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1.
Aust Educ Res ; 49(3): 617-634, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431406

RESUMO

This study draws on the tradition of transdisciplinarity to extend the boundaries of interdisciplinary educational work. In this paper, we apply the concepts of liminality and third space to examine a case of a professional immersive experience (PIEx), designed in response to the catastrophic disruption of work-integrated learning opportunities by the COVID-19 pandemic. The study uses a participatory reflexive methodology to interrogate the range of ways liminality was manifest in PIEx. First, we examine liminal learning in the virtual environment, which facilitated the unfolding of connections between different spaces, locations and people. Second, we seek to understand the PIEx experience through the concept of third space, highlighting the fluidity of roles, where educators, students and industry partners generate new knowledge and practices together. Lastly, we examine the experience through the boundary-crossing lens of transdisciplinarity. We conclude by gesturing towards a new understanding of work integrated learning, as it could take place in the future, well beyond the walls of the university.

2.
Development ; 144(17): 3102-3113, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28760813

RESUMO

The extracellular matrix (ECM) regulates cell migration and sculpts organ shape. AdamTS proteins are extracellular metalloproteases known to modify ECM proteins and promote cell migration, but demonstrated roles for AdamTS proteins in regulating CNS structure and ensuring cell lineages remain fixed in place have not been uncovered. Using forward genetic approaches in Drosophila, we find that reduction of AdamTS-A function induces both the mass exodus of neural lineages out of the CNS and drastic perturbations to CNS structure. Expressed and active in surface glia, AdamTS-A acts in parallel to perlecan and in opposition to viking/collagen IV and ßPS-integrin to keep CNS lineages rooted in place and to preserve the structural integrity of the CNS. viking/collagen IV and ßPS-integrin are known to promote tissue stiffness and oppose the function of perlecan, which reduces tissue stiffness. Our work supports a model in which AdamTS-A anchors cells in place and preserves CNS architecture by reducing tissue stiffness.


Assuntos
Linhagem da Célula , Sistema Nervoso Central/citologia , Proteínas de Drosophila/metabolismo , Matriz Extracelular/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Alelos , Animais , Membrana Basal/metabolismo , Colágeno Tipo IV/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Cadeias alfa de Integrinas/metabolismo , Mutação/genética , Neuroglia/citologia , Neuroglia/metabolismo , Fenótipo , Frações Subcelulares/metabolismo , Análise de Sobrevida
3.
Development ; 141(5): 1011-21, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24550109

RESUMO

Most neurons of the adult Drosophila ventral nerve cord arise from a burst of neurogenesis during the third larval instar stage. Most of this growth occurs in thoracic neuromeres, which contain 25 individually identifiable postembryonic neuronal lineages. Initially, each lineage consists of two hemilineages--'A' (Notch(On)) and 'B' (Notch(Off))--that exhibit distinct axonal trajectories or fates. No reliable method presently exists to identify these lineages or hemilineages unambiguously other than labor-intensive lineage-tracing methods. By combining mosaic analysis with a repressible cell marker (MARCM) analysis with gene expression studies, we constructed a gene expression map that enables the rapid, unambiguous identification of 23 of the 25 postembryonic lineages based on the expression of 15 transcription factors. Pilot genetic studies reveal that these transcription factors regulate the specification and differentiation of postembryonic neurons: for example, Nkx6 is necessary and sufficient to direct axonal pathway selection in lineage 3. The gene expression map thus provides a descriptive foundation for the genetic and molecular dissection of adult-specific neurogenesis and identifies many transcription factors that are likely to regulate the development and differentiation of discrete subsets of postembryonic neurons.


