRNA regulators help modulate the stepwise development of distinct blood cell types. We highlight recent progress, emerging themes and prospective challenges in unravelling the contributions of lncRNAs to haematopoiesis, as well as their implication in blood diseases such as leukaemia.
Signalling mechanisms involved in C‐peptide‐mediated inhibition of low O2‐induced ATP release from human erythrocytes
Authors: Richards J. P. , Bowles E. A. , Ellsworth M. L. , Stephenson A. H. , Sprague R. S.
Published: January 2016

Background and objectives

In vivo, insulin is released with connecting peptide (C‐peptide) which has recently been shown to have biological activity. When erythrocytes are exposed to reduced oxygen (O2) tension, they release O2 as well as the vasodilator ATP enabling them to participate in the appropriate distribution of vascular perfusion and, thereby, O2 supply. Low O2‐induced ATP release is absent in erythrocytes of humans with type 2 diabetes (DM2), but this response is restored by co‐administration of physiological concentrations of insulin and C‐peptide. However, either C‐peptide or insulin, when administered alone, inhibits low O2‐induced ATP release from healthy human erythrocytes. Here, we investigated the mechanism(s) by which C‐peptide inhibits this physiological ATP release from human erythrocytes.

Methods

Erythrocytes from healthy humans (n = 21) or humans with DM2 (n = 4) were incubated with C‐peptide in the absence or presence of inhibitors of either protein kinase C alpha (PKCα) or soluble guanylyl cyclase (sGC). Erythrocytes were then exposed to low O2, and ATP release was determined.

Results

In healthy human erythrocytes, C‐peptide inhibited ATP release in response to low O2. Preincubation with either Gö6976, a PKCα inhibitor, or ODQ, a sGC inhibitor, prevented this effect of C‐peptide. In addition, C‐peptide alone did not rescue low O2‐induced ATP release from DM2 erythrocytes.

Conclusion

Administration of C‐peptide in excess of levels present under physiological conditions or the combination of C‐peptide and insulin at ratios that exceed those observed physiologically to insulin‐deficient individuals can be detrimental for low O2‐induced ATP release from human erythrocytes and could, consequently, interfere with optimal O2 delivery to skeletal muscle.
Can we make the predonation screening process more effective?
Authors: Norda R. , Frazzetto M. L. , Lubenow N. , Knutson F.
Published: January 2016

Blood establishments are responsible for the quality and safety of the blood collected and the final acceptance or deferral of a donor. All donors must undergo a screening process just prior to the blood donation. The elements are: (i) Identification of the donor and linking the identity to all the relevant documentation. (ii) Information timely provided so that the donor can decide whether to donate or to abstain. (iii) The donor health history must be evaluated by a questionnaire and complementary questions. (iv) The donor signs to confirm his/her responses. (v) A few physical parameters are assessed. (vi) Blood samples are collected for hemoglobin and markers for infectious agents. The questionnaire serves to detect exposures to hidden problems with possible consequences for the recipient. The interview clarifies answers and if the donor understood the information. Laboratory investigations of primary importance to the recipient involves screening assays for antigens, antibodies and RNA/DNA as legally required. Continuous improvement has led to shortening of the undetectable infectious period. There is continuous vigilance for emerging new infections or re‐emerging ‘old’ infections leading to modified deferral rules and development of new screening tests. In recent years there has also been modification of deferral criteria concerning sexual behavior with high risk for acquiring transfusion transmitted infections (TTI). Modelling of the risks of TTI in any given epidemiological situation and estimates of donor compliance precedes changes. Tools to study the effectiveness of the pre‐donation screening process include evaluation of recalled units, verified screening‐positive donors and compliance studies.
Introducing the red cell storage lesion
Authors: Chen D. , Serrano K. , Devine D. V.
Published: January 2016

The storage of red blood cells under standard blood‐banking conditions leads to a decline in red cell quality and function known as the red cell storage lesion. These changes are linked to alterations in cellular biochemical processes, biomechanical effects and damage from oxidation. Although storage‐related alterations in red cells can be readily measured in the laboratory, the clinical impact of the storage lesion is not as easy to demonstrate. While some immediate differences between fresh and stored cells can be measured, red cells recover in the circulation to some degree upon transfusion with a concomitant reduction in the effect of the storage lesion. The clinical literature is inconsistent with studies arguing that long‐term stored red cells have a clinical impact and other studies including recent randomized controlled trials have failed to show any effect of the storage lesion on patient outcomes. Amelioration of the storage lesion will require further development of novel storage processes as well as an increased understanding of the role that donor‐specific factors play in product quality.
Managing the patient with haemoglobinopathy and multiple red cell antibodies
Authors: Politis C. , Hassapopoulou E. , Halkia P. , Kourakli A. , Mougiou A. , Zervou E. , Kleronomos E. , Sfyridaki K. , Pappa C. , Tsoumari I. , Lafiatis I. , Kavallierou L. , Parara M. , Richardson C.
Published: January 2016

