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1.
Nucleic Acids Res ; 52(D1): D1668-D1676, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37994696

RESUMO

Europe PMC (https://europepmc.org/) is an open access database of life science journal articles and preprints, which contains over 42 million abstracts and over 9 million full text articles accessible via the website, APIs and bulk download. This publication outlines new developments to the Europe PMC platform since the last database update in 2020 (1) and focuses on five main areas. (i) Improving discoverability, reproducibility and trust in preprints by indexing new preprint content, enriching preprint metadata and identifying withdrawn and removed preprints. (ii) Enhancing support for text and data mining by expanding the types of annotations provided and developing the Europe PMC Annotations Corpus, which can be used to train machine learning models to increase their accuracy and precision. (iii) Developing the Article Status Monitor tool and email alerts, to notify users about new articles and updates to existing records. (iv) Positioning Europe PMC as an open scholarly infrastructure through increasing the portion of open source core software, improving sustainability and accessibility of the service.


Assuntos
Disciplinas das Ciências Biológicas , Bases de Dados Bibliográficas , Mineração de Dados , Europa (Continente) , Software , Bases de Dados Bibliográficas/normas , Internet
2.
Dev Biol ; 514: 50-65, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38880276

RESUMO

To bring about sexual dimorphism in form, information from the sex determination pathway must trigger sex-specific modifications in developmental programs. DM-domain encoding genes have been found to be involved in sex determination in a multitude of animals, often at the level of male somatic gonad formation. Here we report our findings that the DM-domain transcription factors MAB-3 and DMD-3 function together in multiple steps during the late stages of C. elegans male somatic gonad development. Both mab-3 and dmd-3 are expressed in the linker cell and hindgut of L4 males and dmd-3 is also expressed in presumptive vas deferens cells. Furthermore, dmd-3, but not mab-3, expression in the linker cell is downstream of nhr-67, a nuclear hormone receptor that was previously shown to control late stages of linker cell migration. In mab-3; dmd-3 double mutant males, the last stage of linker cell migration is partially defective, resulting in aberrant linker cell shapes and often a failure of the linker cell to complete its migration to the hindgut. When mab-3; dmd-3 double mutant linker cells do complete their migration, they fail to be engulfed by the hindgut, indicating that dmd-3 and mab-3 activity are essential for this process. Furthermore, linker cell death and clearance are delayed in mab-3; dmd-3 double mutants, resulting in the linker cell persisting into adulthood. Finally, DMD-3 and MAB-3 function to activate expression of the bZIP transcription factor encoding gene zip-5 and downregulate the expression of the zinc metalloprotease ZMP-1 in the linker cell. Taken together, these results demonstrate a requirement for DM-domain transcription factors in controlling C. elegans male gonad formation, supporting the notion that the earliest DM-domain genes were involved in male somatic gonad development in the last common ancestor of the bilaterians.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Regulação da Expressão Gênica no Desenvolvimento , Gônadas , Animais , Masculino , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Gônadas/metabolismo , Movimento Celular/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Processos de Determinação Sexual/genética , Mutação/genética , Proteínas de Ligação a DNA
3.
Nucleic Acids Res ; 50(D1): D11-D19, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34850134

RESUMO

The European Bioinformatics Institute (EMBL-EBI) maintains a comprehensive range of freely available and up-to-date molecular data resources, which includes over 40 resources covering every major data type in the life sciences. This year's service update for EMBL-EBI includes new resources, PGS Catalog and AlphaFold DB, and updates on existing resources, including the COVID-19 Data Platform, trRosetta and RoseTTAfold models introduced in Pfam and InterPro, and the launch of Genome Integrations with Function and Sequence by UniProt and Ensembl. Furthermore, we highlight projects through which EMBL-EBI has contributed to the development of community-driven data standards and guidelines, including the Recommended Metadata for Biological Images (REMBI), and the BioModels Reproducibility Scorecard. Training is one of EMBL-EBI's core missions and a key component of the provision of bioinformatics services to users: this year's update includes many of the improvements that have been developed to EMBL-EBI's online training offering.


