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1.
BMC Pregnancy Childbirth ; 24(1): 475, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997658

RESUMO

BACKGROUND: Experiences during the birth hospitalization affect a family's ability to establish and maintain breastfeeding. The Ten Steps to Successful Breastfeeding (Ten Steps) describe evidence-based hospital policies and practices shown to improve breastfeeding outcomes. We aim to describe hospitals' implementation of the Ten Steps, changes over time, and hospitals' implementation of a majority (≥ 6) of the Ten Steps by hospital characteristics and state. METHODS: The biennial Maternity Practices in Infant Nutrition and Care (mPINC) survey assesses all hospitals in the United States (including the District of Columbia and territories) that routinely provide maternity care services. We analyzed data from 2018, 2020, and 2022 survey cycles to describe trends in the prevalence of hospitals implementing maternity care policies and practices that are consistent with the Ten Steps. Differences were calculated using the absolute difference in percentage-points between 2018 and 2022. RESULTS: Between 2018 and 2022, the percentage of hospitals that implemented Step 2: Staff Competency and Step 5: Support Mothers with Breastfeeding increased 12 and 8 percentage points, respectively. The percentage of hospitals that implemented Step 6: Exclusive Breastfeeding Among Breastfed Infants was 7 percentage points lower in 2022 than 2018. Implementation of the remaining seven steps did not change by more than 5 percentage points in either direction between 2018 and 2022. Nationally, the percentage of hospitals that implemented ≥ 6 of the Ten Steps increased from 44.0% in 2018 to 51.1% in 2022. Differences were seen when comparing implementation of ≥ 6 of the Ten Steps by hospital characteristics including state, hospital size, and highest level of neonatal care offered. CONCLUSIONS: Nationally, maternity care policies and practices supportive of breastfeeding continued to improve; however, certain practices lost progress. Differences in implementation of the Ten Steps were observed across states and by certain hospital characteristics, suggesting more work is needed to ensure all people receive optimal breastfeeding support during their delivery hospitalization.


Assuntos
Aleitamento Materno , Humanos , Aleitamento Materno/estatística & dados numéricos , Estados Unidos , Feminino , Gravidez , Recém-Nascido , Política Organizacional , Serviços de Saúde Materna/estatística & dados numéricos , Política de Saúde
2.
bioRxiv ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38746396

RESUMO

Cancer-associated mutations have been documented in normal tissues, but the prevalence and nature of somatic copy number alterations and their role in tumor initiation and evolution is not well understood. Here, using single cell DNA sequencing, we describe the landscape of CNAs in >42,000 breast epithelial cells from women with normal or high risk of developing breast cancer. Accumulation of individual cells with one or two of a specific subset of CNAs (e.g. 1q gain and 16q, 22q, 7q, and 10q loss) is detectable in almost all breast tissues and, in those from BRCA1 or BRCA2 mutations carriers, occurs prior to loss of heterozygosity (LOH) of the wildtype alleles. These CNAs, which are among the most common associated with ductal carcinoma in situ (DCIS) and malignant breast tumors, are enriched almost exclusively in luminal cells not basal myoepithelial cells. Allele-specific analysis of the enriched CNAs reveals that each allele was independently altered, demonstrating convergent evolution of these CNAs in an individual breast. Tissues from BRCA1 or BRCA2 mutation carriers contain a small percentage of cells with extreme aneuploidy, featuring loss of TP53 , LOH of BRCA1 or BRCA2 , and multiple breast cancer-associated CNAs in addition to one or more of the common CNAs in 1q, 10q or 16q. Notably, cells with intermediate levels of CNAs are not detected, arguing against a stepwise gradual accumulation of CNAs. Overall, our findings demonstrate that chromosomal alterations in normal breast epithelium partially mirror those of established cancer genomes and are chromosome- and cell lineage-specific.

