Characteristics of vertebral osteomyelitis after liver transplantation

AbstractWe performed a retrospective single-centre 1:3 case–control study to investigate the characteristics of vertebral osteomyelitis (VO) occurring in orthotopic liver transplant (OLT) recipients between 2000 and 2012. Nine cases were identified in 752 OLT recipients (1.2%), with a median time from OLT to VO of 12 weeks. In comparison with 27 VO not occurring in OLT patients (controls), VO occurring in OLT recipients was characterized by decreased levels of inflammation biomarkers (average C-reactive protein 65.1 mg·L−1 vs. 167 mg·L−1, p 0.02; average white blood cell count 4.8 × 109·L−1 vs. 12.9 × 109·L−1, p < 0.001), higher rate of fungal infections (3/9 vs. 0/27, p 0.01), lower rate of bacterial infections (3/9 vs. 25/27, p 0.001) and decreased proportion of positive blood cultures (1/9 vs. 16/27, p 0.02) despite a trend towards higher rate of multifocal infection. Microbiologic outcomes were similar between the two groups. Overall, VO in OLT patients was more difficult to diagnose as a result of altered inflammation response and specific microbial epidemiology of causal microorganisms

Differences in daptomycin and vancomycin ex vivo behaviour can lead to false interpretation of negative blood cultures

AbstractIn clinical studies on bacteraemia, the negativity of blood cultures is an important endpoint for comparing the efficacy of different therapeutic regimens. In FAN° anaerobic blood culture medium (BacT/ALERT system), daptomycin displayed increased MIC against Staphylococcus aureus and improved abolishment of its carryover effect in charcoal when compared with vancomycin. Differences between these two drugs can lead to a false interpretation of negative blood cultures. To compare different antibiotic regimens for the treatment of bacteraemia, preliminary studies are mandatory to ensure that ex vivo antibiotic behaviour is similar in the blood-culture system used

Screening for fmr1 expanded alleles in patients with autism spectrum disorders in Manaus, Northern Brazil

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by dynamic mutations of a CGG repetition segment in an X chromosome’s single gene. It is considered the leading hereditary cause of both Autism Spectrum Disorders and Intellectual Disability. Some authors suggest that all individuals diagnosed with some of these latter conditions to be clinically and molecularly trialled for FXS due to the high levels of comorbidity between both conditions and also due to the variable expressiveness of this syndrome. This study has focused on verifying the presence of FMR1 expanded alleles since there is a lack of information about this kind of mutation in autism patients from the northern region of Brazil. The presence of large alleles for this gene could offer new therapeutic or pharmacological methods for the treatment of these patients. Both the presence and the frequency of CGG expansions were verified in 90 autism males by molecular analysis. Four of them had intermediate alleles and four others presented premutated alleles. Premutation carriers are on the propensity of developing the late onset Fragile X-associated tremor/ataxia syndrome. No full mutation alleles were found. Further studies are necessary to obtain more accurate statistical data about this kind of dynamic mutation. © 2019, Academia Brasileira de Ciencias. All rights reserved

The non-convex shape of (234) Barbara, the first Barbarian

Asteroid (234) Barbara is the prototype of a category of asteroids that has been shown to be extremely rich in refractory inclusions, the oldest material ever found in the Solar System. It exhibits several peculiar features, most notably its polarimetric behavior. In recent years other objects sharing the same property (collectively known as "Barbarians") have been discovered. Interferometric observations in the mid-infrared with the ESO VLTI suggested that (234) Barbara might have a bi-lobated shape or even a large companion satellite. We use a large set of 57 optical lightcurves acquired between 1979 and 2014, together with the timings of two stellar occultations in 2009, to determine the rotation period, spin-vector coordinates, and 3-D shape of (234) Barbara, using two different shape reconstruction algorithms. By using the lightcurves combined to the results obtained from stellar occultations, we are able to show that the shape of (234) Barbara exhibits large concave areas. Possible links of the shape to the polarimetric properties and the object evolution are discussed. We also show that VLTI data can be modeled without the presence of a satellite.Comment: 10 pages, 6 figure

Neuropilin 1 (NRP1) hypomorphism combined with defective VEGF-A binding reveals novel roles for NRP1 in developmental and pathological angiogenesis.

