bluuebunny/crossref_metadata_2025_split huggingface dataset:
Looking beyond the induction of Th2 responses to explain immunomodulation by helminths
Authors: Nutman T. B. 
Published: April 2015

SummaryAlthough helminth infections are characteristically associated with Th2‐mediated responses that include the production of the prototypical cytokines IL‐4, IL‐5 and IL‐13 by CD4+ cells, the production of IgE, peripheral blood eosinophilia and mucus production in localized sites, these responses are largely attenuated when helminth infections become less acute. This modulation of the immune response that occurs with chronic helminth infection is often induced by molecules secreted by helminth parasites, by non‐Th2 regulatory CD4+ cells, and by nonclassical B cells, macrophages and dendritic cells. This review will focus on those parasite‐ and host‐mediated mechanisms underlying the modulated T‐cell response that occurs as the default in chronic helminth infections.
Clinical concepts for regenerative therapy in intrabony defects
Authors: Cortellini Pierpaolo , Tonetti Maurizio S. 
Published: April 2015

AbstractEvidence indicates that periodontal regeneration is an efficacious and predictable procedure for the treatment of isolated and multiple intrabony defects. Meta‐analyses from systematic reviews indicate an added benefit, in terms of clinical attachment level gain, when demineralized freeze‐dried bone allograft, barrier membranes and active biologic products/compounds are applied in addition to open flap debridement. On the other hand, a consistent amount of variability of the outcomes is evident among different studies and within the experimental population of each study. This variability is explained, at least in part, by different patient and defect characteristics. Patient‐related factors include smoking habit, compliance with home oral hygiene and residual inflammation after cause‐related therapy. Defect‐associated factors include defect depth and radiographic angle, the number of residual bony walls, pocket depth and the degree of hypermobility. In addition, surgical‐related variables, such as surgical skill, clinical experience and knowledge, and application of the different regenerative materials, have a significant impact on clinical outcomes. This paper presents a strategy to optimize the clinical outcomes of periodontal regeneration. The surgical design of the flap, the use of different regenerative materials and the application of appropriate passive sutures are discussed in this review along with the scientific foundations.
Temporal sequence of hard and soft tissue healing around titanium dental implants
Authors: Salvi Giovanni E. , Bosshardt Dieter D. , Lang Niklaus P. , Abrahamsson Ingemar , Berglundh Tord , Lindhe Jan , Ivanovski Saso , Donos Nikos 
Published: April 2015

AbstractThe objective of the present review was to summarize the evidence available on the temporal sequence of hard and soft tissue healing around titanium dental implants in animal models and in humans. A search was undertaken to find animal and human studies reporting on the temporal dynamics of hard and soft tissue integration of titanium dental implants. Moreover, the influence of implant surface roughness and chemistry on the molecular mechanisms associated with osseointegration was also investigated. The findings indicated that the integration of titanium dental implants into hard and soft tissue represents the result of a complex cascade of biological events initiated by the surgical intervention. Implant placement into alveolar bone induces a cascade of healing events starting with clot formation and continuing with the maturation of bone in contact with the implant surface. From a genetic point of view, osseointegration is associated with a decrease in inflammation and an increase in osteogenesis‐, angiogenesis‐ and neurogenesis‐associated gene expression during the early stages of wound healing. The attachment and maturation of the soft tissue complex (i.e. epithelium and connective tissue) to implants becomes established 6–8 weeks following surgery. Based on the findings of the present review it can be concluded that improved understanding of the mechanisms associated with osseointegration will provide leads and targets for strategies aimed at enhancing the clinical performance of titanium dental implants.
Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair
Authors: Chiquet Matthias , Katsaros Christos , Kletsas Dimitris 
Published: April 2015

AbstractFibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal‐like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound‐healing processes of the individual patient.
Experimental models for guided bone regeneration in healthy and medically compromised conditions
Authors: Donos Nikolaos , Dereka Xanthippi , Mardas Nikos 
Published: April 2015

AbstractThe increased use of dental implants and related bone‐augmentation procedures creates a need for reliable proof‐of‐principle preclinical models for evaluating different bone‐regenerative techniques. The simulation of clinical scenarios by such models is of importance when the experiments are designed in order for the outcomes to provide basic points of clinical relevance. At the same time, the increased proportion of the population with different chronic diseases of ageing necessitates the need to reproduce these conditions in the same proof‐of‐principle preclinical models to allow evaluation of the effect of the relevant chronic disease on the bone‐healing process. This review presents a number of ‘proof‐of‐principle’ preclinical models in health and in chronic systemic conditions in which the guided bone regeneration principle was evaluated.
Clinical concepts for regenerative therapy in furcations
Authors: Sanz Mariano , Jepsen Karin , Eickholz Peter , Jepsen Søren 
Published: April 2015

