Wells' prediction rules for pulmonary embolism: valid in all clinical subgroups?

Pulmonary embolism is major cause of hospital death. Clinical prediction rules such as Wells’ prediction rules can help in selection of at-risk patients who need further testing for pulmonary embolism. We evaluated the usefulness of such criteria for detection of patients with diagnosed pulmonary embolism. Patients enrolled in National Research Institute of Tuberculosis and Lung Disease (NRITLD) deep venous thrombosis (DVT) registry were evaluated and those with objective data about presence or absence of pulmonary embolism were selected for this study. Diagnosis of pulmonary embolism was based on computed tomography pulmonary angiography (CTPA). We calculated the embolic burden in those with CTPA-confirmed pulmonary embolism. Eighty-six patients entered the study (58 males, 28 females, mean age = 54.39 ± 1.74 years). Fifty-four cases had coexisting pulmonary embolism (embolic burden score: 10.77 ± 1.181). Embolic burden score was correlated to presence of massive pulmonary embolism (Pearson rho: 0.43, P = 0.002). There was no association between Wells’ pulmonary embolism score and the occurrence of pulmonary embolism (Spearman's rho: 0.085, P = 0.51). Dividing the patients into two, or three, risk groups according to Wells’ model did not reveal an association with occurrence of pulmonary embolism either (P = 0.99 and P = 0.261, respectively). Tachycardia and hemoptysis were the only parameters from the Wells’ pulmonary embolism score correlated to presence of pulmonary embolism (Spearman's rho: 0.373, P < 0.000 and Spearman's rho: 0.297, P = 0.005, correspondingly). Wells’ pulmonary embolism score could not predict the occurrence of pulmonary embolism in DVT patients suspected of having coexisting pulmonary embolism. Until further studies shed light on this patient subset, overreliance on Wells’ prediction rules as the solo decision making tool should be cautioned.Babak Sharif-Kashani, Bavand Bikdeli, Solmaz Ehteshami-Afshar, Mandana Chitsazan, Neda Behzadnia, Ehsan Chitsaz, Saeid Kermani-Randjbar, Leila Saliminejad, Mohammad-Reza Masjedi and Behnood Bikdel

Peptide Nucleic Acids for MicroRNA Targeting

The involvement of microRNAs in human pathologies is firmly established. Accordingly, the pharmacological modulation of microRNA activity appears to be a very interesting approach in the development of new types of drugs (miRNA therapeutics). One important research area is the possible development of miRNA therapeutics in the field of rare diseases. In this respect, appealing molecules are based on peptide nucleic acids (PNAs), displaying, in their first description, a pseudo-peptide backbone composed of N-(2-aminoethyl)glycine units, and found to be excellent candidates for antisense and antigene therapies. The aim of the present article is to describe methods for determining the activity of PNAs designed to target microRNAs involved in cystic fibrosis, using as model system miR-145-5p and its target cystic fibrosis transmembrane conductance regulator (CFTR) mRNA. The methods employed to study the effects of PNAs targeting miR-145-5p are presented here by discussing data obtained using as cellular model system the human lung epithelial Calu-3 cell line

Epigenetics: At the crossroads between genetic and environmental determinants of disease

Epigenetic modifications play an essential role in the functional regulation of genes, including their expression. In contrast to the relative stability of the genome, the epigenome varies in a very dynamic way, through what are known as epigenetic mechanisms. These epigenetic modifications are reversible and are conditioned by environmental pressures. The most well-known epigenetic DNA modifications are the methylation of the cytosines present in the context of cytosine-guanine dinucleotides and the posttranslational modification of histones. Several works have reported that events in the early environment are associated with changes in gene expression and biological function and that such changes persist beyond the immediate influence of the stimulus and into adulthood. While the exact molecular mechanisms underlying developmental programming are largely unknown, there is much epidemiological evidence and data from animal studies linking epigenetic modifications with parental lifestyle (e.g., alcohol or tobacco consumption), nutrition, and environmental factors (such as exposure to UV light or heavy metals and stress). Moreover, pre-existing pathologies in the parents (e.g., diabetes, obesity, or metabolic syndrome) can also increase the susceptibility of the offspring to developing certain diseases over the course of their lifetime.Peer reviewe

Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice

Calcifications in the basal ganglia are a common incidental finding and are sometimes inherited as an autosomal dominant trait (idiopathic basal ganglia calcification (IBGC)). Recently, mutations in the PDGFRB gene coding for the platelet-derived growth factor receptor β (PDGF-Rβ) were linked to IBGC. Here we identify six families of different ancestry with nonsense and missense mutations in the gene encoding PDGF-B, the main ligand for PDGF-Rβ. We also show that mice carrying hypomorphic Pdgfb alleles develop brain calcifications that show age-related expansion. The occurrence of these calcium depositions depends on the loss of endothelial PDGF-B and correlates with the degree of pericyte and blood-brain barrier deficiency. Thus, our data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans