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PURPOSE: It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I-III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. METHODS: Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher's exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes RESULTS: In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p = .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p = .05) and diabetes (p = .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p = .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. CONCLUSION: Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.
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Neoplasias da Mama , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Medidas de Resultados Relatados pelo PacienteRESUMO
Understanding the mechanics of detrimental convective instabilities in drying polymer solutions is crucial in many applications such as the production of film coatings. It is well known that solvent evaporation in polymer solutions can lead to Rayleigh-Bénard or Marangoni-type instabilities. Here, we reveal another mechanism, namely that evaporation can cause the interface to display Rayleigh-Taylor instabilities due to the build-up of a dense layer at the air-liquid interface. We study experimentally the onset time (tp) of the instability as a function of the macroscopic properties of aqueous polymer solutions, which we tune by varying the polymer concentration (c0), molecular weight and polymer type. In dilute solutions, tp shows two limiting behaviours depending on the polymer diffusivity. For high diffusivity polymers (low molecular weight), the pluming time scales as [Formula: see text]. This result agrees with previous studies on gravitational instabilities in miscible systems where diffusion stabilizes the system. On the other hand, in low diffusivity polymers the pluming time scales as [Formula: see text]. The stabilizing effect of an effective interfacial tension, similar to those in immiscible systems, explains this strong concentration dependence. Above a critical concentration, [Formula: see text], viscosity delays the growth of the instability, allowing time for diffusion to act as the dominant stabilizing mechanism. This results in tp scaling as (ν/c0)2/3. This article is part of the theme issue 'Stokes at 200 (Part 1)'.
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Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers' knowledge of a patient's virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider perceptions of VL monitoring and indicate the importance of policies responsive to individual and environmental challenges of VL monitoring program implementation. Findings may inform scale-up by helping policy-makers identify strategies to improve feasibility and sustainability of VL monitoring.
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Fármacos Anti-HIV/uso terapêutico , Monitoramento de Medicamentos/métodos , Infecções por HIV/tratamento farmacológico , Custos de Cuidados de Saúde , Pessoal de Saúde/psicologia , Recursos em Saúde , Carga Viral/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/economia , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/economia , Infecções por HIV/virologia , Humanos , Entrevistas como Assunto , Malaui , Masculino , Percepção , Carga de TrabalhoRESUMO
Since its emergence in North America, West Nile virus (WNV) has had a large impact on equines, humans, and wild bird communities, yet gaps remain in our understanding of how the virus persists at temperate latitudes when winter temperatures preclude virus replication and host-seeking activity by mosquito vectors. Bird-to-bird transmission at large communal American Crow roosts could provide one mechanism for WNV persistence. Herein, we describe seasonal patterns of crow and Culex mosquito abundance, WNV infection rates, and the prevalence of WNV-positive fecal samples at a winter crow roost to test the hypothesis that bird-to-bird transmission allows WNV to persist at winter crow roosts. Samples were collected from large winter crow roosts in the Sacramento Valley of California from January 2013 until August 2014, encompassing two overwintering roost periods. West Nile virus RNA was detected in local crow carcasses in both summer [13/18 (72% WNV positive)] and winter [18/44 (41% WNV positive)] 2013-2014. Winter infections were unlikely to have arisen by recent bites from infected mosquitoes because Culex host-seeking activity was very low in winter and all Culex mosquitoes collected during winter months tested negative for WNV. Opportunities existed for fecal-oral transfer at the overwintering roost: most carcasses that tested positive for WNV had detectable viral RNA in both kidney and cloacal swabs, suggesting that infected crows were shedding virus in their feces, and >50% of crows at the roost were stained with feces by mid-winter. Moreover, 2.3% of fecal samples collected in late summer, when mosquitoes were active, tested positive for WNV RNA. Nevertheless, none of the 1,119 feces collected from three roosts over two winters contained detectable WNV RNA. This study provided evidence of WNV infection in overwintering American crows without mosquito vector activity, but did not elucidate a mechanism of WNV transmission during winter.
