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1.
Cell ; 174(4): 938-952.e13, 2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30096313

RESUMO

Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated epitopes recognized on the viral surface glycoprotein (GP) and secreted glycoprotein (sGP), readouts of multiple neutralization assays, fraction of virions left un-neutralized, glycan structures, phagocytic and natural killer cell functions elicited, and in vivo protection in a mouse challenge model. Neutralization and induction of multiple immune effector functions (IEFs) correlated most strongly with protection. Neutralization predominantly occurred via epitopes maintained on endosomally cleaved GP, whereas maximal IEF mapped to epitopes farthest from the viral membrane. Unexpectedly, sGP cross-reactivity did not significantly influence in vivo protection. This comprehensive dataset provides a rubric to evaluate novel antibodies and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Ebolavirus/imunologia , Epitopos/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Glicoproteínas de Membrana/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Feminino , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Resultado do Tratamento
2.
CA Cancer J Clin ; 74(1): 50-81, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37909877

RESUMO

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.


Assuntos
Neoplasias Pulmonares , Fumar , Feminino , Humanos , Masculino , American Cancer Society , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Programas de Rastreamento/métodos , Medição de Risco , Estados Unidos/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Revisões Sistemáticas como Assunto
3.
Cell ; 167(7): 1762-1773.e12, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27984726

RESUMO

Overlapping genes pose an evolutionary dilemma as one DNA sequence evolves under the selection pressures of multiple proteins. Here, we perform systematic statistical and mutational analyses of the overlapping HIV-1 genes tat and rev and engineer exhaustive libraries of non-overlapped viruses to perform deep mutational scanning of each gene independently. We find a "segregated" organization in which overlapped sites encode functional residues of one gene or the other, but never both. Furthermore, this organization eliminates unfit genotypes, providing a fitness advantage to the population. Our comprehensive analysis reveals the extraordinary manner in which HIV minimizes the constraint of overlapping genes and repurposes that constraint to its own advantage. Thus, overlaps are not just consequences of evolutionary constraints, but rather can provide population fitness advantages.


Assuntos
Evolução Biológica , HIV-1/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Entropia , Aptidão Genética , Infecções por HIV/virologia , Humanos , Mutação , Fases de Leitura Aberta , Produtos do Gene rev do Vírus da Imunodeficiência Humana/genética
4.
CA Cancer J Clin ; 73(2): 120-146, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36346402

RESUMO

American Indian and Alaska Native (AIAN) individuals are diverse culturally and geographically but share a high prevalence of chronic illness, largely because of obstacles to high-quality health care. The authors comprehensively examined cancer incidence and mortality among non-Hispanic AIAN individuals, compared with non-Hispanic White individuals for context, using population-based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Overall cancer rates among AIAN individuals were 2% higher than among White individuals for incidence (2014 through 2018, confined to Purchased/Referred Care Delivery Area counties to reduce racial misclassification) but 18% higher for mortality (2015 through 2019). However, disparities varied widely by cancer type and geographic region. For example, breast and prostate cancer mortality rates are 8% and 31% higher, respectively, in AIAN individuals than in White individuals despite lower incidence and the availability of early detection tests for these cancers. The burden among AIAN individuals is highest for infection-related cancers (liver, stomach, and cervix), for kidney cancer, and for colorectal cancer among indigenous Alaskans (91.3 vs. 35.5 cases per 100,000 for White Alaskans), who have the highest rates in the world. Steep increases for early onset colorectal cancer, from 18.8 cases per 100,000 Native Alaskans aged 20-49 years during 1998 through 2002 to 34.8 cases per 100,000 during 2014 through 2018, exacerbated this disparity. Death rates for infection-related cancers (liver, stomach, and cervix), as well as kidney cancer, were approximately two-fold higher among AIAN individuals compared with White individuals. These findings highlight the need for more effective strategies to reduce the prevalence of chronic oncogenic infections and improve access to high-quality cancer screening and treatment for AIAN individuals. Mitigating the disparate burden will require expanded financial support of tribal health care as well as increased collaboration and engagement with this marginalized population.