3.
J Med Chem ; 67(10): 8141-8160, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38728572

RESUMO

Human interleukin-1ß (IL-1ß) is a pro-inflammatory cytokine that plays a critical role in the regulation of the immune response and the development of various inflammatory diseases. In this publication, we disclose our efforts toward the discovery of IL-1ß binders that interfere with IL-1ß signaling. To this end, several technologies were used in parallel, including fragment-based screening (FBS), DNA-encoded library (DEL) technology, peptide discovery platform (PDP), and virtual screening. The utilization of distinct technologies resulted in the identification of new chemical entities exploiting three different sites on IL-1ß, all of them also inhibiting the interaction with the IL-1R1 receptor. Moreover, we identified lysine 103 of IL-1ß as a target residue suitable for the development of covalent, low-molecular-weight IL-1ß antagonists.


Assuntos
Interleucina-1beta , Humanos , Descoberta de Drogas , Interleucina-1beta/metabolismo , Ligantes , Receptores Tipo I de Interleucina-1/metabolismo , Receptores Tipo I de Interleucina-1/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Estrutura-Atividade , DNA/química , Biblioteca Gênica
5.
Pathogens ; 13(2)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38392854

RESUMO

The high proportion of people with HIV (PWH) in the 2022-2023 mpox outbreak has raised questions surrounding the association between HIV and mpox. The objectives of this study were to evaluate the association between engagement in HIV-associated healthcare and mpox diagnosis, as well as to characterize cases of mpox among PWH. The DC Cohort is a longitudinal cohort of PWH in Washington, DC. We conducted a 5:1 (controls:cases) nested case-cohort study on male participants, matching age and care site. Cases were participants with an identified mpox diagnosis. Conditional logistic regression was used to assess the impact of indicators of engagement in HIV-associated healthcare on mpox diagnosis. We identified 70 cases of mpox in DC Cohort participants randomly matched to 323 controls, for a total of 393 participants included in the analysis. Study participants were primarily non-Hispanic Black (72.3%) with a median age of 41 (IQR: 36, 50). There was no association between engagement in care and mpox diagnosis; however, low CD4 was associated with increased odds of mpox diagnosis (aOR: 4.60 (95% CI: 1.23, 17.11)). Among a cohort of PWH, engagement in care was not associated with mpox diagnosis, suggesting that the overrepresentation of PWH among mpox cases is not due to surveillance bias.

6.
Adv Nutr ; 15(3): 100178, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242444

RESUMO

Timing of eating (TOE) and energy intake (TOEI) has important implications for chronic disease risk beyond diet quality. The 2020 Dietary Guidelines Advisory Committee recommended developing consistent terminology to address the lack of TOE/TOEI standardization. The primary objective of this methodological systematic review was to characterize the conceptualization and assessment of TOE/TOEI within the chronic disease literature (International Prospective Register of Systematic Reviews registration number: CRD42021236621). Literature searches in Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, Embase, PubMed, and Scopus were limited to English language publications from 2000 to August 2022. Eligible studies reported the association between TOE/TOEI and obesity, cardiovascular disease, type 2 diabetes mellitus, cancer, or a related clinical risk factor among adults (≥19 y) in observational and intervention studies. A qualitative synthesis described and compared TOE/TOEI conceptualization, definitions, and assessment methods across studies. Of the 7579 unique publications identified, 259 studies (observational [51.4 %], intervention [47.5 %], or both [1.2 %]) were eligible for inclusion. Key findings indicated that most studies (49.6 %) were conducted in the context of obesity and body weight. TOE/TOEI variables or assigned conditions conceptualized interrelated aspects of time and eating or energy intake in varying ways. Common TOE/TOEI conceptualizations included the following: 1) timepoint (specific time to represent when intake occurs, such as time of breakfast [74.8 %]); 2) duration (length of time or interval when intake does/does not occur, such as "eating window" [56.5 %]); 3) distribution (proportion of daily intake at a given time interval, such as "percentage of energy before noon" [29.8 %]); and 4) cluster (grouping individuals based on temporal ingestive characteristics [5.0 %]). Assessment, definition, and operationalization of 24-h TOE/TOEI variables varied widely across studies. Observational studies most often used surveys or questionnaires (28.9 %), whereas interventions used virtual or in-person meetings (23.8 %) to assess TOE/TOEI adherence. Overall, the diversity of terminology and methods solidifies the need for standardization to guide future research in chrononutrition and to facilitate inter-study comparisons.

