bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA Genotype of Patients with Severe Haemophilia A due to Intron 22 Inversion with and without Inhibitors of Factor VIII
Authors: Oldenburg J , Picard J K , Schwaab R , Brackmann H H , Tuddenham E G D , Simpson E 
Published: July 2018

SummaryMolecular genetic studies have shown that development of antibodies to factor VIII (inhibitors) occurs most frequently in patients with severe haemophilia due to major gene lesions including inversions, stop codons and large deletions. Previous studies of HLA type were performed on inhibitor and non-inhibitor patients with diverse uncharacterised mutations which may have confounded detection of significant associations. We therefore selected a group of patients with a single mutation type, the prevalent intron 22 inversion, with or without inhibitors, to determine HLA genotype. Seventy-one such patients, 42 without and 29 with inhibitors (13 high, 9 low and 7 transient responders) were genotyped for MHC Class I HLA-A, -B, -C and Class II HLA-DQA, -DQB and -DRB loci. No strong correlation of any HLA-allele to inhibitor or non-inhibitor status was found. However, alleles of the haplotype HLA-A3, HLA-B7, HLA-C7, HLA-DQA0102, HLA-DQB0602, HLA-DR15 occurred more often in inhibitor patients. Since the alleles of this extended haplotype are common in the North European population only a very strong association would achieve statistical significance. Further studies of groups of patients similar to those studied here will be needed to confirm or exclude this association.
Coagulation Activation Markers in the Prediction of Venous Thrombosis after Elective Hip Surgery
Authors: Cofrancesco E , Cortellaro M , Corradi A , Ravasi F , Bertocchi F 
Published: July 2018

Summary
Background. Despite prophylaxis, deep vein thrombosis (DVT) after hip surgery continues to occur frequently. Thus it would be helpful if before surgery patients at higher risk of DVT could be identified and more adequate prophylaxis given. As part of an international study on the prevention of DVT after total hip replacement, we investigated whether preoperative levels of three coagulation activation markers, prothrombin fragment F1+2 (F1+2), thrombin-antithrombin III complexes (TAT) and D-dimer, correlate with results of postoperative venography.
Methods. 159 patients undergoing total hip replacement were randomized to receive 10, 15 or 20 mg desirudin bid or 5000 IU unfractionated heparin tid immediately before surgery and then for 11 days, until bilateral venography was performed. Preoperative F1+2, TAT and D-dimer plasma levels were measured using ELISA procedures. As no difference among anticoagulant treatments or in the interaction between treatments and DVT was detected for any of the three variables, results are reported as pooled data.
Findings. The frequency of DVT was 18.8% in the low (0.75-1.33 nM) vs 65.7% in the high third of distribution (1.77-3.47 nM) of F1+2 (p ˂.001), 27.3% in the low (2.00-2.50 μg/1) vs 57% in the high third (5.10-61.00 μg/l) of TAT (p = .042), and 29.4% in the low (39-59 μg/1) vs 57.1% in the high third (129-651 μg/1) of D-dimer (p = .051).
Interpretation. Preoperative F1+2, TAT and D-dimer levels are associated with the risk of development of DVT after total hip replacement.
Expression and Characterization of Recombinant Porcine Plasminogen Activator Inhibitor-1
Authors: Bijnens A P , Knockaert I , Cousin E , Kruithof E K O , Declerck P J 
Published: July 2018

