On the Crashworthiness Behaviour of Innovative Sandwich Shock Absorbers.

Increasing the impact resistance properties of any transport vehicle is a real engineering challenge. This challenge is addressed in this paper by proposing a high-performing structural solution. Hence, the performance, in terms of improvement of the energy absorbing characteristics and the reduction of the peak accelerations, of highly efficient shock absorbers integrated in key locations of a minibus chassis have been assessed by means of numerical crash simulations.

Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial.

Background: Vaccines based on mRNA coding for antigens have been shown to be safe and immunogenic in preclinical models. We aimed to report results of the first-in-human proof-of-concept clinical trial in healthy adults of a prophylactic mRNA-based vaccine encoding rabies virus glycoprotein (CV7201).

Methods: We did an open-label, uncontrolled, prospective, phase 1 clinical trial at one centre in Munich, Germany.

Cross-cultural validation of Lupus Impact Tracker in five European clinical practice settings.

Objectives: The aim was to evaluate the cross-cultural validity of the Lupus Impact Tracker (LIT) in five European countries and to assess its acceptability and feasibility from the patient and physician perspectives.

Methods: A prospective, observational, cross-sectional and multicentre validation study was conducted in clinical settings. Before the visit, patients completed LIT, Short Form 36 (SF-36) and care satisfaction questionnaires.

Bed-side inferior vena cava diameter and mean arterial pressure predict long-term mortality in hospitalized patients with heart failure: 36 months of follow-up.

Background: In discharged patients with heart failure (HF), diverse conditions can intervene to worsen outcome. We would investigate whether such factors present on hospital admission can affect long-term mortality in subjects hospitalized for acute HF.

Methods: One hundred twenty-three consecutive patients hospitalized for acute HF (mean age 74.

Clinical profile and direct medical cost of care of adults presenting with systemic lupus erythematosus in Italy.

Objectives: To determine the clinical profile and estimate the annual direct medical cost of care of adult patients with active, autoantibody positive systemic lupus erythematosus (SLE) in Italy.

Methods: A two-year, retrospective, multicentre, observational study was conducted from January to May 2011. Patients' characteristics, SLE disease activity and severity, rate of flares, healthcare consumption (e.

[Cost of systemic lupus erythematosus for adult patients with active and treated disease in France (LUCIE study)].

Purpose: To evaluate in France the annual direct medical cost of adult patients with active systemic lupus erythematosus (SLE) on medication and estimate the cost of a flare.

Methods: A two-year, observational, retrospective, multicenter study, carried out between December 2010 and February 2011. Patients' characteristics, SLE disease activity and severity, rate of flares, healthcare consumption (medications, hospitalisations, etc.

Patterns of systemic lupus erythematosus expression in Europe.

Objectives: To analyse the differences in disease expression of European SLE patients based on gender, age at diagnosis, and ethnicity.

Methods: A two-year, retrospective, multicentre, observational study was carried out in five countries (France, Germany, Italy, Spain and the UK). Patients' clinical manifestations including disease activity, organ involvement, organ damage and flares were analysed.

Efficacy and safety of collagenase Clostridium histolyticum injection for Dupuytren contracture: report of 40 cases.

Background: Dupuytren's disease (DD) is a fibroproliferative pathology that affects the palmar aponeurosis causing the development of nodules and collagen cords and the progressive flexion of the fingers. The standard procedure is surgical fasciectomy, followed by high recurrence rates. Collagenase Clostridium histolyticum (CCH) injection represents an innovative noninvasive approach to the treatment of DD.

Annual direct medical cost of active systemic lupus erythematosus in five European countries.

Objectives: To evaluate the annual direct medical cost of managing adult systemic lupus erythematosus (SLE) patients with active autoantibody positive disease in Europe.

Methods: A 2-year, retrospective, multicentre, observational study was conducted in five countries (France, Germany, Italy, Spain and the UK). Data included patients' characteristics, disease activity and severity, flare assessments and health resource use (eg, laboratory tests, medications, specialist visits and hospitalisations).

Gastroesophageal reflux disease: impact on work productivity and daily-life activities of daytime workers. A French cross-sectional study.

Background: Few studies have evaluated the impact of gastroesophageal reflux disease symptoms on work productivity and no French data are available.