AbstractFurcation involvements present one of the greatest challenges in periodontal therapy because furcation‐involved molar teeth respond less favorably to conventional periodontal therapy compared with noninvolved molar or nonmolar teeth. Various regenerative procedures have been proposed and applied with the aim of eliminating the furcation defect or reducing the furcation depth. An abundance of studies and several systematic reviews have established the effectiveness of membrane therapy (guided tissue regeneration) for buccal Class II furcation involvement of mandibular and maxillary molars compared with open flap surgery. Bone grafts/substitutes may enhance the results of guided tissue regeneration. However, complete furcation closure is not a predictable outcome. Limited data and no meta‐analyses are available on the effects of enamel matrix proteins for furcation regeneration. Enamel matrix protein therapy has demonstrated clinical improvements in the treatment of buccal Class II furcation defects in mandibular molars; however, complete closure of the furcation lesion is achieved only in a minority of cases. Neither guided tissue regeneration nor enamel matrix protein therapy have demonstrated predictable results for approximal Class II and for Class III furcations. Promising preclinical data from furcation regeneration studies in experimental animals is available for growth factor‐ and differentiation factor‐based technologies, but very limited data are available from human clinical studies. Although cell‐based therapies have received considerable attention in regenerative medicine, their experimental evaluation in the treatment of periodontal furcation lesions is at a very early stage of development. In summary, the indications and the limitations for currently available treatment modalities for furcation defects are well established. New regenerative treatments are clearly needed to improve the predictability of a complete resolution of furcation defects.
Hemolytic events after the administration of lyophilized versus liquid immune globulin: an analysis of a single manufacturer's safety database
Authors: Berg Roger , Jacob Dalia , Fuellenhals Elisabeth 
Published: April 2015

BACKGROUNDRecent publications have raised concerns that liquid immune globulins (IGs) may be associated with either a higher or a lower frequency of hemolytic events compared to lyophilized IGs, among other reasons due to the differences of their isohemagglutinin content. The aim of this study was to evaluate the relationship of hemolytic events to product presentation (liquid versus lyophilized) and to examine the relationship between total IG doses administered and the individual isohemagglutinin titers of IG lots infused.STUDY DESIGN AND METHODSThe reporting rate as well as the proportional reporting rate (PRR) of hemolytic events for liquid (Gammagard liquid [GGL]) and lyophilized IG (Gammagard S/D [GGSD]) received spontaneously from the United States was calculated. For all hemolytic events received spontaneously from global sources, total IG doses (g/kg body weight) and the loading dose of isohemagglutinins (total IG dose infused × isohemagglutinin titers of infused lots) were determined.RESULTSWith 0.27 and 0.33 cases per 1 million grams distributed, the reporting rates for GGL and GGSD are comparable, further confirmed by a PRR of 1.0 (95% confidence interval, 0.4‐2.7). Hemolytic events for GGL and GGSD were observed with low loading doses of isohemagglutinins, and lots with high isohemagglutinin titers did not contribute to the development of hemolytic events in a higher proportion than lots with low titersCONCLUSIONSHemolysis associated with GGL or GGSD can occur even with low loading doses of isohemagglutinins. Data presented do not indicate that high isohemagglutinin titers of IG products play a major role in the development of these events.
First record of autochthonous canine ehrlichiosis caused byEhrlichia canisin Romania
Authors: Morar Doru , Dărăbuş Gheorghe , Imre Mirela , Ilie Marius Stelian , Imre Kálmán 
Published: April 2015

AbstractThis case study describes the first genetically confirmed and clinically manifested autochthonousEhrlichia canisinfection in a 9‐year‐old female mixed‐breed dog from Romania. Health screening of the dog included clinical examination, evaluation of stained peripheral blood smear and hematologic variables, as well as serologic testing and molecular analysis. Clinical signs included fever, apathy, dehydration, pale mucous membranes, and weakness. The microscopic examination of the blood smear and immunologic assays forBorrelia burgdorferi, Anaplasma phagocytophilum, andE canisantibodies, and forDirofilaria immitisantigen yielded negative results. Hematologic abnormalities included moderate nonregenerative anemia, leucopenia with neutropenia, and moderate thrombocytopenia. The biochemical abnormalities identified were hypoalbuminemia, and mildly increased serum enzyme activities ofASTandALT. In addition, increased urea and creatinine levels associated with low urine specific gravity and proteinuria were also present. NestedPCRamplification of the partialE canis16SrRNAgene demonstrated the presence of this rickettsial pathogen in the dog's blood, which subsequently was confirmed through sequencing based on the 100% homology with GenBank depositedE canisisolates. After specific treatment with doxycycline (10 mg/kg, orally,SID) for one month, the proteinuria, and hematologic and serum biochemical abnormalities with the exception of mild azotemia resolved. This report supports the geographical expansion of canine ehrlichiosis caused byE canisin nonendemic regions of Europe.
Red blood cell transfusion‐induced inflammation: myth or reality
Authors: Hod E. A. 
Published: April 2015

