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Ventricular septal rupture (VSR) represents a rare complication of acute myocardial infarction, often presenting with cardiogenic shock and associated with high in-hospital mortality despite prompt intervention. Although immediate surgery is recommended for patients who cannot be effectively stabilized, the ideal timing of intervention remains controversial. Mechanical circulatory support (MCS) may allow hemodynamic stabilization and delay definitive treatment even in critical patients. However, the interactions between MCS and VSR pathophysiology as well as potentially related adverse effects remain unclear. A systematic review was performed, from 2000 onward, to identify reports describing MCS types, effects, complications, and outcomes in the pre-operative VSR-related setting. One hundred eleven studies (2,440 patients) were included. Most patients had well-known negative predictors (e.g., cardiogenic shock, inferior infarction). Almost all patients had intra-aortic balloon pumps, with additional MCS adopted in 129 patients (77.5% being venoarterial extracorporeal membrane oxygenation). Mean MCS bridging time was 6 days (range: 0 to 23 days). In-hospital mortality was 50.4%, with the lowest mortality rate in the extracorporeal membrane oxygenation group (29.2%). MCS may enhance hemodynamic stabilization and delayed VSR treatment. However, the actual effects and interaction of the MCS-VSR association should be carefully assessed to avoid further complications or incorrect MCS-VSR coupling. [Display omitted] • Post-infarction VSR is life threatening, with high mortality despite prompt surgery. • MCS may provide hemodynamic stabilization and support patients for safer procedures. • Interactions and adverse effects of MCS with VSR pathophysiology should be considered. • Patient-tailored MCS may provide optimal support and avoid dangerous effects. [ABSTRACT FROM AUTHOR]

Abstract Background Activating mutations of the epidermal growth factor receptor (EGFR) confer sensitivity to the tyrosine kinase inhibitors (TKi), gefitinib and erlotinib. We analysed EGFR expression, EGFR mutation status and gene expression profiles of prostate cancer (PC) to supply a rationale for EGFR targeted therapies in this disease. Methods Mutational analysis of EGFR TK domain (exons from 18 to 21) and immunohistochemistry for EGFR were performed on tumour tissues derived from radical prostatectomy from 100 PC patients. Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples. Results EGFR protein overexpression (EGFRhigh) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFRhigh tumours experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with patients with tumours expressing low levels of EGFR (EGFRlow). Microarray analysis did not reveal any differences in gene expression between EGFRhigh and EGFRlow tumours. Conversely, in EGFRhigh tumours, we were able to identify a 79 gene signature distinguishing mutated from non-mutated tumours. Additionally, 29 genes were found to be differentially expressed between mutated/EGFRhigh (n=3) and mutated/EGFRlow tumours (n=5). Four of the down-regulated genes, U19/EAF2, ABCC4, KLK3 and ANXA3 and one of the up-regulated genes, FOXC1, are involved in PC progression. Conclusions Based on our findings, we hypothesize that accurate definition of the EGFR status could improve prognostic stratification and we suggest a possible role for EGFR-directed therapies in PC patients. Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.

Abstract Background Osteosarcoma (OS) is the most common primary bone tumour in children and young adults. Despite improved prognosis, metastatic or relapsed OS remains largely incurable and no significant improvement has been observed in the last 20 years. Therefore, the search for alternative agents in OS is mandatory. Results We investigated phospho-ERK 1/2, MCL-1, and phospho-Ezrin/Radixin/Moesin (P-ERM) as potential therapeutic targets in OS. Activation of these pathways was shown by immunohistochemistry in about 70% of cases and in all OS cell lines analyzed. Mutational analysis revealed no activating mutations in KRAS whereas BRAF gene was found to be mutated in 4/30 OS samples from patients. Based on these results we tested the multi-kinase inhibitor sorafenib (BAY 43-9006) in preclinical models of OS. Sorafenib inhibited OS cell line proliferation, induced apoptosis and downregulated P-ERK1/2, MCL-1, and P-ERM in a dose-dependent manner. The dephosphorylation of ERM was not due to ERK inhibition. The downregulation of MCL-1 led to an increase in apoptosis in OS cell lines. In chick embryo chorioallantoic membranes, OS supernatants induced angiogenesis, which was blocked by sorafenib and it was also shown that sorafenib reduced VEGF and MMP2 production. In addition, sorafenib treatment dramatically reduced tumour volume of OS xenografts and lung metastasis in SCID mice. Conclusion In conclusion, ERK1/2, MCL-1 and ERM pathways are shown to be active in OS. Sorafenib is able to inhibit their signal transduction, both in vitro and in vivo, displaying anti-tumoural activity, anti-angiogenic effects, and reducing metastatic colony formation in lungs. These data support the testing of sorafenib as a potential therapeutic option in metastatic or relapsed OS patients unresponsive to standard treatments.

