Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+) and recurrent head and neck squamous cell carcinoma (HNSCC) may increase our understanding of the complex biology of this disease.</p> <p>Methods</p> <p>Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative) or tumor recurrence (recurrent or non-recurrent tumor) after treatment (surgery with neck dissection followed by radiotherapy). Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category.</p> <p>Results</p> <p>The most frequent alterations were the repression of modules in negative lymph node (N0) and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed.</p> <p>Conclusions</p> <p>The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway, specially apoptosis and interactions between tumor cells and the stroma.</p

Risk Factors Associated with Adverse Fetal Outcomes in Pregnancies Affected by Coronavirus Disease 2019 (COVID-19): A Secondary Analysis of the WAPM study on COVID-19

To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Mean gestational age at diagnosis was 30.6\ub19.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible

Rhinitis in the geriatric population

The current geriatric population in the United States accounts for approximately 12% of the total population and is projected to reach nearly 20% (71.5 million people) by 2030[1]. With this expansion of the number of older adults, physicians will face the common complaint of rhinitis with increasing frequency. Nasal symptoms pose a significant burden on the health of older people and require attention to improve quality of life. Several mechanisms likely underlie the pathogenesis of rhinitis in these patients, including inflammatory conditions and the influence of aging on nasal physiology, with the potential for interaction between the two. Various treatments have been proposed to manage this condition; however, more work is needed to enhance our understanding of the pathophysiology of the various forms of geriatric rhinitis and to develop more effective therapies for this important patient population

Perception of male otolaryngologists on gender discrimination: a comparative study

Purpose: To gather information on perception of male otolaryngologists (MORLs) about gender discrimination towards female otolaryngologists (FORLs). Methods: MORLs were invited to participate to an online survey. Minimum participation requirement was completion of at least their first year of residency. The responses were analyzed and compared vis-a-vis with the previously conducted similar survey among FORLs. Results: Statistically significant responses on the Likert scale are classified in four main groups. MORLs and FORLs share the same views about financial factors, benefits and opportunities, housework as burden, establishing work–life balance and physical strength requirements. They have opposing views about FORLs being meticulous, exposed to more negative attitude of the opposite gender and men’s dominance in decision-making. FORLs don’t have consensus, but MORLs disagree about MORLs being favored in pursuing academic careers. On the other hand, MORLs don’t have consensus, but FORLs agree about patients having more confidence in MORLs. Conclusion: MORLs don’t usually have any confrontation with FORLs in regards to the roles of women in the society such as their motherhood role. On the other hand, MORLs show rather a contradiction on their perception towards the gender discrimination mainly in achieving career goals by FORLs such as growing in the profession and holding managing roles. When the views of the both gender group are compared, MORLs don’t seem to fully acknowledge FORLs’ gender discrimination experience. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature

Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 alpha (HIF-1 alpha), and transforming growth factors beta 1 (TGF beta 1) and beta 3 (TGF beta 3) in gestational trophoblastic disease

WOS: 000274585900004PubMed ID: 19836147The aim of this study was to investigate the relationship between the expression of vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta 1 and TGF-beta 3), and hypoxia inducible factor 1 alpha (HIF-1 alpha) in gestational trophoblastic diseases to highlight the possible histogenesis. Twenty-one partial hydatidiform moles (PHM), 19 complete hydatidiform moles (CHM), 13 choriocarcinomas, and 20 nonhydropic spontaneous abortions (control group) were evaluated with immunohistochemistry using VEGF, HIF-1 alpha TGF beta 1, and TGF beta 3. The extent of immunohistochemical positivity (0% = 0, 1-24% = 1, 25-49% = 2, 50-74% = 3, and greater than 75% = 4) and intensity (no staining = 0, weak staining = 1, medium staining = 2, and strong staining = 3) were recorded. The expression of VEGF in spontaneous abortions and choriocarcinoma was higher than the expression in PHM and CHM. HIF-1 alpha was strongly expressed in the choriocarcinomas compared to the other subgroups. Nonhydropic spontaneous abortions (control group) showed the highest TGF beta 1 expression levels among the case subgroups, followed by PHM, CHM, and choriocarcinoma (p<0.001). The expression of TGF beta 3 was seen in all groups, but the highest level of expression was observed in both CHM and choriocarcinoma. We conclude that higher levels of VEGF, HIF-1 alpha and TGF beta 3 expression in choriocarcinoma might be involved in the development of trophoblastic diseases. (C) 2009 Elsevier GmbH. All rights reserved

Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 alpha (HIF-1?), and transforming growth factors ß1 (TGFß1) and ß3 (TGFß3) in gestational trophoblastic disease

PubMedID: 19836147The aim of this study was to investigate the relationship between the expression of vascular endothelial growth factor (VEGF), transforming growth factor ß (TGF-ß1 and TGF-ß3), and hypoxia inducible factor 1 alpha (HIF-1?) in gestational trophoblastic diseases to highlight the possible histogenesis. Twenty-one partial hydatidiform moles (PHM), 19 complete hydatidiform moles (CHM), 13 choriocarcinomas, and 20 nonhydropic spontaneous abortions (control group) were evaluated with immunohistochemistry using VEGF, HIF-1?, TGFß1, and TGFß3. The extent of immunohistochemical positivity (0%=0, 1-24%=1, 25-49%=2, 50-74%=3, and greater than 75%=4) and intensity (no staining=0, weak staining=1, medium staining=2, and strong staining=3) were recorded. The expression of VEGF in spontaneous abortions and choriocarcinoma was higher than the expression in PHM and CHM. HIF-1? was strongly expressed in the choriocarcinomas compared to the other subgroups. Nonhydropic spontaneous abortions (control group) showed the highest TGFß1 expression levels among the case subgroups, followed by PHM, CHM, and choriocarcinoma (p<0.001). The expression of TGFß3 was seen in all groups, but the highest level of expression was observed in both CHM and choriocarcinoma. We conclude that higher levels of VEGF, HIF-1?, and TGFß3 expression in choriocarcinoma might be involved in the development of trophoblastic diseases. © 2009 Elsevier GmbH. All rights reserved