Preliminary evaluation of the climate-induced fatigue in wood: A physical and computational approach

Wood is the organic hygroscopic material for excellence. Due to its extremely easy handling, it has always been used in many applications, especially as building material for artefacts and works of art. However, it is highly climate-susceptible as it swells or shrinks by exchanging moisture with the surrounding environment when natural or artificial microclimatic fluctuations occur. The shrinkage/swelling of wood, if repeated over time, may cause the arising of deformations or damage that may lead to catastrophic failures. For this reason, in this work, a preliminary study about the effect that repeated microclimatic loads have on wooden samples is carried out. To do so, well-established fatigue approaches have been implemented, with few simplifying considerations. The case study is a slice of Scots pine which is assumed to be stored inside Ringebu stave church (Norway). Ringebu indoor microclimate is reconstructed, through a proper transfer function, starting from outdoor temperature data downloaded from web platforms. The reconstructed indoor temperature timeseries cover three periods: far past (1948–1977), recent past (1981–2010) and far future (2071–2100). The results obtained for the three periods made it possible to gain insights about the climate-induced fatigue of wood and to preliminary assess the impact of climate change. It has been observed that successive similar temperature fluctuations can be potentially treated as a block of constant amplitude and constant frequency fatigue-like load. Finally, introducing few simplifying considerations, it has been assessed that the simulated behavior is coherent with the theoretical one coming from exploiting well-established thermo-based methods

Papular-purpuric gloves and socks syndrome due to parvovirus B19: a report of two simultaneous cases in cohabitant families.

The so-called papular-purpuric gloves and socks syndrome (PPGSS) is a condition characterized by acute onset of intense erythema, edema and petechiae with a typical localization on the hands and feet, besides mucosal lesions of the oral cavity. The syndrome has a favorable and self-limited course, requiring only a symptomatic therapy. In the 50% of the cases described in literature (ninety cases in 22 years), is documented an acute infection caused by parvovirus B19 and in only two cases the onset of PPGSS is reported among different members of the same family. The aim of the work is to describe two cases of PPGSS arisen during a short time period in two family members affected by an acute parvovirus B19 infection found by serum sampling. The peculiarity of the study was the infrequence of the syndrome and the rareness of the description of PPGSS in rheumatology. This syndrome is usually described in dermatology, but it is also interesting for the rheumatologist because it comes in differential diagnosis with various autoimmune diseases

circulating and tumor associated caspase 4 a novel diagnostic and prognostic biomarker for non small cell lung cancer patients

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Ex vivo model predicted in vivo efficacy of CFTR modulator therapy in a child with rare genotype

Background: New drugs that target the basic defect in cystic fibrosis (CF) patients may now be used in a large number of patients carrying responsive mutations. Nevertheless, further research is needed to extend the benefit of these treatments to patients with rare mutations that are still uncharacterized in vitro and that are not included in clinical trials. For this purpose, ex vivo models are necessary to preliminary assessing the effect of CFTR modulators in these cases. Method: We report the clinical effectiveness of lumacaftor/ivacaftor therapy prescribed to a CF child with a rare genetic profile (p.Phe508del/p.Gly970Asp) after testing the drug on nasal epithelial cells. We observed a significant drop of the sweat chloride value, as of the lung clearance index. A longer follow-up period is needed to define the effects of therapy on pancreatic status, although an increase of the fecal elastase values was found. Conclusion: Drug response obtained on nasal epithelial cells correlates with changes in vivo therapeutic endpoints and can be a predictor of clinical efficacy of novel drugs especially in pediatric patients

Mesenchymal stromal/stem cells as potential therapy in diabetic retinopathy

Diabetic retinopathy (DR) is a multifactorial microvascular disease induced by hyperglycemia and subsequent metabolic abnormalities. The resulting cell stress causes a sequela of events that ultimately can lead to severe vision impairment and blindness. The early stages are characterized by activation of glia and loss of pericytes, endothelial cells (EC) and neuronal cells. The integrity of the retinal microvasculature becomes affected, and, as a possible late response, macular edema may develop as a common reason for vision loss in patients with non proliferative DR. Moreover, the local ischemia can trigger vasoproliferation leading to vision-threating proliferative DR (PDR) in humans. Available treatment options include control of metabolic and hemodynamic factors. Timely intervention of advanced DR stages with laser photocoagulation, intraocular anti-vascular endothelial growth factor (VEGF) or glucocorticoid drugs can reduce vision loss. As the pathology involves cell loss of both the vascular and neuroglial compartments, cell replacement strategies by stem and progenitor cells have gained considerable interest in the past years. Compared to other disease entities, so far little is known about the efficacy and potential mode of action of cell therapy in treatment of DR. In preclinical models of DR different cell types have been applied ranging from embryonic or induced pluripotent stem cells, hematopoietic stem cells, and endothelial progenitor cells to mesenchymal stromal cells (MSC). The latter cell population can combine various modes of action (MoA), thus they are among the most intensely tested cell types in cell therapy. The aim of this review is to discuss the rationale for using MSC as potential cell therapy to treat DR. Accordingly, we will revise identified MoA of MSCs and speculate how these may support the repair of the damaged retina

Baseline staging tests after a new diagnosis of breast cancer: further evidence of their limited indications

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Senataxin Ortholog Sen1 Limits DNA:RNA Hybrid Accumulation at DNA Double-Strand Breaks to Control End Resection and Repair Fidelity

Summary: An important but still enigmatic function of DNA:RNA hybrids is their role in DNA double-strand break (DSB) repair. Here, we show that Sen1, the budding yeast ortholog of the human helicase Senataxin, is recruited at an HO endonuclease-induced DSB and limits the local accumulation of DNA:RNA hybrids. In the absence of Sen1, hybrid accumulation proximal to the DSB promotes increased binding of the Ku70-80 (KU) complex at the break site, mutagenic non-homologous end joining (NHEJ), micro-homology-mediated end joining (MMEJ), and chromosome translocations. We also show that homology-directed recombination (HDR) by gene conversion is mostly proficient in sen1 mutants after single DSB. However, in the absence of Sen1, DNA:RNA hybrids, Mre11, and Dna2 initiate resection through a non-canonical mechanism. We propose that this resection mechanism through local DNA:RNA hybrids acts as a backup to prime HDR when canonical pathways are altered, but at the expense of genome integrity