Assuntos
Neoplasias Colorretais , Indígenas Norte-Americanos , Neoplasias Renais , Masculino , Feminino , Humanos , Indígena Americano ou Nativo do Alasca
5.
Annu Rev Microbiol ; 75: 515-539, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34348026

RESUMO

To reproduce, prokaryotic viruses must hijack the cellular machinery of their hosts and redirect it toward the production of viral particles. While takeover of the host replication and protein synthesis apparatus has long been considered an essential feature of infection, recent studies indicate that extensive reprogramming of host primary metabolism is a widespread phenomenon among prokaryotic viruses that is required to fulfill the biosynthetic needs of virion production. In this review we provide an overview of the most significant recent findings regarding virus-induced reprogramming of prokaryotic metabolism and suggest how quantitative systems biology approaches may be used to provide a holistic understanding of metabolic remodeling during lytic viral infection.


Assuntos
Vírus , Células Procarióticas
6.
Proc Natl Acad Sci U S A ; 120(8): e2202388120, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36780524

RESUMO

Climate change is radically altering coral reef ecosystems, mainly through increasingly frequent and severe bleaching events. Yet, some reefs have exhibited higher thermal tolerance after bleaching severely the first time. To understand changes in thermal tolerance in the eastern tropical Pacific (ETP), we compiled four decades of temperature, coral cover, coral bleaching, and mortality data, including three mass bleaching events during the 1982 to 1983, 1997 to 1998 and 2015 to 2016 El Niño heatwaves. Higher heat resistance in later bleaching events was detected in the dominant framework-building genus, Pocillopora, while other coral taxa exhibited similar susceptibility across events. Genetic analyses of Pocillopora spp. colonies and their algal symbionts (2014 to 2016) revealed that one of two Pocillopora lineages present in the region (Pocillopora "type 1") increased its association with thermotolerant algal symbionts (Durusdinium glynnii) during the 2015 to 2016 heat stress event. This lineage experienced lower bleaching and mortality compared with Pocillopora "type 3", which did not acquire D. glynnii. Under projected thermal stress, ETP reefs may be able to preserve high coral cover through the 2060s or later, mainly composed of Pocillopora colonies that associate with D. glynnii. However, although the low-diversity, high-cover reefs of the ETP could illustrate a potential functional state for some future reefs, this state may only be temporary unless global greenhouse gas emissions and resultant global warming are curtailed.


Assuntos
Antozoários , Recifes de Corais , Animais , Ecossistema , Resposta ao Choque Térmico , Oceanos e Mares
7.
J Virol ; 98(4): e0193523, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38451085

RESUMO

Placental infection plays a central role in the pathogenesis of congenital human cytomegalovirus (HCMV) infections and is a cause of fetal growth restriction and pregnancy loss. HCMV can replicate in some trophoblast cell types, but it remains unclear how the virus evades antiviral immunity in the placenta and how infection compromises placental development and function. Human trophoblast stem cells (TSCs) can be differentiated into extravillous trophoblasts (EVTs), syncytiotrophoblasts (STBs), and organoids, and this study assessed the utility of TSCs as a model of HCMV infection in the first-trimester placenta. HCMV was found to non-productively infect TSCs, EVTs, and STBs. Immunofluorescence assays and flow cytometry experiments further revealed that infected TSCs frequently only express immediate early viral gene products. Similarly, RNA sequencing found that viral gene expression in TSCs does not follow the kinetic patterns observed during lytic infection in fibroblasts. Canonical antiviral responses were largely not observed in HCMV-infected TSCs and TSC-derived trophoblasts. Rather, infection dysregulated factors involved in cell identity, differentiation, and Wingless/Integrated signaling. Thus, while HCMV does not replicate in TSCs, infection may perturb trophoblast differentiation in ways that could interfere with placental function. IMPORTANCE: Placental infection plays a central role in human cytomegalovirus (HCMV) pathogenesis during pregnancy, but the species specificity of HCMV and the limited availability and lifespan of primary trophoblasts have been persistent barriers to understanding how infection impacts this vital organ. Human trophoblast stem cells (TSCs) represent a new approach to modeling viral infection early in placental development. This study reveals that TSCs, like other stem cell types, restrict HCMV replication. However, infection perturbs the expression of genes involved in differentiation and cell fate determination, pointing to a mechanism by which HCMV could cause placental injury.