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Corvos/virologia , Febre do Nilo Ocidental/transmissão , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/genética , Migração Animal , Animais , California , Culex/virologia , Fezes/virologia , Modelos Lineares , Estações do Ano , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/veterináriaRESUMO
PURPOSE: The Institute of Medicine (2006) has recommended that cancer survivors completing treatment receive a survivorship care plan (SCP). The survivorship needs in advanced cancer have been overlooked and understudied. The potential role of SCPs for survivors with advanced or metastatic cancer is unknown and was explored in this study. METHODS: We conducted two focus groups of survivors with advanced or metastatic cancer. Participants reviewed a sample JourneyForward™ SCP modified for advanced cancer. Sessions were audiotaped and transcribed; transcripts and field notes were evaluated using inductive content analysis. RESULTS: Sixteen survivors with metastatic cancer participated: 12 (75 %) were female, 15 (94 %) were white, and median age was 66 (range 55-80); 9 participants had breast cancer, 4 colon, 2 prostate, and 1 ovarian cancer. Participants believed that an SCP would be most helpful after initial diagnosis and treatment, but not as helpful once the cancer progressed. They thought a "cancer care plan" focusing solely on the current management would be better to concisely summarize the treatment plan and time frame for the next segment of care for those with advanced cancer. Most participants endorsed the need to have written information to reinforce verbal information received during medical visits since it was difficult to remember information provided. Participants expected their oncologist to assume primary responsibility for coordination of the care plan, but anticipated an important supportive role for primary care providers. To this end, they emphasized the need for better communication between providers. CONCLUSIONS: A cancer care plan developed by the oncologist, similar to an SCP but more focused on current management, may be more useful for survivors with advanced cancer. Exploring this topic in larger groups of more diverse survivors with advanced cancer will help to elucidate the details a written plan of care should contain, and how to promote effective coordination between oncology and primary care providers. IMPLICATIONS FOR CANCER SURVIVORS: There are many transitions of care along the cancer journey. A written plan of care, similar to an SCP, may be useful for survivors with advanced cancer.
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Continuidade da Assistência ao Paciente , Neoplasias/terapia , Planejamento de Assistência ao Paciente , Idoso , Comunicação , Feminino , Grupos Focais , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Neoplasias/reabilitação , Taxa de Sobrevida , Sobreviventes , Estados UnidosRESUMO
BACKGROUND: Metastatic outgrowth in breast cancer can occur years after a seeming cure. Existing model systems of dormancy are limited as they do not recapitulate human metastatic dormancy without exogenous manipulations and are unable to query early events of micrometastases. METHODS: Here, we describe a human ex vivo hepatic microphysiologic system. The system is established with fresh human hepatocytes and non-parenchymal cells (NPCs) creating a microenvironment into which breast cancer cells (MCF7 and MDA-MB-231) are added. RESULTS: The hepatic tissue maintains function through 15 days as verified by liver-specific protein production and drug metabolism assays. The NPCs form an integral part of the hepatic niche, demonstrated within the system through their participation in differential signalling cascades and cancer cell outcomes. Breast cancer cells intercalate into the hepatic niche without interfering with hepatocyte function. Examination of cancer cells demonstrated that a significant subset enter a quiescent state of dormancy as shown by lack of cell cycling (EdU(-) or Ki67(-)). The presence of NPCs altered the cancer cell fraction entering quiescence, and lead to differential cytokine profiles in the microenvironment effluent. CONCLUSIONS: These findings establish the liver microphysiologic system as a relevant model for the study of breast cancer metastases and entry into dormancy.
