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1.
J Interpers Violence ; : 8862605241245372, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666670

RESUMO

Culturally sensitive approaches in sexual violence prevention (SVP) refer to the proactive measures and strategies designed to address unique cultural circumstances impacting SVP. It focuses on fostering a culture of consent, respect, and equity and creating a safe and supportive environment for all individuals regardless of your identity. Increasing cultural diversity on university campuses poses unique challenges in preventing sexual violence (SV). Cultural diversity brings different perspectives, norms, and values regarding sex, sexuality, and gender roles. It can contribute to varying understandings of consent, differing attitudes toward SV, and diverse victimization experiences. These differences can create barriers to effectively addressing and preventing SV. The multiphase Culture and Perspectives on Sexual Assault Policy study, conducted at four universities in Eastern Canada, employed a qualitative research design involving focus groups with culturally diverse student participants. The findings revealed a strong desire for more education on sex, sexuality, SVP, and the intersections of culture. Additionally, the findings emphasize the importance of education and comprehensive prevention efforts that consider cultural differences, challenge gender normativity, debunk rape myths, and address the shame and secrecy associated with experiencing SV. These insights have significant implications for promoting a sense of community ownership, increasing the effectiveness and sustainability of prevention efforts, and helping to create a campus environment where all students feel safe, supported, and valued.

3.
J Mens Stud ; 31(3): 371-395, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37693227

RESUMO

Culture and Perspectives on Sexual Assault Policy was a qualitative, focus-group study conducted at four Canadian universities to gather culturally diverse student perspectives on university sexual violence or sexual assault policies and services. This article highlights two categories of dialectical tension expressed during several male focus groups. The Wrongful Blame Dialectic involved tension between anxieties about wrongful accusations and opposition to victim-blaming. Perceived risk of wrongful accusations was often linked to racism or ethnocentrism. The Male Victim Denial/Recognition Dialectic involved tension between denial and recognition of male sexual victimization. Male participants felt more vulnerable to wrongful accusation than to sexual violence. They felt more likely to be blamed and disbelieved, whether as respondents or complainants.

4.
Harmful Algae ; 127: 102476, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37544676

RESUMO

Cyanobacteria can dominate the algal community in wastewater ponds, which can lead to the production of cyanotoxins and their release into the environment. We applied traditional and molecular techniques to identify cyanotoxin hazards and high-risk periods in a tropical wastewater treatment system. Potentially toxic cyanobacteria were identified by microscopy and amplicon sequencing over the course of a year. Toxin gene levels were monitored and compared to toxin production to identify likely toxin producing species and high-risk periods. Cyanobacteria were persistent in the effluent year-round, with Planktothrix and Microcystis the most abundant genera; Microcystis could not be resolved beyond genus using amplicon sequencing, but M. flos-aquae was identified as a dominant species by microscopy. Microcystin toxin was detected for the first time in treated effluent at the beginning of the wet season (December 2018), which correlated with an increase in Microcystis amplicon sequence abundance and elevated microcystin toxin gene (mcyE/ndaF) levels. Concomitantly, microscopy data showed an increase in M. flos-aquae but not M. aeruginosa. These data informed a refined sampling campaign in 2019 and results showed a strong correlation between mcyE/ndaF gene abundance, microcystin toxin levels and Microcystis amplicon sequence abundance. Microscopy data showed that in addition to M. flos-aquae, M. aeruginosa was also abundant in February and March 2019, with highest levels coinciding with toxin detection and toxin gene levels. M. aeruginosa was the most abundant Microcystis species detected in selected treated effluent samples by metagenomics analysis, and elevated levels coincided with toxin production. All microcystin genes in the biosynthesis pathway were detected, but microcystin genes from Planktothrix agardhii were not detected. Gene toxin assays were successfully used to predict microcystin production in this wastewater system. Changes in amplicon sequence relative abundance were a useful indicator of changes in the cyanobacterial community. We found that metagenomics was useful not just for identifying the most abundant Microcystis species, but the detection of microcystin biosynthesis genes helped confirm this genus as the most likely toxin producer in this system. We recommend toxin gene testing for the early detection of potential toxin producing cyanobacteria to manage the risk of toxicity and allow the implementation of risk management strategies.