SummaryPorcine models are, among other animal models, very suitable for in vivo investigations in the vascular field especially with respect to the possible relationship between atherosclerosis and thrombosis. In order to use this model to define the in vivo role of PAI-1, the characterization of porcine PAI-1 and its availability for the generation of immunological tools are a prerequisite. Porcine plasminogen activator inhibitor-1 (poPAI-1) cDNA was isolated from a cDNA library prepared from cultured porcine aortic cells and characterized in comparison with PAI-1 cDNA’s from other species including human, bovine, rabbit, rat and murine. Subsequently the DNA sequence coding the mature protein was cloned into an appropriate vector for expression in Escherichia coli and recombinant porcine PAI-1 was purified and characterized. On SDS-PAGE the apparent molecular weight was estimated to be 45 kDa, identical to the molecular weight of human PAI-1. The purified recombinant porcine PAI-1 (rpoPAI-1) had a specific activity of 508,800 ± 800 U/mg (mean ± SD, n = 3) towards human tissue-type plasminogen activator (ht-PA) and a functional half-life in vitro of 2.1 ± 0.8 h (n = 3). Incubation with a two fold molar excess of ht-PA (n = 3) or human urokinase-type plasminogen activator (hu-PA, n = 2) followed by analysis by SDS-PAGE revealed reaction products corresponding to active (71 ± 7% resp. 96 ± 3.6%), latent (12 ± 0.4% resp. 2.6 ± 2.4%) and substrate (16.6 ± 6.8% resp. 1.5 ± 1.3) forms. Inactivated samples of porcine PAI-1 could be reactivated with guanidinium chloride up to 52% of its original specific activity towards t-PA and u-PA. The second order rate constant of inhibition of ht-PA was 1.64 ± 0.37 1 07M-1 s-1 (n = 9). In gel filtration rpoPAI-1 in buffer eluted at a volume corresponding to 24 kDa, whereas in the presence of porcine plasma, the molecular form containing PAI-1 activity eluted at a volume corresponding to 330 kDa, presumably as a consequence of binding of active PAI-1 to vitronectin.Taken together, these data demonstrate that no obvious functional differences exist between human and porcine PAI-1.
Impaired Prothrombin Consumption in Bernard-Soulier Syndrome Is Corrected In Vitro by Human Factor VIII
Authors: Bellucci S , Girma J P , Lozano M , Meyer D , Caen J P 
Published: July 2018

SummaryThe Bernard-Soulier syndrome (BSS) is characterized by thrombocytopenia with giant platelets, a prolonged bleeding time with defective platelet adhesion to the subendothelium related to a defect in platelet membrane glycoprotein lb (GPIb) and a decreased prothrombin consumption. The mechanism of the latter abnormality remains unknown. In this study, we showed that this defect was corrected by the addition of purified human factor VIII (FVIII) to blood from four patients with BSS. The correction of prothrombin consumption was almost complete at concentrations between 1.5 and 3 IU/ml of FVIII procoagulant activity (VIII.'C) and partially abolished by a monoclonal antibody which neutralizes VIII:C. This correction was specific for FVIII and was not observed after addition of purified human FIX. It was obtained, in the same magnitude range, with FVIII complexed to von Willebrand factor (vWF) but not with free vWF. These data provide a new insight into the knowledge of the physiological interaction between the platelet membrane and the vWF-FVIII complex facilitating plasma coagulation activation and may lead to helpful therapeutic advances.
Outcome of Neonates with Vein of Galen Malformation Presenting with Severe Heart Failure: A Case Series
Authors: De Rosa Gabriella , De Carolis Maria , Tempera Alessia , Pedicelli Alessandro , Rollo Massimo , Luca Ersilia , De Luca Daniele , Conti Giorgio , Piastra Marco , Morena Tony 
Published: July 2018

Background Neonatal presentation of vein of Galen aneurysmal malformations (VGAMs) complicated by cardiac failure and pulmonary hypertension is frequently associated with a poor prognosis. Interventional neuroradiology with embolization can offer a chance for survival, although neurological damage can represent a limitation.
Objective This article determines if aggressive intensive care and drug management of cardiac failure before urgent embolization can influence morbidity and mortality.
Patients and Methods Twelve infants (7 boys, 5 girls) were diagnosed with symptomatic vein of Galen malformations in the neonatal period during the period 2000 to 2014. Due to high output cardiac failure, endovascular treatment was attempted as soon as stabilization was achieved.
Results Endovascular procedures successfully reverted cardiac failure in 5 patients who survived without significant neurological damage, while in 7 patients the causes of death were refractory cardiac failure, multiorgan failure, and severe brain damage. Bidimensional echocardiography assessment was performed at presentation and after early embolization procedures.
Conclusion Aggressive intensive care approach to heart failure and pulmonary hypertension leading to early neurointervention results in good survival rates with low morbidity even in cases of high-risk neonatal VGAM. Combined hemodynamic treatment can improve outcome in neonates with cardiac failure secondary to VGAM, although there is the risk of precipitating systemic hypoperfusion and renal failure. A moderate prematurity may not prevent both interventional approach and good outcome.
Predicting the Outcome of Total Knee Arthroplasty Using the WOMAC Score: A Review of the Literature
Authors: Walker Lucy Camilla , Clement Nick D. , Deehan David J. 
Published: July 2018