Assuntos
Sistema Nervoso Central/metabolismo , Proteínas de Drosophila/metabolismo , Fatores de Transcrição/metabolismo , Animais , Sistema Nervoso Central/citologia , Drosophila , Proteínas de Drosophila/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo , Neurogênese/genética , Neurogênese/fisiologia , Neurônios/citologia , Neurônios/metabolismo , Fatores de Transcrição/genética
4.
Dev Biol ; 388(1): 117-33, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24512689

RESUMO

Hb9 is a homeodomain-containing transcription factor that acts in combination with Nkx6, Lim3, and Tail-up (Islet) to guide the stereotyped differentiation, connectivity, and function of a subset of neurons in Drosophila. The role of Hb9 in directing neuronal differentiation is well documented, but the lineage of Hb9(+) neurons is only partly characterized, its regulation is poorly understood, and most of the downstream genes through which it acts remain at large. Here, we complete the lineage tracing of all embryonic Hb9(+) neurons (to eight neuronal lineages) and provide evidence that hb9, lim3, and tail-up are coordinately regulated by a common set of upstream factors. Through the parallel use of micro-array gene expression profiling and the Dam-ID method, we searched for Hb9-regulated genes, uncovering transcription factors as the most over-represented class of genes regulated by Hb9 (and Nkx6) in the CNS. By a nearly ten-to-one ratio, Hb9 represses rather than activates transcription factors, highlighting transcriptional repression of other transcription factors as a core mechanism by which Hb9 governs neuronal determination. From the small set of genes activated by Hb9, we characterized the expression and function of two - fd59a/foxd, which encodes a transcription factor, and Nitric oxide synthase. Under standard lab conditions, both genes are dispensable for Drosophila development, but Nos appears to inhibit hyper-active behavior and fd59a appears to act in octopaminergic neurons to control egg-laying behavior. Together our data clarify the mechanisms through which Hb9 governs neuronal specification and differentiation and provide an initial characterization of the expression and function of Nos and fd59a in the Drosophila CNS.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição/metabolismo , Alelos , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Diferenciação Celular , Linhagem da Célula , Sistema Nervoso Central/embriologia , Elementos Facilitadores Genéticos , Fatores de Transcrição Forkhead/metabolismo , Estudos de Associação Genética , Genótipo , Hibridização In Situ , Dados de Sequência Molecular , Mutagênese , Neurônios/metabolismo , Óxido Nítrico Sintase/metabolismo , Regiões Promotoras Genéticas , Homologia de Sequência de Aminoácidos , Transcriptoma
5.
G3 (Bethesda) ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996053

RESUMO

Despite increasing in mass approximately 100-fold during larval life, the Drosophila CNS maintains its characteristic form. Dynamic interactions between the overlying basement membrane and underlying surface glia are known to regulate CNS structure in Drosophila, but the genes and pathways that establish and maintain CNS morphology during development remain poorly characterized. To identify genes that regulate CNS shape in Drosophila, we conducted an EMS-based, forward genetic screen of the second chromosome, uncovered 50 mutations that disrupt CNS structure, and mapped these alleles to 17 genes. Analysis of whole genome sequencing data wedded to genetic studies uncovered the affected gene for all but one mutation. Identified genes include well characterized regulators of tissue shape, like LanB1, viking, and Collagen type IV alpha1, and previously characterized genes, such as Toll-2 and Rme-8, with no known role in regulating CNS structure. We also uncovered that papilin and C1GalTA likely act in the same pathway to regulate CNS structure and found that the fly homolog of a glucuronosyltransferase, B4GAT1/LARGE1, that regulates Dystroglycan function in mammals is required to maintain CNS shape in Drosophila. Finally, we show that the senseless-2 transcription factor is expressed and functions specifically in surface glia found on peripheral nerves but not in the CNS to govern CNS structure, identifying a gene that functionally subdivides a glial subtype along the peripheral-central axis. Future work on these genes should clarify the genetic mechanisms that ensure the homeostasis of CNS form during development.

6.
bioRxiv ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38260379

RESUMO

Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), the Drosophila DEGS1 homolog, is expressed primarily in glial cells to promote CNS development by guarding against neurodegeneration. Loss of ifc causes massive dihydroceramide accumulation and severe morphological defects in cortex glia, including endoplasmic reticulum (ER) expansion, failure of neuronal ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ceramide synthase schlank in glia of ifc mutants rescues ER expansion, suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi knockdown of ifc in glia but not neurons drives neuronal cell death, suggesting that ifc function in glia promotes neuronal survival. Our work identifies glia as the primary site of disease progression in HLD-18 and may inform on juvenile forms of ALS, which also feature elevated dihydroceramide levels.