Red blood cells (RBCs) destined for transfusion can be refrigerator‐stored for up to 42 days prior to transfusion. Our studies in mice and dogs suggest that transfusion of older, stored RBCs, but not fresh RBCs, produce acute elevations in circulating pro‐inflammatory cytokine levels. Although our study in healthy adult human volunteers failed to demonstrate a pro‐inflammatory cytokine response following transfusion of RBCs stored for 40–42 days, a recent study in preterm infants suggests that RBC transfusions are associated with a pro‐inflammatory response. Thus, whether RBC transfusions, particularly of older, stored RBCs, result in a pro‐inflammatory cytokine response, is still an unresolved issue. Animal studies suggest this to be true, yet human studies have yet to demonstrate definitively that such an inflammatory response occurs. Potential explanations for this include differences between human and animal biology, the dose of RBCs transfused and baseline differences in levels of inflammation. This review will summarize the currently available evidence and approaches to resolving whether transfusions of older, stored RBCs are associated with inflammation in recipients.
Transfusion of fresh vs. older red blood cells in the context of infection
Authors: Klein H. , Natanson C. , Flegel W. 
Published: April 2015

The red blood cell (RBC) storage interval has been extended from less than a week to the current storage interval of 6–8 weeks. Regulatory criteria for extending storage rely upon a minimal degree of hemolysis and acceptable in vivo 24‐h post transfusion recovery. Clinical studies of safety and efficacy have never been required. Concerns have arisen that RBC toward the end of storage develop a ‘storage lesion’ with previously unrecognized toxicity. Of the several mechanisms proposed, the bolus of iron delivered to macrophages as a result of hemolysis of stored RBC might pose a particular risk to patients with existing infections. We developed a canine model of pneumonia to compare the toxicity of stored RBC transfusion. We described increased mortality after transfusion of old RBC. We found that transfused older RBC increased mortality, in vivo hemolysis, circulating cell‐free hemoglobin that scavenges nitric oxide, and elevations of non‐transferrin bound and plasma labile iron. Disappearance of circulating iron correlated with increased mortality, worsening pulmonary function, and bacterial proliferation. Washing decreased the mortality associated with transfusing older RBC, but had the opposite effect on fresher blood. With low doses of bacteria, survival was unaffected by the age of blood, whereas high bacteria doses masked any effect of RBC age on mortality. Older RBC may have adverse effects, but the patient's clinical status, the age, volume and method of preparation of the RBC may be critical variables. Several mechanisms may account for this toxicity, but in the presence of bacterial infection, availability of iron likely plays a major role.
How to approach an apheresis consultation using the American Society for Apheresis guidelines for therapeutic apheresis procedures
Authors: Pham Huy P. , Schwartz Joseph 
Published: April 2015

Therapeutic apheresis (TA) is a treatment modality currently being used in many disease conditions. However, the decision to treat a patient with TA depends on many factors, including but not limited to the most likely diagnosis the patient has and whether there is a rationale for TA to be used as a treatment modality, the risk versus benefit ratio of the treatment and the technical aspects of the procedure if apheresis is performed. The guidelines on the use of therapeutic apheresis in clinical practice – evidence‐based approach from the writing committee of the American Society for Apheresis (ASFA) are update every 3 years and are based on the review of the most up to date medical literature addressing the rationale as well as technical aspect of apheresis. The guidelines are meant to help with clinical decision‐making in apheresis consultations and to encourage research on the use of apheresis for novel indications. The format used for the different disease conditions is one‐page fact sheet. In this article, the development and application of these fact sheets in those guidelines are discussed along with an example for each of ASFA's four categories.
Assessing infectious threats – trick or threat?
Authors: Kiely P. , Seed C. R. 
Published: April 2015