Assuntos
Cianobactérias , Microcystis , Microcistinas/análise , Lagoas , Águas Residuárias , Cianobactérias/metabolismo , Microcystis/genética , Microcystis/metabolismo
5.
Environ Res ; 181: 108921, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31757407

RESUMO

Elevated faecal indicator levels in beaches around Darwin Harbour including near effluent outfalls have led to concerns about the safety of popular, locally harvested aquatic foods. To address these concerns, the impact of treated effluent discharge on the microbial quality of aquatic foods was assessed using culture-based and molecular tools. Seawater, shellfish (mangrove snails Telescopium and Nerita balteata, the local black lip oyster Saccostrea cucullata) and mud crabs (Scylla serrata) were collected from 13 sites close (impacted) and distal (reference) to two effluent discharge locations, in creeks and coastal areas. Sampling occurred over two dry seasons and one wet season. E. coli, typical sewage related pathogens, Salmonella and norovirus, and the molecular faecal marker Bacteroides, as well as naturally occurring marine bacteria, Vibrio parahaemolyticus and Vibrio vulnificus were tested in biota. E. coli and faecal coliforms were measured in water in water. The highest concentration of faecal coliforms in water was from the Buffalo Creek discharge site. At sites located in creeks including reference creeks, the highest concentrations of faecal coliforms in water were measured in the wet season compared to the dry season, whereas in coastal sites, no or only few (<10) faecal coliforms were detected. E. coli concentrations in both snail species were significantly higher in the wet season compared to the dry season (P < 0.0001) at both the treated effluent discharge sites and reference sites with some samples exceeding the acceptable Australian and New Zealand Food Standards (ANZFS) level based on E. coli levels in bivalves. E. coli concentrations in all of the S. cucullata samples were either below the detection limit or below the ANZFS limit for E. coli. No E. coli exceedances occurred in cooked mud crabs although low E. coli levels were measured in 3 cooked mud crab samples. Only one shellfish sample (T. telescopium) was positive for Salmonella. Norovirus and Bacteroides were not detected in any of the shellfish samples tested. V. parahaemolyticus and V. vulnificus were significantly more prevalent in shellfish samples during the wet season. Twelve virulent strains of V. parahaemolyticus were detected in T. telescopium and two in N. balteata. There was no significant difference in V. parahaemolyticus prevalence between sites. V. parahaemolyticus was detected in cooked S. serrata samples from three sites in the wet season and once in the 2016 dry season. V. vulnificus was detected in both T. telescopium and N. balteata, but not in any of the S. cucullata samples. One cooked crab meat sample from a reference site was positive for V. vulnificus. The prevalence of V. vulnificus was significantly higher at the reference sites compared to the discharge or potential impact sites. The lack of correlation between E. coli and targeted faecal pathogens in biota confirm that traditional faecal markers are not suitable surrogates for faecal pollution, at least not in the tropics. The higher prevalence of E. coli, V. parahaemolyticus and V. vulnificus in biota during the wet season compared to the dry season irrespective of treated sewage influence suggests that marine snails should not be harvested and consumed from creeks during the wet season. Any future aquaculture involving shellfish should consider these data when developing appropriate shellfish quality assurance protocols and for making decisions on where to situate farms.


Assuntos
Estuários , Ostreidae , Frutos do Mar/microbiologia , Animais , Austrália , Escherichia coli
6.
BMC Genet ; 19(1): 16, 2018 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-29566674

RESUMO

BACKGROUND: Syringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance. RESULTS: We identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development. CONCLUSIONS: We identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse diameter. The locus on CFA22 was significantly associated to SM secondary to CM in the CKCS dog breed strengthening its candidacy for this disease. This study will provide an entry point for identification of the genetic factors predisposing to this condition and its underlying pathogenic mechanisms.


