RESUMO
From 2010 to 2015, young (13-24â¯years) Hispanic/Latino gay, bisexual and other men who have sex with men (MSM) experienced the largest increase (18%) in numbers of HIV diagnoses among all racial/ethnic groups. In 2016, the Centers for Disease Control and Prevention (CDC) assembled a team of scientists and public health analysts to develop a programmatic approach for addressing the increasing HIV diagnosis among Hispanic/Latino MSM. The team used a data driven review process, i.e., comprehensive review of surveillance, epidemiologic, and programmatic data, to explore key questions from the literature on factors associated with HIV diagnoses among Hispanic/Latino MSM and to inform the approach. This paper describes key findings from the review and discusses the approach. The approach includes the following activities: increase awareness and support testing by expanding existing campaigns targeting Hispanic/Latino MSM to jurisdictions where diagnoses are increasing; strengthen existing efforts that support treatment as prevention and increase engagement in care and viral suppression among Hispanic/Latino MSM living with HIV and promote prevention, e.g., PrEP uptake and condom use, among Hispanic/Latino MSM who are at high-risk for HIV infection.
Assuntos
Bissexualidade/estatística & dados numéricos , Infecções por HIV , Hispânico ou Latino/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Minorias Sexuais e de Gênero/estatística & dados numéricos , Adolescente , Centers for Disease Control and Prevention, U.S. , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde/métodos , Humanos , Masculino , Sexo Seguro , Estados Unidos , Adulto JovemRESUMO
Six ferrocenecarboxylates with phenyl, 4-(1H-pyrrol-1-yl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl as pendant groups were synthesized and fully characterized by spectroscopic, electrochemical and X-ray diffraction methods. The anti-proliferative activity of these complexes were investigated in hormone dependent MCF-7 breast cancer and MCF-10A normal breast cell lines, to determine the role of the para substituent on the phenoxy pendant group. The 4-fluorophenyl ferrocenecarboxylate is inactive in both cell lines while 4-(1H-pyrrol-1-yl)phenyl ferrocenecarboxylate is highly cytotoxic in both cell lines. 4-chlorophenyl and 4-bromophenyl ferrocenecarboxylates have moderate to good anti-proliferative activity in MCF-7 and low anti-proliferative activity on normal breast cell line, MCF-10A whereas the 4-iodophenyl analog is highly toxic on normal breast cell line. The phenyl ferrocenecarboxylate has proliferative effects on MCF-7 and is inactive in MCF-10A. Docking studies between the complexes and the alpha-estrogen receptor (ERα) were performed to search for key interactions which may explain the anti-proliferative activity of 4-bromophenyl ferrocenecarboxylate. Docking studies suggest the anti-proliferative activity of these ferrocenecarboxylates is attributed to the cytotoxic effects of the ferrocene group and not to anti-estrogenic effects.
RESUMO
On September 6 and 20, 2017, Hurricanes Irma and Maria made landfall as major hurricanes in the US Caribbean Territories of the Virgin Islands and Puerto Rico with devastating effects. As part of the initial response, a public health team (PHT) was initially deployed as part of the US Department of Health and Human Services Incident Response Coordination Team. As a result of increased demands for additional expertise and resources, a public health branch (PHB) was established for coordinating a broad spectrum of public health response activities in support of the affected territories. This paper describes the conceptual framework for organizing these activities; summarizes some key public health activities and roles; outlines partner support and coordination with key agencies; and defines best practices and areas for improvement in disaster future operations.