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Neoplasias da Mama/patologia , Neoplasias Hepáticas/secundário , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Metástase Neoplásica , Transfecção , Microambiente TumoralRESUMO
A fast-growing body of research finds that receptiveness to opposing political views carries reputational benefits. A different body of research finds that opposing political views and the people who hold them are seen as repugnant. How could it be that people receptive to opposing political ideas are viewed positively when the political opponents they are receptive to are seen negatively? In seven main (N = 5,286) and nine supplemental studies (N = 3,983 participants in online studies; N = 124,493 observations in field data), we reconcile this tension by arguing that the identity of the person one is receptive to determines whether receptiveness carries reputational benefits or costs. When the information source belongs to the opposing party, receptiveness to opposing political views often carries reputational costs. We find these reputational costs across both strong and weak signals of receptiveness, eight different political and social issues, and multiple types of prototypical out-party sources. We argue that these costs arise because members of the opposing party are frequently stereotyped as immoral, and thus receptiveness to their ideas is seen negatively. As a boundary condition, we find that the costs of receptiveness are pronounced for sources who are prototypical of the out-party and attenuate (or even reverse) for sources who are nonprototypical. These findings resolve a seeming contradiction between two distinct literatures in psychology, contribute to a rapidly expanding literature on the interpersonal consequences of receptiveness, and lay the groundwork for understanding novel barriers to, and ultimately solutions for, the lack of cross-party openness and political polarization. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Política , Humanos , Adulto , Percepção Social , Feminino , MasculinoRESUMO
Mechanical properties of Arctic sea ice can be inferred by observations of in-ice propagation of compressional, shear, and flexural waves. During the 1980s, impulsive signals were generated by a lead ball or sledgehammer dropped onto the sea ice, and the inference required observation of wave speeds. During ICEX20 and ARCEX23, passive cryophone observations were made of naturally occurring compressional wave resonances. Average first-year ice thicknesses during ICEX20 and ARCEX23 were inferred to be 1.3 and 1.6 m, respectively; these are consistent with independent observations and indicate the potential for remote, autonomous monitoring of sea ice thickness.
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AIMS/HYPOTHESES: Despite oral hypoglycaemic medications being the most commonly used pharmacological treatments for type 2 diabetes, research is limited on their comparative safety, particularly their effects on overall mortality. We compared mortality risk with monotherapy initiation of four oral hypoglycaemic medications in a nationwide cohort of US veterans with type 2 diabetes. METHODS: We identified new users of oral hypoglycaemic medication monotherapy between 2004 and 2009 who received care for at least 1 year from the Veterans Health Administration.Patients were followed until initial monotherapy discontinuation,addition of another diabetes pharmacotherapy, death or end of follow-up. Mortality HRs were estimated using Cox regression adjusted for potential confounding factors. RESULTS: Among new users of metformin, sulfonylureas and rosiglitazone (185,360 men, 7,812 women), 4,256 (2.2%) died during follow-up. Average duration of medication use ranged from 1.4 to 1.7 years. Significantly higher mortality risk was seen for glibenclamide (known as glyburide in the USA and Canada) (HR 1.38, 95% CI 1.27, 1.50) or glipizide (HR 1.55,95% CI 1.43, 1.67) compared with metformin monotherapy,and for glipizide compared with rosiglitazone (HR 1.27, 95%CI 1.01, 1.59) or glibenclamide monotherapy (HR 1.12, 95%CI 1.02, 1.23). A significant sexrosiglitazone interaction was seen (p=0.034) compared with metformin monotherapy, with women having a higher HR (HR 4.36, 95% CI 1.34, 14.20)than men (HR 1.19, 95% CI 0.95, 1.49). CONCLUSIONS/INTERPRETATIONS: Significantly higher mortality was associated with glibenclamide, glipizide and rosiglitazone use compared with metformin, and with glipizide use compared with rosiglitazone or glibenclamide. The potential for residual confounding by indication should be considered in interpreting these results.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Compostos de Sulfonilureia/administração & dosagem , Tiazolidinedionas/administração & dosagem , Veteranos/estatística & dados numéricos , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Seguimentos , Glipizida/administração & dosagem , Glipizida/efeitos adversos , Glibureto/administração & dosagem , Glibureto/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Rosiglitazona , Compostos de Sulfonilureia/efeitos adversos , Tiazolidinedionas/efeitos adversos , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
People often struggle to do what they ideally want because of a conflict between their actual and ideal preferences. âââBy focusing on maximizing engagement, recommendation algorithms appear to be exacerbating this struggle. However, this need not be the case. Here we show that tailoring recommendation algorithms to ideal (vs. actual) preferences would provide meaningful benefits to both users and companies. To examine this, we built algorithmic recommendation systems that generated real-time, personalized recommendations tailored to either a person's actual or ideal preferences. Then, in a high-powered, pre-registered experiment (n = 6488), we measured the effects of these recommendation algorithms. We found that targeting ideal rather than actual preferences resulted in somewhat fewer clicks, but it also increased the extent to which people felt better off and that their time was well spent. Moreover, of note to companies, targeting ideal preferences increased users' willingness to pay for the service, the extent to which they felt the company had their best interest at heart, and their likelihood of using the service again. Our results suggest that users and companies would be better off if recommendation algorithms learned what each person was striving for and nudged individuals toward their own unique ideals.
