Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?

Abstract: In order to prevent new pathogen outbreaks and avoid possible new global health threats, it is important to study the mechanisms of microbial pathogenesis, screen new antiviral agents and test new vaccines using the best methods. In the last decade, organoids have provided a groundbreaking opportunity for modeling pathogen infections in human brains, including Zika virus (ZIKV) infection. ZIKV is a member of the Flavivirus genus, and it is recognized as an emerging infectious agent and a serious threat to global health. Organoids are 3D complex cellular models that offer an inscale organ that is physiologically alike to the original one, useful for exploring the mechanisms behind pathogens infection; additionally, organoids integrate data generated in vitro with traditional tools and often support those obtained in vivo with animal model. In this mini-review the value of organoids for ZIKV research is examined and sustained by the most recent literature. Within a 3D viewpoint, tissue engineered models are proposed as future biological systems to help in deciphering pathogenic processes and evaluate preventive and therapeutic strategies against ZIKV. The next steps in this field constitute a challenge that may protect people and future generations from severe brain defect

A gestão de vendas no mercado industrial (Business to Business): um estudo das práticas no setor de tecido índigo no Brasil

Na atual conjuntura de mercado, em que fatores, como recessão, comoditização de produtos, transformação do varejo, proliferação de mídias, concorrência acirrada, muitas vezes, predatória, torna-se cada vez mais difícil para as empresas encontrar diferenciais competitivos sustentáveis. Destarte, como reflexo dessas pressões econômicas competitivas e alterações sociais bem como culturais, estão sendo forçadas a se fazerem mais orientadas para o mercado e mais responsáveis com o cliente. Ao considerar o mercado industrial (B to B), que produz bens e serviços utilizados na produção de outros bens e serviços por outras organizações, o papel da venda pessoal vem sendo ampliado. O profissional de vendas desse setor é muito mais consultor de negócios do que vendedor. Espera-se de tal profissional a solução de problemas, portanto, este deve focar na construção de relacionamentos duradouros com os clientes. Registre-se que, em relação ao gerente de vendas, a expectativa é a mesma. No Brasil, vários profissionais de vendas foram promovidos ao cargo de gerente pelo sucesso obtido como vendedores, muitas vezes, com pouca ou nenhuma formação específica, antes de assumirem a função. Os objetivos desta pesquisa foram identificar e analisar quais tarefas, dentre as preconizadas pela teoria da administração de vendas, estão presentes na gestão de vendas das empresas fabricantes de tecido índigo, no Brasil, um mercado constituído por treze empresas. Como parâmetro desta avaliação, realizou-se um levantamento de campo, de natureza exploratória, em três fases, a primeira e segunda, quantitativa, por meio de entrevistas estruturadas; a terceira, de natureza qualitativa, por meio de entrevistas pessoais com gerentes de vendas de seis empresas do setor, o equivalente a 78,7% do mercado pesquisado. Constatou-se que, quanto à aplicação das técnicas gerenciais, não há uniformidade na atividade de administração de vendas das empresas pesquisadas. Também não se pôde afirmar que os resultados de faturamento estejam apenas relacionados às práticas de gestão em administração de vendas, embora haja fortes evidências nesse sentido

Hoteles embrujados en Córdoba: nazismo y fantasmas como atractivos de turismo oscuro : Casos de estudio: Hotel Edén y Gran Hotel Viena

La gran mayoría de las investigaciones sobre el turismo oscuro tienden a centrarse en las motivaciones de los turistas al visitar sitios que representan, de manera directa o indirecta, a la muerte y el sufrimiento. Sin embargo, la presente tesis tiene como objetivo mostrar cómo se presentan y se llevan a cabo estas prácticas turísticas desde el lado de la oferta, tomando como casos de estudio dos antiguos hoteles de la provincia de Córdoba: el Hotel Edén y el Gran Hotel Viena. Actualmente ambos comparten características que los incluyen dentro de los sitios de turismo oscuro “más claros” y no tan convencionales, como son las Dark Fun Factories (fábricas de diversión oscura) y los ghost tours (tour de fantasmas). A lo largo del trabajo, se analizan las características históricas y arquitectónicas de los lugares, dado que ambos han sido vinculados con la historia del nazismo y Hitler, lo que ha alimentado ciertos rumores que brindan esa connotación de “oscuridad” y misterio en estos sitios. En este aspecto, y luego de haber realizado un estudio descriptivo y comparativo a través de entrevistas personales y observaciones personales, los resultados mostraron que en ambos establecimientos se pueden distinguir dos atractivos que los incluyen dentro del espectro de turismo oscuro: la historia relacionada al nazismo y la actividad paranormal que se dice que se siente en ellos, puesto que son los fantasmas los que ayudan a relatar la historia del pasado oscuro de estos sitios.Facultad de Ciencias Económica

Host-Pathogen Interactions: Organotypic Cultures to Unravel the Mysteries of the Primordial Hostility among Organisms

Note: In lieu of an abstract, this is an excerpt from the first page. The interaction of humans with microorganisms represents a subtle balance between harm and good [...

Pseudozyma aphidis bloodstream infection in a patient with aggressive lymphoma and a history of intravenous drug use: Case report and review of the literature

Pseudozyma aphidis is an environmental fungus which causes opportunistic infections in immunocompromised patients. Here we report the case of a 54-year-old, intravenous drug user woman, newly diagnosed to have an aggressive lymphoma, who developed a bloodstream infection caused by P. aphidis treated successfully with amphotericin-B therapy. The precise identification was assessed by sequencing. We propose to consider intravenous drug use as a risk factor for invasive infections due to this environmental yeast

Evidence of Common Isolates of Streptococcus agalactiae in Bovines and Humans in Emilia Romagna Region (Northern Italy)

Streptococcus agalactiae (group B Streptococcus, GBS) is one of the most important agents of bovine mastitis and causes remarkable direct and indirect economic losses to the livestock sector. Moreover, this species can cause severe human diseases in susceptible individuals. To investigate the zoonotic potential of S. agalactiae, 203 sympatric isolates from both humans and cattle, isolated in the same time frame (2018) and in the same geographic area (Emilia Romagna region, Northern Italy), were characterized by molecular capsular typing (MCT), pilus island typing (PI), and multi-locus sequence typing (MLST). In addition, antibiotic-resistant phenotypes were investigated. The distribution of the allelic profiles obtained by combining the three genotyping methods (MCT-PI-MLST) resulted in 64 possible genotypes, with greater genetic variability among the human compared to the bovine isolates. Although the combined methods had a high discriminatory power (>96,2%), five genotypes were observed in both species (20,9% of the total isolates). Furthermore, some of these strains shared the same antibiotic resistance profiles. The finding of human and bovine isolates with common genotypes and antibiotic resistance profiles supports the hypothesis of interspecies transmission of S. agalactiae between bovines and humans

Putative role of circulating human papillomavirus DNA in the development of primary squamous cell carcinoma of the middle rectum: A case report

Here we present the case of a patient affected by rectal squamous cell carcinoma in which we demonstrated the presence of Human Papillomavirus (HPV) by a variety of techniques. Collectively, the virus was detected not only in the tumor but also in some regional lymph nodes and in non-neoplastic mucosa of the upper tract of large bowel. By contrast, it was not identifiable in its common sites of entry, namely oral and ano-genital region. We also found HPV DNA in the plasma-derived exosome. Next, by in vitro studies, we confirmed the capability of HPV DNA-positive exosomes, isolated from the supernatant of a HPV DNA positive cell line (CaSki), to transfer its DNA to human colon cancer and normal cell lines. In the stroma nearby the tumor mass we were able to demonstrate the presence of virus DNA in the stromal compartment, supporting its potential to be transferred from epithelial cells to the stromal ones. Thus, this case report favors the notion that human papillomavirus DNA can be vehiculated by exosomes in the blood of neoplastic patients and that it can be transferred, at least in vitro, to normal and neoplastic cells. Furthermore, we showed the presence of viral DNA and RNA in pluripotent stem cells of non-tumor tissue, suggesting that after viral integration (as demonstrated by p16 and RNA in situ hybridization positivity), stem cells might have been activated into cancer stem cells inducing neoplastic transformation of normal tissue through the inactivation of p53, p21, and Rb. It is conceivable that the virus has elicited its oncogenic effect in this specific site and not elsewhere, despite its wide anatomical distribution in the patient, for a local condition of immune suppression, as demonstrated by the increase of T-regulatory (CD4/CD25/FOXP3 positive) and T-exhausted (CD8/PD-1positive) lymphocytes and the M2 polarization (high CD163/CD68 ratio) of macrophages in the neoplastic microenvironment. It is noteworthy that our findings depicted a static picture of a long-lasting dynamic process that might evolve in the development of tumors in other anatomical sites

Evidence of Common Isolates of Streptococcus agalactiae in Bovines and Humans in Emilia Romagna Region (Northern Italy)

