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The COVID-19 pandemic was a challenge for the health systems of many countries. In the USA, COVID-19 accentuated political polarity. On the one hand, the defenders of more severe public health measures and, on the other, the advocates of individual rights and freedom above any other consideration. In this study, we analyse whether political partisanship and the political ideology of the different states of the USA have influenced the way COVID-19 was handled in the outbreak. Specifically, we analyse whether the ideology of each state affected the decrease in NO2 levels (used as a proxy for local economic activity and traffic) observed after the pandemic outbreak.

Flooding imposes considerable property risk, and flood maps and flood insurance help prospective and existing property owners assess the potential risk. The US Federal Emergency Management Agency (FEMA) works with local and state officials to produce flood maps. Using these flood maps and demographic attributes, prior research has demonstrated correlations between the percent of a tract identified as disadvantaged and the percent of the tract covered by flood zones. Until recently, FEMA flood maps were the primary assessment tool for flood risk, but First Street Foundation (FSF) has developed its own flood risk tools. This paper compares these alternative flood risk measures as a percent of census tracts in the Southeastern US states and assesses models of the risk measures with demographic, housing, policy and control variables. The main results are first that the FEMA and FSF maps often reveal diverging levels of risk per tract. Second, the demographics correlating with tract-level risk differ markedly for the two risk measures. Third, the results vary considerably by state with more divergence in some states than others, and who is at risk of flooding across the states varies between the FEMA and FSF measures.

Hospitals play a critical role during disasters where they provide critical medical care to disaster victims and help the community to respond more effectively and recover quicker. However, hospitals face risks from the natural environment, such as floor risks. Amid the increasing flood risks due to climate change, it is essential to examine hospitals’ risk exposure. Motivated by this, this paper aims to answer four specific questions related to hospitals in Florida: 1) Are hospitals located in flood zones? 2) What is the relationship between hospital network size and flood risk? 3) To what extent does hospital flood risk vary by hospital attributes? 4) How do hospitals' flood risks differ from other public structures' flood risks? By leveraging two micro-level datasets, we found that approximately 12% of Florida hospitals are in flood zones, and that hospitals’ flood risk is not influenced by hospital network size or hospital attributes. We also find that hospitals are one of the most flood-prone public structures in our sample, raising questions about public infrastructure in flood management. We conclude by offering recommendations for improving hospital resilience to future disasters.

BACKGROUND The novel coronavirus has a high mortality rate (over 1% for patients older than 50 years). This can only be partially ascribed to other comorbidities. A possible explanation is a factor that assures a prompt response to SARS-CoV-2 in younger people, independent from the novelty of the virus itself. A factor is believed to stimulate the immune system and provide immunity against more antigens. The only external stimulation received by healthy people is vaccination (eg, the diphtheria, tetanus, and pertussis [DTP] vaccine). One hypothesis is that vaccination helps develop specific immunity but generates sprouting immunity against antigens in transit. The underlying immunological phenomena are the “bystander effect” and “trained immunity.” The developed immunity gives protection for years until it naturally fades out. After the fifth decade of life, the immune system is almost incompetent when a viral infection occurs, and thus, at this stage, the novel coronavirus can enter the body and cause acute respiratory distress syndrome. OBJECTIVE The initial aim is to demonstrate that blood monocytes and natural killer cells show overpowering hyperactivity, while CD4+ and CD8+ T cells experience impediments to their defensive functions in patients with severe SARS-CoV-2 infection. The secondary objectives are to correlate clinical data and vaccination history with laboratory immune patterns in order to identify protective factors. Subsequently, we are also interested in characterizing the phenotypes and state of the degree of activation of peripheral blood mononuclear cells, including monocytes, natural killer cells, and CD4+ and CD8+ T cells, in healthy subjects vaccinated with the Pfizer vaccine. METHODS Data will be collected using the following 3 approaches: (1) an experimental analysis to study the innate immune response and to identify genetic profiles; (2) an epidemiological analysis to identify the patients’ vaccination history; and (3) a clinical analysis to detect the immunological profile. RESULTS The protocol was approved by the Ethics Committee on April 16, 2020, and the study started on April 27, 2020. As of February 2021, enrollment has been completed. Immunological analysis is ongoing, and we expect to complete this analysis by December 2022. CONCLUSIONS We will recognize different populations of patients, each one with a specific immunological pattern in terms of cytokines, soluble factor serum levels, and immune cell activity. Anamnestic data, such as preceding vaccinations and comorbidities, biochemical findings like lymphocyte immunophenotyping, and pre-existing persistent cytomegalovirus infection, allow depicting the risk profile of severe COVID-19. Proof of the roles of these immunological phenomena in the development of COVID-19 can be the basis for the implementation of therapeutic immunomodulatory treatments. CLINICALTRIAL ClinicalTrials.gov NCT04375176; https://clinicaltrials.gov/ct2/show/NCT04375176 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/29892