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Algoritmos , Humanos , ProbabilidadeRESUMO
Protonated benzene cluster ions, H(C(6)H(6))(2)(+) and H(C(6)H(6))(3)(+), are produced in a pulsed electrical discharge source coupled to a supersonic expansion. Mass-selected complexes are investigated with infrared photodissociation spectroscopy in the 1000-3200 cm(-1) region using the method of argon tagging. The IR spectra of H(C(6)H(6))(2)(+)-Ar and H(C(6)H(6))(3)(+)-Ar contain broad bands in the high frequency region resulting from CH-π hydrogen bonds. Sharp peaks are observed in the fingerprint region arising from the ring modes of both the C(6)H(7)(+) and C(6)H(6) moieties. M06-2X calculations have been performed to investigate the structures and vibrational spectra of energetically low-lying configurations of these complexes. H(C(6)H(6))(2)(+) is predicted to have three nearly isoenergetic conformers: the parallel displaced (PD), T-shaped (TS), and canted (C) structures [Jaeger, H. M.; Schaefer, H. F.; Hohenstein, E. G.; Sherrill, C. D. Comput. Theor. Chem. 2011, 973, 47-52]. A comparison of the experimental dimer spectrum with those predicted for the three isomers suggests an average structure between the TS and PD conformers, which is consistent with the low energy barrier predicted to separate these two structures. No evidence is found for the C dimer even though it lies only 1.2 kcal/mol above the PD dimer. Although the trimer is also computed to have many low lying isomers, the IR spectrum limits the possible species present.
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Benzeno/química , Dimerização , Prótons , Vibração , Modelos Moleculares , Conformação Molecular , Espectrofotometria InfravermelhoRESUMO
American voters are assigned to vote at a particular polling location (e.g., a church, school, etc.). We show these assigned polling locations can influence how people vote. Analysis of a recent general election demonstrates that people who were assigned to vote in schools were more likely to support a school funding initiative. This effect persisted even when controlling for voters' political views, demographics, and unobservable characteristics of individuals living near schools. A follow-up experiment using random assignment suggests that priming underlies these effects, and that they can occur outside of conscious awareness. These findings underscore the subtle power of situational context to shape important real-world decisions.
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Tomada de Decisões , Política , Arizona , Educação/economia , Humanos , Funções Verossimilhança , Instituições Acadêmicas/economiaRESUMO
This article reviews how objects can serve as indicators of one's identity and signals of important life events. Objects carry both personal and social meaning, and ownership or usage increases the linkage between the object and the self. Owned objects are valued more due to their linkage with the (positively viewed) self. Similarly, self-views can assimilate to the associations of the owned or used object. We rely on the insights of consistency theories (e.g. Balance Theory) to provide a unifying umbrella for the literature, and we review how the acquisition and abandonment of objects can shape self-views, affect task performance, and serve as inward and outward signals of group membership.