AbstractIt is estimated that up to a third of recipients of total knee arthroplasty (TKA) experience chronic pain postoperatively. However, there are no clear indications within the literature that predict which patients are at higher risk of being dissatisfied with their TKA. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) is one of the most commonly used, patient-reported outcome measures in patients with lower limb osteoarthritis. This review discusses the available evidence surrounding the predictability of the outcome of TKA using the WOMAC score as well as considering further patient factors that have been implicated in the level of improvement post TKA. It may be concluded from the available literature that a combination of knee scores and patient factors would be the most accurate way of predicting those patients most likely to have a good outcome from their TKA. There is some disparity within the literature about which patient factors and reported outcome measure scores lead to a positive postoperative outcome. Patient expectations following the procedure also need to be evaluated, as objective measures on a scoring system do not necessarily equate with the subjective patient experience.
Value of Systemic Staging in Asymptomatic Early Breast Cancer
Authors: Soares Gregório Pinheiro , Pereira Allan Andresson Lima , Vilas Boas Mariana Silva , Vaisberg Victor Van , Magalhães Maria Cristina Figueroa , Linck Rudinei Diogo Marques , Mano Max Senna 
Published: July 2018

Objective Metastases are rare in early breast cancer (EBC), and international guidelines recommend against routine systemic staging for asymptomatic patients. However, imaging exams remain widely employed in the clinical practice. The aim of the present study is to evaluate the value of imaging for systemic staging in EBC.
Methods A retrospective analysis of newly-diagnosed breast cancer (BC) patients was performed. Clinical data including BC subtype, stage, presence of symptoms at diagnosis and instrumental procedures performed for staging were recorded.
Results A total of 753 patients were included, with a median age of 57 years. The majority of the patients underwent at least 1 imaging procedure (91%); had invasive ductal carcinoma (83.5%); histological grade 2 (51.4%); stage II (61.8%); and luminal subtype (67.9%). Among the 685 (91%) patients who underwent any radiologic staging, distant metastases (DMs) were detected in 32 (4.7%). In the univariate analyses, stage IIb and pathological lymph node involvement (pN1) showed a statistically significant association with the presence of DMs, versus only a trend for triple negative and human epidermal growth factor receptor 2 (Her2) positive subtype. In an exploratory analysis performed in this same subgroup, when unfavorable biology (triple negative or Her2 positive) was present, patients had a DM rate of 14.4%, one of the highest reported at this stage of the disease.
Conclusion Early breast cancer has a low prevalence of DM at the initial evaluation, and systemic staging of asymptomatic, unselected patients is not warranted as a routine practice. However, we have identified subgroups of patients to whom a full staging could be indicated.
Ticks and dust mites: invasive and health-affecting borderline organisms.
Authors: Simoni S. , Grandi G. 
Published: July 2018

Abstract

According to the situations and cases presented here, organisms belonging to tick and house dust mite groups can be included within alien invasive pests representing a risk for human health. Rhipicephalus sanguineus, the brown dog tick, a vector for many tick-borne pathogens, is able to efficiently colonize households at quite wide ranges in temperature and relative humidity. Cases of the spread of this tick by movements of pets and people are reported. House dust mites and main storage mites - although not strictly alien species - can act not only as allergens' disseminators but even as potential indicators of environmental quality in different settings (newly colonized areas, both geographic and within human dwellings). The impact of alien mites affecting agricultural production has been generally measured by the ecological consequences on biodiversity, but the evaluation of the effects of these species on human health has been mostly neglected. Trading, travelling and modified home conditions can increase the chance for diffusion of ticks and mites affecting human health, i.e. causing higher exposures to vector-borne pathogens and allergens, respectively. A more interdisciplinary approach that takes into account both the dynamics in ecological evaluation and the consequences on human health of these organisms is needed.
Is a Reported Penicillin Allergy Sufficient Grounds to Forgo the Multidimensional Antimicrobial Benefits of β-Lactam Antibiotics?
Authors: Sakoulas George , Geriak Matthew , Nizet Victor 
Published: July 2018