Assuntos
Citomegalovirus , Células-Tronco , Trofoblastos , Replicação Viral , Feminino , Humanos , Gravidez , Diferenciação Celular/genética , Linhagem da Célula/genética , Citomegalovirus/crescimento & desenvolvimento , Citomegalovirus/patogenicidade , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/fisiopatologia , Infecções por Citomegalovirus/virologia , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Placenta/citologia , Placenta/patologia , Placenta/fisiopatologia , Placenta/virologia , Primeiro Trimestre da Gravidez , Células-Tronco/citologia , Células-Tronco/virologia , Trofoblastos/citologia , Trofoblastos/virologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-38867674

RESUMO

We tested the hypothesis that compliance with the National Institute for Occupational Safety and Health (NIOSH) heat stress recommendations will prevent reductions in glomerular filtration rate (GFR) across a range of wet bulb globe temperatures (WBGTs) and work-rest ratios at a fixed work intensity. We also tested the hypothesis that non-compliance would result in a reduction in GFR compared to a work-rest matched compliant trial. Twelve healthy adults completed five trials (four NIOSH compliant, one non-compliant) that consisted of four hours of exposure to a range of WBGTs. Subjects walked on a treadmill (Hprod: ~430 W) and work-rest ratios (work per hour: 60, 45, 30, 15 min) were prescribed as a function of WBGT (24°C, 26.5°C, 28.5°C, 30°C, 36°C), and subjects drank a sport drink ad libitum. Peak core temperature (TC) and percentage change in body weight (%DBW) were measured. Creatinine clearance measured pre- and postexposure provided a primary marker of GFR. Peak TC did not differ among NIOSH compliant trials (p=0.065) but differed between compliant vs. non-compliant trials (p<0.001). %DBW did not differ among NIOSH compliant trials (p=0.131) or between compliant vs. non-compliant trials (p=0.185). Creatinine clearance did not change or differ among compliant trials (p³0.079). Creatinine clearance did not change or differ between compliant vs. non-compliant trials (p³0.661). Compliance with the NIOSH recommendations maintained GFR. Surprisingly, despite a greater heat strain in a non-compliant trial, GFR was maintained highlighting the potential relative importance of hydration.

9.
Am J Physiol Renal Physiol ; 326(5): F802-F813, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38545652

RESUMO

Men are likely at greater risk for heat-induced acute kidney injury compared with women, possibly due to differences in vascular control. We tested the hypothesis that the renal vasoconstrictor and vasodilator responses will be greater in younger women compared with men during passive heat stress. Twenty-five healthy adults [12 women (early follicular phase) and 13 men] completed two experimental visits, heat stress or normothermic time-control, assigned in a block-randomized crossover design. During heat stress, participants wore a water-perfused suit perfused with 50°C water. Core temperature was increased by ∼0.8°C in the first hour before commencing a 2-min cold pressor test (CPT). Core temperature remained clamped and at 1-h post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75 min, and 150 min post-protein. Beat-to-beat blood pressure (Penaz method) was measured and segmental artery vascular resistance (VR, Doppler ultrasound) was calculated as segmental artery blood velocity ÷ mean arterial pressure. CPT-induced increases in segmental artery VR did not differ between trials (trial effect: P = 0.142) nor between men (heat stress: 1.5 ± 1.0 mmHg/cm/s, normothermia: 1.4 ± 1.0 mmHg/cm/s) and women (heat stress: 1.4 ± 1.2 mmHg/cm/s, normothermia: 2.1 ± 1.1 mmHg/cm/s) (group effect: P = 0.429). Reductions in segmental artery VR following oral protein loading did not differ between trials (trial effect: P = 0.080) nor between men (heat stress: -0.6 ± 0.8 mmHg/cm/s, normothermia: -0.6 ± 0.6 mmHg/cm/s) and women (heat stress: -0.5 ± 0.5 mmHg/cm/s, normothermia: -1.1 ± 0.6 mmHg/cm/s) (group effect: P = 0.204). Renal vasoconstrictor responses to the cold pressor test and vasodilator responses following an oral protein load during heat stress or normothermia do not differ between younger men and younger women in the early follicular phase of the menstrual cycle.NEW & NOTEWORTHY The mechanisms underlying greater heat-induced acute kidney injury risk in men versus women remain unknown. This study examined renal vascular control, including both vasodilatory (oral protein load) and vasoconstrictor (cold presser test) responses, during normothermia and heat stress and compared these responses between men and women. The results indicated that in both conditions neither renal vasodilatory nor vasoconstrictor responses differ between younger men and younger women.