Background and Objectives

Sickle cell disease (SCD) and thalassaemia, particularly the β‐type, represent major sources of morbidity. Recommended treatment includes regular blood transfusion following highly uniform strategies across thalassaemia units and monitoring related complications including alloimmunization. This complex problem depends on donor–recipient antigenic diversity, the patient's immune status and specific circumstances such as pregnancy.

Materials and Methods

We examined alloimmunization against RBC antigens and autoimmunization in 983 patients with thalassaemia and SCD in Greece, in relation to applied RBC antigen matching policies and other factors possibly relevant in reducing the rate of alloimmunization and delayed haemolytic transfusion reaction (DHTR).

Results

Up to 2010, 11.6% of all patients had history of alloimmunization and 7.3% of autoimmunization. Frequency was highest in thalassaemia intermedia followed by sickle–thalassaemia and thalassaemia major. New alloimmunization was low at 1.4% after 2010, corresponding to a risk of 1:9405 units of RBCs transfused. Despite the very high transfusion burden in the chronically transfused patients, the use of extended matched donor blood is proven effective in reducing the rate of alloimmunization.

Conclusion

Multiple RBC alloantibodies represent a small but difficult to manage risk for responders prone to combination with autoimmunization. DHTR with hyperhaemolysis is a major clinical problem in haemoglobinopathies, especially during the gestational period and delivery in patients who escape expert medical follow‐up. Progress in the safety and quality of blood transfused in these patients is expected to contribute to prolongation of their life expectancy and to reproduction. Investigation of HLA and other antibodies in patients prone to developing RBC antibodies is suggested.
Preventing bacterial infection in blood components
Authors: Schmidt M. , Seifried E.
Published: January 2016

Background

The prevention of bacterial infections by blood components can be classified into general procedures and blood component‐specific procedures.

General procedures

Donor selection programmes with a temporary deferral of blood donors are sufficient measures to prevent bacterial contaminations of blood components. Secondly, an efficient donor arm disinfection is important to reduce the resident skin flora to a minimum. Since the beginning of this century, all countries have implemented the predonation sampling with the diversion of the first 30–40 ml.

Blood components specific procedures

Many countries have already implemented methods of detecting bacteria in platelets using culture methods. A residual risk for culture methods, however, is the occurrence of sample errors by collecting the test volume within the first 24 h. Some countries have implemented rapid bacterial detection systems like Bactiflow or NAT systems. Different pathogen reduction methods were developed for platelets, plasma and packed red cells. The advantage of these methods is the reduction of all bacteria and potential new pathogens. A disadvantage might be their high cost and limited efficiency in detecting bacteria spores.

Conclusion

General procedures are not sufficient to prevent all bacterial transmissions. Culture methods and pathogen reduction methods that have focused on the prevention of bacterial contamination in platelets are currently in development for erythrocytes and whole‐blood components and might not be feasible for stem cell components. Therefore, the world is still waiting for a new general procedure that will be an addendum to existing systems – such a system is eagerly awaited.
Different sensitivities to calcineurin inhibitors between B cells responding to blood group A and B antigens
Authors: Yamashita M. , Tanaka Y. , Tazawa H. , Sakai H. , Ohdan H.
Published: January 2016

Background and Objectives

We evaluated the phenotypic and functional distinction between B cells with receptors for human blood group A and B determinants in α‐galactosyltransferase‐deficient (GalT−/−) mice.

Materials and Methods

GalT−/− mice were immunized with human blood group A or B red blood cells (RBCs), and the anti‐A or B anti‐bodies (Abs) were determined in their sera. B cells with receptors for group A and B epitopes were identified by the use of synthetic A and B determinants.

Results

The anti‐A and anti‐B Ab levels were comparably elevated in the sera of GalT−/− mice after the immunization with A/B‐RBCs. B cells bearing receptors recognizing B epitopes exhibited the CD5dim/− CD11b+ B‐1b‐cell phenotype, whereas those with receptors for A epitopes showed the CD5+CD11b+ B‐1a‐cell phenotype. Myeloid differentiation factor 88 (MyD88) levels increased in B cells with anti‐B receptors, indicating a contribution of Toll‐like receptor (TLR) signalling, whereas no such elevation was detected in B cells with anti‐A receptors. Calcineurin inhibitor (CNI) treatment prevented the elevation of anti‐A Ab levels after immunization, but did not affect anti‐B Ab levels.

