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1.
Nature ; 626(8001): 1125-1132, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38355796

RESUMO

To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage1,2. In bacteria, two families of hibernation factors have been described, but the low conservation of these proteins and the huge diversity of species, habitats and environmental stressors have confounded their discovery3-6. Here, by combining cryogenic electron microscopy, genetics and biochemistry, we identify Balon, a new hibernation factor in the cold-adapted bacterium Psychrobacter urativorans. We show that Balon is a distant homologue of the archaeo-eukaryotic translation factor aeRF1 and is found in 20% of representative bacteria. During cold shock or stationary phase, Balon occupies the ribosomal A site in both vacant and actively translating ribosomes in complex with EF-Tu, highlighting an unexpected role for EF-Tu in the cellular stress response. Unlike typical A-site substrates, Balon binds to ribosomes in an mRNA-independent manner, initiating a new mode of ribosome hibernation that can commence while ribosomes are still engaged in protein synthesis. Our work suggests that Balon-EF-Tu-regulated ribosome hibernation is a ubiquitous bacterial stress-response mechanism, and we demonstrate that putative Balon homologues in Mycobacteria bind to ribosomes in a similar fashion. This finding calls for a revision of the current model of ribosome hibernation inferred from common model organisms and holds numerous implications for how we understand and study ribosome hibernation.


Assuntos
Proteínas de Bactérias , Resposta ao Choque Frio , Fatores de Terminação de Peptídeos , Biossíntese de Proteínas , Psychrobacter , Proteínas Ribossômicas , Ribossomos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/ultraestrutura , Fator Tu de Elongação de Peptídeos/química , Fator Tu de Elongação de Peptídeos/metabolismo , Fator Tu de Elongação de Peptídeos/ultraestrutura , Proteínas Ribossômicas/química , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/ultraestrutura , Ribossomos/química , Ribossomos/metabolismo , Ribossomos/ultraestrutura , Psychrobacter/química , Psychrobacter/genética , Psychrobacter/metabolismo , Psychrobacter/ultraestrutura , Microscopia Crioeletrônica , Fatores de Terminação de Peptídeos/química , Fatores de Terminação de Peptídeos/genética , Fatores de Terminação de Peptídeos/metabolismo , Fatores de Terminação de Peptídeos/ultraestrutura
2.
Mol Biol Evol ; 41(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37987564

RESUMO

Ribosomes from different species can markedly differ in their composition by including dozens of ribosomal proteins that are unique to specific lineages but absent in others. However, it remains unknown how ribosomes acquire new proteins throughout evolution. Here, to help answer this question, we describe the evolution of the ribosomal protein msL1/msL2 that was recently found in ribosomes from the parasitic microorganism clade, microsporidia. We show that this protein has a conserved location in the ribosome but entirely dissimilar structures in different organisms: in each of the analyzed species, msL1/msL2 exhibits an altered secondary structure, an inverted orientation of the N-termini and C-termini on the ribosomal binding surface, and a completely transformed 3D fold. We then show that this fold switching is likely caused by changes in the ribosomal msL1/msL2-binding site, specifically, by variations in rRNA. These observations allow us to infer an evolutionary scenario in which a small, positively charged, de novo-born unfolded protein was first captured by rRNA to become part of the ribosome and subsequently underwent complete fold switching to optimize its binding to its evolving ribosomal binding site. Overall, our work provides a striking example of how a protein can switch its fold in the context of a complex biological assembly, while retaining its specificity for its molecular partner. This finding will help us better understand the origin and evolution of new protein components of complex molecular assemblies-thereby enhancing our ability to engineer biological molecules, identify protein homologs, and peer into the history of life on Earth.


Assuntos
Parasitos , Proteínas Ribossômicas , Animais , Proteínas Ribossômicas/genética , Ribossomos/genética , Ribossomos/metabolismo , RNA Ribossômico/genética , Sítios de Ligação , Parasitos/genética
3.
Nucleic Acids Res ; 51(15): 8048-8059, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37395434