Assuntos
Resposta ao Choque Térmico , Vasodilatação , Humanos , Feminino , Masculino , Adulto , Adulto Jovem , Resposta ao Choque Térmico/fisiologia , Estudos Cross-Over , Fatores Sexuais , Resistência Vascular , Rim/irrigação sanguínea , Vasoconstrição , Circulação Renal , Artéria Renal , Transtornos de Estresse por Calor/fisiopatologia , Pressão Sanguínea/fisiologia , Fatores Etários
10.
Cancer ; 130(8): 1330-1348, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38279776

RESUMO

Despite decades of declining mortality rates, lung cancer remains the leading cause of cancer death in the United States. This article examines lung cancer incidence, stage at diagnosis, survival, and mortality using population-based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Over the past 5 years, declines in lung cancer mortality became considerably greater than declines in incidence among men (5.0% vs. 2.6% annually) and women (4.3% vs. 1.1% annually), reflecting absolute gains in 2-year relative survival of 1.4% annually. Improved outcomes likely reflect advances in treatment, increased access to care through the Patient Protection and Affordable Care Act, and earlier stage diagnosis; for example, compared with a 4.6% annual decrease for distant-stage disease incidence during 2013-2019, the rate for localized-stage disease rose by 3.6% annually. Localized disease incidence increased more steeply in states with the highest lung cancer screening prevalence (by 3%-5% annually) than in those with the lowest (by 1%-2% annually). Despite progress, disparities remain. For example, Native Americans have the highest incidence and the slowest decline (less than 1% annually among men and stagnant rates among women) of any group. In addition, mortality rates in Mississippi and Kentucky are two to three times higher than in most western states, largely because of elevated historic smoking prevalence that remains. Racial and geographic inequalities highlight longstanding opportunities for more concerted tobacco-control efforts targeted at high-risk populations, including improved access to smoking-cessation treatments and lung cancer screening, as well as state-of-the-art treatment.


Assuntos
Neoplasias Pulmonares , Neoplasias , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Neoplasias/terapia , Detecção Precoce de Câncer , Patient Protection and Affordable Care Act , Programa de SEER , Sistema de Registros , Incidência
11.
Cancer ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38818898