Assuntos
Malformação de Arnold-Chiari/veterinária , Doenças do Cão/genética , Loci Gênicos , Siringomielia/veterinária , Animais , Malformação de Arnold-Chiari/genética , Fossa Craniana Posterior/patologia , Cães , Estudo de Associação Genômica Ampla/veterinária , Haplótipos , Imageamento por Ressonância Magnética/veterinária , Dor/genética , Dor/veterinária , Polimorfismo de Nucleotídeo Único , Siringomielia/genética
7.
Front Microbiol ; 8: 1313, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28751882

RESUMO

Darwin Harbour in northern Australia is an estuary in the wet-dry tropics subject to increasing urbanization with localized water quality degradation due to increased nutrient loads from urban runoff and treated sewage effluent. Tropical estuaries are poorly studied compared to temperate systems and little is known about the microbial community-level response to nutrients. We aimed to examine the spatial and temporal patterns of the bacterial community and its association with abiotic factors. Since Darwin Harbour is macrotidal with strong seasonal patterns and mixing, we sought to determine if a human impact signal was discernible in the microbiota despite the strong hydrodynamic forces. Adopting a single impact-double reference design, we investigated the bacterial community using next-generation sequencing of the 16S rRNA gene from water and sediment from reference creeks and creeks affected by effluent and urban runoff. Samples were collected over two years during neap and spring tides, in the dry and wet seasons. Temporal drivers, namely seasons and tides had the strongest relationship to the water microbiota, reflecting the macrotidal nature of the estuary and its location in the wet-dry tropics. The neap-tide water microbiota provided the clearest spatial resolution while the sediment microbiota reflected current and past water conditions. Differences in patterns of the microbiota between different parts of the harbor reflected the harbor's complex hydrodynamics and bathymetry. Despite these variations, a microbial signature was discernible relating to specific effluent sources and urban runoff, and the composite of nutrient levels accounted for the major part of the explained variation in the microbiota followed by salinity. Our results confirm an overall good water quality but they also reflect the extent of some hypereutrophic areas. Our results show that the microbiota is a sensitive indicator to assess ecosystem health even in this dynamic and complex ecosystem.

8.
Environ Monit Assess ; 189(1): 36, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28013475

RESUMO

Stable nitrogen isotope ratios are routinely used to trace the dispersion and assimilation of wastewater-derived N in receiving environments, but few isotope studies have investigated wastewater treatment plants and ponds themselves. An improved understanding of N isotope compositions in effluent will help assess treatment plant processes and performance and will help trace sources of excess nutrients in receiving environments. Here, we assess N budgets and treatment processes in seven wastewater treatment plants and wastewater stabilisation ponds in northern Australia based on concentrations and isotope ratios of N in effluent. We show that δ15N values in effluent are linked to treatment type, effectiveness of conversion of ammonia and levels of gaseous N emissions. These relationships suggest that N isotope monitoring of wastewater treatment plants and ponds can provide an integrated assessment of treatment performance and gaseous N emissions on a pond- or plant-wide scale that is not readily available through other methods. Our findings further imply that monitoring N isotope ratios in receiving environments cannot be assumed to be universally effective as their sensitivity to uptake of wastewater-derived N will vary with the characteristics of individual treatment systems. Paradoxically, N isotope monitoring is less effective where treatment systems are functioning poorly and where monitoring needs are the greatest.


Assuntos
Nitrogênio/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise , Amônia/análise , Austrália , Meio Ambiente , Monitoramento Ambiental/métodos , Nitrogênio/química , Isótopos de Nitrogênio/análise , Isótopos de Nitrogênio/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Purificação da Água/métodos
9.
Life Sci Soc Policy ; 11: 10, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26412243

RESUMO

Innovations in information technologies have facilitated the development of new styles of research networks and forms of governance. This is evident in genomics where increasingly, research is carried out by large, interdisciplinary consortia focussing on a specific research endeavour. The UK10K project is an example of a human genomics consortium funded to provide insights into the genomics of rare conditions, and establish a community resource from generated sequence data. To achieve its objectives according to the agreed timetable, the UK10K project established an internal governance system to expedite the research and to deal with the complex issues that arose. The project's governance structure exemplifies a new form of network governance called 'pop-up' governance. 'Pop-up' because: it was put together quickly, existed for a specific period, was designed for a specific purpose, and was dismantled easily on project completion. In this paper, we use UK10K to describe how 'pop-up' governance works on the ground and how relational, hierarchical and contractual governance mechanisms are used in this new form of network governance.