7.
J Natl Cancer Inst ; 116(4): 518-529, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38291943

RESUMO

BACKGROUND: Metformin is among the most widely used antidiabetics medications because of its minimal toxicity, favorable safety profile, availability, and low cost. In addition to its role in diabetes management, metformin may reduce cancer risk. METHODS: We conducted a comprehensive systematic review and meta-analysis to investigate the association between metformin use and cancer risk, with evaluation by specific cancer type when possible. Applicable studies were identified in PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus from inception through March 7, 2023, with metformin use categorized as "ever" or "yes" and a cancer diagnosis as the outcome. Article quality was evaluated using National Heart, Lung, and Blood Institute guidelines, and publication bias was evaluated using the Egger test, Begg test, and funnel plots. Pooled relative risk (RR) estimates were calculated using random-effects models, and sensitivity analysis was completed through leave-one-out cross-validation. RESULTS: We included 166 studies with cancer incidence information in the meta-analysis. Reduced risk for overall cancer was observed in case-control studies (RR = 0.55, 95% confidence interval [CI] = 0.30 to 0.80) and prospective cohort studies (RR = 0.65, 95% CI = 0.37 to 0.93). Metformin use was associated with reduced gastrointestinal (RR = 0.79, 95% CI = 0.73 to 0.85), urologic (RR = 0.88, 95% CI = 0.78 to 0.99), and hematologic (RR = 0.87, 95% CI = 0.75 to 0.99) cancer risk. Statistically significant publication bias was observed within the studies (Egger P < .001). CONCLUSIONS: Metformin may be associated with a decreased risk of many cancer types, but high heterogeneity and risk of publication bias limit confidence in these results. Additional studies in populations without diabetes are needed to better understand the utility of metformin in cancer prevention.

8.
J Nutr ; 154(1): 26-40, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37918675

RESUMO

BACKGROUND: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds that may provide cardiometabolic benefits. OBJECTIVES: We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention. Associations between changes in salmon FSCs and changes in cardiometabolic health indicators (CHIs) were also explored. METHODS: For this secondary analysis of a randomized, crossover, controlled feeding trial, 41 participants consumed MED diets with 2 servings of salmon per week for 2 5-wk periods. CHIs were assessed, and fasting plasma was collected pre- and postintervention. Plasma, salmon, and 99 MED foods were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Compounds were characterized as salmon FSCs if detected in all salmon replicates but none of the other foods. Metabolites of salmon FSCs were predicted using machine learning. For salmon FSCs and metabolites found in plasma, linear mixed-effect models were used to assess change from pre- to postintervention and associations with changes in CHIs. RESULTS: Relative to the other 99 MED foods, there were 508 salmon FSCs with 237 unique metabolites. A total of 143 salmon FSCs and 106 metabolites were detected in plasma. Forty-eight salmon FSCs and 30 metabolites increased after the intervention (false discovery rate <0.05). Increases in 2 annotated salmon FSCs and 2 metabolites were associated with improvements in CHIs, including total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B. CONCLUSIONS: A data-driven nutrimetabolomics strategy identified salmon FSCs and their predicted metabolites that were detectable in plasma and changed after consumption of a salmon-containing MED diet. Findings support this approach for the discovery of compounds in foods that may serve, upon further validation, as biomarkers or act as bioactive components influential to health. The trials supporting this work were registered at NCT02573129 (Mediterranean-style diet intervention) and NCT05500976 (ongoing clinical trial).


Assuntos
Doenças Cardiovasculares , Dieta Mediterrânea , Humanos , Animais , Salmão , Alimentos Marinhos , Colesterol , Biomarcadores , Doenças Cardiovasculares/prevenção & controle , Dieta
9.
Mol Pharm ; 20(11): 5790-5799, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37889088

