Morphologic spectrum of the epithelial tumors of the male and female urethra

The classification of the epithelial tumors of the male and female urethra includes benign and malignant neoplasms. Primary urethral carcinomas and adenocarcinomas of the accessory glands are the most relevant tumors, both from the morphologic and clinical point of view. An accurate diagnosis, grading and staging are essential for determining adequate treatment strategies and outcome. Information on anatomy and histology of the urethra is of fundamental importance in understanding the morphology of the tumors, including the clinical importance of their location and origin

Evolution and excitation conditions of outflows in high-mass star-forming regions

Theoretical models suggest that massive stars form via disk-mediated accretion, with bipolar outflows playing a fundamental role. A recent study toward massive molecular outflows has revealed a decrease of the SiO line intensity as the object evolves. The present study aims at characterizing the variation of the molecular outflow properties with time, and at studying the SiO excitation conditions in outflows associated with massive YSOs. We used the IRAM30m telescope to map 14 massive star-forming regions in the SiO(2-1), SiO(5-4) and HCO+(1-0) outflow lines, and in several dense gas and hot core tracers. Hi-GAL data was used to improve the spectral energy distributions and the L/M ratio, which is believed to be a good indicator of the evolutionary stage of the YSO. We detect SiO and HCO+ outflow emission in all the sources, and bipolar structures in six of them. The outflow parameters are similar to those found toward other massive YSOs. We find an increase of the HCO+ outflow energetics as the object evolve, and a decrease of the SiO abundance with time, from 10^(-8) to 10^(-9). The SiO(5-4) to (2-1) line ratio is found to be low at the ambient gas velocity, and increases as we move to high velocities, indicating that the excitation conditions of the SiO change with the velocity of the gas (with larger densities and/or temperatures for the high-velocity gas component). The properties of the SiO and HCO+ outflow emission suggest a scenario in which SiO is largely enhanced in the first evolutionary stages, probably due to strong shocks produced by the protostellar jet. As the object evolves, the power of the jet would decrease and so does the SiO abundance. During this process, however, the material surrounding the protostar would have been been swept up by the jet, and the outflow activity, traced by entrained molecular material (HCO+), would increase with time.Comment: 31 pages, 10 figures and 5 tables (plus 2 figures and 3 tables in the appendix). Accepted for publication in A&A. [Abstract modified to fit the arXiv requirements.

On The Gould’s Formula for Stirling Numbers of The Second Kind

We present an alternative deduction of the Gould’s relation for Stirling numbers of the second kind. Our approach is based in the Nörlund polynomials and in the duality property between the Stirling numbers

Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air)