Aim: To compare the impact of typical symptoms of nocturnal vs diurnal gastroesophageal reflux disease on work productivity and daily activities.

Methods: A French prospective, multicenter, observational study was performed in primary care setting.

Eperisone versus tizanidine for treatment of chronic low back pain.

Aim: Many therapies exist for treatment of chronic low-back pain (LBP) including the use of muscle relaxant and analgesic drugs. The aim of this paper was to compare efficacy and tolerability of eperisone and tizanidine in combination treatment with tramadol in chronic LBP.

Methods: Sixty patients affected by chronic LBP associated with contractures of paravertebral muscles were randomized in two groups: Group E (30 patients) treated with eperisone; Group T (30 patients) treated with tizanidine.

Substrate-inducible versions of internal alternative NADH: ubiquinone oxidoreductase from Yarrowia lipolytica.

In standard laboratory strains of the obligate aerobic yeast Yarrowia lipolytica, respiratory chain complex I (proton-translocating NADH : ubiquinone oxidoreductase) is an essential enzyme, since alternative NADH dehydrogenase activity is located exclusively at the external face of the mitochondrial inner membrane. Deletions and other loss-of-function mutations in genes for nuclear coded subunits of complex I can be obtained only when an internal version of the latter enzyme, termed NDH2i, is introduced. In contrast to recent findings with Neurospora crassa, external alternative NADH dehydrogenase activity is dispensable in complex I deletion strains of Y.

Semisynthesis and screening of a small library of pro-apoptotic squamocin analogues: selection and study of a benzoquinone hybrid with an improved biological profile.

Acetogenins of Annonaceae, including squamocin (1), exert spectacular cytotoxicity and the most potent inhibition of NADH:ubiquinone oxidoreductase known so far. Cell death induced by these natural products was identified as apoptosis and was thought to be linked to alterations in mitochondrial function. Quinone-squamocin hybrid compounds were semisynthesized and evaluated for their pro-apoptotic properties with a screening method based on dissipation of the mitochondrial transmembrane potential (DeltaPsim).

Heterocyclic analogues of squamocin as inhibitors of mitochondrial complex I. On the role of the terminal lactone of annonaceous acetogenins.

Heterocyclic analogues of squamocin have been semisynthesized by condensation reactions between squamocin-derived alpha-keto esters and heterodinucleophiles. The strong complex I inhibitory potency of squamocin-benzimidazole, a hybrid derivative, illustrates for the first time the functional analogy existing between the terminal butenolide of annonaceous acetogenins and heteroaromatic substructures of classic inhibitors of the enzyme. This finding supports the categorization of this atypical group of inhibitors as antagonists of the ubiquinone substrates.

Application of the yeast Yarrowia lipolytica as a model to analyse human pathogenic mutations in mitochondrial complex I (NADH:ubiquinone oxidoreductase).

While diagnosis and genetic analysis of mitochondrial disorders has made remarkable progress, we still do not understand how given molecular defects are correlated to specific patterns of symptoms and their severity. Towards resolving this dilemma for the largest and therefore most affected respiratory chain enzyme, we have established the yeast Yarrowia lipolytica as a eucaryotic model system to analyse respiratory chain complex I. For in vivo analysis, eYFP protein was attached to the 30-kDa subunit to visualize complex I and mitochondria.

Management of French patients with type 2 diabetes mellitus in medical general practice: report of the Mediab observatory.

Objectives: The Mediab study was conducted to estimate the medical care in French patients with type 2 diabetes mellitus managed by general practitioners on an ambulatory basis, but consIdered as requiring new treatment implementation.

Methods: Five thousand one hundred and fourty eight diabetic patients without any treatment or treated with lifestyle measures either alone or combined with an oral antIdiabetic agent given as monotherapy were included in a cross-sectional study that was conducted on a nationwIde basis by using the ORP (R) methodology. The 4088 patients in whom HbA1c was determined with a reliable method were further classified into 3 categories according to whether HbA1c was<=6.

Two aspartic acid residues in the PSST-homologous NUKM subunit of complex I from Yarrowia lipolytica are essential for catalytic activity.