7.
Radiol Manage ; 35(2): 18-23; quiz 24-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23638576

RESUMO

Discussion includes radiation safety and radiographic quality management, continual quality improvement processes, and management review over a three year period. The results of radiation safety and radiographic quality audits conducted on random samples of chest radiographs are included. Specific measures and improvement strategies are presented as they relate to "babygrams" patient positioning, shielding, collimation, exposure technique, exposure index, and patient holding by NICU staff. Discussion of the change management process related to physician ordering, radiologic technologist training, and interdepartmental collaboration and team building.


Assuntos
Unidades de Terapia Intensiva Neonatal , Segurança do Paciente , Melhoria de Qualidade , Proteção Radiológica/métodos , Radiografia Torácica , Humanos , Recém-Nascido , Equipe de Assistência ao Paciente/organização & administração , Doses de Radiação
8.
Development ; 136(19): 3257-66, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19710170

RESUMO

Individual neurons adopt and maintain defined morphological and physiological phenotypes as a result of the expression of specific combinations of transcription factors. In particular, homeodomain-containing transcription factors play key roles in determining neuronal subtype identity in flies and vertebrates. dbx belongs to the highly divergent H2.0 family of homeobox genes. In vertebrates, Dbx1 and Dbx2 promote the development of a subset of interneurons, some of which help mediate left-right coordination of locomotor activity. Here, we identify and show that the single Drosophila ortholog of Dbx1/2 contributes to the development of specific subsets of interneurons via cross-repressive, lineage-specific interactions with the motoneuron-promoting factors eve and hb9 (exex). dbx is expressed primarily in interneurons of the embryonic, larval and adult central nervous system, and these interneurons tend to extend short axons and be GABAergic. Interestingly, many Dbx(+) interneurons share a sibling relationship with Eve(+) or Hb9(+) motoneurons. The non-overlapping expression of dbx and eve, or dbx and hb9, within pairs of sibling neurons is initially established as a result of Notch/Numb-mediated asymmetric divisions. Cross-repressive interactions between dbx and eve, and dbx and hb9, then help maintain the distinct expression profiles of these genes in their respective pairs of sibling neurons. Strict maintenance of the mutually exclusive expression of dbx relative to that of eve and hb9 in sibling neurons is crucial for proper neuronal specification, as misexpression of dbx in motoneurons dramatically hinders motor axon outgrowth.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Proteínas de Homeodomínio/metabolismo , Interneurônios/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Sequência de Bases , Comportamento Animal , Diferenciação Celular , DNA/genética , Drosophila/citologia , Drosophila/genética , Proteínas de Drosophila/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genes Homeobox , Genes de Insetos , Proteínas de Homeodomínio/genética , Interneurônios/citologia , Locomoção , Dados de Sequência Molecular , Neurônios Motores/citologia , Neurônios Motores/metabolismo , Mutação , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/genética , Ácido gama-Aminobutírico/metabolismo
9.
Development ; 136(24): 4089-98, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19906847

RESUMO

Asymmetric cell divisions generate sibling cells of distinct fates ('A', 'B') and constitute a fundamental mechanism that creates cell-type diversity in multicellular organisms. Antagonistic interactions between the Notch pathway and the intrinsic cell-fate determinant Numb appear to regulate asymmetric divisions in flies and vertebrates. During these divisions, productive Notch signaling requires sanpodo, which encodes a novel transmembrane protein. Here, we demonstrate that Drosophila sanpodo plays a dual role to regulate Notch signaling during asymmetric divisions - amplifying Notch signaling in the absence of Numb in the 'A' daughter cell and inhibiting Notch signaling in the presence of Numb in the 'B' daughter cell. In so doing, sanpodo ensures the asymmetry in Notch signaling levels necessary for the acquisition of distinct fates by the two daughter cells. These findings answer long-standing questions about the restricted ability of Numb and Sanpodo to inhibit and to promote, respectively, Notch signaling during asymmetric divisions.