The olive mill wastewater polyphenol extracts exhibit chemopreventive properties in lung cancer cell lines, acting on the CXCR4/CXCL12 axis. Lung cancer still is a leading cause of cancer death worldwide. Although avoidance of tobacco use and smoking cessation will have the greatest impact on lung cancer development, (chemo)prevention could prove to be very effective, particularly in high risk individuals. Diverse diet-derived compounds have been reported to exert antioxidant, anti-proliferative and anti-angiogenic effects. Olive oil production involves the generation of an aqueous phase, defined as olive mill wastewater (OMWW), a polluting effluent rich in soluble polyphenols. We established a polyphenol rich, purified extract, from OMWW, that we termed A009. The effect of A009 on cell proliferation was determined by the crystal violet assay, while induction of apoptosis was measured by flow cytometry. The ability of the A009 to regulate the cell migration/invasion axis CXCR4/CXL12 and the production of pro angiogenic factors (VEGF, CXCL8, CCL2), was investigated by flow cytometry. The sprouting assay on Matrigel was used to functional verify the ability of A009 to limit invasive properties. Hydroxytyrosol, the most abundant polyphenols present in our A009, was used as reference molecules in all the assays performed. We found that the A009 limit A549 and H1560 cell proliferation, in a dose and time dependent manner. These effects were associated with induction of apoptosis at 24 and 48 hours of treatment, that was higher in H1650, as compared to A549 cells. The A009 extracts were effective in inhibiting the production of CXCR4 and CXCL12 in both the A549 and H1650 cells, accompanied with reduction in H1650 cell capability to generate invasive sprouts. in a Matrigel layer. Finally, A009 interfere with the production of VEGF, CXCL8 and CCL2 in both the A549 and H1650 cells. Our preliminary results suggest that A009 exhibit promising preventing and interceptive properties on lung cancer cell lines in vitro. Citation Format: Matteo Gallazzi, Marco Festa, Clementina Sansone, Paola Corradino, Douglas Noonan, Adriana Albini. The CXCR4/CXCL12 axis is a target of a polyphenol extract from olive oil processing with potential cancer prevention and interception activities [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 18.

Heritage-based tourism offers intriguing, and often compelling, opportunities for developing industries and markets, as well as policies to promote such developments. Governments have long histories of undertaking policies that affect heritage industries and the cultural resources of a society. These policies may have direct or indirect effects on heritage resources, and these effects may serve to enhance or undermine those industries and resources. Table 18.1 offers some examples for the United States.

It is widely accepted that the tumor microenvironment (TUMIC) plays a major role in cancer and is indispensable for tumor progression. The TUMIC involves many "players" going well beyond the malignant-transformed cells, including stromal, immune, and endothelial cells (ECs). The non-malignant cells can acquire tumor-promoting functions during carcinogenesis. In particular, these cells can "orchestrate" the "symphony" of the angiogenic switch, permitting the creation of new blood vessels that allows rapid expansion and progression toward malignancy. Considerable attention within the context of tumor angiogenesis should focus not only on the ECs, representing a fundamental unit, but also on immune cells and on the inflammatory tumor infiltrate. Immune cells infiltrating tumors typically show a tumor-induced polarization associated with attenuation of anti-tumor functions and generation of pro-tumor activities, among these angiogenesis. Here, we propose a scenario suggesting that the angiogenic switch is an immune switch arising from the pro-angiogenic polarization of immune cells. This view links immunity, inflammation, and angiogenesis to tumor progression. Here, we review the data in the literature and seek to identify the "conductors" of this "orchestra." We also suggest that interrupting the immune ? inflammation ? angiogenesis ? tumor progression process can delay or prevent tumor insurgence and malignant disease. © 2014 Bruno, Pagani, Pulze, Albini, Dallaglio, Noonan and Mortara

Rationale: Thiodiglycolic acid (TDGA) is a urinary metabolite of the oxazaphosphorine class of chemotherapeutics, in particular of ifosfamide. Ifosfamide metabolism generates chloroacetaldehyde (CAA), a toxic compound associated with neurotoxicity, nephrotoxicity, urotoxicity and cardiotoxicity. CAA, in turn, interacts with cellular thiol groups leading to GSH depletion, cell death and generation of thiodiglycolic acid (TDGA), as a final product. TDGA is mainly excreted in the urine. The ability to accurately measure TDGA in urine, therefore, will be a useful way of monitoring exposure to ifosfamide during chemotherapy. Methods: TDGA in urine samples was measured with liquid chromatography coupled to mass spectrometry (LC/MS) by means of a novel Surface-Activated Chemical Ionization-Electrospray (SACI-ESI) or a classical ESI ion source alone. Results: The SACI-ESI and ESI alone based methods for analysis of urinary TDGA were optimized and compared. A strong reduction in matrix effect together with enhanced quantification performances was obtained with the SACI-ESI when compared with ESI. In particular, an increase in quantification precision (from 85 to 95%) and accuracy (from 59 to 90%) were observed, which allowed for optimal detection of TDGA. Conclusions: The LC/SACI-ESI-MS approach provides a very sensitive and quantitative method for the analysis of TDGA. Thanks to the enhancement in sensitivity and matrix effect reduction, the SACI-ESI source enables the use of a relatively low-cost ion-trap mass spectrometer in the analysis of this toxicity biomarker in urine. Due to these characteristics, this approach would constitute an invaluable tool in the clinical laboratory, for measuring TDGA and other toxicity related biomarkers of chemotherapy with proper sensitivity and accuracy.

We survey concert-goers during the season and gather revealed preference and ex-ante stated preference data. We then survey the same concert goers after the season and gather additional ex-post revealed preference data. Comparing ex-ante stated preference data to the ex-post revealed preference data we find respondents overstate their concert attendance behavior. An ex-ante revealed-stated preference demand model with a stated preference adjustment predicts the revealed preference concerts accurately. Key Words: Revealed preference, stated preference, criterion validity, predictive validity

The retinoblastoma gene (RB1) is frequently deleted or mutated in many tumor types and in all cases of retinoblastoma. Apart from its role in regulation of the cell cycle, the RB1 gene product (p110RB1) appears to be involved in control of differentiation. Malignant metastatic cells show many properties of poorly differentiated cells, and are highly invasive in vitro and in vivo. We have transfected the human RB1 cDNA in an expression vector under the control of the beta-actin promoter into B16F10 murine melanoma cells. These cells highly overexpress RB1 mRNA and the p110RB1 product, show reduced growth rate and increased melanogenesis in vitro. Vector control transfectants showed no alteration of invasiveness. The p110RB1 over-expressing cells also had a reduced capacity to migrate and invade through an artificial basement membrane, key characteristics of metastatic cells. When injected into nude mice, the p110RB1 over-expressing cells showed reduced tumor growth and reduced metastatic potential. The few metastasis observed were predominantly melanotic. These data indicate that RB1 gene expression is involved in melanoma cell differentiation and plays a role in downregulation of migration, invasion and metastatic potential of these cells.