<p>Abstract</p> <p>Background</p> <p>The present study was designed to test the hypothesis that chronic very mild prenatal carbon monoxide (CO) exposure (25 parts per million) subverts the normal development of the rat cerebellar cortex. Studies at this chronic low CO exposure over the earliest periods of mammalian development have not been performed to date. Pregnant rats were exposed chronically to CO from gestational day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to CO from postnatal day 5 (P5) to P20; group C: postnatal exposure only, from P5 to P20, and group D, controls (air without CO). At P20, immunocytochemical analyses of oxidative stress markers, and structural and functional proteins were assessed in the cerebellar cortex of the four groups. Quantitative real time PCR assays were performed for inducible (iNOS), neuronal (nNOS), and endothelial (eNOS) nitric oxide synthases.</p> <p>Results</p> <p>Superoxide dismutase-1 (SOD1), SOD2, and hemeoxygenase-1 (HO-1) immunoreactivity increased in cells of the cerebellar cortex of CO-exposed pups. INOS and nitrotyrosine immunoreactivity also increased in blood vessels and Purkinje cells (PCs) of pups from group-A, B and C. By contrast, nNOS immunoreactivity decreased in PCs from group-B. Endothelial NOS immunoreactivity showed no changes in any CO-exposed group. The mRNA levels for iNOS were significantly up-regulated in the cerebellum of rats from group B; however, mRNA levels for nNOS and eNOS remained relatively unchanged in groups A, B and C. Ferritin-H immunoreactivity increased in group-B. Immunocytochemistry for neurofilaments (structural protein), synapsin-1 (functional protein), and glutamic acid decarboxylase (the enzyme responsible for the synthesis of the inhibitory neurotransmitter GABA), were decreased in groups A and B. Immunoreactivity for two calcium binding proteins, parvalbumin and calbindin, remained unchanged. The immunoreactivity of the astrocytic marker GFAP increased after prenatal exposure.</p> <p>Conclusion</p> <p>We conclude that exogenously supplied CO during the prenatal period promotes oxidative stress as indicated by the up-regulation of SOD-1, SOD-2, HO-1, Ferritin-H, and iNOS with increased nitrotyrosine in the rat cerebella suggesting that deleterious and protective mechanisms were activated. These changes correlate with reductions of proteins important to cerebellar function: pre-synaptic terminals proteins (synapsin-1), proteins for the maintenance of neuronal size, shape and axonal quality (neurofilaments) and protein involved in GABAergic neurotransmission (GAD). Increased GFAP immunoreactivity after prenatal CO-exposure suggests a glial mediated response to the constant presence of CO. There were differential responses to prenatal vs. postnatal CO exposure: Prenatal exposure seems to be more damaging; a feature exemplified by the persistence of markers indicating oxidative stress in pups at P20, following prenatal only CO-exposure. The continuation of this cellular environment up to day 20 after CO exposure suggests the condition is chronic. Postnatal exposure without prenatal exposure shows the least impact, whereas prenatal followed by postnatal exposure exhibits the most pronounced outcome among the groups.</p

Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype

This study evaluated a panel including the molecular taxonomy subtype and the expression of 27 genes as a diagnostic tool to stratify bladder cancer patients at risk of aggressive behavior, using a well-characterized series of non-muscle invasive bladder cancer (NMIBC) as well as muscle-invasive bladder cancer (MIBC). The study was conducted using the novel NanoString nCounter gene expression analysis. This technology allowed us to identify the molecular subtype and to analyze the gene expression of 27 bladder-cancer-related genes selected through a recent literature search. The differential gene expression was correlated with clinicopathological variables, such as the molecular subtypes (luminal, basal, null/double negative), histological subtype (conventional urothelial carcinoma, or carcinoma with variant histology), clinical subtype (NMIBC and MIBC), tumor stage category (Ta, T1, and T2–4), tumor grade, PD-L1 expression (high vs. low expression), and clinical risk categories (low, intermediate, high and very high). The multivariate analysis of the 19 genes significant for cancer-specific survival in our cohort study series identified TP53 (p = 0.0001), CCND1 (p = 0.0001), MKI67 (p < 0.0001), and molecular subtype (p = 0.005) as independent predictors. A scoring system based on the molecular subtype and the gene expression signature of TP53, CCND1, or MKI67 was used for risk assessment. A score ranging from 0 (best prognosis) to 7 (worst prognosis) was obtained and used to stratify our patients into two (low [score 0–2] vs. high [score 3–7], model A) or three (low [score 0–2] vs. intermediate [score 3–4] vs. high [score 5–7], model B) risk categories with different survival characteristics. Mean cancer-specific survival was longer (122 + 2.7 months) in low-risk than intermediate-risk (79.4 + 9.4 months) or high-risk (6.2 + 0.9 months) categories (p < 0.0001; model A); and was longer (122 + 2.7 months) in low-risk than high-risk (58 + 8.3 months) (p < 0.0001; model B). In conclusion, the molecular risk assessment model, as reported here, might be used better to select the appropriate management for patients with bladder cancer

News in the classification of WHO 2022 bladder tumors

The fifth-edition of World Health Organization (WHO) Classification of Tumors series for urinary and male genital tract tumors has been published, six years later the fourth-edition. In these years, new treatment approaches have been implemented and new molecular data on urological cancers are known. Morphology remains the groundwork for taxonomy of the urinary tract tumors. However, a molecular approach to classification of urothelial carcinomas and the management of selected neoplasms with new therapeutic modalities such as immunotherapy are emerging. More data are needed for the application of these advances in routine pathology practice and patient management. The 2022 World Health Organization (WHO) Classification of Tumors of the Urinary System and Male Genital Organs represents an update in classification on urinary tract tumors. It also offers new insights with regards to the grading of heterogeneous non-invasive urothelial neoplasms, the definition of inverted neoplasms, the grading of invasive urothelial carcinomas, the diversity of morphological appearance of urothelial carcinomas, the definition of precursor lesions and the lineage of differentiation of the tumors