Assuntos
Pesquisa Biomédica/organização & administração , Governança Clínica/organização & administração , Genômica , Disseminação de Informação/legislação & jurisprudência , Gestão da Informação/organização & administração , Eficiência Organizacional , Humanos , Reino Unido
10.
Environ Sci Process Impacts ; 17(3): 525-32, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25592874

RESUMO

A nation-wide passive air sampling campaign recorded concentrations of persistent organic pollutants in Australia's atmosphere in 2012. XAD-based passive air samplers were deployed for one year at 15 sampling sites located in remote/background, agricultural and semi-urban and urban areas across the continent. Concentrations of 47 polychlorinated biphenyls ranged from 0.73 to 72 pg m(-3) (median of 8.9 pg m(-3)) and were consistently higher at urban sites. The toxic equivalent concentration for the sum of 12 dioxin-like PCBs was low, ranging from below detection limits to 0.24 fg m(-3) (median of 0.0086 fg m(-3)). Overall, the levels of polychlorinated biphenyls in Australia were among the lowest reported globally to date. Among the organochlorine pesticides, hexachlorobenzene had the highest (median of 41 pg m(-3)) and most uniform concentration (with a ratio between highest and lowest value ∼5). Bushfires may be responsible for atmospheric hexachlorobenzene levels in Australia that exceeded Southern Hemispheric baseline levels by a factor of ∼4. Organochlorine pesticide concentrations generally increased from remote/background and agricultural sites to urban sites, except for high concentrations of α-endosulfan and DDTs at specific agricultural sites. Concentrations of heptachlor (0.47-210 pg m(-3)), dieldrin (ND-160 pg m(-3)) and trans- and cis-chlordanes (0.83-180 pg m(-3), sum of) in Australian air were among the highest reported globally to date, whereas those of DDT and its metabolites (ND-160 pg m(-3), sum of), α-, ß-, γ- and δ-hexachlorocyclohexane (ND-6.7 pg m(-3), sum of) and α-endosulfan (ND-27 pg m(-3)) were among the lowest.


Assuntos
Poluentes Atmosféricos/análise , Atmosfera/química , Monitoramento Ambiental , Poluição do Ar/estatística & dados numéricos , Austrália , Endossulfano , Hexaclorocicloexano , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Bifenilos Policlorados/análise
11.
Cell Commun Signal ; 12: 5, 2014 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-24410844

RESUMO

BACKGROUND: Dual oxidase maturation factor 1 (DUOXA1) has been associated with the maturation of the reactive oxygen species (ROS) producing enzyme, dual oxidase 1 (DUOX1) in the adult thyroid. However, ROS have also been implicated in the development of several tissues. We found that activated muscle satellite cells and primary myoblasts isolated from mice express robust levels of DUOXA1 and that its levels are altered as cells differentiate. RESULTS: To determine whether DUOXA1 levels affect muscle differentiation, we used an adenoviral construct (pCMV5-DUOXA1-GFP) to drive constitutive overexpression of this protein in primary myoblasts. High levels of DUOXA1 throughout myogenesis resulted in enhanced H2O2 production, fusion defects, reduced expression of early (myogenin) and late (myosin heavy chain) markers of differentiation, and elevated levels of apoptosis compared to control cells infected with an empty adenoviral vector (pCMV5-GFP). DUOXA1 knockdown (using a DUOXA1 shRNA construct) resulted in enhanced differentiation compared to cells subjected to a control shRNA, and subjecting DUOXA1 overexpressing cells to siRNAs targeting DUOX1 or apoptosis signal-regulating kinase 1 (ASK1) rescued the phenotype. CONCLUSIONS: This study represents the first to demonstrate the importance of DUOXA1 in skeletal muscle myoblasts and that DUOXA1 overexpression in muscle stem cells induces apoptosis and inhibits differentiation through DUOX1 and ASK1.


Assuntos
Diferenciação Celular , Mioblastos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Animais , Apoptose , Células Cultivadas , Oxidases Duais , MAP Quinase Quinase Quinase 5/genética , MAP Quinase Quinase Quinase 5/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mioblastos/citologia , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Células Satélites de Músculo Esquelético/citologia
12.
Eur J Hum Genet ; 22(9): 1100-4, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24424120

RESUMO

Recent advances in sequencing technology allow data on the human genome to be generated more quickly and in greater detail than ever before. Such detail includes findings that may be of significance to the health of the research participant involved. Although research studies generally do not feed back information on clinically significant findings (CSFs) to participants, this stance is increasingly being questioned. There may be difficulties and risks in feeding clinically significant information back to research participants, however, the UK10K consortium sought to address these by creating a detailed management pathway. This was not intended to create any obligation upon the researchers to feed back any CSFs they discovered. Instead, it provides a mechanism to ensure that any such findings can be passed on to the participant where appropriate. This paper describes this mechanism and the specific criteria, which must be fulfilled in order for a finding and participant to qualify for feedback. This mechanism could be used by future research consortia, and may also assist in the development of sound principles for dealing with CSFs.