Assuntos
Biologia Computacional/educação , Biologia Computacional/métodos , Bases de Dados Factuais , Academias e Institutos , Inteligência Artificial , COVID-19 , Bases de Dados Factuais/economia , Bases de Dados Factuais/estatística & dados numéricos , Bases de Dados de Produtos Farmacêuticos , Bases de Dados de Proteínas , Europa (Continente) , Genoma Humano , Humanos , Armazenamento e Recuperação da Informação , RNA não Traduzido/genética , SARS-CoV-2/genética
4.
Cytopathology ; 35(1): 2-6, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37877689

RESUMO

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.


Assuntos
Currículo , Simbiose , Humanos , Técnicas Citológicas , Instituições Acadêmicas , América do Norte
5.
BMC Med Educ ; 24(1): 382, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589833

RESUMO

BACKGROUND: Racism contributes to health disparities and is a serious threat to public health. Teaching physicians about racism, how to address it in medical practice, and developing high quality and sustainable curricula are essential to combating racism. OBJECTIVE: This study aimed to (1) describe the experience of racism and anti-racism teaching in residency programs, and elicit recommendations from key informants, and (2) use these data and formative research to develop recommendations for other residencies creating, implementing, and evaluating anti-racism curricula in their own programs. METHODS: From May to July 2023, 20 faculty and residents were recruited via convenience sampling for key informant interviews conducted via Microsoft Teams. Interviews were audio recorded, transcribed, and coded. An initial list of themes was developed using theoretical frameworks, and then refined using a grounded-theory approach. A brief online optional anonymous demographic survey was sent to participants in August of 2023.  RESULTS: Eighty percent (20/25) of participants approached were interviewed. Seventy-five percent (15/20) answered a brief optional demographic survey. Seven themes emerged: (1) Racism in medicine is ubiquitous; (2) Anti-racism teaching in medicine varies widely; (3) Sustainability strategies should be multifaceted and include recruitment, resource allocation, and outcome measures; (4) Resources are widely available and accessible if one knows where to look; (5) Outcomes and metrics of success should include resident- faculty-, patient- community-, and system-focused outcomes; (6) Curricular strategies should be multilayered, longitudinal, and woven into the curriculum; and (7) Self-reflection and discomfort are necessary parts of the process.  CONCLUSIONS: This study is one of the first to qualitatively examine perspectives of key stakeholders invested in anti-racism teaching for residents. The Support - Pipeline - Outcomes - Community (SPOC) Model, that was developed using information collected during this study, can be used in the future as a guide for others working to design and implement sustainable and high quality anti-racism curricula for residents.


Assuntos
Internato e Residência , Estados Unidos , Humanos , Antirracismo , Currículo , Docentes , Saúde Pública
6.
Nucleic Acids Res ; 49(D1): D1507-D1514, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33180112

RESUMO

Europe PMC (https://europepmc.org) is a database of research articles, including peer reviewed full text articles and abstracts, and preprints - all freely available for use via website, APIs and bulk download. This article outlines new developments since 2017 where work has focussed on three key areas: (i) Europe PMC has added to its core content to include life science preprint abstracts and a special collection of full text of COVID-19-related preprints. Europe PMC is unique as an aggregator of biomedical preprints alongside peer-reviewed articles, with over 180 000 preprints available to search. (ii) Europe PMC has significantly expanded its links to content related to the publications, such as links to Unpaywall, providing wider access to full text, preprint peer-review platforms, all major curated data resources in the life sciences, and experimental protocols. The redesigned Europe PMC website features the PubMed abstract and corresponding PMC full text merged into one article page; there is more evident and user-friendly navigation within articles and to related content, plus a figure browse feature. (iii) The expanded annotations platform offers ∼1.3 billion text mined biological terms and concepts sourced from 10 providers and over 40 global data resources.