RESUMO

Water-to-ice transformation results in a 10% increase in volume, which can have a significant impact on biopharmaceuticals during freeze-thaw cycles due to the mechanical stresses imparted by the growing ice crystals. Whether these stresses would contribute to the destabilization of biopharmaceuticals depends on both the magnitude of the stress and sensitivity of a particular system to pressure and sheer stresses. To address the gap of the "magnitude" question, a phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), is evaluated as a probe to detect and quantify the freeze-induced pressure. DPPC can form several phases under elevated pressure, and therefore, the detection of a high-pressure DPPC phase during freezing would be indicative of a freeze-induced pressure increase. In this study, the phase behavior of DPPC/water suspensions, which also contain the ice nucleation agent silver iodide, is monitored by synchrotron small/wide-angle X-ray scattering during the freeze-thaw transition. Cooling the suspensions leads to heterogeneous ice nucleation at approximately -7 °C, followed by a phase transition of DPPC between -11 and -40 °C. In this temperature range, the initial gel phase of DPPC, Lß', gradually converts to a second phase, tentatively identified as a high-pressure Gel III phase. The Lß'-to-Gel III phase transition continues during an isothermal hold at -40 °C; a second (homogeneous) ice nucleation event of water confined in the interlamellar space is detected by differential scanning calorimetry (DSC) at the same temperature. The extent of the phase transition depends on the DPPC concentration, with a lower DPPC concentration (and therefore a higher ice fraction), resulting in a higher degree of Lß'-to-Gel III conversion. By comparing the data from this study with the literature data on the pressure/temperature Lß'/Gel III phase boundary and the lamellar lattice constant of the Lß' phase, the freeze-induced pressure is estimated to be approximately 0.2-2.6 kbar. The study introduces DPPC as a probe to detect a pressure increase during freezing, therefore addressing the gap between a theoretical possibility of protein destabilization by freeze-induced pressure and the current lack of methods to detect freeze-induced pressure. In addition, the observation of a freeze-induced phase transition in a phospholipid can improve the mechanistic understanding of factors that could disrupt the structure of lipid-based biopharmaceuticals, such as liposomes and mRNA vaccines, during freezing and thawing.


Assuntos
Produtos Biológicos , Água , Congelamento , Água/química , Fosfolipídeos , Temperatura , Gelo , 1,2-Dipalmitoilfosfatidilcolina/química , Difração de Raios X , Síncrotrons , Transição de Fase , Varredura Diferencial de Calorimetria
10.
Adv Nutr ; 14(6): 1255-1269, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37722488

RESUMO

Our objective was to convene interdisciplinary experts from government, academia, and industry to develop a Research Roadmap to identify research priorities about processed food intake and risk for obesity and cardiometabolic diseases (CMD) among United States populations. We convened attendees at various career stages with diverse viewpoints in the field. We held a "Food Processing Primer" to build foundational knowledge of how and why foods are processed, followed by presentations about how processed foods may affect energy intake, obesity, and CMD risk. Breakout groups discussed potential mechanistic and confounding explanations for associations between processed foods and obesity and CMD risk. Facilitators created research questions (RQs) based on key themes from discussions. Different breakout groups convened to discuss what is known and unknown for each RQ and to develop sub-RQs to address gaps. Workshop attendees focused on ultra-processed foods (UPFs; Nova Group 4) because the preponderance of evidence is based on this classification system. Yet, heterogeneity and subjectivity in UPF classification was a challenge for RQ development. The 6 RQs were: 1) What objective methods or measures could further categorize UPFs, considering food processing, formulation, and the interaction of the two? 2) How can exposure assessment of UPF intake be improved? 3) Does UPF intake influence risk for obesity or CMDs, independent of diet quality? 4) What, if any, attributes of UPFs influence ingestive behavior and contribute to excess energy intake? 5) What, if any, attributes of UPFs contribute to clinically meaningful metabolic responses? 6) What, if any, external environmental factors lead people to consume high amounts of UPFs? Uncertainty and complexity around UPF intake warrant further complementary and interdisciplinary causal, mechanistic, and methodological research related to obesity and CMD risk to understand the utility of applying classification by degree of processing to foods in the United States.