Abstract
The majority of patients with reported penicillin allergy are not allergic when tested or challenged. Penicillin allergy testing has been shown to significantly reduce annual healthcare expenditures. Data have emerged showing β-lactams have multidimensional antibacterial effects in vivo, far beyond what is appreciated in standard bacteriological susceptibility testing media. These include enhancing bacterial killing by the innate immune system. Supporting the clinical relevance of these secondary underappreciated effects are recent clinical and pharmacoeconomic analyses that show worse outcomes in patients with reported penicillin allergies who receive non-β-lactam antibiotics when compared to their non-penicillin-allergic counterparts. This is particularly relevant in the treatment of Staphylococcus aureus bacteremia. This article reviews the tremendous advantages offered by β-lactam therapy and makes a strong case that the debunking of false penicillin allergies through a detailed allergy history and penicillin allergy testing should be a vital component of antimicrobial stewardship practices.
Assessment of Students’ Perception of the Nutrition Curriculum in a Canadian Undergraduate Medical Education Program
Authors: Hanninen Stacy , Rashid Mohsin 
Published: July 2018

AbstractBackgroundNutrition plays an important role in diseases, and physicians need to be proficient in providing nutrition counselling to patients. There is limited information regarding nutrition education in Canadian medical schools.ObjectiveThe objective of this study was to investigate students’ perspectives about nutrition training provided in the undergraduate medical education program at Dalhousie University.MethodsAll medical students in their second, third, and fourth years of training at Dalhousie University were surveyed online with a 23-item questionnaire that included 10 nutrition competencies.ResultsOf 342 students, 89 (26%) completed the survey. Using a five-point Likert scale, ranging from one, indicating ‘very dissatisfied/strongly disagree’ to five, indicating ‘very satisfied/strongly agree,’ the mean overall satisfaction with nutrition curriculum was 2.9 ± 0.81. Perceived competency in nutrition assessment had the highest mean satisfaction rating (3.98 ± 0.89). There was more variance on perceived competency, with other aspects of training including basic nutrition principles (3.51 ± 0.92), disease prevention (3.14 ± 1.12), disease management (3.48 ± 1.00), role of dietitians (2.97 ± 1.05), credible nutrition sources (3.14 ± 1.09), dietary assessment (2.82 ± 1.11), lifecycle nutrition (2.67 ± 1.09), food security (2.4 ± 0.95) and malnutrition (2.74 ± 0.93). Med-4 students agreed significantly more than Med-2 students regarding confidence about their understanding of the role of dietitians. Students recommended a longitudinal nutrition program, inclusion of dietitians as educators, and provision of evidence-based resources in the curriculum. The majority (79%) agreed that more nutrition instruction is needed. Satisfaction with nutrition education has not improved since 2010, despite curricular changes.ConclusionsMedical students’ satisfaction with nutrition education remains problematic. They want more nutrition training. Ongoing assessment and student feedback is important to make changes and improvements in the nutrition curriculum.
Stochastic Variational Inference for Bayesian Phylogenetics: A Case of CAT Model
Authors: Dang Tung , Kishino Hirohisa 
Published: July 2018