Analysis of DDM into Gamma Radiation

We are interested in the purpose of a dipolar fermionic particle as a viable candidate of Dark Matter (DDM). Then, we study the annihilation of dark matter into photons, considering it as a neutral particle with non-vanishing magnetic (M) and electric (D) dipolar moments. The total annihilation cross section σ(χ → γ) is computed by starting from a general form of coupling χγ in a framework beyond to Standard Model (BSM). We found that candidates with O(mχ )∽102GeV, D≈10−16 e cm are required in order to satisfy the current cosmic relic density

Oxidative Stress in the Blood Labyrinthine Barrier in the Macula Utricle of Meniere’s Disease Patients

The blood labyrinthine barrier (BLB) is critical in the maintenance of inner ear ionic and fluid homeostasis. Recent studies using imaging and histopathology demonstrate loss of integrity of the BLB in the affected inner ear of Meniere’s disease (MD) patients. We hypothesized that oxidative stress is involved in the pathogenesis of BLB degeneration, and to date there are no studies of oxidative stress proteins in the human BLB. We investigated the ultrastructural and immunohistochemical changes of the BLB in the vestibular endorgan, the macula utricle, from patients with MD (n = 10), acoustic neuroma (AN) (n = 6) and normative autopsy specimens (n = 3) with no inner ear disease. Each subject had a well-documented clinical history and audiovestibular testing. Utricular maculae were studied using light and transmission electron microscopy and double labeling immunofluorescence. Vascular endothelial cells (VECs) were identified using isolectin B4 (IB4) and glucose-transporter-1 (GLUT-1). Pericytes were identified using alpha smooth muscle actin (αSMA) and phalloidin. IB4 staining of VECS was consistently seen in both AN and normative. In contrast, IB4 was nearly undetectable in all MD specimens, consistent with the significant VEC damage confirmed on transmission electron microscopy. GLUT-1 was present in MD, AN, and normative. αSMA and phalloidin were expressed consistently in the BLB pericytes in normative, AN specimen, and Meniere’s specimens. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and nitrotyrosine were used as markers of oxidative stress. The VECs of the BLB in Meniere’s had significantly higher levels of expression of iNOS and nitrotyrosine compared with normative and AN specimen. eNOS-IF staining showed similar patterns in normative and Meniere’s specimens. Microarray-based gene expression profiling confirmed upregulation of iNOS mRNA from the macula utricle of Meniere’s patients compared with AN. Nitrotyrosine, a marker recognized as a hallmark of inflammation, especially when seen in association with an upregulation of iNOS, was detected in the epithelial and stromal cells in addition to VECs in MD. Immunohistochemical and ultrastructural degenerative changes of the VEC suggest that these cells are the primary targets of oxidative stress, and pericyte pathology including degeneration and migration, likely also plays a role in the loss of integrity of the BLB and triggering of inflammatory pathways in MD. These studies advance our scientific understanding of oxidative stress in the human inner ear BLB and otopathology

Molecular mechanisms related to hormone inhibition resistance in prostate cancer

Management of metastatic or advanced prostate cancer has acquired several therapeutic approaches that have drastically changed the course of the disease. In particular due to the high sensitivity of prostate cancer cells to hormone depletion, several agents able to inhibit hormone production or binding to nuclear receptor have been evaluated and adopted in clinical practice. However, despite several hormonal treatments being available nowadays for the management of advanced or metastatic prostate cancer, the natural history of the disease leads inexorably to the development of resistance to hormone inhibition. Findings regarding the mechanisms that drive this process are of particular and increasing interest as these are potentially related to the identification of new targetable pathways and to the development of new drugs able to improve our patients’ clinical outcomes