Effect of a fixed combination of nimodipine and betahistine versus betahistine as monotherapy in the long-term treatment of M\ue9ni\ue8re's disease: a 10-year experience

Despite an abundance of long-term pharmacological treatments for recurrent vertigo attacks due to M\ue9ni\ue8re's disease, there is no general agreement on the their efficacy. We present the results of a retrospective study based on a 10-year experience with two long-term medical protocols prescribed to patients affected by M\ue9ni\ue8re's disease (diagnosed according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines) who completed treatments in the period 1999-2009. A total of 113 medical records were analysed; 53 patients received betahistine-dihydrochloride at on-label dosage (32 mg die) for six months, and 60 patients were treated with the same regimen and nimodipine (40 mg die) as an add-therapy during the same period. Nimodipine, a 1,4-dihydropyridine that selectively blocks L-type voltage-sensitive calcium channels, has previously been tested as a monotherapy for recurrent vertigo of labyrinthine origin in a multinational, double-blind study with positive results. A moderate reduction of the impact of vertigo on quality of life (as assessed by the Dizziness Handicap Inventory) was obtained in patients after therapy with betahistine (p 0.05), whereas the fixed combination of betahistine and nimodipine was associated with a significant reduction of tinnitus annoyance and improvement of hearing loss (p < 0.005). It was concluded that nimodipine represents not only a valid add-therapy for M\ue9ni\ue8re's disease, and that it may also exert a specific effect on inner ear disorders. Further studies to investigate this possibility are needed

Transcriptional Regulator CNOT3 Defines an Aggressive Colorectal Cancer Subtype.

Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent, and impact of these alterations are still being unraveled. Here, we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers, as compared with corresponding benign precursor adenomas. Modification of certain colorectal cancer sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC). In primary colorectal cancer cells, we observed a scattered pattern of CNOT3 expression, as might be expected for a tumor-initiating cell marker. Colorectal cancer cells exhibited nuclear and cytoplasmic expression of CNOT3, suggesting possible roles in both transcription and mRNA stability. We found that CNOT3 was bound primarily to genes whose expression was affected by CNOT3 loss, and also at sites modulated in certain types of colorectal cancers. These target genes were implicated in ESC and cancer self-renewal and fell into two distinct groups: those dependent on CNOT3 and MYC for optimal transcription and those repressed by CNOT3 binding and promoter hypermethylation. Silencing CNOT3 in colorectal cancer cells resulted in replication arrest. In clinical specimens, early-stage tumors that included >5% CNOT3(+) cells exhibited a correlation to worse clinical outcomes compared with tumors with little to no CNOT3 expression. Together, our findings implicate CNOT3 in the coordination of colonic epithelial cell self-renewal, suggesting this factor as a new biomarker for molecular and prognostic classification of early-stage colorectal cancer. Cancer Res; 77(3); 766-79. ©2016 AACR

The [Tc(N)(PNP)]2+ metal fragment labeled cholecystokinin-8 (CCK8) peptide for CCK-2 receptors imaging: in vitroand in vivo studies

The radiolabeling of the natural octapeptide CCK8, derivatized with a cysteine residue (Cys-Gly-CCK8), by using the metal fragment [99mTc(N)(PNP3)]2+ (PNP3 = N,N-bis(dimethoxypropylphosphinoethyl)methoxyethylamine) is reported. The [99mTc(N)(NS-Cys-Gly-CCK8)(PNP3)]+ complex was obtained according to two methods (one-step or two-step procedure) that gave the desired compound in high yield. The complex is stable in aqueous solution and in phosphate buffer. In vitro challenge experiments with an excess of cysteine and glutathione indicate that no transchelation reactions occur, confirming the high thermodynamic stability and kinetic inertness of this compound. Stability studies carried out in human and mouse serum, as well as in mouse liver homogenates, show that the radiolabeled compound remains intact for prolonged incubation at 37 degrees C. Binding properties give Kd (19.0 +/- 4.6 nmol/l) and Bmax (approximately 10(6) sites/cell) values in A431 cells overexpressing the CCK2-R. In vivo evaluation of the compound shows rapid and specific targeting to CCK2-R, a fourfold higher accumulation compared to nonreceptor expressing tumors

Adenocarcinoma classification: patterns and prognosis

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications

Adenocarcinoma classification: patterns and prognosis

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications

Echo-endoscopic appearance of mediastinal metastasis from papillary renal carcinoma.

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Selection of a New Highly Resistant Strain for Malolactic Fermentation under Difficult Conditions

Malolactic fermentation (MLF) is a biological process that contributes to wine quality, but it is frequently affectedby various vinification conditions. Resistance to four wine-limiting factors was studied with respect to 10 Oenococcusoeni strains in order to select a suitable strain for performing reliable MLF in difficult wines. Resistance to lowfermentation temperature, high SO2 and/or ethanol concentration, and low pH were assayed in laboratory tests. Apool of the most resistant strains was used in a set of laboratory MLFs. At the end of fermentation, the dominantstrains were identified by RAPD-PCR. The PN4 strain was found to be dominant in the majority of cases and underthe most detrimental wine conditions, and it was therefore chosen as the single-strain inoculum for the subsequentMLF trials. The effectiveness of the PN4 strain was confirmed in a series of MLFs carried out in three differentcountries under experimental and industrial conditions. It accomplished MLF in wines with up to 15.8% ethanol,pH as low as 3.0, 60 mg/L of free SO2, and in fermentation temperatures below 17ºC. Our findings indicate that theO. oeni PN4 strain could be an effective starter, guaranteeing regular and reliable MLF fermentation

Design of mechanical properties of poly(butylene-adipate-terephthalate) reinforced with Zein-TiO2 complex

The aim of this work was to realize and mechanically characterize composites based on poly(butyleneadipate-terephthalate) (PBAT) filled with micrometric particles of zein-TiO2 complex (ZTC) at different concentrations. Specimens model 1BA were obtained by injection molding and subjected to a uniaxial tensile test (UTT). The addition of the ZTC proved to have a reinforcing effect on the matrix, an increase in both Young’s modulus (E) and yield stress (σy) being observed. The mechanical properties were modeled applying Kerner’s and Pukánszky’s models, obtaining a good correspondence between theoretical experimental values and good matrix-filler interfacial interaction, respectively. Microscopical analysis revealed a good dispersion of the filler within the matrix

Two mechanisms drive pronuclear migration in mouse zygotes

A new life begins with the unification of the maternal and paternal chromosomes upon fertilization. The parental chromosomes first become enclosed in two separate pronuclei near the surface of the fertilized egg. The mechanisms that then move the pronuclei inwards for their unification are only poorly understood in mammals. Here, we report two mechanisms that act in concert to unite the parental genomes in fertilized mouse eggs. The male pronucleus assembles within the fertilization cone and is rapidly moved inwards by the flattening cone. Rab11a recruits the actin nucleation factors Spire and Formin-2 into the fertilization cone, where they locally nucleate actin and further accelerate the pronucleus inwards. In parallel, a dynamic network of microtubules assembles that slowly moves the male and female pronuclei towards the cell centre in a dynein-dependent manner. Both mechanisms are partially redundant and act in concert to unite the parental pronuclei in the zygote’s centre