bluuebunny/crossref_metadata_2025_split huggingface dataset:
More than a decade of international experience with a pdFVIII/VWF concentrate in immune tolerance
Authors: Santagostino E. 
Published: December 2012

SummaryApproximately 20–30% of patients with severe haemophilia A develop alloantibodies (‘inhibitors’) to infused FVIII rendering use of such replacement therapy ineffective. Once an inhibitor emerges, immune tolerance induction (ITI) is the standard treatment. ITI involves giving regular doses of FVIII concentrate to eradicate the inhibitor and achieve immunogenic acceptance of administered FVIII. In the early 2000s, a retrospective analysis of inhibitor patients treated at a single centre in Germany indicated that success rates were higher when patients were treated with von Willebrand factor (VWF)‐containing plasma‐derived FVIII (pdFVIII/VWF) concentrate compared with recombinant or non‐VWF‐containing pdFVIII products. Importantly, pdFVIII/VWF as rescue therapy was able to convert 8 of 10 patients who had failed primary ITI with recombinant or non‐VWF‐containing pdFVIII product. A subsequent study from Italy in patients with poor prognostic factors for ITI success also reported good success rates with pdFVIII/VWF as rescue therapy (53% success; 41% partial success).The Grifols‐Immune Tolerance Induction (G‐ITI) Study represents the largest group of haemophilia A inhibitor patients treated with a single pdFVIII/VWF concentrate (Alphanate®/Fanhdi®) to be reported to date. Data have been collected for 95 patients who underwent primary or rescue ITI at 46 centres in Europe and the US. Currently, published data are available for 33 patients in the US cohort (11 centres), and data from the European cohort are being analysed. Both groups contained patients with poor prognostic factors and most patients received a high‐dose regimen (≥100 IU pdFVIII/VWF kg−1 daily). As expected, the success rate was better for primary vs. rescue ITI and for patients with good vs. poor prognostic factors. However, more than half the patients in the US cohort receiving rescue ITI achieved success (33% complete success; 20% partial success). These results should encourage clinicians to consider the use of pdFVIII/VWF concentrates for rescue ITI. Published outcomes data from the total global G‐ITI cohort (95 patients) are awaited with anticipation.
Management of patients with long‐term inhibitors: is immune tolerance an underestimated life‐long solution?
Authors: Di Minno G. , Coppola A. 
Published: December 2012

SummaryImmune tolerance induction (ITI) is recognized as the first choice treatment in haemophilic patients with inhibitors, with the aim of restoring safe and effective standard factor VIII replacement and, particularly, prophylaxis in children. For the latter, literature data and clinical practice support the optimal cost utility ratio of ITI. Indeed, the high success rate, the low incidence of inhibitor recurrence after successful ITI and the possibility of preventing joint deterioration, enable one to predict a considerable long‐term reduction of costs in the majority of treated patients. Therefore, in spite of high costs and open issues about optimal regimens, ITI is actually attempted in virtually all children with inhibitors. Few patients with long‐standing inhibitors presently undergo ITI, particularly in the case of severe bleeding tendency. In this setting, uncertainties concerning management are amplified by the paucity of literature data and psychological reluctance by both patients and treaters due to the perceived poor prognosis and the demanding treatment (also in terms of costs). However, clinical data suggest that the role of age at ITI start and of time interval from inhibitor diagnosis, as predictors of ITI outcome, should be considered in a larger framework of proposed and more established prognostic factors. Moreover, optimising ITI management, particularly with respect to inhibitor titre at ITI start and avoidance of adverse events or interruption of treatment, may also contribute to improve outcomes. Although the economic constraints of the present era significantly affect resources for such a high‐cost treatment, the individual cost‐utility ratio (bleeding tendency and risk of fatal bleeding, arthropathy and need for orthopaedic surgery, comorbidities, quality of life) should be assessed carefully to determine whether ITI is a suitable option and thus not preclude adults from the opportunity of inhibitor eradication.
Seroepidemiology of Helicobacter pylori Infection in a Mennonite Community in Durango State, Mexico
Authors: Alvarado‐Esquivel Cosme 
Published: December 2012

AbstractBackgroundThe epidemiology of Helicobacter pylori infection among Mennonites (an ethnic group of German descent living in rural communities in Mexico) has not been previously studied.Materials and MethodsThe prevalence of anti‐H. pylori IgG antibodies was examined in 152 Mennonite individuals in Durango State, Mexico, using enzyme‐linked immunoassays. Seroprevalence association with sociodemographic, clinical, and behavioral characteristics of the Mennonite community was also investigated.ResultsIn total, 77 (50.7%) of the 152 Mennonite participants (mean age, 38.4 ± 15.5 years) had H. pylori IgG antibodies, 35 (45.4%) of whom had H. pylori IgG antibody levels higher than 100 U/mL. Males and females had comparable seroprevalence rates of H. pylori and H. pylori IgG antibody levels. On the other hand, seroprevalence of H. pylori increased significantly with age and was significantly higher among women with history of deliveries and abortions than among those with no such obstetric characteristics. Logistic regression analysis of behavioral characteristics showed that H. pylori infection was associated with a low frequency of eating at restaurants and at fast food outlets (up to 10 times/year) (OR = 2.77; 95% CI: 1.28–5.98; p = .009), and eating meat (up to 3 days/week) (OR = 2.84; 95% CI: 1.36–5.91; p = .005).ConclusionsThis is the first report on the seroprevalence of H. pylori among Mennonites, factors contributing to such infection, and the association of H. pylori infection with abortions and low frequencies of eating out of home and meat. Further research should be conducted on this topic.
Patients' and clinicians' views of comparing the performance of providers of surgery: a qualitative study
Authors: Hildon Zoe , Allwood Dominique , Black Nick 
Published: December 2012

AbstractObjectivesComparison of providers' outcomes is intended to encourage patient choice and stimulate clinicians to improve the quality of their services. Given that success will depend on how patients and clinicians respond, our aim was to explore their views of using outcome data to compare providers.MethodQualitative data from six focus groups with patients (n = 45) and seven meetings with surgical clinicians (n = 107) were collected during autumn 2010. Discussions audio‐taped, transcribed and a thematic analysis carried out.ResultsPatients and clinicians confirmed the value of making comparisons of the outcomes of providers publicly available. However, both groups harboured three principal concerns: the validity of the data; fears that the data would be misinterpreted by the media, politicians and commissioners, and the focus should not just be on providers but also on the performance of individual surgeons. In addition, patients felt that information on providers' outcomes would only ever have a limited impact on their choice because there were other important factors to be taken into account: accessibility, waiting time, the size of the provider and the quality of other aspects such as cleanliness and nursing. Also patients acknowledged the importance of friends' and relatives' experiences and that they would seek their GP's advice.ConclusionsWhile comparisons of providers' outcomes should be available to patients to stimulate improvements in performance, information should be directed principally to hospital clinicians and to GPs. Impact may be enhanced by providing data on individual clinicians rather than providers. The extent to which these findings are generalizable to other areas of health care is uncertain.
Insights from in situ analysis of TCR–pMHC recognition: response of an interaction network
Authors: Zhu Cheng , Jiang Ning , Huang Jun , Zarnitsyna Veronika I. , Evavold Brian D. 
Published: December 2012

SummaryRecognition of peptide presented by the major histocompatibility complex (pMHC) molecule by the T‐cell receptor (TCR) determines T‐cell selection, development, differentiation, fate, and function. Despite intensive studies on the structures, thermodynamic properties, kinetic rates, and affinities of TCR–pMHC interactions in the past two decades, questions regarding the functional outcome of these interactions, i.e. how binding of the αβ TCR heterodimer with distinct pMHCs triggers different intracellular signals via the adjacent CD3 components to produce different T‐cell responses, remain unclear. Most kinetic measurements have used surface plasmon resonance, a three‐dimensional (3D) technique in which fluid‐phase receptors and ligands are removed from their cellular environment. Recently, several two‐dimensional (2D) techniques have been developed to analyze molecular interactions on live T cells with pMHCs presented by surrogate antigen‐presenting cells or supported planar lipid bilayers. The insights from these in situ analyses have provided a sharp contrast of the 2D network biology approach to the 3D reductionist approach and prompted rethinking of our current views of T‐cell triggering. Based on these insights, we propose a mechanochemical coupled triggering hypothesis to explain why the in situ kinetic parameters differ so much from their 3D counterparts, yet correlate so much better with T‐cell functional responses.
Stromal and hematopoietic cells in secondary lymphoid organs: partners in immunity
Authors: Malhotra Deepali , Fletcher Anne L. , Turley Shannon J. 
Published: December 2012