Assuntos
Genética Médica/organização & administração , Achados Incidentais , Disseminação de Informação , Análise de Sequência de DNA/ética , Pesquisa Biomédica/organização & administração , Genética Médica/métodos , Gestão da Informação/organização & administração , Reino Unido
13.
Appl Nurs Res ; 27(2): 104-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23993745

RESUMO

AIM: The study describes the genesis of the University of Alabama at Birmingham's Healthcare Leadership Academy (HLA), highlights the HLA's outcomes, discloses how the HLA has changed, and delineates future directions for academic health center (AHC) interprofessional leadership training. BACKGROUND: While interprofessional training is recognized as an important component of the professional education for health professionals, AHCs have not focused on interprofessional leadership training to prepare future AHC leaders. As professional bureaucracies, AHCs require leadership distributed across different professions; these leaders not only should be technical experts, but also skilled at interprofessional teamwork and collaborative governance. METHODS: The HLA is examined using the case method, which is supplemented with a descriptive analysis of program evaluation data and outcomes. RESULTS: The HLA has created a networked community of AHC leaders; the HLA's interprofessional team projects foster innovative problem solving. CONCLUSIONS: Interprofessional leadership training expands individuals' networks and has multiple organizational benefits.


Assuntos
Centros Médicos Acadêmicos , Atenção à Saúde , Relações Interprofissionais , Liderança , Modelos Educacionais , Modelos de Enfermagem , Desenvolvimento de Pessoal , Alabama , Currículo , Feminino , Humanos , Masculino , Desenvolvimento de Pessoal/métodos , Inquéritos e Questionários , Ensino/métodos
14.
Environ Pollut ; 186: 98-103, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24368313

RESUMO

Perfluorinated chemicals (PFCs) have been recognised as environmental pollutants that require monitoring. A modified polar organic chemical integrative sampler (POCIS) is able to quantify aqueous PFCs. However, with varying external water velocity, PFC sampling rates (Rs) may change, affecting accuracy of derived water concentrations. To facilitate field deployment of this sampler, two methods of in-situ calibration were investigated: performance reference compounds (PRCs) and passive flow monitors (PFMs). Increased Rs's (by factors of 1.2-1.9) with PFM loss rate (g d(-1)) were observed for some PFCs. Results indicate PFMs can be used to correct PFC specific Rs's for more reliable estimates of environmental concentrations with a precision of about 0.01 L d(-1). Empirical models presented provide an improved means for aquatic monitoring of PFCs. The PRC approach was unsuccessful, confirming concern as to its applicability with such samplers.


Assuntos
Monitoramento Ambiental/métodos , Fluorocarbonos/análise , Modelos Químicos , Poluentes Químicos da Água/análise , Calibragem
15.
Healthc Financ Manage ; 67(9): 38-42, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24050053

RESUMO

The Medical Clinic of North Texas (MCNT) launched a population health initiative in 2010 that has involved working with self-insured companies to manage the health of their employee populations. To achieve the goals of providing high-quality care at a low cost, MCNT uses historical electronic health record and claims data to calculate state-of-health (SOH) scores for a company's individual employees and for the entire employee population. SOH scores reflect risks related to chronic conditions for each patient, thereby providing clinical teams and care coordinators with the information they need to design and execute patient-specific care plans.


Assuntos
Organizações de Assistência Responsáveis , Prática de Grupo/organização & administração , Assistência Centrada no Paciente , Modelos Organizacionais , Estudos de Casos Organizacionais , Inovação Organizacional , Texas
16.
Environ Pollut ; 177: 58-63, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23466732

RESUMO

A recently developed modified polar organic chemical integrative sampler (POCIS) provides a means for monitoring perfluorinated chemicals (PFCs) in water. However, changes in external flow rates may alter POCIS sampling behaviour and consequently affect estimated water concentrations of analytes. In this work, uptake kinetics of selected PFCs, over 15 days, were investigated. A flow-through channel system was employed with spiked river water at flow rates between 0.02 and 0.34 m s(-1). PFC sampling rates (Rs) (0.09-0.29 L d(-1) depending on analyte and flow rate) increased from the lowest to highest flow rate employed for some PFCs (MW ≤ 464) but not for others (MW ≥ 500). Rs's for some of these smaller PFCs were increasingly less sensitive to flow rate as this increased within the range investigated. This device shows promise as a sampling tool to support monitoring efforts for PFCs in a range of flow rate conditions.