Assuntos
Disciplinas das Ciências Biológicas/estatística & dados numéricos , COVID-19/prevenção & controle , Curadoria de Dados/estatística & dados numéricos , Mineração de Dados/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , PubMed , SARS-CoV-2/isolamento & purificação , Disciplinas das Ciências Biológicas/métodos , Pesquisa Biomédica/métodos , Pesquisa Biomédica/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/virologia , Curadoria de Dados/métodos , Mineração de Dados/métodos , Epidemias , Europa (Continente) , Humanos , Internet , SARS-CoV-2/fisiologia
7.
J Clin Psychol ; 79(4): 1082-1098, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36490357

RESUMO

OBJECTIVE: How individuals differentially implement specific emotion regulation (ER) strategies is a critical indicator of the progression of depressive and anxiety disorders. Symptoms of anxiety and depression may be associated with differences in ER, but little evidence to date had examined whether anxiety and depression were associated with individual differences in the real-time use of ER strategies. METHODS: This study used ecological momentary assessment (EMA) in two samples (n = 276) of undergraduate students from a single university who were assessed for 8-10 days. Baseline surveys captured participant self-reported anxiety symptoms and depressive symptoms using the PROMIS-Anxiety scale and the PROMIS-Depression scale, respectively. We measured ER through EMA-adapted prompts from the Cognitive Emotion Regulation Questionnaire (CERQ), which participants received on their internet-enabled cell phones. In pre-registered analyses, we tested the associations between anxiety symptoms with the use of discrete ER strategies in EMA using generalized estimating equations with a log-link function to account for nesting of EMA observations within participants, and further tested whether the findings generalized to depression (not pre-registered). RESULTS: Symptoms of anxiety and depression were associated with greater odds of using both maladaptive and adaptive ER strategy use during the EMA period, and with lower odds of reporting no strategy use. Moreover, associations were generally stronger for maladaptive than adaptive ER strategies. CONCLUSION: Anxiety and depressive symptoms are related to increased regulatory efforts overall, and results suggest that individuals with anxiety and depressive symptoms may be especially prone to use maladaptive ER strategies. Tracking ER strategies in a natural environment can further inform our understanding of how anxious and depressed individuals attempt to regulate emotions.


Assuntos
Depressão , Regulação Emocional , Humanos , Depressão/psicologia , Ansiedade/psicologia , Emoções/fisiologia , Transtornos de Ansiedade
8.
J Community Psychol ; 51(5): 2098-2116, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36776019

RESUMO

Study examined predictors and mental health consequences of appraisal (threat, support satisfaction) and coping (active, avoidant) in a sample of low-income women during coronavirus disease 2019 (COVID-19). Pre-COVID-19 contextual risk and individual resources and COVID-19-specific risk factors were examined as predictors of COVID-19 appraisal and coping, which, in turn, were tested as predictors of changes in depression and anxiety across the pandemic. Pre-COVID-19 resilience predicted more active coping, whereas pre-COVID-19 anxiety and depression predicted more avoidant coping and lower support satisfaction, respectively. Increases in anxiety were predicted by lower pre-COVID-19 self-compassion and higher concurrent threat appraisal and avoidant coping. Increases in depression were related to lower pre-COVID-19 self-compassion, active coping and support satisfaction, and higher COVID-19 hardships and health risk. Findings highlight contextual and individual factors and processes that contribute to mental health problems in a vulnerable population during community-level stressors, with implications for prevention and intervention.


Assuntos
COVID-19 , Humanos , Feminino , COVID-19/psicologia , Saúde Mental , Pandemias , Inquéritos e Questionários , Adaptação Psicológica
9.
BMC Public Health ; 22(1): 1620, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-36028827

RESUMO

BACKGROUND: Over the last decade, the provision of online gambling has intensified with increased access, enhanced betting markets, a broader product range, and prolific marketing. However, little research has explored how this intensification is influencing contemporary gambling experiences. This study focused on two research questions: 1) What changes in online gambling have online gamblers observed over the past decade? 2) How have these changes influenced the online gambling experiences and behaviours reported by treatment-seeking and non-treatment-seeking gamblers? METHODS: Two samples of Australian adults were interviewed: 1) 19 people who had been gambling online for at least a decade and with no history of treatment-seeking for online gambling, and 2) 10 people who had recently sought professional help for an online gambling problem. Telephone interviews were semi-structured, with questions that encouraged participants to consider how their online gambling, including any harmful gambling, had been influenced by changes in operator practices and online gambling environments. Data were analysed using thematic analysis. RESULTS: Both treatment- and non-treatment-seekers noted the increased speed and ease of online gambling, which now enables instant access from anywhere at any time and increased their gambling opportunities. Both groups highlighted the continued proliferation of advertising and inducements for online gambling, particularly during televised sports and racing events, in social media, and through targeted push marketing. Many treatment- and non-treatment-seekers were aware of the vast range of recently introduced bet types, particularly multi-bets. Treatment-seekers disproportionately reported negative effects from these changes, and described how and why they fostered their increased gambling, impulsive gambling, persistence and loss-chasing. They reported limited uptake and effectiveness of current harm minimisation tools. CONCLUSIONS: Counter to stated policy and practice objectives to minimise gambling harm, industry changes that have made online gambling easier, faster, and more heavily incentivised, and increased the array of complex bets with poorer odds, unduly affect addicted and harmed individuals - who are also the most profitable customers. Further consideration is needed to ensure gambling policy, industry practices and public health measures more effectively reduce gambling harm in contemporary settings. Inducements and the poor pricing of complex bets such as multi-bets, and their outsized attraction to players with problems, should be a key focus.