Assuntos
Fast Foods , Alimento Processado , Humanos , Fast Foods/efeitos adversos , Dieta , Ingestão de Energia , Obesidade/etiologia , Manipulação de Alimentos
11.
AIDS Res Hum Retroviruses ; 39(12): 662-670, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37392022

RESUMO

With the advancement of effective antiretroviral therapy, people with HIV live longer, and many are developing non-AIDS comorbidities. It is important to assess how comorbidities are associated with HIV-related health outcomes, such as viral suppression (VS). The aim of this study was to analyze the association between comorbidity burden, measured using a modified Quan-Charlson Comorbidity Index (QCCI), and VS (viral load result of <200 copies/mL). We hypothesized that an increase in QCCI score, indicating a higher risk for mortality, would correlate with lower likelihood of VS because of the burden of comorbidity treatment, possibly leading to worse antiretroviral adherence. Our analysis included participants from the DC Cohort Longitudinal HIV Study in Washington, DC. Eligible participants were aged ≥18 years and enrolled in the cohort as of January 1, 2018 (n = 2,471). A modified QCCI score, which weighs selected comorbidities (not including HIV/AIDS) and predicts mortality, was calculated using International Classification of Disease-9/10 codes from electronic health records. Multivariable logistic regressions were used to characterize the association between QCCI composite scores and VS. Participants were predominantly virally suppressed (89.6%), male (73.9%), non-Hispanic Black (74.7%), and between 18 and 55 years (59.3%). The median QCCI score was 1 (range = 1-12, interquartile range = 0-2), demonstrating predominately low mortality risk. We did not establish a statistically significant association between QCCI score and VS (adjusted odds ratio = 1.06, 95% confidence interval 0.96-1.17). Our findings suggest that a higher QCCI score was not associated with lower VS in this population, which may be partly due to the high retention in care among cohort participants.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Masculino , Adolescente , Adulto , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Estudos Transversais , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Antirretrovirais/uso terapêutico , Comorbidade , Carga Viral
12.
J Nutr ; 153(8): 2413-2420, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37343626

RESUMO

BACKGROUND: High intake of ultra-processed foods (UPFs) is associated with increased risk of chronic disease; thus, it is important to understand how UPFs influence diet quality early in life. OBJECTIVES: We describe complementary foods and beverages (CFBs) according to the Nova Classification System of Food Processing for infants and toddlers in the United States and estimate how Nova groups and subgroups contribute to energy and select nutrients and food groups. METHODS: We used day 1 24-h recall from infants and toddlers aged 6-23 mo from the cross-sectional, nationally representative 2013-18 National Health and Nutrition Examination Survey (n = 1140). We estimated contributions of Nova groups and subgroups to energy and select nutrients and food groups consumed as CFBs (excluding human milk and formula) using the population ratio with weighted survey commands in SAS. RESULTS: For infants and toddlers in the United States, 42 ± 0.9% (mean ± standard error of the mean) of energy intake from CFBs came from unprocessed/minimally processed foods (U/MPFs) and 45 ± 0.8% from UPFs. U/MPFs contributed most to nutrient intakes (except iron, zinc, and sodium); ≥20% of all selected nutrients was from UPFs. UPFs contributed most to iron (75 ± 1.0%) and zinc (48 ± 1.3%); breakfast cereals were the top source. Most fruit, vegetables, and dairy were from U/MPFs. More than 80% of total grains, whole grains, refined grains, and added sugars were UPFs. CONCLUSIONS: U/MPFs support healthy dietary intake of infants and toddlers in the United States, whereas UPFs contribute meaningfully to nutrients and food groups to be encouraged (iron, zinc, and whole grains), as well as some that should be limited (added sugars and sodium). More research is needed to better understand the utility and sensitivities of using Nova for providing dietary guidance for infants and toddlers in the United States.


Assuntos
Dieta , Ingestão de Alimentos , Humanos , Lactente , Pré-Escolar , Estados Unidos , Inquéritos Nutricionais , Estudos Transversais , Ingestão de Energia , Leite Humano , Ferro , Zinco , Sódio , Açúcares , Manipulação de Alimentos
13.
J Nutr ; 153(8): 2181-2192, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37276937