Assuntos
Linhagem da Célula/fisiologia , Proteínas de Drosophila/fisiologia , Drosophila , Receptores Notch/fisiologia , Animais , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Drosophila/embriologia , Drosophila/metabolismo , Embrião não Mamífero/embriologia , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Hormônios Juvenis/fisiologia , Proteínas dos Microfilamentos/fisiologia , Transdução de Sinais
10.
Mol Ther ; 18(7): 1268-74, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20442709

RESUMO

Guanidinylated neomycin (GNeo) can transport bioactive, high molecular weight cargo into the interior of cells in a process that depends on cell surface heparan sulfate proteoglycans. In this report, we show that GNeo-modified quantum dots bind to cell surface heparan sulfate, undergo endocytosis and eventually reach the lysosomal compartment. An N-hydroxysuccinimide activated ester of GNeo (GNeo-NHS) was prepared and conjugated to two lysosomal enzymes, beta-D-glucuronidase (GUS) and alpha-L-iduronidase. Conjugation did not interfere with enzyme activity and enabled binding of the enzymes to heparin-Sepharose and heparan sulfate on primary human fibroblasts. Cells lacking the corresponding lysosomal enzyme took up sufficient amounts of the conjugated enzymes to restore normal turnover of glycosaminoglycans. The high capacity of proteoglycan-mediated uptake suggests that this method of delivery might be used for enzyme replacement or introduction of foreign enzymes into cells.


Assuntos
Heparitina Sulfato/metabolismo , Lisossomos/metabolismo , Neomicina/metabolismo , Animais , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Endocitose/fisiologia , Glucuronidase/química , Glucuronidase/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Iduronidase/química , Iduronidase/metabolismo , Microscopia de Fluorescência , Estrutura Molecular , Neomicina/química , Pontos Quânticos
11.
Nurs Child Young People ; 33(1): 32-42, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410607

RESUMO

This article is the sixth in a series on the biological basis of child health. It provides an overview of the development of the skeletal system before and after birth, and outlines the potential congenital anomalies that may occur. The article explains the structure and function of the bones before describing the role of the joints, tendons and ligaments. It also outlines the presentation and management of some of the common orthopaedic conditions seen in infants and children, including fractures, osteogenesis imperfecta, scoliosis, juvenile idiopathic arthritis, developmental dysplasia of the hip and achondroplasia.


Assuntos
Osso e Ossos/fisiopatologia , Crescimento e Desenvolvimento/fisiologia , Doenças Musculoesqueléticas/terapia , Osso e Ossos/cirurgia , Saúde da Criança , Pré-Escolar , Feminino , Fraturas Ósseas/fisiopatologia , Fraturas Ósseas/terapia , Luxação do Quadril/fisiopatologia , Luxação do Quadril/terapia , Humanos , Lactente , Masculino , Doenças Musculoesqueléticas/fisiopatologia , Ortopedia/métodos , Osteogênese Imperfeita/fisiopatologia , Osteogênese Imperfeita/terapia , Escoliose/fisiopatologia , Escoliose/terapia
12.
JBI Evid Synth ; 19(12): 3315-3323, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34410231

RESUMO

OBJECTIVE: The objective of this review is to gain insight about the experience of emerging adults who are coping with a chronic illness diagnosis. INTRODUCTION: Receiving a chronic illness diagnosis is filled with challenges and changes to a person's life. Coping is not an easy or linear process, and is particularly complex for emerging adults. The emerging adult stage is important to consider, as this is a stage characterized by identity exploration, transition to adulthood, and future planning. A chronic illness diagnosis interrupts these processes and affects the coping process in emerging adults. INCLUSION CRITERIA: The population included will be persons between 18 and 25 years of age living in the community. Sources will focus on the experience of being diagnosed with a chronic illness, including its impacts on the individual's life. METHODS: This qualitative review will be conducted following JBI qualitative review methodology. An initial search was conducted in order to identify relevant articles on the topic. Databases to be searched include CINAHL, PubMed, PsycINFO, and Nursing and Allied Health Database. A gray literature search will also be conducted. There will be no date or language limits on the search. The titles and abstracts will be screened by two independent reviewers, followed by an assessment of the full-text articles. Any disagreements will be resolved through discussion or in consultation with a third reviewer. Critical appraisal of included articles and data extraction will be conducted independently by two reviewers. Meta-aggregation of the articles will be completed and textually pooled in tabular format. Where that is not possible, results will be presented in a narrative format. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021224772.