RESUMO

BACKGROUND: Individuals who identify as lesbian, gay, bisexual, transgender, queer, intersex, or gender-nonconforming (LGBTQ+) experience discrimination and minority stress that may lead to elevated cancer risk. METHODS: In the absence of population-based cancer occurrence information for this population, this article comprehensively examines contemporary, age-adjusted cancer risk factor and screening prevalence using data from the National Health Interview Survey, Behavioral Risk Factor Surveillance System, and National Youth Tobacco Survey, and provides a literature review of cancer incidence and barriers to care. RESULTS: Lesbian, gay, and bisexual adults are more likely to smoke cigarettes than heterosexual adults (16% compared to 12% in 2021-2022), with the largest disparity among bisexual women. For example, 34% of bisexual women aged 40-49 years and 24% of those 50 and older smoke compared to 12% and 11%, respectively, of heterosexual women. Smoking is also elevated among youth who identify as lesbian, gay, or bisexual (4%) or transgender (5%) compared to heterosexual or cisgender (1%). Excess body weight is elevated among lesbian and bisexual women (68% vs. 61% among heterosexual women), largely due to higher obesity prevalence among bisexual women (43% vs. 38% among lesbian women and 33% among heterosexual women). Bisexual women also have a higher prevalence of no leisure-time physical activity (35% vs. 28% among heterosexual women), as do transgender individuals (30%-31% vs. 21%-25% among cisgender individuals). Heavier alcohol intake among lesbian, gay, and bisexual individuals is confined to bisexual women, with 14% consuming more than 7 drinks/week versus 6% of heterosexual women. In contrast, prevalence of cancer screening and risk reducing vaccinations in LGBTQ+ individuals is similar to or higher than their heterosexual/cisgender counterparts except for lower cervical and colorectal cancer screening among transgender men. CONCLUSIONS: People within the LGBTQ+ population have a higher prevalence of smoking, obesity, and alcohol consumption compared to heterosexual and cisgender people, suggesting a higher cancer burden. Health systems have an opportunity to help inform these disparities through the routine collection of information on sexual orientation and gender identity to facilitate cancer surveillance and to mitigate them through education to increase awareness of LGBTQ+ health needs.

12.
Immunity ; 42(1): 186-98, 2015 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-25607463

RESUMO

Most B-cell lymphomas arise in the germinal center (GC), where humoral immune responses evolve from potentially oncogenic cycles of mutation, proliferation, and clonal selection. Although lymphoma gene expression diverges significantly from GC B cells, underlying mechanisms that alter the activities of corresponding regulatory elements (REs) remain elusive. Here we define the complete pathogenic circuitry of human follicular lymphoma (FL), which activates or decommissions REs from normal GC B cells and commandeers enhancers from other lineages. Moreover, independent sets of transcription factors, whose expression was deregulated in FL, targeted commandeered versus decommissioned REs. Our approach revealed two distinct subtypes of low-grade FL, whose pathogenic circuitries resembled GC B or activated B cells. FL-altered enhancers also were enriched for sequence variants, including somatic mutations, which disrupt transcription-factor binding and expression of circuit-linked genes. Thus, the pathogenic regulatory circuitry of FL reveals distinct genetic and epigenetic etiologies for GC B-cell transformation.


Assuntos
Linfócitos B/fisiologia , Redes Reguladoras de Genes , Centro Germinativo/patologia , Linfoma de Células B/genética , Elementos Reguladores de Transcrição/imunologia , Adulto , Idoso , Transformação Celular Neoplásica , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Ativação Linfocitária/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Elementos Reguladores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Br J Nutr ; 131(7): 1181-1188, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38012859

RESUMO

The weight, urine colour and thirst (WUT) Venn diagram is a practical hydration assessment tool; however, it has only been investigated during first-morning. This study investigated accuracy of the WUT Venn diagram at morning and afternoon timepoints compared with blood and urine markers. Twelve men (21 ± 2 years; 81·0 ± 15·9 kg) and twelve women (22 ± 3 years; 68·8 ± 15·2 kg) completed the study. Body mass, urine colour, urine specific gravity (USG), urine osmolality (UOSM), thirst and plasma osmolality (POSM) were collected at first-morning and afternoon for 3 consecutive days in free-living (FL) and euhydrated states. Number of markers indicating dehydration levels were categorised into either 3, 2, 1 or 0 WUT markers. Receiver operating characteristics analysis calculated the sensitivity and specificity of 1, 2 or 3 hydration markers in detecting dehydration or euhydration. Specificity values across morning and afternoon exhibited high diagnostic accuracy for USG (0·890-1·000), UOSM (0·869-1·000) and POSM (0·787-0·990) when 2 and 3 WUT markers were met. Sensitivity values across both timepoints exhibited high diagnostic accuracy for USG (0·826-0·941) and UOSM (0·826-0·941), but not POSM in the afternoon (0·324) when 0 and 1 WUT markers were met. The WUT Venn diagram is accurate in detecting dehydration for WUT2 and WUT3 based off USG, UOSM and POSM during first-morning and afternoon. Applied medical, sport and occupational practitioners can use this tool in field settings for hydration assessment not only at various timepoints throughout the day but also in FL individuals.