Assuntos
Tempestades Ciclônicas , Governo Federal , Humanos , Saúde Pública , Porto Rico , Ilhas Virgens AmericanasRESUMO
The possible inclusion complexes of Cp(2)NbCl(2) into calixarenes hosts have been investigated. The existence of a true inclusion complex in the solid state was confirmed by a combination of NMR, ab-initio calculations, thermogravimetric analysis, FTIR, Raman and PXRD. Ab-initio calculations, (1)H NMR solution and solid state (13)C CP MAS NMR results demonstrated that p-sulfonic calix[6]arene does form an inclusion complex with Cp(2)NbCl(2). Raman spectroscopy showed, for the inclusion compound of p-sulfonic calix[6]arene-Cp(2)NbCl(2), a band between 500-850 cm(-1) characteristic of Nb-O vibration. This result suggests that Nb(V) may engage in coordination with the oxygen of the sulfonate group, as part of the host-guest interaction. However, it is important to mention that the niobocene dichloride (Cp(2)NbCl(2)) dissolves in water and undergoes oxidation and hydrolysis processes to yield Cp(2)NbCl(2)(OH) species. For that reason this band does not exclude that the Nb-O band belongs to Cp(2)NbCl(2)(OH). Solid State (13)C CP MAS NMR and solution (1)H NMR spectroscopies together with ab-initio results showed that Cp(2)NbCl(2) is included in the p-sulfonic calix[6]arene cavity, with both Cp rings inside the cavity. In contrast, the solution (1)H NMR results demonstrated that calix[6]arene does not form inclusion complex with Cp(2)NbCl(2) in CDCl(3) solution. Cp(2)NbCl(2) is not included in the calix[6]arene cavity, possibly due to the lack of sulfonate heads which promote Nb-O interactions and assist the inclusion of Cp(2)NbCl(2) into the cavity.
RESUMO
Population-based HIV/AIDS prevalence estimates among men who have sex with men (MSM) have been unavailable, but have implications for effective prevention efforts. Prevalent (living) Florida HIV/AIDS cases reported through 2006 (numerators) were stratified by race/ethnicity and HIV exposure category. Based on previous research, MSM populations were posited as 4-10% of all males aged > or =13 years in each subgroup (denominators). At the estimated lower and upper plausible bounds, respectively, HIV/AIDS prevalence per 100,000 MSM was significantly higher among black (8,292.6-20,731.4); Hispanic (5,599.5-13,998.7); and Asian/Pacific Islander, American Indian or multi-racial (4,942.6-12,356.8) MSM than among white MSM (3,444.9-8,612.3). HIV/AIDS prevalence among all MSM was 13.8-36.9 times that among all other males. Across 19 high-morbidity counties, MSM HIV/AIDS prevalence was highest among those in the most populous counties and highest among blacks. This methodology, adaptable by other states, facilitates calculation of plausible MSM HIV/AIDS prevalence to guide HIV prevention/care community planners and MSM.
Assuntos
Etnicidade/estatística & dados numéricos , Infecções por HIV , Homossexualidade Masculina/estatística & dados numéricos , Doenças Virais Sexualmente Transmissíveis , Adolescente , Adulto , Florida/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/etnologia , Soroprevalência de HIV , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Fatores de Risco , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Doenças Virais Sexualmente Transmissíveis/etnologia , Estatísticas não Paramétricas , Adulto JovemRESUMO
Previously, ferrocene incorporation into the principal structural component of biologically active molecules resulted in enhanced cytotoxic activity against hormone-dependent MCF-7 and T-47D and hormone-independent MDA-MB-231 breast-cancer cell lines. Here we explore 4 new ferrocene estrogen conjugates at position 16 of the estrogen hormone and compared them to the previously reported ferrocene estrogen conjugate 3-ferrocenyl-estra-1,3,5(10)-triene-17ß-ol. The ferrocene conjugate 16-ferrocenylidene-3-hydroxyestra-1,3,5(10)-trien-17-one was synthesized using estrone and ferrocene carboxaldehyde as starting materials in 86% yield. This ferrocene complex was used as the starting material for the synthesis of new ferrocene estrogen conjugates by a short linker group at position 16 of the estrogen hormone. The position and stereochemistry of the linker was verified by its crystal structure. The ferrocene redox behavior, in vitro studies on breast-cancer cell lines and docking studies on ERα are presented. The data suggest that the ferrocene conjugates presented, either at position 3 or 16 of the estrogen, could serve as vectors and can be recognized by ERα as a delivery mechanism into the cell. These new ferrocene hormone conjugates showed cytotoxic activity comparable to that of conventional therapeutic drugs such as tamoxifen and cisplatin.