RESUMO

Ribosomal genes are widely used as 'molecular clocks' to infer evolutionary relationships between species. However, their utility as 'molecular thermometers' for estimating optimal growth temperature of microorganisms remains uncertain. Previously, some estimations were made using the nucleotide composition of ribosomal RNA (rRNA), but the universal application of this approach was hindered by numerous outliers. In this study, we aimed to address this problem by identifying additional indicators of thermal adaptation within the sequences of ribosomal proteins. By comparing sequences from 2021 bacteria with known optimal growth temperature, we identified novel indicators among the metal-binding residues of ribosomal proteins. We found that these residues serve as conserved adaptive features for bacteria thriving above 40°C, but not at lower temperatures. Furthermore, the presence of these metal-binding residues exhibited a stronger correlation with the optimal growth temperature of bacteria compared to the commonly used correlation with the 16S rRNA GC content. And an even more accurate correlation was observed between the optimal growth temperature and the YVIWREL amino acid content within ribosomal proteins. Overall, our work suggests that ribosomal proteins contain a more accurate record of bacterial thermal adaptation compared to rRNA. This finding may simplify the analysis of unculturable and extinct species.


Assuntos
RNA Ribossômico , Proteínas Ribossômicas , Bactérias/genética , Filogenia , Proteínas Ribossômicas/genética , RNA Ribossômico/genética , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/química , Temperatura , Thermus thermophilus/genética
4.
Eur Urban Reg Stud ; 31(2): 184-199, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38618199

RESUMO

The capacity of the state to develop and implement policy at the complex nexus of energy infrastructure, social inequality and housing is indicative of the political priorities of governing structures and, by extension, the nature of statecraft more generally. We compare and contrast the energy poverty amelioration policies of two former Yugoslav and two post-Soviet states located outside the European Union, but seeking to join its regulatory sphere - Serbia, Montenegro, Ukraine and Georgia - against the background of deep and persistent patterns of domestic energy hardship. We are particularly interested in uncovering the time horizons, socio-technical systems and target constituencies of different policy measures, as well as energy sector-specific responses to the COVID-19 pandemic. We find that most states in the region have done little to address some of the more substantive challenges around improving housing quality, energy efficiency and gender inequality. However, energy poverty is present in the policy lexicon of all case study countries, and Ukraine, in particular, has advanced a number of more sophisticated approaches and programmes.

5.
Mol Ecol ; 32(24): 6924-6938, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37873915

RESUMO

Environmental circumstances shaping soil microbial communities have been studied extensively. However, due to disparate study designs, it has been difficult to resolve whether a globally consistent set of predictors exists, or context-dependency prevails. Here, we used a network of 18 grassland sites (11 of those containing regional plant productivity gradients) to examine (i) if similar abiotic or biotic factors predict both large-scale (across sites) and regional-scale (within sites) patterns in bacterial and fungal community composition, and (ii) if microbial community composition differs consistently at two levels of regional plant productivity (low vs. high). Our results revealed that bacteria were associated with particular soil properties (such as base saturation) and both bacteria and fungi were associated with plant community composition across sites and within the majority of sites. Moreover, a discernible microbial community signal emerged, clearly distinguishing high and low-productivity soils across different grasslands independent of their location in the world. Hence, regional productivity differences may be typified by characteristic soil microbial communities across the grassland biome. These results could encourage future research aiming to predict the general effects of global changes on soil microbial community composition in grasslands and to discriminate fertile from infertile systems using generally applicable microbial indicators.


Assuntos
Pradaria , Microbiota , Microbiologia do Solo , Microbiota/genética , Fungos/genética , Bactérias/genética , Plantas/microbiologia , Solo
6.
J Biol Chem ; 297(3): 100987, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34364871

RESUMO

Progressive fibrosis leads to loss of organ function and affects many organs as a result of excessive extracellular matrix production. The ubiquitous matrix polysaccharide hyaluronan (HA) is central to this through association with its primary receptor, CD44, which exists as standard CD44 (CD44s) or multiple splice variants. Mediators such as profibrotic transforming growth factor (TGF)-ß1 and proinflammatory interleukin (IL)-1ß are widely associated with fibrotic progression. TGF-ß1 induces myofibroblast differentiation, while IL-1ß induces a proinflammatory fibroblast phenotype that promotes fibroblast binding to monocyte/macrophages. CD44 expression is essential for both responses. Potential CD44 splice variants involved, however, are unidentified. The TGF-ß1-activated CD44/epidermal growth factor receptor complex induces differentiation of metastatic cells through interactions with the matrix metalloproteinase inducer, CD147. This study aimed to determine the CD44 variants involved in TGF-ß1- and IL-1ß-mediated responses and to investigate the potential profibrotic role of CD147. Using immunocytochemistry and quantitative PCR, standard CD44s were shown to be essential for both TGF-ß1-induced fibroblast/myofibroblast differentiation and IL-1ß-induced monocyte binding. Co-immunoprecipitation identified that CD147 associated with CD44s. Using CD147-siRNA and confocal microscopy, we also determined that incorporation of the myofibroblast marker, αSMA, into F-actin stress fibers was prevented in the absence of CD147 and myofibroblast-dependent collagen gel contraction was inhibited. CD147 did not associate with HA, but removal of HA prevented the association of CD44s with CD147 at points of cell-cell contact. Taken together, our data suggest that CD44s/CD147 colocalization is essential in regulating the mechanical tension required for the αSMA incorporation into F-actin stress fibers that regulates myofibroblast phenotype.


