Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis

Cigarette smoking is an established cause of lung cancer. However, pulmonary fibrosis is also an independent risk factor for the development of lung cancer. Smoking-related interstitial fibrosis (SRIF) has recently been reported. We hypothesized that adenocarcinomas in lungs with SRIF might show distinct molecular changes and examined the molecular phenotype of 168 resected lung adenocarcinomas in lungs with and without SRIF. The diagnosis of SRIF was determined by histological examination, based on the presence of alveolar septal thickening, due to pauci-inflamed, hyalinized, “ropy” collagen, in areas of lung greater than 1 cm away from the tumor. Tumors were concomitantly examined genotypically for mutations in genes frequently altered in cancer, including EGFR and KRAS, by SNaPshot and by fluorescence in situ hybridization for possible ALK rearrangements. Fluorescence in situ hybridization for ROS1 rearrangement (n=36) and/or MET amplification (n=31) were performed when no mutation was identified by either SNaPshot or ALK analysis. Sixty-five cases (38.7%) showed SRIF, which was distributed in all lobes of the lungs examined. No differences were observed in sex, average age, or smoking history in patients with and without SRIF. There was no difference in either the percent or types of adenocarcinoma genetic mutations in patients with SRIF versus those without. This data suggests that SRIF does not represent an independent risk factor for the development of the major known and targeted mutations seen in pulmonary adenocarcinoma. However, additional research is required to investigate the potential significance of SRIF in the pathogenesis of lung cancer

Controlled HIV-HCV Viremia and Immune-Reconstitution are Associated with Slow Progression of Liver Disease in Co-infected Hemophilic Patients After 30 Years of Follow-Up

Introduction and aim: Controversial results have been reported about the progressionof liver disease in HIV-HCV coinfected populations. The purpose of this study is to assesslong-term liver disease progression in a group of coinfected patients with hemophilia.1.2. Materials and Methods: From 1995 to 2015, liver disease was assessed through enzymelevels, platelet counts, Hepatitis C and HIV viral loads (VL), and CD4+T cell counts. Evolution of the APRI liver index was used to estimate hepatic disease (APRI > 1.0 indicatingsevere fibrosis).1.3. Results: 2005-2015 proportional liver-related mortality was below 17% while AIDSand other causes including hemorrhagic events reached 42% each. APRI index >1.0 wasfound in 3 of 32 (9%) patients alive, showing significant liver disease after more than 30years of infection. Analyzing the evolution of liver disease markers, liver enzymes increasedsignificantly only in those patients with detectable HIV and /or HCV VL (for AST and ALT,p<0.0001; for GGT, p=0.001). HIV suppression and reconstitution of CD4+T cell countswere required to achieve HCV eradication. Through multivariate logistic regression, pre ART(pre-antiretroviral therapy) HIV VL was associated with the development of liver fibrosis(OR=4.755; IC95: 1.057 21.387) and with altered liver enzyme values (OR=4.091; IC95:1.293 ? 12.947). No persistent increase in enzyme levels or APRI index was observed in thegroup controlling HIV and HCV replication and adequate immune recovery.1.4. Conclusions: The suppression of both viruses, HIV and HCV, together with adequateimmune recovery is associated with minimal or slow progression of liver disease.Fil: Badano, Maria Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Monzani, María Cecili. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aloisi Zavala, Natalia Andrea. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Gualtieri, Ariel Félix. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Corti, Marcelo. Fundacion de la Hemofilia; ArgentinaFil: Parodi, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pinto, Tezanos. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Primiani, Laura. Fundacion de la Hemofilia; ArgentinaFil: Bracco, M. M. E. D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Chuit, Roberto. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Epidemiológicas; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Profilaxis secundaria con rFVIIIFc en adultos jóvenes con hemofilia A severa

