Successful hip arthroplasty in an adult male with severe factor XI deficiency using Hemoleven®, a factor XI concentrate.

Severe factor XI (sFXI) deficiency is a rare bleeding disorder (RBD). FXI replacement is most often required for surgical hemostasis. Plasma, the sole US treatment option, is often complicated by life-threatening allergic reactions.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) associates with huntingtin protein and promotes its atypical ubiquitination to enhance aggregate formation.

Huntington disease (HD) is a neurodegenerative disorder caused by an expansion of polyglutamines in the first exon of huntingtin (HTT), which confers aggregation-promoting properties to amino-terminal fragments of the protein (N-HTT). Mutant N-HTT aggregates are enriched for ubiquitin and contain ubiquitin E3 ligases, thus suggesting a role for ubiquitination in aggregate formation. Here, we report that tumor necrosis factor receptor-associated factor 6 (TRAF6) binds to WT and polyQ-expanded N-HTT in vitro as well as to endogenous full-length proteins in mouse and human brain in vivo.

Finding new genes for non-syndromic hearing loss through an in silico prioritization study.

At present, 51 genes are already known to be responsible for Non-Syndromic hereditary Hearing Loss (NSHL), but the knowledge of 121 NSHL-linked chromosomal regions brings to the hypothesis that a number of disease genes have still to be uncovered. To help scientists to find new NSHL genes, we built a gene-scoring system, integrating Gene Ontology, NCBI Gene and Map Viewer databases, which prioritizes the candidate genes according to their probability to cause NSHL. We defined a set of candidates and measured their functional similarity with respect to the disease gene set, computing a score ( S S M avg) that relies on the assumption that functionally related genes might contribute to the same (disease) phenotype.

Characterisation of Staphylococcus aureus and Enterococcus faecalis mutants with reduced susceptibility to the investigational oxazolidinone RWJ-416457.

RWJ-416457 is a novel investigational oxazolidinone with minimum inhibitory concentrations (MICs) to staphylococci and enterococci that are two- to four-fold lower than those of linezolid. Single-step and serial passage in vitro resistance selection experiments were performed for RWJ-416457 and linezolid with Staphylococcus aureus and Enterococcus faecalis laboratory and clinical isolates. RWJ-416457 selected for resistant mutants in single-step selections at a frequency of ≤1×10(-10), similar to that of linezolid.

Comparison of broth microdilution, agar dilution, and Etest for susceptibility testing of doripenem against gram-negative and gram-positive pathogens.

The susceptibility of 513 clinical isolates to doripenem was determined by broth microdilution, agar dilution, and Etest. Overall agreements for Etest and agar dilution MIC values compared to reference broth microdilution at +/-1 log(2) dilution were 88% and 94%, respectively. Etest MIC values demonstrated 98% agreement within +/-2 log(2) dilutions compared to the reference broth microdilution method.

[Origins of Changos. Mitochondrial DNA analysis suggests Chinchorro culture fishermen ancestry].

Sophisticated molecular genetics techniques allow the typification and posterior comparison of antique haplogroups and mitochondrial DNA sequences from prehistoric groups with contemporary populations. This adds a chronological dimension to these studies and contributes to have a better knowledge of the genetic composition of the Chilean population. This article gives scientific support, using molecular methodology, to the alleged biological links that joined the descendants of proto historic Chango fishermen from Paposo cove, a place located 15 kilometers north of Taltal, with prehistoric fishermen from Chinchorro culture, that developed in Northern Chile and Southern Peru between 7900 and 4000 A.

Impaired glycosylation blocks DPP10 cell surface expression and alters the electrophysiology of Ito channel complex.

DPP10 is a transmembrane glycosylated protein belonging to the family of dipeptidyl aminopeptidase-like proteins (DPPLs). DPPLs are auxiliary subunits involved in the regulation of voltage-gated Kv4 channels, key determinants of cardiac and neuronal excitability. Although it is known that DPPLs are needed to generate native-like currents in heterologous expression systems, the molecular basis of this involvement are still poorly defined.

Prevalence of allo-immunization anti-HLA and anti-integrin alphaIIbbeta3 in Glanzmann Thromboasthenia patients.

Platelet transfusions, main therapy of Glanzmann Thromboasthenia (GT), can induce an allo-immunization against human leucocyte antigen and integrin alphaIIbbeta3. We have investigated in our GT patients the rate of allo-immunization and of refractoriness to platelet transfusions. From 1975 until December 2005, we have followed 17 GT patients: 14 type 1, 3 variant type; nine females, eight males; median age at diagnosis 9.

Mortality and causes of death in Italian persons with haemophilia, 1990-2007.

Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co-morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate.

Rapid interactome profiling by massive sequencing.

We have developed a high-throughput protein expression and interaction analysis platform that combines cDNA phage display library selection and massive gene sequencing using the 454 platform. A phage display library of open reading frame (ORF) fragments was created from mRNA derived from different tissues. This was used to study the interaction network of the enzyme transglutaminase 2 (TG2), a multifunctional enzyme involved in the regulation of cell growth, differentiation and apoptosis, associated with many different pathologies.

Understanding inhibitor development in haemophilia A: towards clinical prediction and prevention strategies.

Inhibitor development, because of its impact on patients' morbidity and quality of life, is presently the most serious complication of haemophilia A treatment. The identification of several genetic and non-genetic risk factors may be used for the stratification of inhibitor risk and the definition of prevention strategies, particularly for patients with a high-risk genetic profile. The most extensively studied genetic factor is the type of F8 mutation, i.

Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia.