Assuntos
Jogo de Azar , Adulto , Publicidade , Austrália , Humanos , Comportamento Impulsivo , Pesquisa Qualitativa
10.
Infant Child Dev ; 31(4)2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060792

RESUMO

This study examined bidirectional relations between television exposure and effortful control accounting for the effects of family contextual risk factors. Methods: Data were from a sample (N=306) of parents and their preschool-age children (T1 M = 36 mos. in 2008-2010) assessed four times, once every 9 mos. Results: At T1, adolescent parent status predicted lower child delay ability (DA), and maternal depression predicted higher TV time. Above these effects, higher T1 and T2 child executive control (EC) prospectively predicted lower T2 and T3 TV time, while higher T1 TV time predicted lower T2 EC. Higher EC at T4 predicted fewer total problems, greater social competence, and greater academic readiness at T4, and higher TV time at T4 predicted lower academic readiness. DA was unrelated to TV time or adjustment. Conclusion: Findings suggest executive control and TV time predict changes in each other in early childhood, and in turn, executive control predicts better child adjustment while TV time might be more relevant for academic readiness. Moreover, family risk factors appear to play a role in both TV viewing time and effortful control.

11.
Prev Med ; 138: 106157, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32473267

RESUMO

Adolescents' engage in new behaviours such as substance use and change others, such as reducing physical activity. Risks to health from these tend to be considered separately. We examined the association between multiple risk behaviours at age 16 years and outcomes in early adulthood. 5591 young people enrolled in the Avon Longitudinal Study of Parents and Children provided data on at least one of seven adverse outcomes at age ~18 years. We used logistic regression to examine associations between total number of risk behaviours and rates of depression, anxiety, problem gambling, getting into trouble with the police, harmful drinking, obesity and not in education, employment or training (NEET) at age 18 years. We found strong associations between multiple risk behaviours and all seven adverse outcomes. For each additional risk behaviour engaged in the odds of harmful drinking increased by OR = 1.58[95%CI:1.48,1.69], getting into trouble with the police OR = 1.49[95%CI:1.42,1.57], having depression OR = 1.24[95%CI:1.17,1.31], problem gambling OR = 1.20[95%CI:1.13,1.27], NEET OR = 1.19[95%CI:1.11,1.29], anxiety OR = 1.18[95%CI:1.12,1.24] and obesity OR = 1.09[95%CI:1.03,1.15]. Neither adjustment for sex, parental socio-economic position and maternal risk behaviours, nor confining analyses to adolescents with no previous presentation of these adverse outcomes, resulted in any notable reductions in the odds ratios. Investment in interventions and environments that effectively prevent multiple risk behaviour is likely to improve a range of health outcomes in young adults.


Assuntos
Assunção de Riscos , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Adulto , Criança , Estudos de Coortes , Humanos , Estudos Longitudinais , Estudos Prospectivos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem
12.
J Exp Child Psychol ; 192: 104757, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31887486

RESUMO

The current study broadens our understanding of preschoolers' early math experiences with parents, recognizing that math knowledge and experiences are inclusive of numeracy as well as non-numeracy domains. Parents and preschoolers (N = 45) were observed exploring three domains of early mathematics knowledge (i.e., number, space, and pattern) during play in three activities (playing cards, building with blocks, and stringing beads, all with activity suggestions). Children were administered a broad math and numeracy measure and individual measures of spatial and patterning skills concurrently and 7 months later. Dyads explored math broadly across most activities but emphasized number more than space or patterning. In addition, there was more overall math exploration during card and bead play than during block play, with the greatest parent support during card play. Parent support was not linked to children's skills, although children's exploration of space and patterns related moderately to their concurrent spatial and pattern skills. Overall, parents and young children explored a variety of early math domains in guided play contexts, with an emphasis on numeracy. Future work should aim to increase the breadth and rigor of individual concepts that parents and preschoolers explore during play.