Introducción: La profilaxis secundaria en adultos con hemofilia severa no resuelve la artropatía establecida, pero puede reducir el número de hemorragias articulares. Los productos de vida media extendida permiten infusiones menos frecuentes.Objetivo: En este estudio prospectivo, evaluamos la eficacia de la profilaxis con FVIII recombinante asociado a proteína de fusión (rFVIIIFc) en un grupo de pacientes adultos jóvenes.Métodos: Pacientes mayores de 18 años de un solo centro fueron tratados con rFVIIIFc 20-40 UI/kg dos veces por semana, durante un período de 6 meses. Analizamos la tasa de hemorragia y la comparamos con el período pre-profilaxis (tratamiento a demanda de eventos hemorrágicos).Resultados: 24 pacientes recibieron una dosis media de rFVIIIFc 32,1 UI/kg dos veces por semana. Hubo 58 hemorragias menores, todas tratadas con 1-2 dosis diaria de rFVIIIFc. La tasa de hemorragia anualizada promedio fue de 15,3 en el período pre-profilaxis frente a 2,4 durante la profilaxis. No se detectaron inhibidores.Conclusión: rFVIIIFc fue bien tolerado en pacientes adultos jóvenes con hemofilia A severa, y resultó en una tasa de hemorragia anualizada baja cuando se administró 2 veces por semana como tratamiento profiláctico secundario.Introduction: Secondary prophylaxis in adults with severe haemophilia will not resolve the established arthropathy but may reduce the number of joint bleeds. Extend ed half-life products permit less frequent infusions.Aim: In this prospective study, we evaluated the efficacy of prophylaxis with recombinant FVIII Fc fusionprotein (rFVIIIFc) in a group of young adult patients.Methods: Patients older than 18 years old from a single center were treated with rFVIIIFc 20-40 IU kg-1 twice a week, during a period of 6 months. We analyzed the annualized bleeding rate and compared it with the pre-prophylaxis period (on demand treatment).Results: 24 patients received a mean dose of rFVIIIFc 32.1 kg-1 twice a week. There were 58 minor bleedings,all treated with 1-2 daily dose of rFVIIIFc. The mean annualized bleeding rate was 15.3 in the pre-prophylaxis period vs. 2.4 during prophylaxis. No inhibitors were detected.Conclusion: rFVIIIFc was well-tolerated in young adult patients with severe hemophilia A, and resulted in low bleeding rate when dosed 2 times per week as a secondary prophylactic treatment

Atlas of Essential Dermatopathology

XI, 126 p. 157 illus. in color.online resource

Lupus and scleroderma overlap features in a 28-year-old man with anti-PL-12 anti-synthetase syndrome

A 28-year-old man with clinically and laboratory diagnosed anti-PL-12 anti-synthetase syndrome (AS) in 2009 developed cutaneous lupus lesions, discoid lupus lesions, and sclerodacytly with finger-tip ulcerations four years following his AS diagnosis. Laboratory tests including +ANA, +anti-dsDNA antibody, +anti-Smith antibody, and +anti-RNP antibody in 2014 confirmed the diagnosis of progression to an overlap syndrome including systemic lupus erythematosus. The patient now also has clinical findings (sclerodacytly, Raynaud phenomenon, finger-tip ulcerations) consistent with scleroderma overlap. In each stage of his evolving connective tissue disease, cutaneous findings have been central to the recognition and monitoring of his overlap syndromes

Lupus and scleroderma overlap features in a 28-year-old man with anti-PL-12 anti-synthetase syndrome

A 28-year-old man with clinically and laboratory diagnosed anti-PL-12 anti-synthetase syndrome (AS) in 2009 developed cutaneous lupus lesions, discoid lupus lesions, and sclerodacytly with finger-tip ulcerations four years following his AS diagnosis. Laboratory tests including +ANA, +anti-dsDNA antibody, +anti-Smith antibody, and +anti-RNP antibody in 2014 confirmed the diagnosis of progression to an overlap syndrome including systemic lupus erythematosus. The patient now also has clinical findings (sclerodacytly, Raynaud phenomenon, finger-tip ulcerations) consistent with scleroderma overlap. In each stage of his evolving connective tissue disease, cutaneous findings have been central to the recognition and monitoring of his overlap syndromes

Ballistic and electromagnetic shielding behaviour of multifunctional Kevlar fiber reinforced epoxy composites modified by carbon nanotubes

