Cripto-1 as a novel therapeutic target for triple negative breast cancer

Triple-negative breast cancer (TNBC) presents the poorest prognosis among the breast cancer subtypes and no current standard therapy. Here, we performed an in-depth molecular analysis of a mouse model that establishes spontaneous lung metastasis from JygMC(A) cells. These primary tumors resembled the triple-negative breast cancer (TNBC) both phenotypically and molecularly. Morphologically, primary tumors presented both epithelial and spindle-like cells but displayed only adenocarcinoma-like features in lung parenchyma. The use of laser-capture microdissection combined with Nanostring mRNA and microRNA analysis revealed overexpression of either epithelial and miRNA-200 family or mesenchymal markers in adenocarcinoma and mesenchymal regions, respectively. Cripto-1, an embryonic stem cell marker, was present in spindle-like areas and its promoter showed activity in primary tumors. Cripto-1 knockout by the CRISPR-Cas9 system inhibited tumor growth and pulmonary metastasis. Our findings show characterization of a novel mouse model that mimics the TNBC and reveal Cripto-1 as a TNBC target hence may offer alternative treatment strategies for TNBC.     

Deportation experiences of women who inject drugs in Tijuana, Mexico

Deportation from the United States for drug offenses is common, yet the consequences of deportation for women drug users are poorly documented. In 2008, in Tijuana, Mexico, we conducted an exploratory qualitative study of migration, deportation, and drug abuse by interviewing 12 Mexican injection-drug-using women reporting U.S. deportation. Women reported heavy drug use before and after deportation, but greater financial instability and physical danger following deportation than when in the United States. We identified an unmet need for health and social services among deported drug-using women, including HIV prevention, drug treatment, physical and mental health services, and vocational training. Binational coordination is needed to help deported women resettle in Mexico.     

Evaluation of tropical water sources and mollusks in southern Brazil using microbiological, biochemical, and chemical parameters

Florianópolis, a city located in the Santa Catarina State in southern Brazil, is the national leading producer of bivalve mollusks. The quality of bivalve mollusks is closely related to the sanitary conditions of surrounding waters where they are cultivated. Presently, cultivation areas receive large amounts of effluents derived mainly from treated and non-treated domestic, rural, and urban sewage. This contributes to the contamination of mollusks with trace metals, pesticides, other organic compounds, and human pathogens such as viruses, bacteria, and protozoan. The aim of this study was to perform a thorough diagnosis of the shellfish growing areas in Florianópolis, on the coast of Santa Catarina. The contamination levels of seawater, sediments, and oysters were evaluated for their microbiological, biochemical, and chemical parameters at five sea sites in Florianópolis, namely three regular oyster cultivation areas (Sites 1, 2, and oyster supplier), a polluted site (Site 3), and a heavily polluted site (Site 4). Samples were evaluated at day zero and after 14 days. Seawater and sediment samples were collected just once, at the end of the experiment. Antioxidant defenses, which may occur in contaminated environments in response to the increased production of reactive oxygen species (ROS) by organisms, were analyzed in oysters, as well as organic compounds (in oysters and sediment samples) and microbiological contamination (in oysters and seawater samples). The results showed the presence of the following contaminants: fecal coliforms in seawater samples (four sites), human adenovirus (all sites), human noroviruses GI and GII (two sites), Hepatitis A viruses (one site), JC Polyomavirus in an oyster sample from the oyster supplier, Giardia duodenalis cysts, and Cryptosporidium sp oocysts (one site). Among organochlorine pesticides, only DDT (dichlorodiphenyltrichloroethane) and HCH (hexachlorocyclohexane) were detected in some sediment and oysters samples in very low levels; site 4 had the highest concentrations of total aliphatic hydrocarbons, PAHs, and linear alkylbenzenes (LABs) found either in oysters or in sediment samples. The major concentration of fecal sterol coprostanol was found at site 4, followed by site 3. After 14 days of allocation in the four selected sites, there was a significant difference in the enzymes analyzed at the monitored spots. The detection of different contaminants in oysters, seawater, and sediment samples in the present study shows the impact untreated or inadequately treated effluents have on coastal areas. These results highlight the need for public investment in adequate wastewater treatment and adequate treatment of oysters, ensuring safe areas for shellfish production as well as healthier bivalve mollusks for consumption.     

Immunoarchitecture of the human spleen

New immunochemical staining techniques reveal key topographic aspects of splenic immune function. Distinct compartmentalization of B and T cells and lymphocytic subtypes within the white and red pulp of the human spleen provide a morphologic basis for division of labor in the immune response.     

Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication

OBJECTIVE: Mechanisms underlying mucosal transmission of HIV-1 are incompletely understood. We describe the anti-HIV-1 activity of human beta-defensins (hBD), small cationic molecules that provide protection at mucosal surfaces. METHODS AND RESULTS: HIV-1 induced expression of hBD-2 and -3 mRNA (but not that of hBD-1) 4- to 78-fold, respectively, above baseline in normal human oral epithelial cells. HIV-1 failed to infect these cells, even after 5 days of exposure. Recombinant hBD-1 had no antiviral activity, while rhBD-2 and rhBD-3 showed concentration-dependent inhibition of HIV-1 replication without cellular toxicity. Inhibition was greater against CXCR4-tropic than against the CCR5-tropic HIV-1 isolates. hBD-2 and hBD-3 induced an irreversible effect on virion infectivity, with electron microscopy confirming binding of hBDs to viral particles. Finally, hBD-2 and -3 induced downmodulation of the HIV-1 coreceptor CXCR4 (but not CCR5) in peripheral blood mononuclear cells and T lymphocytic cells as shown by confocal microscopy and flow cytometry. CONCLUSIONS: This study shows for the first time that HIV-1 induces beta-defensin expression in human oral epithelial cells and that beta-defensins block HIV-1 replication via a direct interaction with virions and through modulation of the CXCR4 coreceptor. These properties may be exploited as strategies for mucosal protection against HIV-1 transmission.     