Assuntos
Conceitos Matemáticos , Poder Familiar , Jogos e Brinquedos , Pré-Escolar , Feminino , Humanos , Masculino
13.
Nucleic Acids Res ; 46(D1): D1254-D1260, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29161421

RESUMO

Europe PMC (https://europepmc.org) is a comprehensive resource of biomedical research publications that offers advanced tools for search, retrieval, and interaction with the scientific literature. This article outlines new developments since 2014. In addition to delivering the core database and services, Europe PMC focuses on three areas of development: individual user services, data integration, and infrastructure to support text and data mining. Europe PMC now provides user accounts to save search queries and claim publications to ORCIDs, as well as open access profiles for authors based on public ORCID records. We continue to foster connections between scientific data and literature in a number of ways. All the data behind the paper - whether in structured archives, generic archives or as supplemental files - are now available via links to the BioStudies database. Text-mined biological concepts, including database accession numbers and data DOIs, are highlighted in the text and linked to the appropriate data resources. The SciLite community annotation platform accepts text-mining results from various contributors and overlays them on research articles as licence allows. In addition, text miners and developers can access all open content via APIs or via the FTP site.


Assuntos
Pesquisa Biomédica , Bases de Dados Bibliográficas , Mineração de Dados , Internet , Publicações Seriadas , Interface Usuário-Computador
14.
Dev Psychopathol ; 31(3): 999-1009, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31097052

RESUMO

Difficulties with emotion regulation can take many forms, including increased sensitivity to emotional cues and habitual use of maladaptive cognitive or behavioral regulation strategies. Despite extensive research on emotion regulation and youth adjustment, few studies integrate multiple measures of emotion regulation. The present study evaluated the underlying structure of emotion regulation processes in adolescence using both task- and survey-based measures and determined whether differences in these emotion regulation latent factors mediated the association between peer victimization and internalizing psychopathology. Adolescents aged 16-17 years (n = 287; 55% female; 42% White) recruited in three urban centers in the United States completed baseline and follow-up assessments 4 months apart. Three models of emotion regulation were evaluated with confirmatory factor analysis. A three-factor model fit the data best, including cognitive regulation, behavioral regulation, and emotional reactivity latent factors. Task-based measures did not load onto these latent factors. Difficulties with behavioral regulation mediated the association between peer victimization and depression symptoms, whereas cognitive regulation difficulties mediated the association with anxiety symptoms. Findings point to potential targets for intervention efforts to reduce risk for internalizing problems in adolescents following experiences of peer victimization.


Assuntos
Ansiedade/psicologia , Bullying/psicologia , Vítimas de Crime/psicologia , Depressão/psicologia , Emoções/fisiologia , Grupo Associado , Adolescente , Mecanismos de Defesa , Feminino , Humanos , Masculino
15.
J Clin Child Adolesc Psychol ; 48(6): 855-865, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29877730

RESUMO

Coping and emotion regulation are central features of risk and resilience in childhood and adolescence, but research on these constructs has relied on different methods of assessment. The current study aimed to bridge the gap between questionnaire and experimental methods of measuring secondary control coping strategies, specifically distraction and cognitive reappraisal, and examine associations with symptoms of anxiety and depression in youth. A community sample of 70 youth (ages 9-15) completed a novel experimental coping and emotion regulation paradigm and self-report measures of coping and emotion regulation and symptoms. Findings indicate that use of distraction and reappraisal during the laboratory paradigm was associated with lower levels of negative emotion during the task. Youth emotion ratings while implementing distraction, but not reappraisal, during the laboratory task were associated with youth self-reported use of secondary control coping in response to family stress. Youth symptoms of anxiety and depression were also significantly positively associated with negative emotion ratings during the laboratory task, and both laboratory task and self-reported coping and emotion regulation accounted for significant variance in symptoms in youth. Both questionnaire and laboratory methods to assess coping and emotion regulation in youth are important for understanding these processes as possible mechanisms of risk and resilience and continued integration of these methods is a priority for future research.