AbstractThe pattern of molecular evolution varies among gene sites and genes in a genome. By taking into account the complex heterogeneity of evolutionary processes among sites in a genome, Bayesian infinite mixture models of genomic evolution enable robust phylogenetic inference. With large modern data sets, however, the computational burden of Markov chain Monte Carlo sampling techniques becomes prohibitive. Here, we have developed a variational Bayesian procedure to speed up the widely used PhyloBayes MPI program, which deals with the heterogeneity of amino acid profiles. Rather than sampling from the posterior distribution, the procedure approximates the (unknown) posterior distribution using a manageable distribution called the variational distribution. The parameters in the variational distribution are estimated by minimizing Kullback-Leibler divergence. To examine performance, we analyzed three empirical data sets consisting of mitochondrial, plastid-encoded, and nuclear proteins. Our variational method accurately approximated the Bayesian phylogenetic tree, mixture proportions, and the amino acid propensity of each component of the mixture while using orders of magnitude less computational time.
Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates
Authors: Sul Jae Hoon , Service Susan K. , Huang Alden Y. , Ramensky Vasily , Hwang Sun-Goo , Teshiba Terri M. , Park YoungJun , Ori Anil P. S. , Zhang Zhongyang , Mullins Niamh , Loohuis Loes M. Olde , Fears Scott C. , Araya Carmen , Araya Xinia , Spesny Mitzi , Bejarano Julio , Ramirez Margarita , Castrillón Gabriel , Gomez-Makhinson Juliana , Lopez Maria C. , Montoya Gabriel , Montoya Claudia P. , Aldana Ileana , Escobar Javier I. , Ospina-Duque Jorge , Kremeyer Barbara , Bedoya Gabriel , Ruiz-Linares Andres , Cantor Rita M. , Molina Julio , Coppola Giovanni , Ophoff Roel A. , Macaya Gabriel , Lopez-Jaramillo Carlos , Reus Victor , Bearden Carrie E. , Sabatti Chiara , Freimer Nelson B. 
Published: July 2018

AbstractCurrent evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To evaluate this hypothesis, we conducted genetic analyses in 26 Colombian (CO) and Costa Rican (CR) pedigrees ascertained for BP1, the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 856 individuals and high-coverage whole-genome sequencing of 454 individuals. Compared to their unaffected relatives, BP1 individuals had higher polygenic risk scores estimated from SNPs associated with BP discovered in independent genome-wide association studies, and also displayed a higher burden of rare deleterious single nucleotide variants (SNVs) and rare copy number variants (CNVs) in genes likely to be relevant to BP1. Parametric and non-parametric linkage analyses identified 15 BP1 linkage peaks, encompassing about 100 genes, although we observed no significant segregation pattern for any particular rare SNVs and CNVs. These results suggest that even in extended pedigrees, genetic risk for BP appears to derive mainly from small to moderate effect rare and common variants.
Profiling of urine bacterial DNA to identify an “oncobiome” in a mouse model of bladder cancer
Authors: Forster Catherine S. , Cody James J. , Banskota Nirad , Stroud Crystal , Hsieh Yi-Ju , Farah Dannah , Lamanna Olivia , Hammam Olfat , Caldovic Ljubica , Hsieh Michael H. 
Published: July 2018

AbstractIntroductionRecurrent urinary tract infections have been linked to increased risk of bladder cancer, suggesting a potential role of the urinary microbiome in bladder cancer pathogenesis.ObjectiveCompare the urinary microbiomes in mice with and without bladder.MethodsLongitudinal study of mice exposed to a dilute bladder-specific carcinogen (0.05% n-butyl-n-(4-hydroxybutyl) nitrosamine, BBN mice, n=10), and control mice (n=10). Urine was sampled monthly from individual mice for 4 months. Microbial DNA was extracted from the urine, and the V4 region of the 16S rRNA gene sequenced. Animals were sacrificed and their bladders harvested for histopathology. Bladder sections were graded by a blinded pathologist. The composition and diversity of the urinary microbiome were compared between the BBN and control mice. Metabolic pathway analysis was completed using PICRUST.ResultsBladder histology in the BBN group showed normal tissue with inflammation (BBN-normal, n=5), precancerous pathologies, (BBN-precancerous, n=3), and invasive cancer (BBN-cancer, n=2). Alpha diversity did not differ between the mice exposed to BBN and the control mice at any timepoint. There were no differences in the urinary microbiomes between the BBN and control mice at baseline. At month 4, mice exposed to BBN had higher proportion of both Gardnerella and Bifidobacterium compared to control mice. There were no differences in proportions of specific bacteria between either the BBN-precancer or BBN-cancer and controls at month 4. However, the BBN-normal mice had higher proportions of Gardnerella, Haemophilus, Bifidobacterium, and Ureaplasma Actinobaculum, and lower proportions of Actinomyces, compared to control mice at month 4. Functional pathway analysis demonstrated increases in genes related to purine metabolism, phosphotransferase systems, peptidases, protein folding, and bacterial toxins in the BBN-mice compared to control mice at month 4.ConclusionMice exposed to 4 months of BBN, a bladder-specific carcinogen, have distinct urine microbial profiles compared to control mice.