Temporal and spatial patterns of malaria reinfection in northeastern Venezuela

We stratified the risk of malaria transmission (Plasmodium vivax) in 35 villages along a coastal range in northeastern Venezuela (51 km2) where the main vector is the mosquito Anopheles aquasalis. After 20 years without local malaria transmission, reinfection of the entire area occurred from May to December 1985 by local (continuous) and jump (discontinuous) dispersal. Epidemiologic, environmental, and vector variables were investigated with the aid of a Geographic Information System. Risk factors for malaria transmission were human population density, proximity to pre-adult mosquito habitats (< 500 m), and the number of pre-adult habitats nearby. Most inhabitants, immature mosquito habitats, and malaria cases were located at low elevations and on gentle slopes. High prevalence of malaria during the dry seasons was associated with the presence of permanent bodies of water containing An. aquasalis. Occurrence of a La Ni?a event in 1988 (wet and cool phase of the El Ni?o Southern Oscillation) triggered malaria transmission to unusually high levels, consolidating infection in the area, and rendering traditional control efforts useless. We recommend tracking malaria persistence per village and associated risk factors as methods to reduce the cost of malaria control programs.     

Impact of malocclusion on affective/romantic relationships among young adults

Objective: To evaluate the extent to which different types of malocclusion influence the development of affective/romantic relationships among young adults of both sexes.Materials and Methods: A cross-sectional study was conducted with 360 men and women ranging in age from 18 years to 25 years. Criteria for exclusion from the sample were the following: participants could not be married, visually impaired, or students of a higher education course in the area of health. In this study, images of young adult men and women in the same age range as that of the evaluators were used. These images were manipulated to create different types of malocclusion: diastema, open bite, crowding, gingival (or gummy) smile, little exposure of teeth. Six groups of images containing six images each were formed and consisted of two experimental images (digitally manipulated) and four control images. These images were provided to the participants, who evaluated them by means of a questionnaire and a visual analog scale. The Kruskal-Wallis, Mann-Whitney, chi-square, and Fisher exact tests were used for data analysis.Results: All malocclusions had a negative impact on acceptance by the evaluators for the purposes of affective/romantic relationships, with crowding being the type of malocclusion that led to the highest level of rejection (P < .01).Conclusion: Malocclusions have a negative influence on the development of affective/romantic relationships among young adults. Individuals with good occlusion are seen in a more positive light, from the perspective of affective life.     

Hospital readmission after management of appendicitis at freestanding children's hospitals: contemporary trends and financial implications

IntroductionThe purpose of this study was to characterize epidemiologic trends and cost implications of hospital readmission after treatment of pediatric appendicitis.MethodsWe conducted a 5-year retrospective cohort analysis of 30-day readmission rates for 52,054 patients admitted with appendicitis at 38 children's hospitals participating in the Pediatric Health Information System database. Patients were categorized as “uncomplicated” (postoperative length of stay [LOS] ≤2 days) or “complicated” (LOS ≥3 days and ≥4 consecutive days of antibiotics) and analyzed for demographic data, treatment received during the index admission, readmission rates, and excess LOS and hospital-related costs attributable to readmission encounters.ResultsThe aggregate 30-day readmission rate was 8.7%, and this varied significantly by disease severity and management approach (uncomplicated appendectomy, 5.6%; complicated appendectomy, 12.8%; drainage, 22.6%; antibiotics only, 24.6%; P < .0001). The median hospital cost per case attributable to readmission was $3401 (reflecting a 44% relative increase in cumulative treatment-related cost), and this varied significantly by disease severity and management approach (uncomplicated appendectomy, $1946 [31% relative increase]; complicated appendectomy, $6524 [53% increase]; drainage, $6827 [48% increase]; antibiotics only, $5835 [58% increase]; P < .0001).ConclusionIn freestanding children's hospitals, readmission after treatment of pediatric appendicitis is a relatively common and costly occurrence. Collaborative efforts are needed to characterize patient, treatment, and hospital-related risk factors as a basis for developing preventative strategies.     

Application of Plastic Wastes in Construction Materials: A Review Using the Concept of Life-Cycle Assessment in the Context of Recent Research for Future Perspectives

The urbanization process contributes to the growth of solid waste generation and causes an increase in environmental impacts and failures in the management of solid waste. The number of dumps is a concern due to the limited implementation and safe disposal of this waste. The interest in sustainable techniques has been growing in relation to waste management, which is largely absorbed by the civil construction sector. This work aimed to review plastic waste, especially polyethylene terephthalate (PET), that can be incorporated with construction materials, such as concrete, mortars, asphalt mixtures, and paving. The use of life-cycle assessment (LCA) is related, as a tool that allows the sustainability of products and processes to be enhanced in the long term. After analyzing the recent literature, it was identified that studies related to plastic wastes in construction materials concentrate sustainability around the alternative destination of waste. Since the plastic waste from different production chains are obtained, it was possible to affirm the need for a broader assessment, such as the LCA, providing greater quantification of data making the alternative processes and products more sustainable. The study contributes to enhance sustainability in alternative building materials through LCA.