Assuntos
Antineoplásicos/síntese química , Neoplasias da Mama/tratamento farmacológico , Estrogênios/química , Compostos Ferrosos/síntese química , Metalocenos/síntese química , Aminoácidos/química , Antineoplásicos/metabolismo , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Receptor alfa de Estrogênio/efeitos dos fármacos , Estrogênios/metabolismo , Feminino , Compostos Ferrosos/metabolismo , Humanos , Metalocenos/metabolismo , Simulação de Acoplamento Molecular/métodos , Estrutura Molecular , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
Three ferrocene complexes vectorized with estrogens and vitamin D(2) were synthesized and fully characterized by spectroscopic, electrochemical and computational methods. The synthesis of these esters was accomplished by reacting ferrocenoyl chloride with the corresponding ROH groups (R = ergocalciferol, estradiol, estrone). The cytotoxicity of these complexes in HT-29 colon cancer and MCF-7 breast cancer cell lines was investigated in vitro. Only ferrocenoyl 17ß-hydroxy-estra-1,3,5(10)-trien-3-olate showed good cytotoxic activity in both cell lines, exceeding those of ferrocenium and ferrocene. In MCF-7, ferrocenoyl 17ß-hydroxy-estra-1,3,5(10)-trien-3-olate exhibited remarkable IC(50), in the low micromolar range. This may be attributed to the presence of the estradiol vector. Docking studies between alpha-estrogen receptor ligand binding site and ferrocenoyl 17ß-hydroxy-estra-1,3,5(10)-trien-3-olate revealed some key hydrophobic interactions that might explain the cytotoxic activity of this ester.
Assuntos
Antineoplásicos/química , Ergocalciferóis/química , Estrogênios/química , Compostos Ferrosos/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Ergocalciferóis/síntese química , Ergocalciferóis/farmacologia , Receptor alfa de Estrogênio/metabolismo , Estrogênios/síntese química , Estrogênios/farmacologia , Feminino , Compostos Ferrosos/síntese química , Compostos Ferrosos/farmacologia , Humanos , Metalocenos , Modelos Moleculares , Ligação ProteicaRESUMO
Haemoglobin I from Lucina pectinata is a monomeric protein consisting of 142 amino acids. Its active site contains a peculiar arrangement of phenylalanine residues (PheB10, PheCD1 and PheE11) and a distal Gln at position E7. Active site mutations at positions B10, E7 and E11 were performed in deoxy haemoglobin I (HbI), followed by 10 ns molecular dynamic simulations. The results showed that the mutations induced changes in domains far from the active site producing more flexible structures than the native HbI. Distance analyses revealed that the heme pocket amino acids at positions E7 and B10 are extremely sensitive to any heme pocket residue mutation. The high flexibility observed by the E7 position suggests an important role in the ligand binding kinetics in ferrous HbI, while both positions play a major role in the ligand stabilisation processes. Furthermore, our results showed that E11Phe plays a pivotal role in protein stability.
RESUMO
Surfactant protein C (SP-C) is a membrane-associated protein essential for normal respiration. It has been found that the alpha-helix form of SP-C can undergo, under certain conditions, a transformation from an alpha-helix to a beta-strand conformation that closely resembles amyloid fibrils, which are possible contributors to the pathogenesis of pulmonary alveolar proteinosis. Molecular dynamics simulations using the NAMD2 package were performed for systems containing from one to seven SP-C molecules to study their behavior in water. The results of our simulations show that unfolding of the protein occurs at the amino terminal, and despite this unfolding, no transition from alpha-helix to beta-strand was observed.