Mitochondrial proton-translocating NADH:ubiquinone oxidoreductase (complex I) couples the transfer of two electrons from NADH to ubiquinone to the translocation of four protons across the mitochondrial inner membrane. Subunit PSST is the most likely carrier of iron-sulfur cluster N2, which has been proposed to play a crucial role in ubiquinone reduction and proton pumping. To explore the function of this subunit we have generated site-directed mutants of all eight highly conserved acidic residues in the Yarrowia lipolytica homologue, the NUKM protein.

Phase II trial of thalidomide in renal-cell carcinoma.

Background: Thalidomide has been reported to yield anti-tumor activity in cancer. We performed a phase II trial of this drug in patients with metastatic renal cell carcinoma to determine its efficacy.

Patients And Methods: Patients with proven metastatic renal cell cancer, measurable progressive disease and a performance status of 0-2 were enrolled in this study.

Impaired beta-cell regeneration in perinatally malnourished rats: a study with STZ.

We investigated the mechanisms implicated in beta-cell mass reduction observed during late fetal and early postnatal malnutrition in the rat. Beta-cell regeneration, including proliferation and neogenesis, was studied after neonatal beta-cell destruction by streptozotocin (STZ). STZ was injected at birth and maternal food restriction was continued until weaning.

Application of the obligate aerobic yeast Yarrowia lipolytica as a eucaryotic model to analyse Leigh syndrome mutations in the complex I core subunits PSST and TYKY.

We have used the obligate aerobic yeast Yarrowia lipolytica to reconstruct and analyse three missense mutations in the nuclear coded subunits homologous to bovine TYKY and PSST of mitochondrial complex I (proton translocating NADH:ubiquinone oxidoreductase) that have been shown to cause Leigh syndrome (MIM 25600), a severe progressive neurodegenerative disorder. While homozygosity for a V122M substitution in NDUFS7 (PSST) has been found in two siblings with neuropathologically proven Leigh syndrome (R. Triepels et al.

Age-dependent inability of the endocrine pancreas to adapt to pregnancy: a long-term consequence of perinatal malnutrition in the rat.

We have recently shown that maternal food restriction during late pregnancy decreased beta-cell mass in the offspring at birth. Prolonged maternal malnutrition until weaning led to irreversible decrease of beta-cell mass in the adult male progeny. During pregnancy, the maternal endocrine pancreas demonstrates an acute and reversible increase in beta-cell mass.

Effect of ageing on beta-cell mass and function in rats malnourished during the perinatal period.

Aims/hypothesis: In a recently developed rat model, maternal food restriction from day 15 of pregnancy until weaning induced low birth weight and a 70% reduction of beta-cell mass in the offspring at day 21 after birth. Subsequent renutrition from weaning was insufficient to fully restore beta-cell mass in young adult rats. The aim of this study is to investigate the long-term consequences of early malnutrition on beta-cell mass and function.

Beta-cell mass and proliferation following late fetal and early postnatal malnutrition in the rat.

We have recently shown that maternal food restriction during late pregnancy in rats decreased beta-cell mass in the offspring at birth, without altering beta-cell proliferation. The aim of the present work was to determine: 1) whether sustained maternal undernutrition until weaning (R group) more dramatically alters beta-cell mass in the offspring and if normal food supply from weaning until adulthood could reverse the deleterious effects and; 2) if altered beta-cell proliferation was responsible for the decreased beta-cell mass. Beta-cell fraction and proliferative capacity were determined during the suckling period and at adult age after ad libitum feeding from weaning in the R animals and in age-matched controls (C group).

Postnatal somatic growth and insulin contents in moderate or severe intrauterine growth retardation in the rat.

A rat model of perinatal malnutrition was designed to study the role of nutrition in postnatal somatic growth and insulin stores until adulthood. Maternal food restriction (50%) from day 15 of pregnancy resulted in intrauterine growth retardation (IUGR) in the offspring. The outcome of moderate or severe IUGR was investigated.

In utero undernutrition impairs rat beta-cell development.

The role of nutrition on the development of the endocrine pancreas was studied in a rat model obtained by maternal food restriction. A 50% food restriction was applied to female rats from day 15 of pregnancy and resulted in intrauterine growth-retardation (IUGR) in the offspring. At day 1 postnatal, beta-cell mass was significantly decreased in IUGR pups as compared to controls (0.