Prognostic impact of the TP53 rs1625895 polymorphism in DLBCL patients

This study aimed to clarify the association between the TP53 rs1625895 polymorphism and the efficiency of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy in 106 patients with diffuse large B cell lymphoma (DLBCL). All patients received six to eight courses of R‐CHOP therapy as a first‐line treatment. The rs1625895 polymorphism was genotyped by polymerase chain reaction with restriction fragment length polymorphism assay. The G/G genotype of the TP53 rs1625895 polymorphism was shown to be associated with a high probability of R‐CHOP therapy failure in DLBCL patients according to the probability of remission as well as 5‐year overall and relapse‐free survivals.     

MOLECULAR IDENTIFICATION AND ANTIMICROBIAL RESISTANCE PATTERN OF SEVEN CLINICAL ISOLATES OF Nocardia spp. IN BRAZIL

Nocardia is a ubiquitous microorganism related to pyogranulomatousinfection, which is difficult to treat in humans and animals. The occurrence of thedisease is on the rise in many countries due to an increase in immunosuppressivediseases and treatments. This report of cases from Brazil presents the genotypiccharacterization and the antimicrobial susceptibility pattern using thedisk-diffusion method and inhibitory minimal concentration with E-test® strips. Insummary, this report focuses on infections in young adult men, of which three caseswere cutaneous, two pulmonary, one neurological and one systemic. The pulmonary,neurological and systemic cases were attributed to immunosuppressive diseases ortreatments. Sequencing analysis of the 16S rRNA segments (1491 bp) identified fourisolates of Nocardia farcinica, two isolates of Nocardianova and one isolate of Nocardia asiatica. N.farcinica was involved in two cutaneous, one systemic and other pulmonarycases; N. nova was involved in one neurological and one pulmonarycase; and Nocardia asiatica in one cutaneous case. Thedisk-diffusion antimicrobial susceptibility test showed that the most effectiveantimicrobials were amikacin (100%), amoxicillin/clavulanate (100%), cephalexin(100%) and ceftiofur (100%), while isolates had presented most resistance togentamicin (43%), sulfamethoxazole/trimethoprim (43%) and ampicillin (29%). However,on the inhibitory minimal concentration test (MIC test), only one of the fourisolates of Nocardia farcinica was resistant tosulfamethoxazole/trimethoprim.     

Rapatar,a nanoformulation of rapamycin,decreases chemically-induced benign prostate hyperplasia in rats

Benign prostatic hyperplasia (BPH) is the most common age-related disease in men. Here we tested the efficacy of Rapatar, a micellar nanoformulation of rapamycin, in two rat models of BPH: testosterone-induced and sulpiride-induced hyperplasia in ventral lobes and lateral/dorsal lobes, respectively. We found that Rapatar prevented hypertrophic and hyperplastic abnormalities and degenerative alterations in both BPH models. Rapatar normalized weight of the lateral lobes in sulpiride-induced BPH, the most relevant animal model of human BPH. Unlike Finasteride, a standard therapy of BPH, Rapatar reduced inflammation caused by sulpiride. No obvious side effects of Rapatar were detected. Our data provide a rationale for clinical trials of Rapatar in patients suffering from BPH.     

Marine alkaloid Monanchocidin a overcomes drug resistance by induction of autophagy and lysosomal membrane permeabilization

Monanchocidin A (MonA) is a novel alkaloid recently isolated from the marine sponge Monanchora pulchra. The compound reveals cytotoxic activity in genitourinary cancers including cisplatin-sensitive and -resistant germ cell tumor (GCT) cell lines, hormone-sensitive and castration-resistant prostate carcinoma cell lines and different bladder carcinoma cell lines. In contrast, non-malignant cells were significantly less sensitive. MonA is highly synergistic with cisplatin in GCT cells. Induction of autophagy at lower and lysosomal membrane permeabilization (LMP) at higher concentrations were identified as the dominating modes of action. Cytotoxicity and protein degradation could be inhibited by 3-methyladenine, an inhibitor of autophagy. LMP was confirmed by loss of acridine orange staining of lysosoms and by release of cathepsin B. In conclusion, MonA exerts cytotoxiс activity by mechanisms different from “classical” apoptosis, and could be a promising new compound to overcome resistance to standard therapies in genitourinary malignancies.     