Gene transfer delivery of endogenous angiogenesis inhibitors such as angiostatin would circumvent problems associated with long-term administration of proteins. Kaposi's sarcoma (KS), a highly vascular neoplasm, is an excellent model for studying tumor angiogenesis and antiangiogenic agent efficacy. We investigated the effects of angiostatin gene transfer in in vitro and in vivo models of KS-induced neovascularization and tumor growth. A eukaryotic expression plasmid and a Moloney leukemia virus-based retroviral vector for expression of murine angiostatin were generated harboring the angiostatin cDNA with cleavable leader signals under the control of either the strong cytomegalovirus promoter/enhancer or the Moloney leukemia virus long terminal repeat. Angiostatin secretion was confirmed by radioimmunoprecipitation and Western blot analysis. Supernatants of angiostatin-transfected cells inhibited endothelial cell migration in vitro. Stable gene transfer of the angiostatin cDNA by retroviral vectors in KS-IMM cells resulted in sustained angiostatin expression and delayed tumor growth in nude mice, which was associated with reduced vascularization. These findings suggest that gene therapy with angiostatin might be useful for treatment of KS and possibly other highly angiogenic tumors.

Mutations that affect oncosuppressor genes contribute to transformed phenotype. The recessive characteristics of these genes require mutations on both alleles. For this reason alterations of the oncosuppressor genes can be transmitted with the germ line. In this review we focus on mechanisms of inactivation of the retinoblastoma gene and p53. The products of these genes are nuclear phosphoproteins involved in controlling cellular proliferation. Inactivated Rb genes have been found in several tumor types. The phosphorylation of the Rb gene product, p105Rb, is regulated by cyclin-dependent kinases in accordance with the cell cycle. Hypophosphorylated wild-type p105Rb is tightly bound to the nuclear matrix and seems to be critical in inhibition of cellular proliferation. Hyperphosphorylation is a physiological mechanism of inactivation of p105Rb. The p53 gene product is a transcriptional factor that blocks the progression of cell division. Mutations in the p53 gene are frequently found in many human cancers and are localized in the highly conserved region of the gene. The protein product of the mutated gene looses its function as a negative regulator of cellular proliferation. The wild-type protein can also be inactivated by forming stable complex with a mutated p53 protein or with the SV large T antigen.

This review highlights the current strategies being employed towards gene therapy of cancer. Conceptually, the most simple diseases to treat with gene therapy would be monogenic inherited diseases, such as hemophilia. However, the vast majority of current gene therapy trials are for treatment of cancer patients, due to the recognition of gene alterations in cancer and the critical need for improvement of cancer therapy. Gene-based therapies for cancer in clinical trials include strategies that involve immuno-therapy, induction of drug sensitivity in tumor cells or resistance to chemotherapy of critical host tissues, and compensation for oncosuppressor loss or ablation of oncogenes. Two broad approaches have been used to deliver DNA to cells, a series of viral vectors and the use of plasmid DNA vectors, which have different advantages with regard to efficiency of gene transfer, ease of production and safety. Examined objectively, many of the first studies in cancer gene therapy clinical trials have provided information of critical importance for the design of more efficient second-generation protocols. Gene therapy represents one of the most important developments in oncology, however, before this can be realized as standard treatment the technical problems of gene delivery and safety must be overcome. Here we focus on methods and strategies used to achieve cancer gene therapy and the current clinical trials.

The RNASET2 gene, mapped in 6q27, was previously found to exert control of tumorigenesis in an ovarian cancer system. We present here results indicating a similar control in a melanoma cancer model. Thus, this gene is most likely involved in a common general pathway of tumorigenesis. Moreover, its antitumorigenic activity is manifested in vivo but not in vitro, suggesting that this gene belongs to the growing category of tumor antagonizing/malignancy suppressor genes. A possible role of RNASET2 in the activation of a senescence program, whose responsible locus was mapped in the same chromosomal 6q27 region, seems to be inconsistent with our data.