SummarySecondary lymphoid organs (SLOs), including lymph nodes, Peyer's patches, and the spleen, have evolved to bring cells of the immune system together. In these collaborative environments, lymphocytes scan the surfaces of antigen‐presenting cells for cognate antigens, while moving along stromal networks. The cell‐cell interactions between stromal and hematopoietic cells in SLOs are therefore integral to the normal functioning of these tissues. Not only do stromal cells physically construct SLO architecture but they are essential for regulating hematopoietic populations within these domains. Stromal cells interact closely with lymphocytes and dendritic cells, providing scaffolds on which these cells migrate, and recruiting them into niches by secreting chemokines. Within lymph nodes, stromal cell‐ensheathed conduit networks transport small antigens deep into the SLO parenchyma. More recently, stromal cells have been found to induce peripheral CD8+ T‐cell tolerance and control the extent to which newly activated T cells proliferate within lymph nodes. Thus, stromal‐hematopoietic crosstalk has important consequences for regulating immune cell function within SLOs. In addition, stromal cell interactions with hematopoietic cells, other stroma, and the inflammatory milieu have profound effects on key stromal functions. Here, we examine ways in which these interactions within the lymph node environment influence the adaptive immune response.
Cloak of compassion, or evidence of elitism? An empirical analysis of white coat ceremonies
Authors: Karnieli‐Miller Orit , Frankel Richard M , Inui Thomas S 
Published: December 2012

Context  White coat ceremonies (WCCs) are widely prevalent as a celebration of matriculation in medical schools. Critics have questioned whether these ceremonies can successfully combine the themes of professionalism and humanism, as well as whether the white coat is an appropriate symbol.Objectives  This study aimed to add a process of empirical assessment to the discussion of these criticisms by analysing the content and messages communicated during these ceremonies.Methods  Multiple qualitative methods were used to discern the core meanings expressed in a sample of 18 ceremonies through the analysis of artefacts, words, phrases, statements and narratives. Out of a stratified random sample of 25 US schools of medicine conducting WCCs in 2009, 18 schools submitted video, audio and written materials.Results  All ceremonies followed the same general format, but varied in their content, messages and context. Ceremonies included five principal descriptions of what is symbolised by the white coat, including: commitment to humanistic professional care; a reminder of obligations and privileges; power; the student’s need to ‘grow’, and the white coat as a mantle. Statements about obligations were made three times more frequently than statements about privileges. Key words or phrases in WCCs mapped to four domains: professionalism; morality; humanism, and spirituality. Spoken narratives focused on humility and generosity.Conclusions  The WCCs studied did not celebrate the status of an elite class, but marked the beginning of educational, personal and professional formation processes and urged matriculants to develop into doctors ‘worthy of trust’. The ceremonies centred on the persons entering the vocation, who were invited to affirm its calling and obligations by donning a symbolic garb, and to join an ancient and modern tradition of healing and immersion in their community. The schools’ articulated construct of the white coat situated it as a symbol of humanism. This study’s findings may clarify and guide schools’ choices in designing their own WCCs.
Low temperatures counteract short‐day induced nitrogen storage, but not accumulation of bark storage protein transcripts in bark of grey poplar (Populus × canescens) trees
Authors: Wildhagen H. , Bilela S. , Rennenberg H. 
Published: December 2012