RESUMO

BACKGROUND: Objective markers of ultraprocessed foods (UPF) may improve the assessment of UPF intake and provide insight into how UPF influences health. OBJECTIVES: To identify metabolites that differed between dietary patterns (DPs) high in or void of UPF according to Nova classification. METHODS: In a randomized, crossover, controlled-feeding trial (clinicaltrials.govNCT03407053), 20 domiciled healthy participants (mean ± standard deviation: age 31 ± 7 y, body mass index [kg/m2] 22 ± 11.6) consumed ad libitum a UPF-DP (80% UPF) and an unprocessed DP (UN-DP; 0% UPF) for 2 wk each. Metabolites were measured using liquid chromatography with tandem mass spectrometry in ethylenediaminetetraacetic acid plasma, collected at week 2 and 24-h, and spot urine, collected at weeks 1 and 2, of each DP. Linear mixed models, adjusted for energy intake, were used to identify metabolites that differed between DPs. RESULTS: After multiple comparisons correction, 257 out of 993 plasma and 606 out of 1279 24-h urine metabolites differed between UPF-DP and UN-DP. Overall, 21 known and 9 unknown metabolites differed between DPs across all time points and biospecimen types. Six metabolites were higher (4-hydroxy-L-glutamic acid, N-acetylaminooctanoic acid, 2-methoxyhydroquinone sulfate, 4-ethylphenylsulfate, 4-vinylphenol sulfate, and acesulfame) and 14 were lower following the UPF-DP; pimelic acid, was lower in plasma but higher in urine following the UPF-DP. CONCLUSIONS: Consuming a DP high in, compared with 1 void of, UPF has a measurable impact on the short-term human metabolome. Observed differential metabolites could serve as candidate biomarkers of UPF intake or metabolic response in larger samples with varying UPF-DPs. This trial was registered at clinicaltrials.gov as NCT03407053 and NCT03878108.


Assuntos
Dieta , Metabolômica , Humanos , Adulto Jovem , Adulto , Metabolômica/métodos , Ingestão de Energia , Alimentos , Índice de Massa Corporal , Manipulação de Alimentos , Fast Foods
14.
Water Res ; 242: 120154, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37327545

RESUMO

The insecticide and current use pesticide chlorpyrifos (CLP) is transported via global distillation to the Arctic where it may pose a threat to this ecosystem. CLP is readily detected in Arctic environmental compartments, but current research has not studied its partitioning between water and dissolved organic matter (DOM) nor the role of photochemistry in CLP's fate in aquatic systems. Here, the partition coefficients of CLP were quantified with various types of DOM isolated from the Arctic and an International Humic Substances Society (IHSS) reference material Suwannee River natural organic matter (SRNOM). While CLP readily partitions to DOM, CLP exhibits a significantly higher binding constant with Arctic lacustrine DOM relative to fluvial DOM or SRNOM. The experimental partitioning coefficients (KDOC) were compared to a calculated value estimated using poly parameter linear free energy relationship (pp-LFER) and was found to be in good agreement with SRNOM, but none of the Arctic DOMs. We found that Arctic KDOC values decrease with increasing SUVA254, but no correlations were observed for the other DOM compositional parameters. DOM also mediates the photodegradation of CLP, with stark differences in photo-kinetics using Arctic DOM isolated over time and space. This work highlights the chemo-diversity of Arctic DOM relative to IHSS reference materials and highlights the need for in-depth characterization of DOM that transcends the current paradigm based upon terrestrial and microbial precursors.


Assuntos
Clorpirifos , Matéria Orgânica Dissolvida , Ecossistema , Substâncias Húmicas/análise , Água/química
15.
Elife ; 122023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-37083456

RESUMO

Growth and destruction are central components of the neuronal injury response. Injured axons that are capable of repair, including axons in the mammalian peripheral nervous system and in many invertebrate animals, often regenerate and degenerate on either side of the injury. Here we show that TIR-1/dSarm/SARM1, a key regulator of axon degeneration, also inhibits regeneration of injured motor axons. The increased regeneration in tir-1 mutants is not a secondary consequence of its effects on degeneration, nor is it determined by the NADase activity of TIR-1. Rather, we found that TIR-1 functions cell-autonomously to regulate each of the seemingly opposite processes through distinct interactions with two MAP kinase pathways. On one side of the injury, TIR-1 inhibits axon regeneration by activating the NSY-1/ASK1 MAPK signaling cascade, while on the other side of the injury, TIR-1 simultaneously promotes axon degeneration by interacting with the DLK-1 mitogen-activated protein kinase (MAPK) signaling cascade. In parallel, we found that the ability to cell-intrinsically inhibit axon regeneration is conserved in human SARM1. Our finding that TIR-1/SARM1 regulates axon regeneration provides critical insight into how axons coordinate a multidimensional response to injury, consequently informing approaches to manipulate the response toward repair.