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Propriedade , Análise e Desempenho de Tarefas , Humanos , Resolução de Problemas , AutoimagemRESUMO
PURPOSE: To assess the prevalence of visual disturbances among school-aged children in prioritized education zones in France. METHODS: The PlanVue® pilot project was designed to detect and manage visual disturbances in school-aged children in the prioritized education areas of the city of Nanterre, France. During this pilot study, a cohort of 515 children aged 4 to 13 years underwent a school vision screening between January and March 2019, consisting of an overall evaluation of the child's visual behavior, measurement of uncorrected visual acuity in each eye, objective refraction with a photoscreener and strabismus screening. If the examination was abnormal as determined by impaired vision or an algorithm based on the abnormalities found, the children were referred to an ophthalmologist. RESULTS: Decreased visual acuity was found in 20% of school-aged children. Out of the 515 children screened, 22% were referred to an ophthalmologist. Among these children, 13% were diagnosed with amblyopia, 73% with spherical ametropia, 57% with astigmatism and 2% with strabismus. Of the entire population screened, 12% of the children needed optical correction but had not received glasses. CONCLUSION: This study confirms the high prevalence of uncorrected refractive errors among school-age children. A screening program carried out in a school environment by paramedical professionals might make it possible to considerably reduce the rate of uncorrected visual disorders and their consequences.
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Erros de Refração , Seleção Visual , Criança , Análise de Dados , Humanos , Projetos Piloto , Prevalência , Erros de Refração/diagnóstico , Erros de Refração/epidemiologia , Instituições Acadêmicas , Transtornos da Visão/diagnóstico , Transtornos da Visão/epidemiologiaRESUMO
OBJECTIVE: Teenagers are susceptible to delivering small-for-gestational-age (SGA) infants. Previous studies suggest that maternal growth may contribute, as a result of preferential nutrient partitioning to the mother. We investigated the impact of maternal growth on birthweight in pregnant teenagers in the UK, and examined endocrine mediators of nutrient partitioning. DESIGN: A prospective observational multicentre study, About Teenage Eating, conducted between 2004 and 2007. SETTING: Four hospitals in socially-deprived areas of Manchester and London. POPULATION: A total of 500 pregnant adolescents (14-18 years of age) with a singleton pregnancy were recruited at 10-21 weeks of gestation, with follow-up studies on 368 subjects. A cohort of 80 pregnant adults (25-40 years of age) provided a control group for determining growth. METHODS: Skeletal growth, weight gain and skinfold thickness were measured from first to third trimester, together with maternal levels of micronutrients and metabolic hormones: insulin-like growth factor (IGF) system and leptin. Dietary analyses were performed. MAIN OUTCOME MEASURE: SGA birth. RESULTS: Maternal growth was not associated with SGA birth: growing mothers delivered more large-for-gestational-age infants (OR 2.51; P < 0.05). Growers had greater weight gain (P < 0.001), fat accrual (P < 0.001) and red cell folate concentrations (P < 0.01) than non-growers. Maternal IGF-I (P < 0.01) and leptin (P < 0.001) were positively associated with maternal and fetal growth, whereas IGF-I (P < 0.001) was negatively associated. Teenagers that were underweight at booking or with low weight gain were at greater risk of SGA birth. CONCLUSIONS: Maternal growth was not detrimental to fetal growth in this UK population of teenagers. Greater weight gain and higher concentrations of IGF-I in growing teenagers may provide anabolic drive for maternal and fetal growth.
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Desenvolvimento Fetal/fisiologia , Recém-Nascido de Baixo Peso , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez na Adolescência/fisiologia , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Adolescente , Adulto , Inglaterra/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Ácido Fólico/sangue , Humanos , Recém-Nascido , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Joelho/anatomia & histologia , Leptina/metabolismo , Micronutrientes/sangue , Gravidez , Gravidez na Adolescência/metabolismo , Gravidez na Adolescência/estatística & dados numéricos , Estudos Prospectivos , Aumento de Peso/fisiologiaRESUMO
In June 2019 the first equine case of Hendra virus in the Hunter Valley, New South Wales, Australia was detected. An urgent human and animal health response took place, involving biosecurity measures, contact tracing, promotion of equine vaccinations and investigation of flying fox activity in the area. No human or additional animal cases occurred. Equine vaccination uptake increased by over 30-fold in the surrounding region in the three months following the case. Black flying fox and grey-headed flying fox species were detected in the Valley. The incident prompted review of Hendra virus resources at local and national levels. This event near the "horse capital of Australia", is the southernmost known equine Hendra case. Management of the event was facilitated by interagency collaboration involving human and animal health experts. Ongoing One Health partnerships are essential for successful responses to future zoonotic events.
