Effect of COVID‐19 in selecting otolaryngology as a specialty

Coronavirus disease 2019 has undoubtedly impacted the health care system while causing lasting and profound implications for medical education. Senior medical students seeking exposure to the field of otolaryngology now find themselves in the challenging position of obtaining the experiences to make an informed decision on a future specialty. Virtual electives using comprehensive online material, discussion, and videos as well as the advent of telemedicine may be potential solutions to increase exposure to otolaryngology. While incorporating opportunities for authentic patient interactions is still a challenge, it is crucial that the academic otolaryngology community prioritize seeking solutions for interested medical students.     

Antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies

Two gene-targeted immunoglobulin heavy chain transgenic mouse strains, TgH(KL25) and TgH(VI10), expressing neutralizing specificities for lymphocytic choriomeningitis virus and vesicular stomatitis virus, respectively, have been generated. Three days after lymphocytic choriomeningitis virus infection, TgH(KL25) mice showed a thymus-independent neutralizing IgM response followed by thymus-dependent (TD) IgG. In contrast, WT mice mounted only a TD IgG response around day 80. These observations indicated that not only structural properties of the virus but also immunological parameters such as the frequency of B cells were indicative for the induction of thymus-independent versus TD Ig responses. Na?ve vesicular stomatitis virusspecific Ig heavy chain transgenic mice displayed greatly elevated natural antibody titers. However, despite these high na?ve titers, de novo activation of na?ve CD4+ T and B cells was not blocked. Therefore, B cells giving rise to natural antibodies do not participate in virus-induced antibody responses.     

Angiogenic activity of rat mast cells in the chick embryo chorioallantoic membrane is down-regulated by treatment with recombinant human alpha-2a interferon and partly mediated by fibroblast growth factor-2

BACKGROUND AND OBJECTIVES: Many data suggest that the density of mast cells (MC) is strongly correlated with the extent of both normal and pathologic angiogenesis, such as the vessel formation that occurs in chronic inflammatory diseases and tumors. We have previously demonstrated that isolated MC and their secretory granules, but not degranulated MC, induce an angiogenic response in the chick embryo chorioallantoic membrane (CAM) assay. DESIGN AND METHODS: The aim of this study was to investigate whether pre-treatment of MC with an anti-angiogenic molecule, namely recombinant human interferon-alpha2a (rhIFN-alpha2a), reduced the angiogenic activity of their conditioned media (CM) in the CAM assay. RESULTS: Our data indicate that rhIFN-alpha2a at 500-1000 IU is able to reduce the angiogenic activity of CM significantly. When MC were treated with rhIFN-alpha2a at 25-250 IU they retained their angiogenic activity. Addition of anti-fibroblast growth factor-2 (FGF-2) antibodies (but not anti-vascular endothelial growth factor) substantially reduced the angiogenic activity of CM treated with sub-optimal concentrations of rhIFN-alpha2a. INTERPRETATION AND CONCLUSIONS: FGF-2 may be the main angiogenic factor secreted by MC and higher concentrations of rhIFN-alpha2a possibly inhibit angiogenesis by blocking the actions of FGF-2 produced by MC. Finally, the morphologic features of MC treated with rhIFN-alpha2a, characterized by an atypical secretory pathway, are compatible with a slow release of the angiogenic cytokines stored in MC granules.     

Trading in your spindles for blebs： the amoeboid tumor cell phenotype in prostate cancer

Prostate cancer （PCa） remains a principal cause ofmortalityin developed countries.Because no clinical interventions overcome resistance to androgen ablation therapy, management of castration resistance and metastatic disease remains largely untreatable. Metastasis is a multistep process in which tumor cells lose cell-cell contacts, egress from the primary tumor, intravasate, survive shear stress within the vasculature and extravasate into tissues to colonize ectopic sites. Tumor ceils reestablish migratory behaviors employed during nonneoplastic processes such as embryonic development, leukocyte trafficking and wound healing. While mesenchymal motility is an established paradigm of dissemination, an alternate, ＇amoeboid＇ phenotype is increasingly appreciated as relevant to human cancer.     

Calcium Influx,But Not Intracellular Calcium Release,Supports PACAP-Mediated ERK Activation in HEK PAC1 Receptor Cells

In HEK cells expressing GFP-tagged PAC1Hop1 receptors, PACAP augments ERK phosphorylation through two parallel pathways: one through PACAP/PAC1 receptor internalization/endosome MEK/ERK signaling and the other through PLC/DAG/PKC activation. We examined whether elevation of intracellular calcium ([Ca²⁺]_i) was required for either of the PACAP/PAC1 receptor-mediated ERK activation mechanisms. The PACAP (25 nM)-induced elevation of [Ca²⁺]_i was greater with cells maintained in Ca²⁺-containing than in Ca²⁺-deficient solution, suggesting that both calcium release from internal stores and calcium influx contributed to the rise in [Ca²⁺]_i. A thapsigargin-induced increase in [Ca²⁺]_i also was greater with calcium in the external solution. OAG, the cell permeable analogue of DAG, increased [Ca²⁺]_i, but only in Ca²⁺-containing solution. Decreasing external calcium or depleting internal calcium stores did not block PACAP-induced PAC1 receptor internalization. Omission of calcium from the external solution, but not thapsigargin pretreatment, significantly blunted PACAP-stimulated ERK phosphorylation. The PKC inhibitor BimI decreased PACAP-mediated ERK activation in both Ca²⁺-containing or Ca²⁺-deficient solutions. In contrast, following Pitstop 2 pretreatment to block endocytic mechanisms, PACAP activated ERK only when calcium was present in the external solution. We conclude that the endosome signaling pathway is largely calcium-independent whereas calcium influx appears necessary for the PLC/DAG/PKC component of PACAP-induced ERK activation.     

Characterizing impulsivity profile in patients with obsessive–compulsive disorder

Objective. Impulsivity represents a key dimension in obsessive–compulsive disorder (OCD), in relation to outcome and course. It can be assessed through the Barratt Impulsiveness Scale (BIS), which explores three main areas: attentional, motor, and nonplanning. Present study was aimed to assess level of impulsivity in a sample of OCD patients, in comparison with healthy controls, using the BIS. Methods. Seventy-five OCD outpatients, 48 of them having psychiatric comorbidities and 70 healthy controls, were assessed through the BIS, and their scores were analyzed using Student's t-test for independent samples, on the basis of demographic and clinical characteristics. Results. BIS total scores were significantly higher (P: 0.01) in patients compared to controls, with no difference between pure and comorbid patients. Attentional impulsivity scores were significantly higher than controls in patients with pure (P < 0.001) and comorbid OCD (P < 0.001), without differences among them. Patients with multiple OC phenotypes showed higher, though statistically non significant, total and attentional scores, compared to single phenotype patients. In addition, patients with comorbid major depressive disorder had higher, though statistically non significant, total and attentional scores, compared to patients with comorbid bipolar disorder, generalized anxiety disorder, and other disorders. Conclusions. Present findings showed higher impulsivity levels in OCD patients versus controls, particularly in the attentional area, and ultimately suggest a potential cognitive implication.