AbstractAccording to climate change scenarios, the seasonal course of temperature will change in most regions of the world, raising the question of how this will influence seasonal nitrogen (N) storage in deciduous trees. The key to this question is a detailed understanding of the underlying regulatory mechanisms, which was addressed in this study by analysing (i) the effects of low temperatures (13–1 °C) on bark storage protein (BSP) transcription, BSP and total protein accumulation and amino acid metabolism; (ii) the effects of interactions between low temperatures and photoperiod on these processes; and (iii) the regulatory role of amino acids in the bark. For this purpose, we exposed grey poplar trees (Populus × canescens) to three different treatments of changing photoperiod at constant temperature, changing temperature at constant photoperiod, and both changing photoperiod and temperature. Under a shortened photoperiod, a substantial increase of BSP transcripts was observed that was correlated with the accumulation of bark proteins, indicating a metabolic shift to promote long‐term N storage. Irrespective of the applied photoperiod, exposure to low temperatures (5 or 1 °C) caused a strong increase of BSP transcripts, which was not paralled by significant increases of BSP and total bark proteins. We conclude that the interaction between effects of photoperiod and temperature is dependent on the carbon status of the trees, and reflects a metabolic adjustment of reduced carbon consumption for BSP synthesis. These results demonstrate the differential temperature sensitivity of processes involved in seasonal N storage, implying vulnerability to changing environmental conditions.
Inter‐ and intra‐specific variability in isoprene production and photosynthesis of Central European oak species
Authors: Steinbrecher R. , Contran N. , Gugerli F. , Schnitzler J.‐P. , Zimmer I. , Menard T. , Günthardt‐Goerg M.S. 
Published: December 2012

AbstractEuropean deciduous oaks are closely related and are known for their strong emission of volatile isoprenoids. They are chemo‐taxonomically diverse, but hybridise frequently. Four‐year‐old oak seedlings growing together in a model ecosystem facility under near‐natural conditions were studied. The leaves were morphologically classified in the three oak species Quercus robur, Q. pubescens and Q. petraea (with four provenances each) and further investigated by a molecular‐genetic approach. Q. robur was morphologically and genetically clearly different from Q. pubescens and Q. petraea, whereas Q. pubescens and Q. petraea individuals used in this study were morphologically and genetically more similar. There was a minor impact of among and within species variability on isoprene synthesis, isoprene emission and photosynthesis. Isoprene emission rates normalised to 25 °C leaf temperature ranged from 5.78 to 10.66 nmol m−2 s−1, whereas photosynthesis ranged from 12.8 to 17.6 μmol m−2 s−1. On cloudy days, among the provenances of each species, only net photosynthesis of the Q. robur provenance Hünenberg was reduced and isoprene synthase activity of the Q. pubescens provenance Promotogno increased. On sunny days, photosynthesis did not differ among the provenances. Over all provenances, gas exchange on cloudy days did not differ significantly from sunny days. In the combined data of cloudy and sunny days, no differences between the studied provenances and oak species were detected in isoprene emission and photosynthesis. Thus, isoprene emission and photosynthesis rates were remarkably stable among oak species and provenances. The results indicate that taxonomic differences in the studied oak species are not reflected in isoprene emission and photosynthesis, probably because of the high plasticity of gene expression resulting in high phenotypic flexibility.
Mirtazapine protects against cisplatin‐induced oxidative stress and DNA damage in the rat brain
Authors: Gulec Mustafa , Oral Elif , Dursun Onur B. , Yucel Atakan , Hacimuftuoglu Ahmet , Akcay Fatih , Suleyman Halis 
Published: December 2012