Assuntos
Basigina/fisiologia , Diferenciação Celular/fisiologia , Receptores de Hialuronatos/fisiologia , Miofibroblastos/citologia , Fator de Crescimento Transformador beta1/fisiologia , Basigina/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/metabolismo , Interleucina-1beta/fisiologia , Miofibroblastos/metabolismo
7.
J Pediatr ; 240: 228-234.e1, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478747

RESUMO

OBJECTIVE: To evaluate associations of race/ethnicity and social determinants with 90-day rehospitalization for mental health conditions to acute care nonpsychiatric children's hospitals. STUDY DESIGN: We conducted a retrospective cohort analysis of mental health hospitalizations for children aged 5-18 years from 2016 to 2018 at 32 freestanding US children's hospitals using the Children's Hospital Association's Pediatric Health Information System database to assess the association of race/ethnicity and social determinants (insurance payer, neighborhood median household income, and rurality of patient home location) with 90-day rehospitalization. Risk factors for rehospitalization were modeled using mixed-effects multivariable logistic regression. RESULTS: Among 23 556 index hospitalizations, there were 1382 mental health rehospitalizations (5.9%) within 90 days. Non-Hispanic Black children were 26% more likely to be rehospitalized than non-Hispanic White children (aOR 1.26, 95% CI 1.08-1.48). Those with government insurance were 18% more likely to be rehospitalized than those with private insurance (aOR 1.18, 95% CI 1.04-1.34). In contrast, those living in a suburban location were 22% less likely to be rehospitalized than those living in an urban location (suburban: aOR 0.78, 95% CI 0.63-0.97). CONCLUSIONS: Non-Hispanic Black children and those with public insurance were at greatest risk for 90-day rehospitalization, and risk was lower in those residing in suburban locations. Future work should focus on upstream interventions that will best attenuate social disparities to promote equity in pediatric mental healthcare.


Assuntos
Transtornos Mentais/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Determinantes Sociais da Saúde/etnologia , Adolescente , Criança , Pré-Escolar , Feminino , Disparidades nos Níveis de Saúde , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco
8.
Am J Pathol ; 190(6): 1236-1255, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32201263

RESUMO

Hyaluronidase (HYAL)-2 is a weak, acid-active, hyaluronan-degrading enzyme broadly expressed in somatic tissues. Aberrant HYAL2 expression is implicated in diverse pathology. However, a significant proportion of HYAL2 is enzymatically inactive; thus the mechanisms through which HYAL2 dysregulation influences pathobiology are unclear. Recently, nonenzymatic HYAL2 functions have been described, and nuclear HYAL2 has been shown to influence mRNA splicing to prevent myofibroblast differentiation. Myofibroblasts drive fibrosis, thereby promoting progressive tissue damage and leading to multimorbidity. This study identifies a novel HYAL2 cytoplasmic function in myofibroblasts that is unrelated to its enzymatic activity. In fibroblasts and myofibroblasts, HYAL2 interacts with the GTPase-signaling small molecule ras homolog family member A (RhoA). Transforming growth factor beta 1-driven fibroblast-to-myofibroblast differentiation promotes HYAL2 cytoplasmic relocalization to bind to the actin cytoskeleton. Cytoskeletal-bound HYAL2 functions as a key regulator of downstream RhoA signaling and influences profibrotic myofibroblast functions, including myosin light-chain kinase-mediated myofibroblast contractility, myofibroblast migration, myofibroblast collagen/fibronectin deposition, as well as connective tissue growth factor and matrix metalloproteinase-2 expression. These data demonstrate that, in certain biological contexts, the nonenzymatic effects of HYAL2 are crucial in orchestrating RhoA signaling and downstream pathways that are important for full profibrotic myofibroblast functionality. In conjunction with previous data demonstrating the influence of HYAL2 on RNA splicing, these findings begin to explain the broad biological effects of HYAL2.