Assuntos
Desidratação , Sede , Masculino , Humanos , Feminino , Desidratação/diagnóstico , Cor , Concentração Osmolar , Urinálise , Urina
14.
AIDS Behav ; 28(4): 1356-1369, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37971613

RESUMO

Suboptimal adherence to oral PrEP medications, particularly among younger sexual minority men (SMM), continues to be a key barrier to achieving more substantial declines in new HIV infections. Although variety of interventions, including web and text-message-based applications, have successfully addressed PrEP adherence, very few have addressed the potential influence of alcohol. This pilot study explored whether the Game Plan for PrEP, a brief, web-based and text messaging intervention, helped promote PrEP persistence and adherence and reduced condomless sex and alcohol use. Seventy-three heavy-drinking SMM on PrEP were recruited online from states with Ending the HIV Epidemic jurisdictions and randomly assigned 1:1 to receive either the Game Plan for PrEP intervention or an attention-matched control. We collected online surveys assessing primary outcomes at one, three, and six months post-enrollment. As secondary outcomes, we also collected dried blood spot samples at baseline, three, and six months to analyze for biomarkers of PrEP and alcohol use. Our results showed that the odds of stopping PrEP or experiencing a clinically meaningful lapse in PrEP adherence (≥ 4 consecutive missed doses) were not different across the two conditions. We also did not find evidence of any differences in condomless sex or drinking outcomes across conditions, although participants in both conditions reported drinking less often over time. These findings were consistent across both self-reported outcomes and biomarkers. Overall, we did not find evidence that our brief, web and text messaging intervention encouraged more optimal PrEP coverage or moderate their alcohol use.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Envio de Mensagens de Texto , Masculino , Humanos , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Projetos Piloto , Homossexualidade Masculina , Fármacos Anti-HIV/uso terapêutico , Adesão à Medicação , Profilaxia Pré-Exposição/métodos , Biomarcadores
15.
Chem Rev ; 122(14): 12046-12109, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35763791

RESUMO

One of the hallmark advances in our understanding of metalloprotein function is showcased in our ability to design new, non-native, catalytically active protein scaffolds. This review highlights progress and milestone achievements in the field of de novo metalloprotein design focused on reports from the past decade with special emphasis on de novo designs couched within common subfields of bioinorganic study: heme binding proteins, monometal- and dimetal-containing catalytic sites, and metal-containing electron transfer sites. Within each subfield, we highlight several of what we have identified as significant and important contributions to either our understanding of that subfield or de novo metalloprotein design as a discipline. These reports are placed in context both historically and scientifically. General suggestions for future directions that we feel will be important to advance our understanding or accelerate discovery are discussed.


Assuntos
Metaloproteínas , Sítios de Ligação , Catálise , Domínio Catalítico , Elétrons , Metaloproteínas/metabolismo , Modelos Moleculares
16.
Appetite ; 193: 107125, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37980952

RESUMO

The purpose of the current study was to examine main and interaction effects of parental feeding characteristics and adolescent emotional eating in relation to adolescents' unhealthful food and sugar-sweetened beverage intake. Data was used from the Family Life, Activity, Sun, Health, and Eating (FLASHE) study, which is an internet-administered cross-sectional study of adolescent-parent dyads. There were 1573 dyads who completed all study questionnaires. Adolescents completed measures of their emotional eating and dietary intake and parents completed items of parental feeding practices and legitimacy of parental authority. Adolescents with parents who reported higher instrumental feeding, higher limiting and legitimacy of authority, and lower role modeling and stimulus control had greater unhealthful eating and sugar-sweetened beverage intake. Elevated adolescent emotional eating strengthened the positive association between parental instrumental feeding and adolescent unhealthful food and sugar-sweetened beverage intake. Elevated adolescent emotional eating weakened the negative association between parental role modeling and stimulus control and adolescent sugar-sweetened beverage consumption. There was no interaction between parental role modeling and stimulus control and adolescent emotional eating for unhealthful food intake and no interaction between parental limiting and legitimacy of authority and adolescent emotional eating for unhealthful food or sugar-sweetened beverage intake. Given these findings, adolescent obesity and nutrition interventions and preventions should target both parental feeding characteristics and adolescent emotional eating.


Assuntos
Obesidade Infantil , Bebidas Adoçadas com Açúcar , Humanos , Adolescente , Estudos Transversais , Pais/psicologia , Alimentos , Comportamento Alimentar , Bebidas
17.
Appetite ; 195: 107231, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38246427

RESUMO

Although parenting styles and child feeding practices are conceptualized as distal, static predictors of child eating and weight outcomes, few studies have examined the temporal stability (i.e., change over time) of these parenting measures. Also, parental characteristics, such as mental health or socio-demographics, may make it more or less difficult to sustain consistent parenting behavior. This study examined the temporal stability of parenting styles and child feeding practices and the association between temporal stability indices with maternal sociodemographic and mental health characteristics. The analytic sample included 161 ethnically diverse mothers enrolled in a six-wave bi-annual longitudinal study. During each wave, mothers reported on their parenting styles and child feeding practices using validated self-report questionnaires. Temporal stability indices for parenting styles were moderate for authoritative (ICC = 0.57) and authoritarian (ICC = 0.70) styles, yet high for permissive (ICC = 0.78) styles. Temporal stability scores for child feeding practices were low for discipline (ICC = 0.33), limit setting (ICC = 0.33), monitoring (ICC = 0.36), and pressure to eat (ICC = 0.34); however, restriction (ICC = 0.53) and role modeling of healthy eating were moderate (ICC = 0.73). Greater income and education status were positively associated with stability in authoritative, authoritarian, and permissive parenting styles, as well as with limit setting, monitoring, role modeling of healthy eating, and pressure to eat feeding practices. Higher anxiety and depressive symptoms and lower self-esteem were negatively associated with permissive parenting styles and role modeling of healthy eating. Findings show that maternal parenting styles and child feeding practices fluctuate over time, and sociodemographic and mental health characteristics are related to stability of some of these parenting styles and behaviors.


Assuntos
Poder Familiar , Pais , Criança , Feminino , Humanos , Poder Familiar/psicologia , Estudos Longitudinais , Pais/psicologia , Mães/psicologia , Inquéritos e Questionários , Comportamento Alimentar/psicologia , Comportamento Infantil/psicologia
18.
Appetite ; 192: 107127, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37980955

RESUMO

Food addiction (FA) is a concept centered around the addictive potential of highly palatable processed foods, though there is debate over the discriminative validity of FA as a distinct construct from binge-eating symptomatology. This study explored how trait measures of FA and binge-eating symptoms independently and interactively predicted eating behaviors and posited correlates of FA and binge eating measured via ecological momentary assessment (EMA). Adult participants (N = 49) who met the criteria for FA and/or binge-eating disorder completed baseline measures of FA (Yale Food Addiction Scale [YFAS 2.0]) and binge-eating symptoms (Eating Pathology Symptom Inventory [EPSI] binge eating scale) followed by a 10-day EMA protocol. Generalized linear mixed models examined the independent effects of YFAS 2.0, EPSI, and their interaction predicting EMA outcomes. Higher YFAS 2.0 symptom count scores were uniquely related to greater EMA-measured overeating, loss of control eating, negative and positive affect, and impulsivity when controlling for EPSI scores. Conversely, higher EPSI scores were uniquely related to greater EMA-measured eagerness and urge to eat, and expectancies that eating would improve mood. No interaction effects were significant. These results highlight potential distinctions between phenomena captured by FA and other measures of binge eating, in that FA symptoms may be a marker of heightened binge-eating severity, emotional arousal, and impulsivity.


Assuntos
Transtorno da Compulsão Alimentar , Bulimia , Dependência de Alimentos , Adulto , Humanos , Transtorno da Compulsão Alimentar/psicologia , Dependência de Alimentos/diagnóstico , Avaliação Momentânea Ecológica , Comportamento Alimentar/psicologia
19.
Am J Otolaryngol ; 45(1): 104069, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37862881

RESUMO

BACKGROUND: While nasal epistaxis balloons are generally seen as safe and routinely utilized by both surgical and nonsurgical providers, the complication profile related to this type of device has not been well defined. OBJECTIVE: The objective of this study was to utilize the FDA MAUDE (Manufacturer and User Facility Device Experience) database to better assess adverse events (AE) related to use of nasal epistaxis balloons. Reports were individually tabulated and events were categorized with special attention to AEs. METHODS: The FDA MAUDE database was queried for all medical device reports (MDR) related to nasal epistaxis balloon devices from January 2012 to November 2022. RESULTS: 19 MDRs met inclusion criteria. 5 MDRs were classified as device related (26.3 %); two events were reported for balloon leak and deflation, two events were reported for device breakage, and one device related event was unknown. 14 MDRs (73.7 %) were classified as patient related. Two documented MDRs were patient deaths due to exsanguination. Additional serious AEs included balloon ingestion and subsequent small bowel perforation (n = 1), cerebrospinal fluid leak (n = 1), skull base violation and intracranial placement of the device (n = 1), and respiratory distress (n = 3). CONCLUSION: Though epistaxis control with nasal balloons is generally seen as a safe procedure, there have been several concerning AEs reported. While two reports of death due to exsanguination were the most severe AEs, multiple other life-threatening AEs were also documented. Increased awareness of associated complications can be used to better counsel patients during the informed consent process as well as providers in their clinical decision making.


Assuntos
Epistaxe , Exsanguinação , Humanos , Estados Unidos , Epistaxe/etiologia , Epistaxe/terapia , Bases de Dados Factuais
20.
Subst Use Misuse ; 59(4): 608-615, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38149796

RESUMO

Background: Recent research has shown obesity to be associated with e-cigarette use and appeal, but models have yet to examine how weight status may be related to e-cigarette dependence among e-cigarette users. Objectives: To increase our understanding of pathways from body mass index (BMI) to e-cigarette dependence, the present cross-sectional observational study investigated a model in which BMI, sweet taste responsiveness, and the interaction of BMI and sweet taste responsiveness are associated with e-cigarette dependence indirectly via seven conceptually-distinct motives for e-cigarette use. Data from several e-cigarette clinical laboratory research studies were pooled and analyzed; only current e-cigarette users were included in the analyses (N=330). Structural equation modeling was used to analyze the hypothesized model. Results: BMI was positively associated with lower social/environmental goad motives and higher weight control motives, and BMI x sweet taste interaction terms found that sweet taste responsiveness strengthened the association of BMI and weight control motives. BMI was not directly or indirectly associated with e-cigarette dependence nor was there a bivariate association between BMI and e-cigarette dependence. Sweet taste responsiveness was positively associated with greater affiliative attachment motives, cognitive enhancement motives, cue exposure-associative process motives, weight control motives, and affect enhancement motives. Sweet taste responsiveness was bivariately associated with e-cigarette dependence and mediation paths show indirect relations to e-cigarette dependence via three of the seven motives. Conclusions: The findings suggest that sweet taste responsiveness, opposed to BMI, is associated with a wider range of e-cigarette use motives and indirectly relates to e-cigarette dependence via several e-cigarette use motives.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Índice de Massa Corporal , Paladar , Estudos Transversais
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