There is evidence that leukocytosis is associated with an increased risk of first thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Whether it is a risk factor for recurrent thrombosis too is currently unknown. In the frame of a multicenter retrospective cohort study, we recruited 253 patients with PV (n = 133) or ET (n = 120), who were selected on the basis of a first arterial (70%) or venous major thrombosis (27.

Impact of empire expansion on household diet: the Inka in Northern Chile's Atacama Desert.

The impact of expanding civilization on the health of American indigenous societies has long been studied. Most studies have focused on infections and malnutrition that occurred when less complex societies were incorporated into more complex civilizations. The details of dietary change, however, have rarely been explored.

The 423Q polymorphism of the X-linked inhibitor of apoptosis gene influences monocyte function and is associated with periodic fever.

Objective: Hereditary periodic fever syndromes (HPFs) develop as a result of uncontrolled activation of the inflammatory response, with a substantial contribution from interleukin-1beta or tumor necrosis factor alpha (TNFalpha). The HPFs include familial Mediterranean fever (FMF), hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), TNF receptor-associated syndrome (TRAPS), and cryopyrinopathies, which are attributable to mutations of the MEFV, MVK, TNFRSF1A, and CIAS1 genes, respectively. However, in many patients, the mutated gene has not been determined; therefore, the condition in these patients with an HPF-like clinical picture is referred to as idiopathic periodic fever (IPF).

Delirium in patients admitted to a step-down unit: analysis of incidence and risk factors.

Background: Delirium is a rather common complication among patients admitted in intensive care units (ICUs), and rather than a single entity, it can be considered a spectrum of diseases where, besides overt cases, there are also many subsyndromal forms. Although there are many data about ICU delirium, there are few data concerning this complication in patients transferred from the ICU to a step-down unit (SDU) once clinically stable.

Objectives: With the present study, we wanted to assess the incidence of and risk factors for delirium and subsyndromal forms and their impact on clinical outcome in a group of patients transferred from an ICU to an SDU.

Unexpected expression of alpha- and beta-globin in mesencephalic dopaminergic neurons and glial cells.

The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the substantia nigra (SN) (A9 neurons) and the ventral tegmental area (VTA) (A10 cells). A9 neurons form the nigrostriatal pathway and are involved in regulating voluntary movements and postural reflexes. Their selective degeneration leads to Parkinson's disease.

Decisional flow with a scoring system to start platelet-lowering treatment in patients with essential thrombocythemia: long-term results.

We prospectively tested, at diagnosis in essential thrombocythemia (ET) patients with no clear indication to platelet (PLT)-lowering treatment, a scoring system based on age, PLT level, cardiovascular diseases, previous thrombotic events, smoking and dysmetabolic diseases. From 04/92 to 03/98, 168 consecutive patients were enrolled. Hydroxyurea (HU) was started at diagnosis in 32 "symptomatic" patients and in 33 patients aged >70 years.

Profiling the autoantibody repertoire by screening phage-displayed human cDNA libraries.

The advent of the serological identification of antigens by procedures such as cDNA cloning and recombinant protein expression has allowed the direct molecular definition of immunogenic proteins. The phage-display technology provides several advantages over conventional immunoscreening procedures based on plasmid or lambda-phage cDNA libraries. So far, attempts to display open reading frames, such as those encoded by cDNA fragments, on filamentous phages have not been very successful.

Increased risk of recurrent thrombosis in patients with essential thrombocythemia carrying the homozygous JAK2 V617F mutation.

Evidence suggests that the JAK2 V617F mutation is associated with an increased risk of first thrombosis in patients with essential thrombocythemia (ET). Whether this mutation is also a risk factor for recurrent thrombosis is currently unknown. To investigate the impact of the JAK2 V617F mutation on the risk of recurrent thrombosis in patients with ET, we carried out a multicentre retrospective cohort study.

Comparison of the rates of joint arthroplasty in patients with severe factor VIII and IX deficiency: an index of different clinical severity of the 2 coagulation disorders.

Data from the Italian Hemophilia Centres were collected to perform a retrospective survey of joint arthroplasty in patients with severe hemophilia. Twenty-nine of 49 hemophilia centers reported that 328 of the 347 operations were carried out in 253 patients with severe hemophilia A (HA) and 19 in 15 patients with severe hemophilia B (HB). When results were normalized to the whole Italian hemophilia population (1770 severe HA and 319 severe HB), patients with HA had a 3-fold higher risk of undergoing joint arthroplasty (odds ratio [OR], 3.

Performance of recalibrated ReFacto laboratory standard in the measurement of FVIII plasma concentration via the chromogenic and one-stage assays after infusion of recalibrated ReFacto (B-domain deleted recombinant factor VIII).

The use of ReFacto Laboratory Standard (RLS) in the one-stage clotting assay was proposed to reduce the underestimation of factor VIII (FVIII) plasma concentration after the infusion of 'ReFacto' (B-domain deleted recombinant FVIII) in haemophilia A patients. Both ReFacto and RLS were recently recalibrated, with the resulting materials containing approximately 20% more protein than the previous products. The aim of this study was to evaluate the performance of recalibrated RLS in the measurement of FVIII plasma concentration after the infusion of recalibrated ReFacto.

Forum on: the role of recombinant factor VIII in children with severe haemophilia A.

The development of recombinant FVIII (rFVIII) products, fuelled by the need for improved safety of treatment arising from the dramatic widespread blood-borne virus transmission in the 1970-1980s revolutionized the care of children with haemophilia A over the last two decades. The larger availability of perceived safer replacement therapy associated with the introduction of rFVIII products reassured the haemophilia community and there was a strong push in some Western countries to treat haemophilic children only with rFVIII. Moreover, this significantly contributed in the 1990s to the diffusion outside Northern Europe of prophylactic regimens implemented at an early age to prevent bleeding and the resultant joint damage (i.