Assuntos
Fibroblastos/metabolismo , Hialuronoglucosaminidase/metabolismo , Miofibroblastos/metabolismo , Transdução de Sinais/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Fibrose/metabolismo , Humanos , Masculino , Splicing de RNA , Ratos
9.
J Pediatr ; 239: 32-38.e5, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34216629

RESUMO

OBJECTIVE: To determine the frequency of neurologic complications associated with influenza in hospitalized children. STUD DESIGN: We performed a cross-sectional study of children (2 months through 17 years of age) with influenza discharged from 49 children's hospitals in the Pediatric Health Information System during the influenza seasons of 2015-2020. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. We assessed length of stay (LOS), intensive care unit (ICU) admission, ICU LOS, 30-day hospital readmissions, deaths, and hospital costs associated with these events. Patient-level risk factors associated with neurologic complications were identified using multivariable logistic regression. RESULTS: Of 29 676 children hospitalized with influenza, 2246 (7.6%) had a concurrent diagnosis of a neurologic complication; the most frequent were febrile seizures (5.0%), encephalopathy (1.7%), and nonfebrile seizures (1.2%). Hospital LOS, ICU admission, ICU LOS, deaths, and hospital costs were greater in children with neurologic complications compared with those without complications. Risk factors associated with neurologic complications included male sex (aOR 1.1, 95% CI 1.02-1.21), Asian race/ethnicity (aOR 1.7, 95% CI 1.4-2.1) (compared with non-Hispanic White), and the presence of a chronic neurologic condition (aOR 3.7, 95% CI 3.1-4.2). CONCLUSIONS: Neurologic complications are common in children hospitalized with influenza, especially among those with chronic neurologic conditions, and are associated with worse outcomes compared with children without neurologic complications. These findings emphasize the strategic importance of influenza immunization and treatment, especially in high-risk populations.


Assuntos
Influenza Humana/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Influenza Humana/mortalidade , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Doenças do Sistema Nervoso/etiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
10.
New Phytol ; 231(2): 763-776, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33507570

RESUMO

The arbuscular mycorrhizal (AM) fungi are a globally distributed group of soil organisms that play critical roles in ecosystem function. However, the ecological niches of individual AM fungal taxa are poorly understood. We collected > 300 soil samples from natural ecosystems worldwide and modelled the realised niches of AM fungal virtual taxa (VT; approximately species-level phylogroups). We found that environmental and spatial variables jointly explained VT distribution worldwide, with temperature and pH being the most important abiotic drivers, and spatial effects generally occurring at local to regional scales. While dispersal limitation could explain some variation in VT distribution, VT relative abundance was almost exclusively driven by environmental variables. Several environmental and spatial effects on VT distribution and relative abundance were correlated with phylogeny, indicating that closely related VT exhibit similar niche optima and widths. Major clades within the Glomeraceae exhibited distinct niche optima, Acaulosporaceae generally had niche optima in low pH and low temperature conditions, and Gigasporaceae generally had niche optima in high precipitation conditions. Identification of the realised niche space occupied by individual and phylogenetic groups of soil microbial taxa provides a basis for building detailed hypotheses about how soil communities respond to gradients and manipulation in ecosystems worldwide.


Assuntos
Micorrizas , Ecossistema , Fungos , Concentração de Íons de Hidrogênio , Filogenia , Solo , Microbiologia do Solo , Temperatura
11.
Home Health Care Serv Q ; 40(4): 324-339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34467824

RESUMO

The Care Transitions Intervention (CTI) is an evidence-based intervention aimed at supporting the transition from hospital back to the community for patients to ultimately reduce preventable re-hospitalization. In a pilot randomized controlled trial, we examined the preliminary effectiveness of an Enhanced Care Transitions Intervention (ECTI), CTI with the addition of peer support, for a racially/ethnically diverse sample of older adults (age 60+) with co-morbid major depression. We observed a significant decline in health-related quality of life (HRQOL) after being discharged from the hospital among those who received CTI. Additionally, those who received ECTI either maintained HRQOL scores, or, saw improvement in HRQOL scores. Findings suggest the Enhanced Care Transitions Intervention can maintain or improve HRQOL and reduce disparities for older participants from diverse racial/ethnic backgrounds with clinical depression.