Overall goal of the research is to develop a material simultaneously able to absorb mechanical shocks and shield from electromagnetic interferences. Several layered composite materials aimed at such multi-functionality have been conceived and realized: the characterization has been carried out in terms of electromagnetic shielding effectiveness in the range 0.8–8.0 GHz and of energy absorbing capability upon impact of metallic bullets fired at about 400 m/s and 1000 m/s (such velocity allows to explore the low energy range of potential mechanical shocks in aerospace structures). The composite specimens under test are ∼3.5 mm thick tiles made of hybrid multi-scale material: the manufacturing has been performed by integrating several layers of Kevlar fabric and carbon fiber plies within a polymeric matrix reinforced by carbon nanotubes. The electromagnetic shielding effectiveness has been measured by means of a reverberation chamber; the performances of the layered composites approach the metallic behavior with values of shielding up to 80 dB. The impact tests have been carried out by using an in-house built linear electromagnetic accelerator, known as railgun; the results show that a thin and light tile of the designed composite material is able to absorb high energy impacts with local delamination of the layered structure

Bioensaio rápido de determinação da sensibilidade da acetolactato sintase (ALS) a herbicidas inibidores Rapid bioassay to determine the sensitivity of acetolactate synthase (ALS) to inhibitor herbicides

Foi avaliada a atividade da acetolactato sintase (ALS), em plantas resistentes e suscetíveis de B. pilosa e A. quitensis após a aplicação de herbicidas inibidores da ALS. O método baseia-se na utilização do ácido ciclopropanodicarboxílico (CPCA) para inibir a cetoácido reductoisomerase (KARI), enzima que catalisa a reação seguinte do acetolactato na cadeia de biossíntese dos aminoácidos valina, leucina e isoleucina, provocando assim, o acúmulo de acetolactato, que na presença de um ácido forte forma acetoína. A base para a distinção entre os biotipos resistentes e suscetíveis é a quantidade de acetoína formada, que será maior nos biotipos em que a enzima ALS não sofreu inibição, ou seja, nos biotipos resistentes. A quantificação da acetoína acumulada ocorreu através da formação de um complexo colorido vermelho, devido a reação entre acetoína, creatina e naftol, cuja densidade ótica a 530 nm é proporcional à concentração do acetolactato formado na reação. Sendo assim, foi desenvolvido um ensaio utilizando este método após a aplicação dos herbicidas chlorimuron-ethyl e imazethapyr nos biotipos R e S de Bidens pilosa, Amaranthus quitensis no estádio de dois pares de folhas. O bioensaio demonstrou que a enzima ALS dos biotipos resistentes é insensível aos herbicidas inibidores da ALS e que este tipo de bioensaio é uma forma rápida e eficaz de diferenciação entre biotipos resistentes e suscetíveis.<br>In order to compare the acetolactate synthase (ALS) activity of resistant and susceptible biotypes of Bidens pilosa and Amaranthus quitensis to ALS inhibitor herbicides, a method based on ciclopronocarboxilic acid (CPCA) to inhibit the enzyme ketoacidredutoisomerase (KARI) is used. This enzyme catalyzes the reaction after acetolactate in the biosynthesis reaction chain of the aminoacids valine, leucine and isoleucine. In the presence of a KARI inhibitor, carbon from pyruvate flows through the branched chain aminoacid biosynthetic pathway and accumulates in acetolactate, which in the presence of sulfuric acid can be converted to acetoin. The base to distinguish between the resistant and susceptible biotypes is the amount of acetoin formed, which will be much higher in the biotype where the ALS was not inhibited by the herbicide. If acetoin is mixed with naphtol and creatine the solution will develop a reddish color, so that it is possible to quantify indirectly the sensitivity of the ALS to the herbicide by the color of the solution formed. An experiment was carried out with suspected resistant biotypes of Bidens pilosa and Amaranthus quitensis using this method after spraying the plants at the two pair leaf stage with chlorimuron-ethyl and imazethapyr. The ALS of the resistant biotype has insensitivity to ALS inhibitor herbicides