Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. METHODS: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents. CONCLUSIONS: SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM before death

Detection of the Cherenkov light diffused by Sea Water with the ULTRA Experiment

The study of Ultra High Energy Cosmic Rays represents one of the most challenging topic in the Cosmic Rays and in the Astroparticle Physics fields. The interaction of primary particles with atmospheric nuclei produces a huge Extensive Air Shower together with isotropic emission of UV fluorescence light and highly directional Cherenkov photons, that are reflected/diffused isotropically by the impact on the Earth's surface or on high optical depth clouds. For space-based observations, detecting the reflected Cherenkov signal in a delayed coincidence with the fluorescence light improves the accuracy of the shower reconstruction in space and in particular the measurement of the shower maximum, giving a strong signature for discriminating hadrons and neutrinos, and helping to estimate the primary chemical composition. Since the Earth's surface is mostly covered by water, the ULTRA (UV Light Transmission and Reflection in the Atmosphere)experiment has been designed to provide the diffusing properties of sea water, overcoming the lack of information in this specific field. A small EAS array, made up of 5 particle detectors, and an UV optical device, have been coupled to detect in coincidence both electromagnetic and UV components. The detector was in operation from May to December, 2005, in a small private harbor in Capo Granitola (Italy); the results of these measurements in terms of diffusion coefficient and threshold energy are presented here.Comment: 4 pages, 3 figures, PDF format, Proceedings of 30th ICRC, International Cosmic Ray Conference 2007, Merida, Yucatan, Mexico, 3-11 July 200

Trabectedin arrests a doxorubicin-resistant PDGFRA-activated liposarcoma patient-derived orthotopic xenograft (PDOX) nude mouse model.

BACKGROUND:Pleomorphic liposarcoma (PLPS) is a rare, heterogeneous and an aggressive variant of liposarcoma. Therefore, individualized therapy is urgently needed. Our recent reports suggest that trabectedin (TRAB) is effective against several patient-derived orthotopic xenograft (PDOX) mouse models. Here, we compared the efficacy of first-line therapy, doxorubicin (DOX), and TRAB in a platelet-derived growth factor receptor-α (PDGFRA)-amplified PLPS. METHODS:We used a fresh sample of PLPS tumor derived from a 68-year-old male patient diagnosed with a recurrent PLPS. Subcutaneous implantation of tumor tissue was performed in a nude mouse. After three weeks of implantation, tumor tissues were isolated and cut into small pieces. To match the patient a PDGFRA-amplified PLPS PDOX was created in the biceps femoris of nude mice. Mice were randomized into three groups: Group 1 (G1), control (untreated); Group 2 (G2), DOX-treated; Group 3 (G3), TRAB-treated. Measurement was done twice a week for tumor width, length, and mouse body weight. RESULTS:The PLPS PDOX&nbsp;showed&nbsp;resistance towards DOX. However, TRAB could arrest the PLPS (p &lt; 0.05 compared&nbsp;to control; p &lt; 0.05 compared to DOX) without any significant changes in body-weight. CONCLUSIONS:The data presented here suggest that for the individual patient the PLPS PDOX model could specifically distinguish both effective and ineffective drugs. This is especially crucial for PLPS because effective&nbsp;first-line therapy is harder to establish if it is not individualized

N-Acetylcysteine Serves as Substrate of 3-Mercaptopyruvate Sulfurtransferase and Stimulates Sulfide Metabolism in Colon Cancer Cells

Hydrogen sulfide (H2S) is an endogenously produced signaling molecule. The enzymes 3-mercaptopyruvate sulfurtransferase (MST), partly localized in mitochondria, and the inner mitochondrial membrane-associated sulfide:quinone oxidoreductase (SQR), besides being respectively involved in the synthesis and catabolism of H2S, generate sulfane sulfur species such as persulfides and polysulfides, currently recognized as mediating some of the H2S biological effects. Reprogramming of H2S metabolism was reported to support cellular proliferation and energy metabolism in cancer cells. As oxidative stress is a cancer hallmark and N-acetylcysteine (NAC) was recently suggested to act as an antioxidant by increasing intracellular levels of sulfane sulfur species, here we evaluated the effect of prolonged exposure to NAC on the H2S metabolism of SW480 colon cancer cells. Cells exposed to NAC for 24 h displayed increased expression and activity of MST and SQR. Furthermore, NAC was shown to: (i) persist at detectable levels inside the cells exposed to the drug for up to 24 h and (ii) sustain H2S synthesis by human MST more effectively than cysteine, as shown working on the isolated recombinant enzyme. We conclude that prolonged exposure of colon cancer cells to NAC stimulates H2S metabolism and that NAC can serve as a substrate for human MST

Modelagem de funções no cálculo dos índices DRIS.

O objetivo deste trabalho foi modelar o fator k e as funções DRIS para a diagnose foliar de mangueirascultivadas. Dez pomares comerciais, no estágio de produção, localizados no vale do Rio São Francisco, forammonitorados, mensalmente, durante dois anos, por meio da coleta de amostras foliares para determinação dosteores de N, P, K, Ca, Mg, B, Fe, Mn, Zn e Cu. Os dados foram testados quanto à normalidade e as relações entreas concentrações dos nutrientes foram usadas para calcular as normas DRIS, obtendo-se média, variância elimites máximo e mínimo de cada relação dentro da população amostrada. Os nutrientes foram classificadoscomo macronutrientes de resposta freqüente (MAF) (N, P e K), macronutrientes de resposta rara (MAR) (Ca eMg); micronutrientes de resposta freqüente (MIF) (B, Fe, Mn e Zn) e, micronutrientes de resposta rara (MIR)(Cu). Funções DRIS foram desenvolvidas para cada classe de nutrientes. O modelo desenvolvido expressa obalanço nutricional das plantas cultivadas ajustado a cada nutriente e reflete o comportamento biológico dasplantas como resultado da variação da disponibilidade dos nutrientes

Modelagem de funções no cálculo dos índices DRIS.

O objetivo deste trabalho foi modelar o fator k e as funções DRIS para a diagnose foliar de mangueiras cultivadas. Dez pomares comerciais, no estágio de produção, localizados no vale do Rio São Francisco, foram monitorados, mensalmente, durante dois anos, por meio da coleta de amostras foliares para determinação dos teores de N, P, K, Ca, Mg, B, Fe, Mn, Zn e Cu. Os dados foram testados quanto à normalidade e as relações entre as concentrações dos nutrientes foram usadas para calcular as normas DRIS, obtendo-se média, variância e limites máximo e mínimo de cada relação dentro da população amostrada. Os nutrientes foram classificados como macronutrientes de resposta freqüente (MAF) (N, P e K), macronutrientes de resposta rara (MAR) (Ca e Mg); micronutrientes de resposta freqüente (MIF) (B, Fe, Mn e Zn) e, micronutrientes de resposta rara (MIR) (Cu). Funções DRIS foram desenvolvidas para cada classe de nutrientes. O modelo desenvolvido expressa o balanço nutricional das plantas cultivadas ajustado a cada nutriente e reflete o comportamento biológico das plantas como resultado da variação da disponibilidade dos nutrientes