Assuntos
Transferência de Pacientes , Qualidade de Vida , Idoso , Depressão/terapia , Humanos , Pessoa de Meia-Idade , Alta do Paciente , Projetos Piloto
12.
Ecol Lett ; 23(8): 1298-1309, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32369874

RESUMO

Anthropogenic disturbance has generated a significant loss of biodiversity worldwide and grazing by domestic herbivores is a contributing disturbance. Although the effects of grazing on plants are commonly explored, here we address the potential multi-trophic effects on animal biodiversity (e.g. herbivores, pollinators and predators). We conducted a meta-analysis on 109 independent studies that tested the response of animals or plants to livestock grazing relative to livestock excluded. Across all animals, livestock exclusion increased abundance and diversity, but these effects were greatest for trophic levels directly dependent on plants, such as herbivores and pollinators. Detritivores were the only trophic level whose abundance decreased with livestock exclusion. We also found that the number of years since livestock was excluded influenced the community and that the effects of grazer exclusion on animal diversity were strongest in temperate climates. These findings synthesise the effects of livestock grazing beyond plants and demonstrate the indirect impacts of livestock grazing on multiple trophic levels in the animal community. We identified the potentially long-term impacts that livestock grazing can have on lower trophic levels and consequences for biological conservation. We also highlight the potentially inevitable cost to global biodiversity from livestock grazing that must be balanced against socio-economic benefits.


Assuntos
Biodiversidade , Gado , Animais , Ecossistema , Herbivoria , Estado Nutricional , Plantas
13.
Oncologist ; 25(11): 943-953, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32869930

RESUMO

BACKGROUND: We examined the current biomarker landscape in breast cancer when programmed death-ligand 1 (PD-L1) testing is integrated with comprehensive genomic profiling (CGP). MATERIAL AND METHODS: We analyzed data from samples of 312 consecutive patients with breast carcinoma tested with both CGP and PD-L1 (SP142) immunohistochemistry (IHC) during routine clinical care. These samples were stratified into hormone receptor positive (HR+)/human epidermal growth factor receptor negative (HER2-; n = 159), HER2-positive (n = 32), and triple-negative breast cancer (TNBC) cohorts (n = 121). RESULTS: We found that in the TNBC cohort, 43% (52/121) were immunocyte PD-L1-positive, and in the HR+/HER2- cohort, 30% (48/159) had PIK3CA companion diagnostics mutations, and hence were potentially eligible for atezolizumab plus nab-paclitaxel or alpelisib plus fulvestrant, respectively. Of the remaining 212 patients, 10.4% (22/212) had a BRCA1/2 mutation, which, if confirmed by germline testing, would allow olaparib plus talazoparib therapy. Of the remaining 190 patients, 169 (88.9%) were positive for another therapy-associated marker or a marker that would potentially qualify the patient for a clinical trial. In addition, we examined the relationship between immunocyte PD-L1 positivity and different tumor mutation burden (TMB) cutoffs and found that when a TMB cutoff of ≥9 mutations per Mb was applied (cutoff determined based on prior publication), 11.6% (14/121) patients were TMB ≥9 mutations/Mb and of these, TMB ≥9 mutations per Mb, 71.4% (10/14) were also positive for PD-L1 IHC. CONCLUSION: Our integrated PD-L1 and CGP methodology identified 32% of the tested patients as potentially eligible for at least one of the two new Food and Drug Administration approved therapies, atezolizumab or alpelisib, and an additional 61.2% (191/312) had other biomarker-guided potential therapeutic options. IMPLICATIONS FOR PRACTICE: This integrated programmed death-ligand 1 immunohistochemistry and comprehensive genomic profiling methodology identified 32% of the tested patients as eligible for at least one of the two new Food and Drug Administration-approved therapies, atezolizumab or alpelisib, and an additional 61.2% (191/312) had other biomarker-guided potential therapeutic options. These findings suggest new research opportunities to evaluate the predictive utility of other commonly seen PIK3CA mutations in hormone receptor-positive breast cancers and to standardize tumor mutation burden cutoffs to evaluate its potentially predictive role in triple-negative breast cancer.


Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Genômica , Humanos , Imuno-Histoquímica
14.
Oncologist ; 24(3): 372-374, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30181314

RESUMO

BCR-ABL1-like B-Acute Lymphoblastic Leukemia (B-ALL) is a subset of B-ALL with a poor prognosis that is found in all age groups. Definitive identification of these patients is difficult in routine clinical practice as gene expression profiling, the gold standard test, is not widely available. Comprehensive genomic profiling performed on 450 patients with extensive fusion profiling revealed a wide range of genomic alterations which were consistent with a classification of BCR-ABL1-like B-ALL in 29% of cases. This manuscript highlights a clinically available alternative method for identifying a large subset of patients with BCR-ABL1-like B-ALL.


Assuntos
Proteínas de Fusão bcr-abl/genética , Perfilação da Expressão Gênica/métodos , Genômica/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Análise de Sequência de DNA/métodos , Análise de Sequência de RNA/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Ann Behav Med ; 53(7): 608-620, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-30247506

RESUMO

BACKGROUND: Interpersonal discrimination is linked to greater risk for cardiovascular disease (CVD) and this association varies by race/ethnicity. PURPOSE: To examine whether exposure to everyday discrimination prospectively predicts elevated blood pressure (BP), whether this association differs by race/ethnicity, and is mediated by adiposity indices. METHODS: Using data for 2,180 self-identified White, Black, Chinese, Japanese, and Hispanic participants from the Study of Women's Health Across the Nation, we examined associations among exposure to (higher vs. lower) everyday discrimination at baseline and BP and hypertension (HTN; systolic blood pressure [SBP] ≥ 140 mmHg; diastolic blood pressure [DBP] ≥ 90 mmHg; or self-reported HTN medication use) risk over a 10 year period. Additionally, we used the bootstrap method to assess repeated, time-varying markers of central and overall adiposity (waist circumference and body mass index [BMI] (kg/m2), respectively) as potential mediators. RESULTS: Exposure to everyday discrimination predicted increases in SBP and DBP over time, even after adjusting for known demographic, behavioral, or medical risk factors. However, greater waist circumference or BMI (examined separately) mediated these observations. Notably, there were no racial/ethnic differences in the observed association and HTN risk was not predicted. CONCLUSIONS: The current findings suggest that everyday discrimination may contribute to elevated BP over time in U.S. women, in part, through increased adiposity. These findings demonstrate the complexity of the linkage of discrimination to CVD risk and raise the need to closely examine biobehavioral pathways that may serve as potential mediators.


Assuntos
Adiposidade , Pressão Sanguínea , Índice de Massa Corporal , Hipertensão/etnologia , Discriminação Social/etnologia , Circunferência da Cintura , Adulto , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Racismo/etnologia , Estados Unidos/etnologia
16.
Psychosom Med ; 80(1): 114-121, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28787363

RESUMO

OBJECTIVE: Everyday discrimination may contribute to incident metabolic syndrome (MetS) in the United States and related racial/ethnic differences in MetS. The study investigated whether everyday discrimination predicted MetS in a diverse sample. METHODS: A longitudinal, cohort study of 2132 women (mean [standard deviation] = 45.8 [2.7] years) who self-reported as black (n = 523), white (n = 1065), Chinese (n = 194), Japanese (n = 227), or Hispanic (n = 123) at baseline drawn from seven cities across the United States was conducted. MetS was defined in accordance with the National Cholesterol Education Program Adult Treatment Panel III criteria. The Everyday Discrimination scale was used to assess exposure to and level of everyday discrimination. RESULTS: Everyday discrimination exposure at baseline predicted a 33% greater incidence of MetS during the 13.89-year (standard deviation = 3.83, hazard ratio (HR) = 1.33, 95% confidence interval [CI] = 1.11-1.64, p = .001) follow-up in the full sample and was most pronounced in black, Hispanic, and Japanese women. Each 1-point increase in the continuous everyday discrimination score (HR = 1.03, 95% CI =1.01-1.05, p = .001) predicted a 3% greater incidence of MetS and, specifically, blood pressure (HR = 1.01, 95% CI = 1.00-1.03, p = .04), waist circumference (HR = 1.05, 95% CI =1.03-1.06, p < .001), and triglyceride level (HR = 1.02, 95% CI =1.00-1.04, p = .01). These associations were independent of risk factors including physical activity, socioeconomic status, smoking, and alcohol consumption. CONCLUSIONS: Everyday discrimination contributes to poorer metabolic health in midlife women in the United States. These findings have clinical implications for the development of MetS and, ultimately, cardiovascular disease and diabetes, and intervention strategies to reduce these outcomes.