Assuntos
Monitoramento Ambiental/métodos , Fluorocarbonos/análise , Movimentos da Água , Poluentes Químicos da Água/análise , Monitoramento Ambiental/instrumentação , Fluorocarbonos/química , Poluentes Químicos da Água/química
17.
Stem Cells Transl Med ; 2(1): 2-15, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23283491

RESUMO

Elastin haploinsufficiency in Williams-Beuren syndrome (WBS) leads to increased vascular smooth muscle cell (SMC) proliferation and stenoses. Our objective was to generate a human induced pluripotent stem (hiPS) cell model for in vitro assessment of the WBS phenotype and to test the ability of candidate agents to rescue the phenotype. hiPS cells were reprogrammed from skin fibroblasts of a WBS patient with aortic and pulmonary stenosis and healthy control BJ fibroblasts using four-factor retrovirus reprogramming and were differentiated into SMCs. Differentiated SMCs were treated with synthetic elastin-binding protein ligand 2 (EBPL2) (20 µg/ml) or the antiproliferative drug rapamycin (100 nM) for 5 days. We generated four WBS induced pluripotent stem (iPS) cell lines that expressed pluripotency genes and differentiated into all three germ layers. Directed differentiation of BJ iPS cells yielded an 85%-92% pure SMC population that expressed differentiated SMC markers, were functionally contractile, and formed tube-like structures on three-dimensional gel assay. Unlike BJ iPS cells, WBS iPS cells generated immature SMCs that were highly proliferative, showed lower expression of differentiated SMC markers, reduced response to the vasoactive agonists, carbachol and endothelin-1, impaired vascular tube formation, and reduced calcium flux. EBPL2 partially rescued and rapamycin fully rescued the abnormal SMC phenotype by decreasing the smooth muscle proliferation rate and enhancing differentiation and tube formation. WBS iPS cell-derived SMCs demonstrate an immature proliferative phenotype with reduced functional and contractile properties, thereby recapitulating the human disease phenotype. The ability of rapamycin to rescue the phenotype provides an attractive therapeutic candidate for patients with WBS and vascular stenoses.


Assuntos
Células-Tronco Pluripotentes Induzidas/fisiologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Síndrome de Williams/patologia , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , Sinalização do Cálcio , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Hemizigoto , Células Endoteliais da Veia Umbilical Humana , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/biossíntese , Masculino , Contração Muscular , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Fator 3 de Transcrição de Octâmero/biossíntese , Fragmentos de Peptídeos/farmacologia , Fenótipo , Proteínas Proto-Oncogênicas c-myc/biossíntese , Proteínas Recombinantes/biossíntese , Fatores de Transcrição SOXB1/biossíntese , Análise de Sequência de DNA , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Transcriptoma/efeitos dos fármacos , Síndrome de Williams/genética
18.
Rev. derecho genoma hum ; (37): 15-34, jul.-dic. 2012.
Artigo em Inglês | IBECS | ID: ibc-114336

RESUMO

Existe una notable carencia de regulación internacional sobre el intercambio de datos personales y la gestión de la investigación. Este artículo arroja luz en este ámbito mediante la descripción de cómo el Consorcio Internacional del Genoma del Cáncer está desarrollando políticas y procedimientos para abordar las cuestiones éticas y jurídicas que plantea la transferencia internacional de datos y resultados. El objetivo de estas políticas y procedimientos, es, en primer y más importante lugar, salvaguardar los intereses de los participantes en la investigación y de otros actores involucrados y, en segundo lugar, facilitar el intercambio de datos y resultados a fin de obtener mayores beneficios de este tipo de investigación genética de colaboración internacional (AU)


There is noticeable lack of international regulation on personal data Exchange and management in research. This article sheds light in this area by describing how the International Cancer Genome Consortium is developing policies and procedures to address the ethical and legal issues raised by the international transfer of data and results. These policies and procedures aim, first and most importantly, to safe guard the interests of the research participants and other involved stakeholders and, secondly, to facilitate the sharing of data and results to realize greater from this kind internationally collaborative genetic research (AU)