Assuntos
Adaptação Psicológica/fisiologia , Emoções/fisiologia , Autorrelato , Adolescente , Criança , Feminino , Humanos , Laboratórios , Masculino
16.
J Aging Phys Act ; 27(2): 284-289, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29989472

RESUMO

Exercise has proven health benefits for older adults independent of age, disability, and disease. However, barriers to exercise participation exist, including travel to, and access to, appropriate facilities and programs. Evidence shows that in-home exercise delivered by allied health professionals can improve physical health and prolong independence among individuals with government supported aged care packages. A less costly alternative is program delivery by home care workers. However, effective training for workers and resources to guide the consumer is required. This project evaluated an exercise training module for home care workers and a consumer resource to promote in-home exercise participation among older Australians with government supported aged care packages. Outcomes included a significant improvement in functional capacity as measured by the short physical performance battery (mean increase of 1.4 points), a 19% reduction in participants classified as frail and a reduction in healthcare service access of 47% across the intervention.


Assuntos
Terapia por Exercício , Serviços de Assistência Domiciliar , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Idoso Fragilizado , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Desempenho Físico Funcional , Avaliação de Programas e Projetos de Saúde
17.
Eur J Public Health ; 25(1): 44-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24963150

RESUMO

BACKGROUND: Patterns of risk behaviour during teenage years may vary by socio-economic status (SES). We aimed to examine possible associations between individual and multiple risk behaviours and three measures of SES in mid-adolescence. METHODS: The sample (n = 6406) comprised participants from the Avon Longitudinal Study of Parents and Children, a UK birth cohort. Thirteen risk behaviours spanning sexual health, substance use, self-harm, vehicle-related injury, criminality and physical inactivity were assessed in mid-adolescence (age 15-16 years). Associations between three measures of SES (maternal education, household income and parental social class) and (i) individual risk behaviours and (ii) the total number of risk behaviours were examined. RESULTS: For a one-category reduction in social class, maternal education or income, the odds of having a greater number of multiple risk behaviours increased by 22, 15 and 12%, respectively. At the individual level, there was evidence of a strong relationship with decreasing SES across all three measures of SES and criminality, car passenger risk, TV viewing, scooter risk, early sexual behaviour and weekly tobacco use but insufficient evidence of a relationship for physical inactivity, cycling without a helmet and illicit substance use. There was weak evidence of association between SES and hazardous drinking, self-harm, cannabis use and unprotected sex, but this was not consistent across the SES measures. CONCLUSION: The association between multiple risk behaviours and SES suggests that prevention strategies should apply the principal of proportionate universalism with a focus on more deprived populations, within a population-wide strategy, to prevent widening of social inequalities.


Assuntos
Comportamento do Adolescente , Assunção de Riscos , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Estudos de Coortes , Comorbidade , Crime/estatística & dados numéricos , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco , Comportamento Sedentário , Comportamento Autodestrutivo/epidemiologia , Comportamento Sexual/estatística & dados numéricos , Fatores Socioeconômicos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Reino Unido/epidemiologia
18.
J Biol Chem ; 288(5): 3500-11, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23239881

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD(+), essential for cellular metabolism, energy production, and DNA repair. NAMPT has been extensively studied because of its critical role in these cellular processes and the prospect of developing therapeutics against the target, yet how it regulates cellular metabolism is not fully understood. In this study we utilized liquid chromatography-mass spectrometry to examine the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and serine biosynthesis in cancer cells and tumor xenografts. We show for the first time that NAMPT inhibition leads to the attenuation of glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step due to the reduced availability of NAD(+) for the enzyme. The attenuation of glycolysis results in the accumulation of glycolytic intermediates before and at the glyceraldehyde 3-phosphate dehydrogenase step, promoting carbon overflow into the pentose phosphate pathway as evidenced by the increased intermediate levels. The attenuation of glycolysis also causes decreased glycolytic intermediates after the glyceraldehyde 3-phosphate dehydrogenase step, thereby reducing carbon flow into serine biosynthesis and the TCA cycle. Labeling studies establish that the carbon overflow into the pentose phosphate pathway is mainly through its non-oxidative branch. Together, these studies establish the blockade of glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step as the central metabolic basis of NAMPT inhibition responsible for ATP depletion, metabolic perturbation, and subsequent tumor growth inhibition. These studies also suggest that altered metabolite levels in tumors can be used as robust pharmacodynamic markers for evaluating NAMPT inhibitors in the clinic.