BackgroundEffective surveillance for, and response to, emerging infectious disease (EID) agents is a pivotal component of blood safety risk management policy. The rate of emergence of new potential agents is increasing which demands a robust risk management strategy for rapidly assessing and ranking potential threats. This review discusses the general principles of threat assessment for EID agents.MethodsVarious schema for the management of the risk posed by EID agents have been proposed. Examples are the AABB ‘toolkit’ for EIDs which includes a framework for recognition, assessment and management of EID agents, and the Australian Red Cross Blood Service's EID management strategy. Both systems incorporate EID agent ‘templates’ to assist with ranking the threat level and formulating an appropriate response.ResultsThreats are primarily assessed based on three main criteria: prevalence in donor population, transmissibility by blood and the severity of clinical disease in recipients. Where the threat is deemed significant, quantitative risk assessment and cost‐effectiveness analysis for potential interventions can assist in defining the most appropriate mitigation strategy. Hepatitis E virus (HEV) is an excellent contemporary case study with transfusion–transmissibility now proven, but further studies required to define the extent of clinically significant disease in immunocompetent recipients.ConclusionsThe emergence of vCJD and subsequently West Nile virus underscored the importance of an effective EID risk management framework. However, not all EIDs necessarily pose a significant threat to blood safety, and therefore, an effective ranking system is required which we suggest should primarily assess prevalence, transmissibility and recipient disease outcome.
Plasmodium knowlesi – an emerging pathogen
Authors: Ahmed M. A. , Cox‐Singh J. 
Published: April 2015

Ten years have passed since the publication of a large focus of Plasmodium knowlesi infections in the human population. The discovery was made during a molecular investigation of atypical P. malariae cases in the Kapit Health Division, Sarawak, Malaysian Borneo. Patients were more symptomatic with higher parasite counts than expected in P. malariae infections. The investigation found only P. knowlesi DNA present in patient blood samples. Morphological similarity had allowed P. knowlesi to masquerade as P. malariae during routine diagnostic microscopy for malaria. P. knowlesi, a malaria parasite of macaque monkeys, had entered the human population. The subsequent development of P. knowlesi species‐specific PCR assays soon demonstrated that the entry was not confined to the Kapit Division but extended across island and mainland Southeast Asia. Relevant clinical descriptions and guidelines for the treatment and management of patents with P. knowlesi malaria were not available. Nor was it clear whether P. knowlesi had undergone a host switch event into the human population or if infections were zoonotic. The outputs of studies on P. knowlesi malaria during the past 10 years will be summarized, highlighting major findings within the context of pathophysiology, virulence, host switch events, treatment, control and importantly malaria elimination.
Organizing a national blood service with limited resources – developments in the South African National Blood Service
Authors: Mpuntsha L. , Reddy R. 
Published: April 2015

BackgroundSouth Africa has a population of 52 million people and is classified as a Middle Human Development Index (HDI) Country. Up until 1994, the majority Black population lived under discriminatory apartheid laws with resulting in significant socio‐economic disparities between the various population groups. The health system is two tier with Government funding health care in the public sector and medical insurance schemes funding health care in the private sector for those who can afford it. Fiscal allocation for health care in the public sector has been averaging at about 8·5% of the country's gross domestic product (GDP) and is utilized by 84% of the population as the majority of the population cannot afford medical insurance. There is inadequate value contribution due to high disease burden, increasing demand for services from previously disadvantaged groups and inefficiencies in service delivery. The blood services operate on a fee‐for‐service basis supplying about 60% of blood to public sector hospitals and about 40% to private health facilities. The South African National blood service (SANBS) supplies blood and blood products to 88% of the population in eight of the nine provinces and the Western Province Blood Transfusion Service (WPBTS) which operates independently in the Western Cape Province supplies the remaining 12%. Both blood services operate on a ‘vein to vein’ basis managing blood collections from 100% voluntary non‐remunerated donors, processing whole blood into various components, testing for viral markers and cross matching and issuing blood products to doctors on request. SANBS was formed as a National Blood Service in 2001 as a result of the amalgamation of 6 regional blood service organizations. The mission of SANBS is ‘to provide all patients with sufficient, safe, quality blood products and related medical services in a sustainable manner’. Blood safety and sufficiency are the most critical objectives of both blood establishments (BEs).AimTo present historical developments and achievements of SANBS in pursuit of its mandate over the last 12 years. The objective is to share outcomes of various strategies that enabled and strengthened delivery in the South African resource‐constrained environment and challenging socio‐economic context.MethodsA review of the strategic plans, governance framework, operational service delivery and efficiency, human resource management, financial efficiency and stakeholder management was performed to highlight the strategy, challenges and successes of organizing a national blood service.ResultsDespite significant socio‐economic challenges and limited resources SANBS has managed to effectively provide a low risk and sustainable blood supply to the patients that it serves.