Short-Term Association Between Ambient Air Pollution and Risk of Hospitalization for Acute Myocardial Infarction: Results of the Cardiovascular Risk and Air Pollution in Tuscany (RISCAT) Study

n/

Spondyloarthritis: Matrix Metalloproteinasesas Biomarkers of Pathogenesis and Response to Tumor Necrosis Factor (TNF) Inhibitors

The term spondyloarthritis (SpA) is used to describe a group of multifactorial chronic inflammatory diseases characterized by a predisposing genetic background and clinical manifestations typically involving the sacroiliac joint. The absence of pathognomonic clinical and/or laboratory findings generally results in a delay in diagnosis and, consequently, in treatment. In addition, 20-40% of SpA patients are non-responders to tumor necrosis factor (TNF) inhibitor therapies. Given these considerations, it is important to identify biomarkers that can facilitate the diagnosis and assessment of disease activity. As inflammation plays a key role in the pathogenesis of SpA, inflammatory mediators have been investigated as potential biomarkers for diagnosing the disease and predicting response to therapy. Some investigators have focused their attention on the role of matrix metalloproteinases (MMPs), which are known to be markers of synovial inflammation that is generated in the joint in reaction to inflammatory stimuli. Several studies have been carried out to verify if serum MMPs levels could be useful to diagnose SpA, to assess disease severity, and to predict response to TNF inhibitor therapy. The current review focuses on MMPs' role in SpA pathogenesis, diagnosis and therapeutic implications

Breeding for black rot resistance in grapevine: advanced approaches for germplasm screening

Crop improvement by means of traditional or molecular breeding is a key strategy to accomplish the European Green Deal target of reducing pesticides by 50% by 2030. Regarding viticulture, this is exacerbated by the massive use of chemicals to control pathogen infections. Black rot is an emergent disease caused by the ascomycete Phyllosticta ampelicida, and its destructiveness is alarming vine growers. Implementing and improving effective phenotyping strategies are fundamental preliminary steps to breed disease resistant varieties and this work suggests good practices adopted for this purpose. Primarily, the pedigree of black rot resistance donors was reconstructed based on the collection of phenotypic historical data, highlighting unexplored sources of black rot resistance. Strains used for artificial infections were isolated, genetically characterized and mixed to avoid race-specific resistance selection. A new inoculation protocol based on the use of leaf mature lesions was developed. Ex vivo inoculation on detached leaves was effective for the evaluation of conidia germination and hyphal growth, but not for disease progression. Finally, the pedigree was used for the identification of 23 genotypes to be tested. Two breeding selections (NY39 and NY24) resulted symptomless in all assessments and a third one (F25P52) also showed very high resistance, although with a greater variability. Other two genotypes (F12P19 and ‘Charvir’) fell within the medium resistance category, making them good candidates in a regime of well-timed preventive treatments. In conclusion, this work was effective to a comprehensive parental line characterization and preparatory towards grapevine breeding programs for black rot resistanc

ECPGR recommended simple sequence repeat loci for analyses of European plum (Prunus domestica) collections

A set of nine Simple Sequence Repeat (SSR) loci, approved by the ECPGR Prunus working group, are proposed as a standard set for genotyping European plum accessions. These loci show sufficient reliability in spite of problems caused by hexaploidy. Polymorphism in the loci is high and enables differentiation between unique plum accessions as well as analyses of genetic grouping and overall genetic structure. A set of seven reference accessions are described. A compiled dataset with allelic information for 165 accessions is presented. Genetic structure reveals three different K-values (2, 4 and 9) demonstrating a major dichotomy between Prunus insititia-related accessions and cultivars belonging to Prunus domestica sensu stricto, as well as differentiation among minor subgroups defined by pomological traits and geographical origin

Economic evaluation of “pulse dose” radiofrequency in the treatment of occipital neuralgia headache

Headache occipital neuralgia is an example of pain-disease for which treatment both pharmacological protocols and invasive methods are used. Among the latter, the RF (Radiofrequency) pulse-dose has been of interest for the prospects of analgesic efficacy, safety and patient compliance, although at the moment only data concerning the pulsed RF and not the RF pulse-dose, that represents its evolution, are discussed in scientific literature. The purpose of this study is a "simple" economic evaluation of this method in headache occipital neuralgia

Constraints on a Stochastic Background of Primordial Magnetic Fields with WMAP and South Pole Telescope data

We constrain a stochastic background of primordial magnetic fields (PMF) by its contribution to the cosmic microwave background (CMB) anisotropy angular power spectrum with the combination of WMAP 7 year and South Pole Telescope (SPT) data. The contamination in the SPT data by unresolved point sources and by the Sunyaev Zeldovich (SZ) effect due to galaxy clusters has been taken into account as modelled by the SPT collaboration. With this combination of WMAP 7 yr and SPT data, we constrain the amplitude Gaussian smoothed over 1 Mpc scale of a stochatic background of non-helical PMF to $B_{\rm 1 Mpc}<3.5$ nG at 95% confidence level. Our analysis shows that SPT data up to $\ell=3000$ bring an improvement of almost a factor two with respect to results with previous CMB high-$\ell$ data. We then discuss the forecasted impact from unresolved points sources and SZ effect for {\sc Planck} capabilities in constraining PMF.Comment: 6 pages, 6 figures, matches the version published in Phys. Lett.