Assuntos
Humanos , Bases de Dados Genéticas/legislação & jurisprudência , Pesquisa em Genética/legislação & jurisprudência , Pesquisa Biomédica/legislação & jurisprudência , Genômica/legislação & jurisprudência , Legislação Médica/tendências , Genoma Humano , Biblioteca Genômica
19.
Health Aff (Millwood) ; 31(11): 2379-87, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23129667

RESUMO

Cigna's Collaborative Accountable Care initiative provides financial incentives to physician groups and integrated delivery systems to improve the quality and efficiency of care for patients in commercial open-access benefit plans. Registered nurses who serve as care coordinators employed by participating practices are a central feature of the initiative. They use patient-specific reports and practice performance reports provided by Cigna to improve care coordination, identify and close care gaps, and address other opportunities for quality improvement. We report interim quality and cost results for three geographically and structurally diverse provider practices in Arizona, New Hampshire, and Texas. Although not statistically significant, these early results revealed favorable trends in total medical costs and quality of care, suggesting that a shared-savings accountable care model and collaborative support from the payer can enable practices to take meaningful steps toward full accountability for care quality and efficiency.


Assuntos
Organizações de Assistência Responsáveis/organização & administração , Comportamento Cooperativo , Custos de Cuidados de Saúde , Administração da Prática Médica/organização & administração , Qualidade da Assistência à Saúde , Arizona , Prestação Integrada de Cuidados de Saúde/economia , Prestação Integrada de Cuidados de Saúde/normas , Feminino , Prática de Grupo/organização & administração , Humanos , Modelos Logísticos , Masculino , Programas de Assistência Gerenciada/organização & administração , New Hampshire , Planos de Incentivos Médicos/organização & administração , Padrões de Prática Médica/economia , Avaliação de Programas e Projetos de Saúde , Texas
20.
Environ Health ; 11: 72, 2012 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-23013369

RESUMO

BACKGROUND: Urban air pollution is an increasing health problem, particularly in Asia, where the combustion of fossil fuels has increased rapidly as a result of industrialization and socio-economic development. The adverse health impacts of urban air pollution are well established, but less is known about effective intervention strategies. In this demonstration study we set out to establish methods to assess whether wearing an R95 activated carbon respirator could reduce intake of polycyclic aromatic hydrocarbons (PAH) in street workers in Hanoi, Vietnam. METHODS: In this demonstration study we performed a cross-over study in which non-smoking participants that worked at least 4 hours per day on the street in Hanoi were randomly allocated to specific respirator wearing sequences for a duration of 2 weeks. Urines were collected after each period, i.e., twice per week, at the end of the working day to measure hydroxy PAHs (OH-PAH) using gas chromatography/high resolution mass spectrometry. The primary endpoint was the urinary concentration of 1-hydroxypyrene (1-OHP). RESULTS: Forty-four participants (54.5% male, median age 40 years) were enrolled with the majority being motorbike taxi drivers (38.6%) or street vendors (34.1%). The baseline creatinine corrected urinary level for 1-OHP was much higher than other international comparisons: 1020 ng/g creatinine (IQR: 604-1551). Wearing a R95 mask had no significant effect on 1-OHP levels: estimated multiplicative effect 1.0 (95% CI: 0.92-1.09) or other OH-PAHs, except 1-hydroxynaphthalene (1-OHN): 0.86 (95% CI: 0.11-0.96). CONCLUSIONS: High levels of urine OH-PAHs were found in Hanoi street workers. No effect was seen on urine OH-PAH levels by wearing R95 particulate respirators in an area of high urban air pollution, except for 1-OHN. A lack of effect may be de to gaseous phase PAHs that were not filtered efficiently by the respirator. The high levels of urinary OH-PAHs found, urges for effective interventions. TRIAL REGISTRATION: ISRCTN74390617 (date of assignation: 04/08/2009).


Assuntos
Exposição Ambiental/prevenção & controle , Exposição por Inalação/prevenção & controle , Dispositivos de Proteção Respiratória , Adulto , Poluentes Atmosféricos/metabolismo , Carbono/química , Monitoramento Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veículos Automotores , Naftóis/urina , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Pirenos/urina , Vietnã
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