Conclusions

These findings indicate different sensitivities of B cells with blood group A and B antigens in the response to CNIs.
Culturing red blood cells from stem cells: a solution to present and future challenges of transfusion medicine?
Authors: Rousseau G. F. , Mazurier C. , Douay L.
Published: January 2016

Transfusion needs are diversely fulfilled globally. Besides, with population ageing, the various problems faced by healthcare systems will become more and more prominent. As a consequence, the current model of blood supply has to be strengthened, and new sources of red blood cells (RBC) are welcome. A cell therapy approach, in which so‐called ‘culturedRBC’ (cRBC) are generatedin vitro,might be a solution. We report here on the various obstacles that were overcome during the past decade to generatecRBCfrom various sources of stem cells (SC) and also discuss the next developments which will be required to achieve this goal. To date, the culmination point in the field has been the proof of principle of transfusion ofcRBCinto human, produced from autologous haematopoietic stem and progenitor cells (HSPC), which allowed to demonstrate a favourable life span ofcRBCwhen compared with their native counterpart. The best available source of highly proliferative adultSCis cord blood (CB), which could allow to produce tens ofRBCconcentrates (RBCC) from one averageCB. However, this source is quantitatively limited in number, and more research onHSPCisolated from peripheral blood (PB) is needed. In parallel, critical advances have allowedin vitroproduction of functionalRBCfrom human pluripotentSC, either embryonic (ESC) or induced (iPS). AsiPScan proliferate indefinitely and can be selected for a specific patient phenotype, they appear to be the most favourableSCsource, but the protocols still need to be optimized. Most recently, erythroid cell lines have also been envisaged to produceRBC. The major challenges remaining today are economic and technological in order to lead to a cost‐effective process for large‐scale production.
Nursing Practice Guidelines in China do Need Reform: A Critical Appraisal Using the AGREE II Instrument
Authors: Jin Yinghui , Wang Yunyun , Zhang Yao , Ma Yue , Li Yan , Lu Cui , Wang Wei , Li Ge , Shang Hongcai
Published: January 2016

Background

An increasing number of nursing practice guidelines (NPGs) of varying methodological and reporting quality have been issued and published in international journals. Currently, the quality of NPGs in mainland China has not been explored.

Objective

To assess the quality of NPGs in China mainland using the AGREE II (Advancing Guideline Development, Reporting and Evaluation in Health Care) instrument.

Methods

The authors searched the electronic databases of Chinese Biomedical Literature Database, China National Knowledge Infrastructure, The VIP Database, Wan Fang Database, Chinese Master's Theses Full‐Text Database, China Doctor Dissertation Full‐Text Database, and China Proceedings of Conference Full‐Text Database and the web of China Guideline Clearinghouse for NPGs in China published from the inception of databases to December, 2013. Four independent assessors rated the quality of each guideline using AGREE II. The authors classified NPGs into two types: evidence‐based NPG (EB‐NPG) and consensus‐based NPG (CB‐NPG), and compared their quality. The authors also considered whether the quality of NPGs changed over time.

Results

Forty‐two NPGs were appraised. Methodological rigor and reporting of NPGs were poor. Across all guidelines, the appraisers assigned the highest scores to the domain “scope and purpose,” and the lowest scored to the domain of “editorial independence.” EB‐NPGs were significantly superior to the CB‐NPGs in the domains of “stakeholder involvement,” “rigor of development,” and “editorial independence.” There was no improvement over time for all domains.

Linking Evidence to Action

This research found an absence of a systematic guideline development methodology and a tendency to rely on expert opinion in the process of developing NPGs. The readers should consider these flaws and limitations when using recommendations in those NPGs.
On the sum of the square of a prime and a square-free number
Authors: Dudek Adrian W. , Platt David J.
Published: January 2016

We prove that every integer$n\geqslant 10$such that$n\not \equiv 1\text{ mod }4$can be written as the sum of the square of a prime and a square-free number. This makes explicit a theorem of Erdős that every sufficiently large integer of this type may be written in such a way. Our proof requires us to construct new explicit results for primes in arithmetic progressions. As such, we use the second author’s numerical computation regarding the generalised Riemann hypothesis to extend the explicit bounds of Ramaré–Rumely.