Streptococcus agalactiae (group B Streptococcus, GBS) is one of the most important agents of bovine mastitis and causes remarkable direct and indirect economic losses to the livestock sector. Moreover, this species can cause severe human diseases in susceptible individuals. To investigate the zoonotic potential of S. agalactiae, 203 sympatric isolates from both humans and cattle, isolated in the same time frame (2018) and in the same geographic area (Emilia Romagna region, Northern Italy), were characterized by molecular capsular typing (MCT), pilus island typing (PI), and multi-locus sequence typing (MLST). In addition, antibiotic-resistant phenotypes were investigated. The distribution of the allelic profiles obtained by combining the three genotyping methods (MCT-PI-MLST) resulted in 64 possible genotypes, with greater genetic variability among the human compared to the bovine isolates. Although the combined methods had a high discriminatory power (>96,2%), five genotypes were observed in both species (20,9% of the total isolates). Furthermore, some of these strains shared the same antibiotic resistance profiles. The finding of human and bovine isolates with common genotypes and antibiotic resistance profiles supports the hypothesis of interspecies transmission of S. agalactiae between bovines and humans

HPV DNA Associates With Breast Cancer Malignancy and It Is Transferred to Breast Cancer Stromal Cells by Extracellular Vesicles

A causal link between Human Papillomavirus (HPV) and breast cancer (BC) remains controversial. In spite of this, the observation that HPV DNA is over-represented in the Triple Negative (TN) BC has been reported. Here we remark the high prevalence of HPV DNA (44.4%) in aggressive BC subtypes (TN and HER2+) in a population of 273 Italian women and we convey the presence of HPV DNA in the epithelial and stromal compartments by in situ hybridization. As previously reported, we also found that serum derived-extracellular vesicles (EVs) from BC affected patients contain HPV DNA. Interestingly, in one TNBC patient, the same HPV DNA type was detected in the serum-derived EVs, cervical and BC tissue samples. Then, we report that HPV DNA can be transferred by EVs to recipient BC stromal cells that show an activated phenotype (e.g., CD44, IL6 expression) and an enhanced capability to sustain mammospheres (MS) formation. These data suggest that HPV DNA vehiculated by EVs is a potential trigger for BC niche aggressiveness

Putative role of circulating human papillomavirus DNA in the development of primary squamous cell carcinoma of the middle rectum: a case report

Here we present the case of a patient affected by rectal squamous cell carcinoma in which we demonstrated the presence of Human Papillomavirus (HPV) by a variety of techniques. Collectively, the virus was detected not only in the tumor but also in some regional lymph nodes and in non-neoplastic mucosa of the upper tract of large bowel. By contrast, it was not identifiable in its common sites of entry, namely oral and ano-genital region. We also found HPV DNA in the plasma-derived exosome. Next, by in vitro studies, we confirmed the capability of HPV DNA-positive exosomes, isolated from the supernatant of a HPV DNA positive cell line (CaSki), to transfer its DNA to human colon cancer and normal cell lines. In the stroma nearby the tumor mass we were able to demonstrate the presence of virus DNA in the stromal compartment, supporting its potential to be transferred from epithelial cells to the stromal ones. Thus, this case report favors the notion that human papillomavirus DNA can be vehiculated by exosomes in the blood of neoplastic patients and that it can be transferred, at least in vitro, to normal and neoplastic cells. Furthermore, we showed the presence of viral DNA and RNA in pluripotent stem cells of non-tumor tissue, suggesting that after viral integration (as demonstrated by p16 and RNA in situ hybridization positivity), stem cells might have been activated into cancer stem cells inducing neoplastic transformation of normal tissue through the inactivation of p53, p21, and Rb. It is conceivable that the virus has elicited its oncogenic effect in this specific site and not elsewhere, despite its wide anatomical distribution in the patient, for a local condition of immune suppression, as demonstrated by the increase of T-regulatory (CD4/CD25/FOXP3 positive) and T-exhausted (CD8/PD-1positive) lymphocytes and the M2 polarization (high CD163/CD68 ratio) of macrophages in the neoplastic microenvironment. It is noteworthy that our findings depicted a static picture of a long-lasting dynamic process that might evolve in the development of tumors in other anatomical sites. Copyright © 2019 Ambrosio, Vernillo, De Carolis, Carducci, Mundo, Ginori, Rocca, Nardone, Lucenti Fei, Carfagno, Lazzi, Cricca and Tosi