Assuntos
Adaptação Psicológica , Atenção à Saúde , Adulto , Doença Crônica , Humanos , Pesquisa Qualitativa , Revisões Sistemáticas como Assunto , Adulto Jovem
13.
G3 (Bethesda) ; 11(8)2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-33993253

RESUMO

The mechanisms that determine the final topology of skeletal muscles remain largely unknown. We have been developing Drosophila body wall musculature as a model to identify and characterize the pathways that control muscle size, shape, and orientation during embryogenesis. Our working model argues muscle morphogenesis is regulated by (1) extracellular guidance cues that direct muscle cells toward muscle attachment sites, and (2) contact-dependent interactions between muscles and tendon cells. While we have identified several pathways that regulate muscle morphogenesis, our understanding is far from complete. Here, we report the results of a recent EMS-based forward genetic screen that identified a myriad of loci not previously associated with muscle morphogenesis. We recovered new alleles of known muscle morphogenesis genes, including back seat driver, kon-tiki, thisbe, and tumbleweed, arguing our screen had the depth and precision to uncover myogenic genes. We also identified new alleles of spalt-major, barren, and patched that presumably disrupt independent muscle morphogenesis pathways. Equally as important, our screen shows that at least 11 morphogenetic loci remain to be mapped and characterized. Our screen has developed exciting new tools to study muscle morphogenesis, which may provide future insights into the mechanisms that regulate skeletal muscle topology.


Assuntos
Proteínas de Drosophila , Drosophila , Desenvolvimento Muscular , Animais , Drosophila/genética , Drosophila/crescimento & desenvolvimento , Proteínas de Drosophila/genética , Morfogênese/genética , Desenvolvimento Muscular/genética
14.
JBI Evid Synth ; 19(10): 2695-2738, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34264899

RESUMO

OBJECTIVE: The objective of this review was to chart the literature on assistive technologies (excluding robots) that support social interaction of older adults in long-term care homes, and to advance a definition of socially assistive technologies. INTRODUCTION: Loneliness and social isolation have adverse effects on the health and well-being of older adults. Many long-term care homes provide recreational programming intended to entertain or distract residents, yet the evidence of their effectiveness is limited. Absent from the literature are comprehensive reviews of assistive technologies (other than robots) that are used to support social interaction in long-term care homes. INCLUSION CRITERIA: The review considered research studies as well as gray literature that included older adults (≥65 years) living in long-term care homes. The concept of interest was the use of assistive technologies (excluding robots) that support social interaction in long-term care homes. METHODS: The databases were searched on June 26, 2019, and included CINAHL Full Text (EBSCO), MEDLINE (Ovid), PsycINFO (EBSCO), Sociological Abstracts (ProQuest), Embase (Elsevier), and Web of Science (Clarivate). The search for gray literature was conducted in ProQuest Dissertations and Theses Databases and across 11 websites during September and October 2019. The recommended JBI approach to study selection, data extraction, and data synthesis was used. RESULTS: Twenty-five articles were included in this review, with comparable numbers of quantitative (n = 6), qualitative (n = 9), and mixed methods (n = 7) studies, with the remaining articles employing non-empirical designs (n = 3). Technologies were categorized as low (easily recognizable to everyone), medium (more electronics), or high (involves internet). Two studies reported on low-assistive technologies, including videotapes and the telephone. Medium-assistive technologies were identified in nine studies and included videophones; Nintendo Wii; tablet-based games; picture- and video-viewing tools; and CRDL (pronounced "cradle"), a special instrument that translates touch into sound. More than half (n = 14) of the included articles utilized high-assistive technologies, such as computer labs/kiosks, tablet-based applications, social media (eg, Facebook), videoconferencing, and multi-functional systems. Five studies measured whether assistive technologies had an impact on the quantity of long-term care residents' social interaction levels. Qualitative themes were related to residents' social connections and experiences after using various technologies. Four studies systematically incorporated a framework/model, and Social Structuration Theory was considered the most comprehensive. In the absence of a definition of socially assistive technologies, the definition advanced from this review is as follows: Socially assistive technologies are user-appropriate devices and tools that enable real-time connectivity to enhance social interaction. CONCLUSIONS: Included literature reported the benefits of technology use, with considerable variability in engagement and no cost estimates. We recommend that future research continue to advance our definition of socially assistive technologies, make promising assistive technologies available in long-term care homes after studies are completed, report the costs of assistive technologies, and include participants with dementia and culturally and linguistically diverse backgrounds.