AimCisplatin chemotherapy is associated with neurotoxicity, and oxidative stress might play an important role in the pathogenesis. Mirtazapine may be a preventative agent via its less‐known antioxidant properties. The aim of this study was to examine the potential chemoprotective effects of mirtazapine against cisplatin‐induced oxidative stress and DNA damage.MethodsTwenty‐four rats were divided equally into four groups: control; cisplatin (10 mg/kg i.p.); cisplatin plus mirtazapine (10–30 mg/kg, respectively i.p and p.o.); and mirtazapine (30 mg/kg p.o.). The rats were killed at the end of the 14th day of treatment. Brain tissue was examined with regard to antioxidant/oxidant biochemical parameters.ResultsAlthough glutathione (tGSH) and nitric oxide (NO) end product mean scores were found to be statistically higher in the control group when compared with the cisplatin group (72.44% and 61.99% percentage change [PC], respectively), malondialdehyde (MDA), myeloperoxidase (MPO), and 8‐hydroxyguanine (8‐OH‐GUA) mean scores were statistically lower in the control group in comparison with the cisplatin group (−55.48%, −67.99%, and −48.81% PC, respectively; P < 0.01). Finally, tGSH and NO end product levels were restored to normal (85.90% and 55.30% PC, respectively), and MDA, MPO, and 8‐OH‐GUA were significantly reduced by treatment with mirtazapine (−60.50%, −78.59%, and −38.10% PC, respectively; P < 0.01).ConclusionMirtazapine has chemoprotective effects against cisplatin‐induced oxidative stress and DNA damage in the rat brain, which may be attributed to its antioxidant capabilities. It would be useful to investigate whether cisplatin at the desired doses can be given concurrently with mirtazapine.
Thoracic computed tomography in absent pulmonary valve syndrome management
Authors: Vincenti Marie , Jacquot Aurélien , Guillaumont Sophie , Milési Christophe , Saguintaah Magali , Pidoux Odile , Kreitmann Bernard , Rideau Aline , Cambonie Gilles 
Published: December 2012

AbstractA neonate with absent pulmonary valve syndrome (APVS) and features of tetralogy of Fallot presented respiratory distress. The prolonged need for mechanical ventilation was an indication for surgical repair. Preoperative thoracic CT imaging showed nearly complete closure of the distal trachea, compressed by the aneurysmal dilatation of the pulmonary arteries, and its reopening after ventilator pressure was increased. Management of APVS may require high‐pressure ventilation to prevent bronchial collapse due to compression by the pulmonary arteries. In this context, thoracic CT imaging is very useful for adjusting ventilation support so that surgical repair can be performed in optimal conditions.
Child‐onset systemic sclerosis positive for anticentromere antibodies: Two Japanese cases
Authors: Inamo Yasuji 
Published: December 2012

AbstractSystemic sclerosis (SSc) is an uncommon connective tissue disease of childhood. Moreover, pediatric SSc positive for anticentromere antibodies (ACA) is extremely rare. We describe two cases of ACA‐positive SSc in Japanese girls with clinical findings. Case 1 is a 15‐year‐old female. From disease onset at 7 years, she developed limited cutaneous (no internal involvement) SSc positive for ACA and anti‐U1RNP antibodies, but negative for antitopoisomerase I antibodies (ATA). She also showed calcinosis, sclerodactyly, and telangiectasia, but not Raynaud's phenomenon. Case 2 is also a 15‐year‐old female with onset at the same age. Her diagnosis was limited cutaneous SSc positive for ACA, anti‐SSA/Ro antibodies, and anti‐thyroid antibodies, but not ATA. She showed sclerodactyly, telangiectasia, and Raynaud phenomenon, as well as complicated Sjögren's syndrome and chronic thyroiditis with euthyroidism. We reported that two Japanese girls with SSc were positive for ACA and other antibodies with the exception of ATA.
Completely infarcted smooth muscle tumor of the placental membrane
Authors: Haltas Hacer , Bayrak Reyhan , Yenidunya Sibel , Tevrizci Hatice 
Published: December 2012

AbstractNon‐trophoblastic tumor of the placenta is rare, and so is placental smooth muscle tumor. We report leiomyoma of the placental membrane, which was discovered on cesarean section. Histologically, the tumor was a benign leiomyoma with complete necrosis, and this finding was confirmed immunohistochemically. Only six cases of smooth muscle tumors of the placenta have been reported to date. This is the third report of leiomyoma involving the placental membrane.