Neuropilin 1 (NRP1) is a receptor for class 3 semaphorins and vascular endothelial growth factor (VEGF) A and is essential for cardiovascular development. Biochemical evidence supports a model for NRP1 function in which VEGF binding induces complex formation between NRP1 and VEGFR2 to enhance endothelial VEGF signalling. However, the relevance of VEGF binding to NRP1 for angiogenesis in vivo has not yet been examined. We therefore generated knock-in mice expressing Nrp1 with a mutation of tyrosine (Y) 297 in the VEGF binding pocket of the NRP1 b1 domain, as this residue was previously shown to be important for high affinity VEGF binding and NRP1?VEGFR2 complex formation. Unexpectedly, this targeting strategy also severely reduced NRP1 expression and therefore generated a NRP1 hypomorph. Despite the loss of VEGF binding and attenuated NRP1 expression, homozygous Nrp1(Y297A/Y297A) mice were born at normal Mendelian ratios, arguing against NRP1 functioning exclusively as a VEGF164 receptor in embryonic angiogenesis. By overcoming the mid-gestation lethality of full Nrp1-null mice, homozygous Nrp1(Y297A/Y297A) mice revealed essential roles for NRP1 in postnatal angiogenesis and arteriogenesis in the heart and retina, pathological neovascularisation of the retina and angiogenesis-dependent tumour growth

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

A Small Molecule Inhibitor of PDK1/PLCγ1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion

Strong evidence suggests that phospholipase Cγ1 (PLCγ1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCγ1 activation which involves formation of a protein complex with 3-phosphoinositide-dependent protein kinase 1 (PDK1). In an effort to define novel strategies to inhibit PLCγ1-dependent signals we tested here whether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP5), could affect PDK1/PLCγ1 interaction and impair PLCγ1-dependent cellular functions in cancer cells. Here, we demonstrate that 2-O-Bn-InsP5 interacts specifically with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCγ1 complex. 2-O-Bn-InsP5 is able to inhibit the epidermal growth factor-induced PLCγ1 phosphorylation and activity, ultimately resulting in impaired cancer cell migration and invasion. Importantly, we report that 2-O-Bn-InsP5 inhibits cancer cell dissemination in zebrafish xenotransplants. This work demonstrates that the PDK1/PLCγ1 complex is a potential therapeutic target to prevent metastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drugs

Clinical and pathological findings of a fatal systemic capillary leak syndrome (Clarkson Disease)

Systemic capillary leak syndrome (SCLS) is a rare disorder with episodes of hypotension, hypoalbuminemia, and hemoconcentration. During attacks endothelial hyperpermeability results in leakage of plasma proteins into the interstitial space. Attacks vary in severity and may be lethal.A 49-year-old previously healthy man was admitted to hospital for hypovolemic shock, anasarca with pleuropericardial effusion, muscle fatigue, and oliguria occurring after a flu-like syndrome. Laboratory data showed an increase in hematocrit (65%), leucocytes (24.590\u200a\u3bc/L), creatinine (2.5\u200amg/dL), creatine phosphokinase (10.000\u200aU/L), and a decrease in serum albumin (17\u200ag/L) without proteinuria. Immunoglobulins of class G/\u3bb monoclonal gammopathy were detected (1.3\u200ag/L). The initial suspicions addressed to a protein-loosing syndrome or to an effort-related rhabdomyolysis. Initial therapy was based on steroids, albumin, and high molecular weight plasma expanders (hydroxyethyl starch). Because of high hematocrit, phlebotomy was also performed. The patient had complete clinical remission and a diagnosis of SCLS was finally made. He received prophylactic therapy with verapamil and theophylline that was self-stopped for intolerance (hypotension and tachycardia). He had a new crisis 2 days after a physical effort, and was admitted in intensive care unit. The patient died for severe hypovolemic shock with multiorgan failure and sudden cardiac arrest 15 hours after hospital admission. Postmortem investigation revealed massive interstitial edema of main organs with myocardial hyperacute ischemia.Studies on SCLS are limited for the rarity of the disease and its unpredictable course. Both prophylactic and acute crisis treatments are empirical and optimal management of severe attacks is still lacking

The non-convex shape of (234) Barbara, the first Barbarian

Asteroid (234) Barbara is the prototype of a category of asteroids that has been shown to be extremely rich in refractory inclusions, the oldest material ever found in the Solar system. It exhibits several peculiar features, most notably its polarimetric behaviour. In recent years other objects sharing the same property (collectively known as ‘Barbarians') have been discovered. Interferometric observations in the mid-infrared with the ESO VLTI (Very Large Telescope Interferometer) suggested that (234) Barbara might have a bi-lobated shape or even a large companion satellite. We use a large set of 57 optical light curves acquired between 1979 and 2014, together with the timings of two stellar occultations in 2009, to determine the rotation period, spin-vector coordinates, and 3-D shape of (234) Barbara, using two different shape reconstruction algorithms. By using the light curves combined to the results obtained from stellar occultations, we are able to show that the shape of (234) Barbara exhibits large concave areas. Possible links of the shape to the polarimetric properties and the object evolution are discussed. We also show that VLTI data can be modelled without the presence of a satellit