Different Patterns of Neurodegeneration and Glia Activation in CA1 and CA3 Hippocampal Regions of TgCRND8 Mice

We investigated the different patterns of neurodegeneration and glia activation in CA1 and CA3 hippocampal areas of TgCRND8 mice. The main feature of this transgenic model is the rapid development of the amyloid pathology, which starts already at 3 months of age. We performed immunohistochemical analyses to compare the different sensibility of the two hippocampal regions to neurodegeneration. We performed qualitative and quantitative evaluations by fluorescence immunohistochemistry with double or triple staining, followed by confocal microscopy and digital image analysis in stratum pyramidale (SP) and stratum radiatum (SR) of CA1 and CA3, separately. We evaluated time-dependent Aβ plaques deposition, expression of inflammatory markers, as well as quantitative and morphological alterations of neurons and glia in transgenic mice at 3 (Tg 3M) and 6 (Tg 6M) months of age, compared to WT mice. In CA1 SR of Tg 6M mice, we found significantly more Medium and Large plaques than in CA3. The pattern of neurodegeneration and astrocytes activation was different in the two areas, indicating higher sensitivity of CA1. In the CA1 SP of Tg 6M mice, we found signs of reactive astrogliosis, such as increase of astrocytes density in SP, increase of GFAP expression in SR, and elongation of astrocytes branches. We found also common patterns of glia activation and neurodegenerative processes in CA1 and CA3 of Tg 6M mice: significant increase of total and reactive microglia density in SP and SR, increased expression of TNFα, of iNOS, and IL1β in astrocytes and increased density of neurons–astrocytes–microglia triads. In CA1 SP, we found decrease of volume and number of pyramidal neurons, paralleled by increase of apoptosis, and, consequently, shrinkage of CA1 SP. These data demonstrate that in TgCRND8 mice, the responses of neurons and glia to neurodegenerative patterns induced by Aβ plaques deposition is not uniform in the two hippocampal areas, and in CA1 pyramidal neurons, the higher sensitivity may be related to the different plaque distribution in this area. All these modifications may be at the basis of memory loss, the peculiar symptom of AD, which was demonstrated in this transgenic mouse model of Aβ deposition, even at early stages

Fine mapping of the peach pollen sterility gene (Ps/ps) and detection of markers for marker-assisted selection

Altres ajuts: CERCA Programme/Generalitat de CatalunyaIn peach, pollen sterility, expressed as absence of pollen in the anthers, segregates as an undesired trait in breeding programs. Pollen fertility screening in progenies is not a common practice mainly because it does not affect fruit set since cross-pollination is frequent. It is also a time-consuming activity that coincides with the busy pollination season. Segregation for this trait could be avoided by using molecular markers to identify appropriate parents or male sterile plants for early culling in progenies expected to segregate, thus increasing breeding efficiency. In peach, pollen sterility is determined by a recessive allele in homozygosis of the major gene, Ps/ps, located on chromosome 6. In this work, using a conventional mapping approach combined with bulked segregant analysis using resequencing data, we fine mapped Ps to a region of almost 160 kb and developed molecular markers for marker-assisted breeding. These markers were validated in plant materials from three peach breeding programs, including progenies, advanced selections and cultivars, allowing us to determine that the frequency of the ps allele is high (0.23) and also to infer the genotypes of a large collection of cultivars and advanced breeding lines

In hepatocellular carcinoma miR-221 modulates sorafenib resistance through inhibition of caspase-3\u2013mediated apoptosis

Purpose: The aberrant expression of miR-221 is a hallmark of human cancers, including hepatocellular carcinoma (HCC), and its involvement in drug resistance, together with a proved in vivo efficacy of anti-miR-221 molecules, strengthen its role as an attractive target candidate in the oncologic field. The discovery of biomarkers predicting the response to treatments represents a clinical challenge in the personalized treatment era. This study aimed to investigate the possible role of miR-221 as a circulating biomarker in HCC patients undergoing sorafenib treatment as well as to evaluate its contribution to sorafenib resistance in advanced HCC. Experimental Design: A chemically induced HCC rat model and a xenograft mouse model, together with HCC-derived cell lines were employed to analyze miR-221 modulation by Sorafenib treatment. Data from the functional analysis were validated in tissue samples from surgically resected HCCs. The variation of circulating miR-221 levels in relation to Sorafenib treatment were assayed in the animal models and in two independent cohorts of patients with advanced HCC. Results: MiR-221 over-expression was associated with Sorafenib resistance in two HCC animal models and caspase-3 was identified as its target gene, driving miR-221 anti-apoptotic activity following Sorafenib administration. Lower pre-treatment miR-221 serum levels were found in patients subsequently experiencing response to Sorafenib and an increase of circulating miR-221 at the two months assessment was observed in responder patients. Conclusions: MiR-221 might represent a candidate biomarker of likelihood of response to Sorafenib in HCC patients to be tested in future studies. Caspase-3 modulation by miR-221 participates to Sorafenib resistance