Assuntos
Assistência de Longa Duração , Tecnologia Assistiva , Idoso , Humanos , Solidão , Interação Social , Isolamento Social
15.
JBI Evid Synth ; 18(3): 592-598, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32197019

RESUMO

OBJECTIVE: The objective of this scoping review is to chart the literature on assistive technologies that support social interaction (excluding robots) used with older adults in long-term care (LTC). INTRODUCTION: The need for LTC in institutional settings is in high demand. Loneliness and social isolation are common in these settings. Technology holds potential to contribute to mitigation of loneliness. As there are no systematic reviews examining forms of assistive technologies to support social interaction other than robots, used within LTC settings, there is a need to categorize the current research regarding such technologies to inform practice, policy and any need for further research. INCLUSION CRITERIA: The review will consider studies based in LTC institutional settings with participants (≥65 years), institutional staff and visiting family members METHODS:: The JBI methodology for scoping reviews will be employed. This includes a three-step search strategy: i) identify keywords from CINAHL and PsycINFO, ii) conduct a second search using all identified keywords across select databases, and iii) screen the reference lists of all included articles and reports for additional studies. Titles and abstracts will be screened by two independent reviewers. Full text of selected citations will be assessed against inclusion criteria by two independent reviewers. A data extraction tool will be used, and extracted data will be presented in a narrative accompanied by diagrams or tables that reflect the objective of the review.


Assuntos
Assistência de Longa Duração , Tecnologia Assistiva , Interação Social , Idoso , Humanos , Solidão , Projetos de Pesquisa , Literatura de Revisão como Assunto , Isolamento Social
16.
Org Biomol Chem ; 6(21): 4026-35, 2008 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-18931811

RESUMO

We report the synthesis and characterization of N,N-bis[(7-dimethylamino)phenothiazin-5-ium-3-yl]-4,4-ethylenedipiperidine diiodide (3), consisting of two photosensitizing phenothiazinium rings attached to a central ethylenedipiperidine linker. At all time points (10, 30, 60 min) and all wavelengths (676, 700, 710 nm) tested, photocleavage of pUC19 plasmid DNA (22 degrees C and pH 7.0) was markedly enhanced by 1 microM of 3 in comparison to 1 microM of the parent phenothiazine methylene blue (MB). At concentrations of phenothiazine ranging from 5 to 0.5 microM, the photocleavage levels produced by compound 3 were consistently higher than the cleavage produced using approximately twice the amount of MB (e.g., 710 nm irradiation of 5 microM of 3 and 10 microM of MB cleaved the plasmid DNA in 93% and 71% yields, respectively). Scavenger assays provided evidence for the involvement of singlet oxygen and, to a lesser extent, hydroxyl radicals in DNA damage. Analysis of photocleavage products at nucleotide resolution revealed that direct strand breaks and alkaline-labile lesions occurred predominantly at guanine bases. While compound 3 and MB were both shown to stabilize duplex DNA, the DeltaTm values of calf thymus (CT) and C. perfringens DNAs were approximately three fold higher in the presence of compound 3. Finally, viscometric data indicated that CT DNA interacts with compound 3 and MB by a combination of groove binding and monofunctional intercalation, and with compound 3 by a third, bisintercalative binding mode.