Assuntos
Axônios , Regeneração Nervosa , Animais , Humanos , Axônios/metabolismo , Neurônios/metabolismo , Sistema de Sinalização das MAP Quinases , Mamíferos/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas do Domínio Armadillo/genética , Proteínas do Domínio Armadillo/metabolismo
16.
J Nutr ; 153(1): 225-241, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36913457

RESUMO

BACKGROUND: The degree of food processing may be an important dimension of diet in how it relates to health outcomes. A major challenge is standardizing food processing classification systems for commonly used datasets. OBJECTIVES: To standardize and increase transparency in its application, we describe the approach used to classify foods and beverages according to the Nova food processing classification in the 24-h dietary recalls from the 2001-2018 cycles of What We Eat in America (WWEIA), NHANES, and investigate variability and potential for Nova misclassification within WWEIA, NHANES 2017-2018 data via various sensitivity analyses. METHODS: First, we described how the Nova classification system was applied to the 2001-2018 WWEIA, NHANES data using the reference approach. Second, we calculated the percentage energy from Nova groups [1: unprocessed or minimally processed foods, 2: processed culinary ingredients, 3: processed foods, and 4: ultraprocessed foods (UPFs)] for the reference approach using day 1 dietary recall data from non-breastfed participants aged ≥1 y from the 2017-2018 WWEIA, NHANES. We then conducted 4 sensitivity analyses comparing potential alternative approaches (e.g., opting for more vs. less degree of processing for ambiguous items) to the reference approach, to assess how estimates differed. RESULTS: The energy contribution of UPFs using the reference approach was 58.2% ± 0.9% of the total energy; unprocessed or minimally processed foods contributed 27.6% ± 0.7%, processed culinary ingredients contributed 5.2% ± 0.1%, and processed foods contributed 9.0% ± 0.3%. In sensitivity analyses, the dietary energy contribution of UPFs ranged from 53.4% ± 0.8% to 60.1% ± 0.8% across alternative approaches. CONCLUSIONS: We present a reference approach for applying the Nova classification system to WWEIA, NHANES 2001-2018 data to promote standardization and comparability of future research. Alternative approaches are also described, with total energy from UPFs differing by ∼6% between approaches for 2017-2018 WWEIA, NHANES.


Assuntos
Dieta , Fast Foods , Humanos , Inquéritos Nutricionais , Manipulação de Alimentos , Ingestão de Alimentos , Ingestão de Energia
17.
J Occup Environ Med ; 65(6): 529-532, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36914379

RESUMO

OBJECTIVE: Evaluate potential risk factors for severe coronavirus disease 2019 (COVID-19) among health care workers (HCWs) at the University of Virginia Medical Center in Charlottesville, Virginia. METHODS: We conducted a retrospective manual chart review of data from HCWs who were diagnosed with COVID-19 from March 2020 to March 2021. Using data from patient medical histories, we ascertained risk factors for COVID-19-related emergency department encounter, hospitalization, or death. RESULTS: We had 634 patients in total, and 9.8% had a severe COVID-19-related outcome. A history of deep vein thrombosis/pulmonary embolism/stroke (odds ratio, 19.6; 95% confidence interval, 5.11 to 94.7), as well as asthma, chronic lung disease, diabetes, or current immunocompromised status, was associated with increased adjusted odds of COVID-19-related emergency department encounter/hospitalization/death. CONCLUSIONS: A preexisting history of deep vein thrombosis/pulmonary embolism/stroke is a novel risk factor for poor COVID-19 outcomes among a cohort of HCWs.