Patients with sporadic neuroendocrine neoplasms may exhibit a higher risk of a second primary tumor than the general population. This study aimed to analyze the occurrence of second primary malignancies. A retrospective cohort of 2757 patients with sporadic lung and gastro-entero-pancreatic neuroendocrine neoplasms, managed at eight Italian tertiary referral Centers, was included. Between 2000 and 2019, a second primary malignancy was observed in 271 (9.8%) neuroendocrine neoplasms patients with 32 developing a third tumor. There were 135 (49.8%) females and the median age was 64 years. The most frequent locations of the second tumors were breast (18.8%), prostate (12.5%), colon (9.6%), blood tumors (8.5%), and lung (7.7%). The second primary tumor was synchronous in 19.2% of cases, metachronous in 43.2%, and previous in 37.6%. As concerned the neuroendocrine neoplasms, the 5- and 10-year survival rates were 87.8% and 74.4%, respectively. PFS for patients with a second primary malignancy was shorter than for patients without a second primary malignancy. Death was mainly related to neuroendocrine neoplasms. In NEN patients the prevalence of second primary malignancies was not negligible, suggesting a possible neoplastic susceptibility. Overall survival was not affected by the occurrence of a second primary malignancy. [ABSTRACT FROM AUTHOR]

The electrical and optical properties of MoO3/Ag/MoO3 multilayer structures have been studied using the Ag deposition rate and layer thicknesses as parameters. When the silver film is deposited at 0.20 nm/s rate, the silver layer thickness necessary to achieve the percolation threshold of the resistivity ρ towards conductive structures is 10 nm. Below 10 nm, the films are semiconductor and above the films are conductors. In the present work, the variation of the thicknesses of top and bottom MoO3 layers is shown to strongly modify the optical properties of the multilayer structures. By using a Ag thickness of 10 nm, we demonstrate an increasing of the transmittance of the MoO3/Ag/MoO3 structures by optimizing the MoO3 layers thicknesses. When the MoO3 bottom layer is 20 nm thick, and the MoO3 top layer is 35 nm, the maximum transmission is 86% at the wavelength of 465 nm, while the averaged transmission in the visible range (350 nm-800 nm) is 70%. The best measured conductivity, σ = 1.1 × 105 (Ω cm)-1, corresponds also to this MoO3 (20 nm)/Ag (10 nm)/MoO3 (35 nm) structure. A good qualitative agreement between the theoretical calculations of the variation of the optical transmittance and reflectance of the MoO3/Ag/MoO3 structures is also highlighted. [ABSTRACT FROM AUTHOR]

The melting line of cobalt has been investigated both experimentally, using synchrotron X-ray diffraction coupled with laser-heated diamond anvil cells, and theoretically, using ab initio simulations. Over the investigated pressure and temperature range – between 30 and 100 GPa and from ambient temperature up to 4000 K – the hexagonal close-packed structure, stable at ambient conditions, is replaced at high temperature by the face-centered cubic structure, observed stable till melting. The melting temperatures obtained by the two methods are in remarkable agreement and the melting line can be well described by a Simon–Glatzel equation of the form T m = 1768(K)(P(GPa)/35.62+1) 0. 64. Finally, from the obtained results it was possible to determine a thermal equation of state for the cubic face-centered phase of Co. [Display omitted] • First in situ determination of the melting line of Co via LH-DAC and XRD. • Excellent agreement between the DFT models and the obtained experimental data. • Thermal equation of state for fcc-Co extended up to 1 Mbar and 4000 K. [ABSTRACT FROM AUTHOR]

Byline: L. Escoubas, F. Flory, J.J. Simon, P. Torchio A general overview of the determination, by guided waves, of optical, anisotropic, thermal, non-linear and electro-optical properties of materials in thin film form is presented. Several set-up allowing guided wave characterisations of thin films are described. Examples of the various characterisations are discussed.

Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches. The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes. Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy. This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors. [ABSTRACT FROM AUTHOR]

A paracoccidioidomicose é doença sistêmica que atinge mais o sexo masculino do que o feminino. Modelos experimentais mostram maior sensibilidade dos machos do que as fêmeas à dsseminação da doença. A literatura médica é rica em relatos de casos de Pbmicose do trato genital masculino. A raridade da Pbmicose sistêmica na mulher devido à ação hormonal tornou inusitada a descrição de um caso com envolvimneto genital. Paciente de 57 anos, branca, procedente de Conchas (SP), queixando-se de dor abdominal há 10 anos, difusa, seguida de eólica periumbelical periódica, com diarréia e obstipação alternadas. Piorou desse quadro e evoluiu para abdome agudo cirúrgico. O anátomo patológico revelou Pbmicose no epiplon e ovário direito. A biópsia do endométrio mostrou endometrite crônica granulomatosa. A radiologia e a planigrafia revelaram nódulo parahilar direito. Os achados clínicos e laboratoriais permitiram explicar a provável origem do envolvimento genital.

A paracoccidioidomicose (Pbmicose) atinge os pulmões pela via inalatória, onde se estabelece o complexo primário semelhante ao da tuberculose. A traquéia comprometida pela via tubohemolinfática desenvolveria reação inflamatória em processo granulomatoso levando à obstrução estenosante com asíixia. Acompanhou-se um doente, masculino, 32 anos, branco, natural de Sarutaiá (SP), lavrador, que há 8 meses desenvolveu tosse expectorativa branco-amarelada, diária, sem fatores de melhora ou piora e dispnéia inicial discreta. Há 4 meses, anorexia, fraqueza e astenia. Há 1 mês a dispneia se agravou. Perdeu 15 kg. Tabagista e etilista há 16 anos. Exame físico revelou: PA — 10/7 mmHg, FR = 28 bpm, peso 31 kg, hipocratismo digital e hipotrofia muscular Tórax enfisematoso e síndrome obstrutivo aos testes de função pulmonar. Coração: P2 desdobrada e hiperfonética. Hepatesplenomegalia. Desenvolveu cor-pulmonale e insuficiência adrenal à internação, evoluindo após 45 dias para óbito em insuficiência respiratória aguda asfixiante, apesar da terapia antifúngica ter sido completa. A literatura médica revista não mostrou registro de caso semelhante de cor-pulmonale e insuficiência adrenal de evolução subaguda.

OBJECTIVE: The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients. METHODS: We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays. RESULTS: Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected ∼70.6% of pathogenic changes. CONCLUSION: The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis.