Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy.

Various translocations and mutations have been identified in myeloma, and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41 known oncogenes and tumor suppressor genes in tumor samples from 133 relapsed myeloma patients participating in phase 2 or 3 clinical trials of bortezomib. DNA mutations were identified in 14 genes.

Development of a neuromedin U-human serum albumin conjugate as a long-acting candidate for the treatment of obesity and diabetes. Comparison with the PEGylated peptide.

Neuromedin U (NMU) is an endogenous peptide implicated in the regulation of feeding, energy homeostasis, and glycemic control, which is being considered for the therapy of obesity and diabetes. A key liability of NMU as a therapeutic is its very short half-life in vivo. We show here that conjugation of NMU to human serum albumin (HSA) yields a compound with long circulatory half-life, which maintains full potency at both the peripheral and central NMU receptors.

Iodine contributes to thyroid autoimmunity in humans by unmasking a cryptic epitope on thyroglobulin.

Context: The mechanisms linking thyroid autoimmunity and iodine use in humans are unknown.

Objective: Our aim was to correlate iodine intake, thyroid autoimmunity, and recognition of thyroglobulin (Tg) epitopes after implementation of iodine prophylaxis.

Setting: The general community living in an Italian village was evaluated.

Evaluation of Epstein-Barr virus-specific immunologic response in solid organ transplant recipients with an enzyme-linked ImmunoSpot assay.

Epstein-Barr virus (EBV) is a γ-herpes virus, responsible for infectious mononucleosis in immunocompetent hosts. Cellular immunity appears rapidly during EBV primary infection, keeping it silent despite long-life persistence in B lymphocytes. Defects of the EBV-specific cellular immunity are supposed to be the basis of post-transplantation lymphoproliferative disorders, promoted by high levels of immunosuppression.

Inhaled nitric oxide versus sodium nitroprusside for preoperative evaluation of pulmonary hypertension in heart transplant candidates.

Objective: The development of pulmonary hypertension before heart transplantation increases the risk for postoperative right ventricular failure. Reversibility of pulmonary vascular resistance (PVR), which indicates the feasibility of heart transplantation, can be tested with the use of intravenous vasodilators, such as sodium nitroprusside (NaNTP) or prostacyclin. However, the drawback of these drugs is the development of systemic hypotension.

Tailored cytomegalovirus management in lung transplant recipient: a single-center experience.

Introduction: Among solid organ recipients lung transplant recipients are at highest risk to be affected by cytomegalovirus infection (CMV) or to die from CMV disease. Two strategies are usually adopted in the clinical management of transplant recipients: antiviral prophylaxis and pre-emptive therapy.

Methods: In our center we adopted from 2007 a combined prophylaxis with anti-CMV immunoglobulins in the first post-transplant year and antiviral therapy (gancyclovir or valgancyclovir) from post-transplant day 15 for 3 weeks and in case of CMV bronchoalveolar lavage specimen positivity (polymerase chain reaction or shell vial).

Ex vivo lung perfusion increases the pool of lung grafts: analysis of its potential and real impact on a lung transplant program.

Background: Among the strategies to increase the number of lung transplants, ex vivo lung perfusion (EVLP) represents a novel technique to expand the donor pool.

Methods: Data from donors referred to our center were retrospectively analyzed to identify grafts that could potentially be potentially reconditioned by EVLP and for comparison with those obtained by clinical application of EVLP program in our center.

Results: Among 75 rejected lungs, 23 organs have been identified as potentially treatable with EVLP with a hypothetic increase of lung transplant activity of 53%.

The activity and specificity of the outer membrane protein chaperone SurA are modulated by a proline isomerase domain.

Unlabelled: SurA is a component of the periplasmic chaperone network that plays a central role in biogenesis of integral outer membrane β-barrel proteins (OMPs) in Escherichia coli. Although SurA contains two well-conserved proline isomerase (PPIase) domains, the contribution of these domains to SurA function is unclear. In the present work, we show that defects in OMP assembly caused by mutation of the β-barrel assembly factors BamA or BamB can be corrected by gain-of-function mutations in SurA that map to the first PPIase domain.

Predicting functionally informative mutations in Escherichia coli BamA using evolutionary covariance analysis.

The essential outer membrane β-barrel protein BamA forms a complex with four lipoprotein partners BamBCDE that assembles β-barrel proteins into the outer membrane of Escherichia coli. Detailed genetic studies have shown that BamA cycles through multiple conformations during substrate assembly, suggesting that a complex network of residues may be involved in coordinating conformational changes and lipoprotein partner function. While genetic analysis of BamA has been informative, it has also been slow in the absence of a straightforward selection for mutants.

Perceptual-motor abilities in pre-school preterm children.

Background: Several studies report a high percentage of premature infants presenting perceptual motor difficulties at school age. The new version of the Movement Assessment Battery for Children allows the assessment of perceptual-motor abilities in children from the age of 3years.

Aims: To evaluate early perceptual-motor abilities in prematurely born children below the age of 4years.

Essential oil composition and antimicrobial activity of aerial parts and ripe fruits of Echinophora spinosa (Apiaceae) from Italy.

The chemical composition and antimicrobial activity of the essential oils obtained from the flowering aerial parts and ripe fruits of Echinophora spinosa L. (Apiaceae) from central Italy were analyzed by GC/MS. The major constituents of the oil from the aerial parts were beta-phellandrene (34.

Green tea catechins can bind and modify ERp57/PDIA3 activity.

Background: Green tea is a rich source of polyphenols, mainly catechins (flavanols), which significantly contribute to the beneficial health effects of green tea in the prevention and treatment of various diseases. In this study the effects of four green tea catechins on protein ERp57, also known as protein disulfide isomerase isoform A3 (PDIA3), have been investigated in an in vitro model.

Methods: The interaction of catechins with ERp57 was explored by fluorescence quenching and surface plasmon resonance techniques and their effect on ERp57 activities was investigated.

Minimally invasive tricuspid valve surgery in patients at high risk.

Objective: Reports of minimally invasive tricuspid valve operations are rare, and results are often contradictory. This study analyzes our 5-year experience with minimally invasive tricuspid valve operations in high-risk patients.

Methods: Between November 2005 and December 2011, tricuspid valve surgery using a nonsternotomy minimally invasive technique was performed in 64 patients (19 male, 45 female; mean age, 63.

Biologically compatible neural interface to safely couple nanocoated electrodes to the surface of the brain.

The ongoing interest in densely packed miniaturized electrode arrays for high-resolution epicortical recordings has induced many researchers to explore the use of nanomaterial coatings to reduce electrode impedance while increasing signal-to-noise ratio and charge injection capability. Although these materials are very effective, their use in clinical practice is strongly inhibited by concerns about the potential risks derived from the use of nanomaterials in direct contact with the human brain. In this work we propose a novel approach to safely couple nanocoated electrodes to the brain surface by encapsulating them with a biocompatible hydrogel.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

Purpose: Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study.

Experimental Design: A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective.

Conformation-specific labeling of BamA and suppressor analysis suggest a cyclic mechanism for β-barrel assembly in Escherichia coli.

In gram-negative bacteria, integral outer membrane β-barrel proteins (OMPs) are assembled by the beta-barrel assembly machine (Bam) complex. The essential components of this complex are the OMP BamA [which contains a carboxyl-terminal β-barrel and an amino-terminal periplasmic module composed of five polypeptide transport associated (POTRA) domains] and the lipoprotein BamD. In Escherichia coli, the Bam complex also contains three nonessential lipoproteins (BamBCE), all of which require the barrel-proximal POTRA domain (P5) for stable interactions with BamA.

Neonatal neurological examination of late preterm babies.

Backgrounds: Healthy late-preterm (LP) infants examined at term equivalent age showed wider median and range of neurological scores than full-term infants; differences between infants born at 34 and those born at 35-36 weeks were also observed.

Aims: The aim of this study is to establish the range and frequency distribution of neonatal neurological scores in a cohort of low risk LP infants assessed during the first 3 days from birth.

Study Design And Subjects: 118 low-risk infants born between 34 and 36 weeks of gestational age (GA) were assessed between 48 and 72 h from birth.

Application of the sleep disturbance scale for children (SDSC) in preschool age.

Background: The Sleep Disturbance Scale for Children (SDSC) was originally validated on a sample of healthy children aged 6-16 years, investigating the occurrence of sleep disorders during the previous 6 months.

Aims: The aim of this new study was to assess the psychometric properties of the SDSC in an Italian population of preschool children.

Methods: The SDSC was distributed to the primary caregivers of children recruited via nurseries.

Case report: Osteoid osteoma of the acetabulum treated with arthroscopy-assisted radiofrequency ablation.

Background: Osteoid osteomas consist of a nidus surrounded by reactive sclerotic bone. The diagnosis typically is based on imaging and clinical presentation involving nocturnal pain. Removal of the lesion is essential and currently is performed mainly with image-guided, minimally invasive techniques.

Spontaneous coronary artery dissection: prevalence of predisposing conditions including fibromuscular dysplasia in a tertiary center cohort.

Objectives: We sought to evaluate the prevalence of fibromuscular dysplasia (FMD) and other predisposing conditions among spontaneous coronary artery dissection (SCAD) patients.

Background: Spontaneous coronary artery dissection is considered rare. However, we observed many young women with SCAD and concomitant FMD.