Assuntos
DNA/química , Fenotiazinas/química , Fenotiazinas/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Piperidinas/química , Piperidinas/síntese química , Clivagem do DNA , Elétrons , Indicadores e Reagentes/química , Substâncias Intercalantes/química , Desnaturação de Ácido Nucleico , Nucleotídeos/metabolismo , Fotoquímica , Espectrofotometria Ultravioleta , Temperatura de Transição , Viscosidade
17.
Mutat Res ; 623(1-2): 3-13, 2007 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-17445837

RESUMO

Over the last four decades, intense research has focused on the effects of small organic compounds that noncovalently bind to nucleic acids. These interactions have been shown to disrupt replication and/or transcription culminating in cellular death. Accordingly, DNA binding compounds have potential applications as anti-cancer and anti-viral agents. This report provides an overview of the different DNA-binding modes with an emphasis on DNA groove specificity for the groove-binding and intercalation modes. While most DNA-interacting agents selectively bind to DNA by either groove binding or intercalation, some compounds can exhibit both binding modes. The binding mode with the most favorable free energy for complex formation depends on the DNA sequence and structural features of the bound ligand.


Assuntos
DNA/química , DNA/metabolismo , Sequência de Bases , Sítios de Ligação , DNA/genética , DNA Topoisomerases Tipo I/química , DNA Topoisomerases Tipo I/metabolismo , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Ligantes , Substâncias Macromoleculares , Modelos Moleculares , Mutação , Conformação de Ácido Nucleico , Eletricidade Estática
18.
J Anxiety Disord ; 20(7): 915-30, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16503112

RESUMO

Social phobia is a common, highly comorbid, poorly understood and relatively understudied condition. The origins of social phobia share familial and biological features common with those of other anxiety disorders, but seldom have precursors of the fear of social communication been examined as a possible pathway to social phobia. Here we examine the role of early childhood language impairment as an antecedent to social phobia in late adolescence. Participants in a prospective longitudinal community study identified as having language impairment at age 5 and matched controls were followed up at age 19. Compared to normal language controls, individuals with a history of early language impairment had 2.7 times the odds of having a social phobia by age 19. Results suggest that early language impairment represents a distinct pathway to late adolescent social phobia.


Assuntos
Transtornos da Linguagem/psicologia , Transtornos Fóbicos/etiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Transtornos da Linguagem/epidemiologia , Modelos Logísticos , Masculino , Transtornos Mentais/epidemiologia , Ontário/epidemiologia , Transtornos Fóbicos/epidemiologia , Transtornos Fóbicos/psicologia , Prevalência , Estudos Prospectivos , Fatores de Risco
19.
Aust Health Rev ; 30(3): 322-32, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16879091

RESUMO

OBJECTIVE: To validate earlier findings that lack of access to health services is the most likely issue of complaint by rural consumers, and that lack of knowledge about how to make effective complaints and scepticism that responses to complaints bring about service improvement account for the under-representation of complaints from rural consumers. DESIGN: Unaddressed reply-paid mail survey to 100% of households in small communities, and 50%, 20% or 10% in progressively larger communities. SETTING: Eight communities in the Loddon-Mallee region of Victoria. PARTICIPANTS: 983 householders most responsible for the health care of household members, responding to a mailed questionnaire. MAIN OUTCOME MEASURES: Issues of complaints actually made; issues of unsatisfactory situations when a complaint was not made; reasons for not complaining; to whom complaints are made; and plans for dealing with any future complaint. RESULTS: Earlier findings were confirmed. Lack of access to health services was the most important issue, indicated by 54.8% of those who had made a complaint, and 72% of those who wanted to but did not. The most common reason given for not complaining was that it was futile to do so. Lack of knowledge of how to make effective complaints which might contribute to the quality assurance cycle was evident. CONCLUSIONS: Rural consumers' disaffection with health complaints as a means to quality improvement poses a significant barrier to consumer engagement in quality assurance processes. Provider practices may need to change to regain community confidence in quality improvement processes.