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The present research suggests that biased interpersonal perceptions can mediate prime-to-behavior effects and introduces a new moderator for when such mediation will occur. Across 5 experiments, the authors provide evidence that priming effects on behavior in interpersonal contexts are mediated by social perceptions, but only when participants are focused on the other person. These effects occur when other-focus is primed (Experiment 1), when other-focus is high owing to the decision-making situation (Experiment 2), and when other-focus is dispositionally high (Experiment 3). Experiments 4 and 5 bring additional support for a biased perception account by ruling out an alternative behavior-perception link and showing that other-focus can moderate not only the mediating mechanism of prime-to-behavior effects but also the behavioral effects themselves. The implications of these results for increasing understanding of behavioral priming effects in rich social contexts are discussed.
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Relações Interpessoais , Comportamento Social , Percepção Social , Humanos , IdiomaRESUMO
AIM: Glucagon-like peptide-1 is an incretin hormone secreted by the intestinal L-cell with a circadian rhythm that parallels expression of the core clock gene, Bmal1. Although feeding rats a high-fat/high-sucrose Western diet impairs rhythmic glucagon-like peptide-1 release, the mechanisms underlying this effect remain unclear. Therefore, the aim of this study was to determine the pathway(s) by which the saturated fat, palmitate, a major component of the Western diet, impairs circadian glucagon-like peptide-1 secretion. METHODS: Murine mGLUTag L-cells were synchronized, and the effects of palmitate pre-treatment on gene expression and glucagon-like peptide-1 secretion were determined, in addition to metabolite quantification, mitochondrial function analysis and enzyme inhibition and activation assays. Glucagon-like peptide-1 secretion was also analysed in ileal crypt cultures from control and Bmal1 knockout mice. RESULTS: Pre-treatment with palmitate dampened Bmal1 mRNA and protein expression and glucagon-like peptide-1 secretion at 8 but not 20 hours after cell synchronization (P < .05-.001). Glucagon-like peptide-1 release was also impaired in Bmal1 knockout cultures as compared to wild-type controls (P < .001). Palmitate pre-treatment reduced expression of the Bmal1 downstream target, nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the synthesis of NAD+ . This was paralleled by dampening of total NAD+ levels, as well as impaired mitochondrial function and ATP production (P < .05-.001). Whereas direct inhibition of nicotinamide phosphoribosyltransferase also decreased glucagon-like peptide-1 release, activation of this enzyme restored glucagon-like peptide-1 secretion in the presence of palmitate. CONCLUSION: Palmitate impairs L-cell clock function at the peak of Bmal1 gene expression, thereby impairing mitochondrial function and ultimately rhythmic glucagon-like peptide-1 secretion.
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Fatores de Transcrição ARNTL/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Células Enteroendócrinas/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Palmitatos/farmacologia , Fatores de Transcrição ARNTL/efeitos dos fármacos , Animais , Células Enteroendócrinas/metabolismo , CamundongosRESUMO
The major heat shock protein, hsp 70, of Dictyostelium discoideum was found to be rapidly phosphorylated. Analysis of [35S]methionine- and 32Pi-labeled hsp 70 revealed that two similar but distinct proteins of about 70,000 daltons each are synthesized at a high rate after a heat shock, and that each has a phosphorylated member. The phosphorylation chiefly modifies threonine residues. Rapid turnover of the phosphate group occurs, resulting in a steady-state condition in which only about half of the hsp 70 is phosphorylated at a given time.