High-Level Systemic Expression of Conserved Influenza Epitope in Plants on the Surface of Rod-Shaped Chimeric Particles

Recombinant viruses based on the cDNA copy of the tobacco mosaic virus (TMV) genome carrying different versions of the conserved M2e epitope from influenza virus A cloned into the coat protein (CP) gene were obtained and partially characterized by our group previously; cysteines in the human consensus M2e sequence were changed to serine residues. This work intends to show some biological properties of these viruses following plant infections. Agroinfiltration experiments on Nicotiana benthamiana confirmed the efficient systemic expression of M2e peptides, and two point amino acid substitutions in recombinant CPs significantly influenced the symptoms and development of viral infections. Joint expression of RNA interference suppressor protein p19 from tomato bushy stunt virus (TBSV) did not affect the accumulation of CP-M2e-ser recombinant protein in non-inoculated leaves. RT-PCR analysis of RNA isolated from either infected leaves or purified TMV-M2e particles proved the genetic stability of TMV‑based viral vectors. Immunoelectron microscopy of crude plant extracts demonstrated that foreign epitopes are located on the surface of chimeric virions. The rod‑shaped geometry of plant-produced M2e epitopes is different from the icosahedral or helical filamentous arrangement of M2e antigens on the carrier virus-like particles (VLP) described earlier. Thereby, we created a simple and efficient system that employs agrobacteria and plant viral vectors in order to produce a candidate broad-spectrum flu vaccine.     

Diagnostic performance of CT esophagography in patients with suspected esophageal rupture

Esophageal rupture is a surgical catastrophe. The gold standard for diagnosing is iodine, water-soluble contrast medium esophagography. CT esophagography has shown promising results. This study aimed to assess the diagnostic performance of CT esophagography in patients with a suspicion of esophageal rupture. This prospective study assessed the performance of a diagnostic test and was approved by local IRB committee. Patients who presented with a clinical suspicion of esophageal rupture were included. CT esophagography findings were described by the emergency radiologist. Clinical outcomes (presence or absence of esophageal rupture) were reported by surgeons. The operative characteristics were calculated. A final predictive scale for rupture was built. A total of 64 patients were recruited (age 26.5 years, 90 % male, 82 % trauma). Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were 77.7 % (95 % confidence interval (CI) 45–100), 94.3 % (87.2–100), 14 (9.81–19.9), and 0.24 (0.05–1.22), respectively. The final model for predicting rupture included five variables: age (odds ratio (OR) 1.03; 95 % CI, 0.95–1.11; p?=?0.04), leakage of contrast media into the mediastinum or pleural space (OR 10.0; 95 % CI, 0.64–156.9; p?=?0.10), extraluminal air or fluid collections (OR 43.1; 95 % CI, 1.52–1217.3; p?=?0.027), esophageal wall thickening (OR 10.1; 95 % CI, 0.50–202.8; p?=?0.12), and left pneumothorax or pleural effusion (OR 6.5; 95 % CI, 0.31–132.7; p?=?0.2). The overall agreement was 0.40 (95 % CI, 0.09–0.72) for the predictive model. The model sensitivity was 50.0 %, and the specificity was 98.4 %. CT esophagography shows a good diagnostic performance in patients with a suspected esophageal rupture.     

The Ilizarov paradigm: thirty years with the Ilizarov method, current concerns and future research

The Ilizarov method of bone lengthening, reconstruction and osteosynthesis has developed immensely since its introduction by G.A. Ilizarov in the Soviet Union in the 1960s and in the Western countries in the early 1980s. It has become an integral part of the arsenal used by the orthopaedic community worldwide. The evolutionary development of the method and its current role has considerably improved the quality of life for millions of people around the whole world. Despite the great versatility of its possible applications for bone injuries and diseases, the Ilizarov method could not and cannot be the alternative to a range of other methods that are applied for some specific bone conditions, but rather is a method of choice. Its combination with the current methods of internal fixation or the means of internal fixation that use the biological principles that were laid down by G.A. Ilizarov have demonstrated the importance of tension stress, blood supply, functional loading, and fragment control during bone treatment. The objective of this study was to present an overview of the current state and concerns in the application of the Ilizarov method and define the prospective research trends aimed at regeneration stimulation, better control of treatment, infection barriers and patient comfort.