Assuntos
COVID-19 , Embolia Pulmonar , Acidente Vascular Cerebral , Trombose Venosa , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Estudos Retrospectivos , Fatores de Risco , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/complicações , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Pessoal de Saúde
18.
Plant Genome ; 16(1): e20296, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36484157

RESUMO

As genome resources for wheat (Triticum L.) expand at a rapid pace, it is important to update targeted sequencing tools to incorporate improved sequence assemblies and regions of previously unknown significance. Here, we developed an updated regulatory region enrichment capture for wheat and other Triticeae species. The core target space includes sequences from 2-Kbp upstream of each gene predicted in the Chinese Spring wheat genome (IWGSC RefSeq Annotation v1.0) and regions of open chromatin identified with an assay for transposase-accessible chromatin using sequencing from wheat leaf and root samples. To improve specificity, we aggressively filtered candidate repetitive sequences using a combination of nucleotide basic local alignment search tool (BLASTN) searches to the Triticeae Repetitive Sequence Database (TREP), identification of regions with read over-coverage from previous target enrichment experiments, and k-mer frequency analyses. The final design comprises 216.5 Mbp of predicted hybridization space in hexaploid wheat and showed increased specificity and coverage of targeted sequences relative to previous protocols. Test captures on hexaploid and tetraploid wheat and other diploid cereals show that the assay has broad potential utility for cost-effective promoter and open chromatin resequencing and general-purpose genotyping of various Triticeae species.


Assuntos
Genoma de Planta , Triticum , Triticum/genética , Análise Custo-Benefício , Poliploidia , Regiões Promotoras Genéticas , Cromatina
19.
Abdom Radiol (NY) ; 48(1): 411-417, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36210369

RESUMO

PURPOSE: The majority of newly diagnosed renal tumors are masses < 4 cm in size with treatment options, including active surveillance, partial nephrectomy, and ablative therapies. The cost-effectiveness literature on the management of small renal masses (SRMs) does not account for recent advances in technology and improvements in technical expertise. We aim to perform a cost-effectiveness analysis for percutaneous microwave ablation (MWA) and robotic-assisted partial nephrectomy (RA-PN) for the treatment of SRMs. METHODS: We created a decision analytic Markov model depicting management of the SRM incorporating costs, health utilities, and probabilities of complications and recurrence as model inputs using TreeAge. A willingness to pay (WTP) threshold of $100,000 and a lifetime horizon were used. Probabilistic and one-way sensitivity analyses were performed. RESULTS: Percutaneous MWA was the preferred treatment modality. MWA dominated RA-PN, meaning it resulted in more quality-adjusted life years (QALYs) at a lower cost. Cost-effectiveness analysis revealed a negative Incremental Cost-Effectiveness Ratio (ICER), indicating dominance of MWA. The model revealed MWA had a mean cost of $8,507 and 12.51 QALYs. RA-PN had a mean cost of $21,521 and 12.43 QALYs. Relative preference of MWA was robust to sensitivity analysis of all other variables. Patient starting age and cost of RA-PN had the most dramatic impact on ICER. CONCLUSION: MWA is more cost-effective for the treatment of SRM when compared with RA-PN and accounting for complication and recurrence risk.


Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Humanos , Análise Custo-Benefício , Micro-Ondas/uso terapêutico , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodos
20.
Sci Data ; 9(1): 753, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36473868

RESUMO

Paleotemperature proxy data form the cornerstone of paleoclimate research and are integral to understanding the evolution of the Earth system across the Phanerozoic Eon. Here, we present PhanSST, a database containing over 150,000 data points from five proxy systems that can be used to estimate past sea surface temperature. The geochemical data have a near-global spatial distribution and temporally span most of the Phanerozoic. Each proxy value is associated with consistent and queryable metadata fields, including information about the location, age, and taxonomy of the organism from which the data derive. To promote transparency and reproducibility, we include all available published data, regardless of interpreted preservation state or vital effects. However, we also provide expert-assigned diagenetic assessments, ecological and environmental flags, and other proxy-specific fields, which facilitate informed and responsible reuse of the database. The data are quality control checked and the foraminiferal taxonomy has been updated. PhanSST will serve as a valuable resource to the paleoclimate community and has myriad applications, including evolutionary, geochemical, diagenetic, and proxy calibration studies.


Assuntos
Reprodutibilidade dos Testes
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