Assuntos
Acessibilidade aos Serviços de Saúde , Satisfação do Paciente/estatística & dados numéricos , Serviços de Saúde Rural/provisão & distribuição , População Rural , Adolescente , Adulto , Características da Família , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Garantia da Qualidade dos Cuidados de Saúde , Vitória
20.
J Manag Care Spec Pharm ; 22(12): 1417-1425, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27882838

RESUMO

BACKGROUND: Smoking is the leading preventable cause of death, and tobacco control professionals continue to make progress in cessation efforts. Pharmacists can assist smokers seeking to quit by offering counseling on smoking cessation pharmacotherapies. Pragmatic randomized trials are useful for investigating practical questions about an intervention's risks, benefits, and costs in routine clinical practice. OBJECTIVE: To evaluate an enhanced pharmacy care (EPC) program involving personalized pharmacist-provided telephone counseling for supporting prescription smoking cessation medications compared with usual care (UC). METHODS: Cigarette smokers filling a newly prescribed smoking cessation pharmacotherapy and with pharmacy benefits managed by Express Scripts were recruited. Qualified subjects were randomized 1:1 to EPC and UC. Subjects in EPC received 3 telephone-counseling sessions from specialist pharmacists during the early course of the study, while subjects in UC did not receive any counseling sessions. Study outcomes were collected through telephone contact and using the Express Scripts prescription database. The primary outcome assessed the 1-week point prevalence (PP) of smoking abstinence at the end of the trial (week 12). Secondary outcomes included 4-week PP at week 12 and adherence, evaluated by proportion of days covered (PDC), to prescribed smoking cessation pharmacotherapies. RESULTS: There were 1,017 randomized subjects. Among them, 1,002 subjects were included in the analysis, and 513 were randomized into EPC and 489 into UC. Baseline demographics, smoking history, and prescribed smoking cessation pharmacotherapies were comparable. Varenicline and nicotine replacement therapy (NRT) were most frequently prescribed for smoking cessation. In EPC, 46.0% received all 3 counseling sessions; 29.4% received 2 sessions; and 14.6% received 1 session. Overall, 353 subjects in EPC and 383 subjects in UC completed the week 12 assessment. In the analysis for 1-week PP of smoking abstinence at week 12, the percentage of abstainers in EPC was numerically higher than in UC (42.3% vs. 38.2%) with OR = 1.24, 95% CI = 0.96-1.61. It was not statistically significant. Adherence to prescription smoking cessation medication was significantly higher in EPC versus UC (49.7% vs. 45.6%; P = 0.033). CONCLUSIONS: This study evaluated whether a telephone-based pharmacy care program, provided by pharmacists and designed to support attempted quitters, improved quitting and increased adherence over usual care. The findings suggest that an enhanced program may benefit smokers by increasing prescription smoking cessation medication adherence. Future research should explore this program's effect on smokers who are compliant, based on insights on quitting provided by the post hoc analyses and limitations of the current study design. DISCLOSURES: This study was sponsored by Pfizer. Gong, Baker, Zou, Bruno, Jumadilova, and Lawrence are employees and stockholders of Pfizer. Wilson and Ewel are employees of United BioSource Corporation, which received funding from Pfizer for conducting this study and for the development of this manuscript. Study concept and design were contributed by Gong, Bruno, and Ewel, with assistance from Jumadilova, Lawrence, and Zou. Gong, Jumadilova, Lawrence, and Ewel collected the data. Data interpretation was performed by Baker, Zou, and Wilson, assisted by Gong, Lawrence, and Ewel. The manuscript was written by Baker, Ewel, and Gong, with assistance from the other authors, and revised by Baker, Wilson, Zou, and Gong, with assistance from Bruno and Jumadilova.


Assuntos
Aconselhamento/métodos , Assistência Farmacêutica , Farmacêuticos , Abandono do Hábito de Fumar/métodos , Fumar/terapia , Telefone , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Agonistas Nicotínicos/efeitos adversos , Agonistas Nicotínicos/uso terapêutico , Assistência ao Paciente/métodos , Papel Profissional , Estudos Prospectivos , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Telefone/estatística & dados numéricos , Vareniclina/efeitos adversos , Vareniclina/uso terapêutico
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