Assuntos
Inibidores Enzimáticos/farmacologia , NAD/biossíntese , Neoplasias/metabolismo , Neoplasias/patologia , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Acrilamidas/farmacologia , Trifosfato de Adenosina/deficiência , Trifosfato de Adenosina/metabolismo , Animais , Isótopos de Carbono , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclo do Ácido Cítrico/efeitos dos fármacos , Feminino , Glicólise/efeitos dos fármacos , Humanos , Marcação por Isótopo , Camundongos , Camundongos SCID , Nicotinamida Fosforribosiltransferase/metabolismo , Via de Pentose Fosfato/efeitos dos fármacos , Piperidinas/farmacologia , Serina/biossíntese , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Ann Am Thorac Soc ; 21(4): 612-619, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38241011

RESUMO

Rationale: Over 20,000 children are hospitalized in the United States for asthma every year. Although initial treatment guidelines are well established, there is a lack of high-quality evidence regarding the optimal respiratory support devices for these patients.Objectives: The objective of this study was to evaluate institutional and temporal variability in the use of respiratory support modalities for pediatric critical asthma.Methods: We conducted a retrospective cohort study using data from the Virtual Pediatrics Systems database. Our study population included children older than 2 years old admitted to a VPS contributing pediatric intensive care unit from January 2012 to December 2021 with a primary diagnosis of asthma or status asthmaticus. We evaluated the percentage of encounters using a high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive bilevel positive pressure ventilation (NIV), and invasive mechanical ventilation (IMV) for all institutions, then divided institutions into quintiles based on the volume of patients. We created logistic regression models to determine the influence of institutional volume and year of admission on respiratory support modality use. We also conducted time-series analyses using Kendall's tau.Results: Our population included 77,115 patient encounters from 163 separate institutions. Institutional use of respiratory modalities had significant variation in HFNC (28.3%, interquartile range [IQR], 11.0-49.0%; P < 0.01), CPAP (1.4%; IQR, 0.3-4.3%; P < 0.01), NIV (8.6%; IQR, 3.5-16.1%; P < 0.01), and IMV (5.1%; IQR, 3.1-8.2%; P < 0.01). Increased institutional patient volume was associated with significantly increased use of NIV (odds ratio [OR], 1.33; 1.29-1.36; P < 0.01) and CPAP (OR, 1.20; 1.15-1.25; P < 0.01), and significantly decreased use of HFNC (OR, 0.80; 0.79-0.81; P < 0.01) and IMV (OR, 0.82; 0.79-0.86; P < 0.01). Time was also associated with a significant increase in the use of HFNC (11.0-52.3%; P < 0.01), CPAP (1.6-5.4%; P < 0.01), and NIV (3.7-21.2%; P < 0.01), whereas there was no significant change in IMV use (6.1-4.0%; P = 0.11).Conclusions: Higher-volume centers are using noninvasive positive pressure ventilation more frequently for pediatric critical asthma and lower frequencies of HFNC and IMV. Treatment with HFNC, CPAP, and NIV for this population is increasing in the last decade.


Assuntos
Asma , Ventilação não Invasiva , Insuficiência Respiratória , Humanos , Criança , Pré-Escolar , Estudos Retrospectivos , Asma/terapia , Respiração Artificial , Hospitalização , Oxigenoterapia , Insuficiência Respiratória/terapia
20.
J Am Soc Cytopathol ; 13(1): 4-9, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38184364

RESUMO

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.


Assuntos
Técnicas Citológicas , Instituições Acadêmicas , Simbiose , Humanos , Escolaridade , América do Norte
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