Assuntos
Asiático/estatística & dados numéricos , Negro ou Afro-Americano/etnologia , Hispânico ou Latino/estatística & dados numéricos , Síndrome Metabólica/etnologia , Discriminação Social/etnologia , População Branca/etnologia , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Estados Unidos/etnologia , Saúde da Mulher
17.
Curr Treat Options Oncol ; 19(8): 41, 2018 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-29931654

RESUMO

OPINION STATEMENT: In recent years, large-scale genomic studies have expanded our knowledge regarding genomic drivers in tumors of the central nervous system. While histopathologic analysis of brain tumors remains the primary method for tumor classification, the clinical utility of molecular and genomic testing to support and/or complement tumor classification continues to expand. This approach enhances diagnostic accuracy and provides clinicians with objective data to facilitate discussions regarding prognosis and treatment decisions, including selection of clinical trials. Ensuring accurate diagnoses is fundamental to the management of brain tumor patients. However, given the morphologic overlap among primary brain tumors, genomic data can be used to help distinguish tumor lineage. In its clearest form, we have embraced the concept of an integrated diagnosis, which combines traditional histopathology findings with molecular and genomic data. Patient prognosis varies significantly based on a tumor's genomic profile. For neuro-oncology patients, outcome studies linking diagnoses with genomic profiles show significant differences based on tumor biomarkers such as IDH1/2, H3F3A, BRAF, and CDKN2A and TERT status. Therefore, easy access to reliable genomic data is important in understanding a patient's disease and developing a clinical strategy wherein targeted molecular or immune therapies can be incorporated into the discussion.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Glioma/diagnóstico , Glioma/terapia , Medicina de Precisão , Fatores Etários , Biomarcadores Tumorais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Ensaios Clínicos como Assunto , Terapia Combinada , Gerenciamento Clínico , Predisposição Genética para Doença , Testes Genéticos , Genômica/métodos , Glioma/genética , Glioma/mortalidade , Humanos , Imunoterapia , Terapia de Alvo Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Medicina de Precisão/métodos , Prognóstico , Resultado do Tratamento
18.
Disasters ; 42(3): 519-540, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29105811

RESUMO

This paper presents a Business Recovery Assessment Framework (BRAF) to help researchers and practitioners design robust, repeatable, and comparable studies of business recovery in various post-disruption contexts. Studies assessing business recovery without adequately considering the research aims, recovery definitions, and indicators can produce misleading findings. The BRAF is composed of a series of steps that guide the decisions that researchers need to make to ensure: (i) that recovery is indeed being measured; (ii) that the indicators of recovery that are selected align with the objectives of the study and the definition of recovery; and, where necessary, (iii) that appropriate comparative control variables are in place. The paper draws on a large dataset of business surveys collected following the earthquakes in Canterbury, New Zealand, on 4 September 2010 and 22 February 2011 to demonstrate the varied conclusions that different recovery indicators can produce and to justify the need for a systematic approach to business recovery assessments.


Assuntos
Comércio/organização & administração , Desastres , Terremotos , Humanos , Nova Zelândia , Inquéritos e Questionários
19.
Disasters ; 41(2): 388-408, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27238231

RESUMO

Insurance is widely acknowledged to be an important component of an organisation's disaster preparedness and resilience. Yet, little analysis exists of how well current commercial insurance policies and practices support organisational recovery in the wake of a major disaster. This exploratory qualitative research, supported by some quantitative survey data, evaluated the efficacy of commercial insurance following the sequence of earthquakes in Canterbury, New Zealand, in 2010 and 2011. The study found that, generally, the commercial insurance sector performed adequately, given the complexity of the events. However, there are a number of ways in which insurers could improve their operations to increase the efficacy of commercial insurance cover and to assist organisational recovery following a disaster. The most notable of these are: (i) better wording of policies; (ii) the availability of sector-specific policies; (iii) the enhancement of claims assessment systems; and (iv) risk-based policy pricing to incentivise risk reduction measures.


Assuntos
Desastres , Terremotos , Eficiência Organizacional , Seguro/organização & administração , Comércio , Humanos , Revisão da Utilização de Seguros , Nova Zelândia , Estudos de Casos Organizacionais , Políticas , Pesquisa Qualitativa
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