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1.
Nutr Clin Pract ; 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39073166

RESUMO

Nutrition plays a key role in the comprehensive care of critically ill patients. Determining optimal nutrition strategy, however, remains a subject of intense debate. Artificial intelligence (AI) applications are becoming increasingly common in medicine, and specifically in critical care, driven by the data-rich environment of intensive care units. In this review, we will examine the evidence regarding the application of AI in critical care nutrition. As of now, the use of AI in critical care nutrition is relatively limited, with its primary emphasis on malnutrition screening and tolerance of enteral nutrition. Despite the current scarcity of evidence, the potential for AI for more personalized nutrition management for critically ill patients is substantial. This stems from the ability of AI to integrate multiple data streams reflecting patients' changing needs while addressing inherent heterogeneity. The application of AI in critical care nutrition holds promise for optimizing patient outcomes through tailored and adaptive nutrition interventions. A successful implementation of AI, however, necessitates a multidisciplinary approach, coupled with careful consideration of challenges related to data management, financial aspects, and patient privacy.

2.
Nutr Neurosci ; : 1-13, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989695

RESUMO

ABSTRACTObjectives: Carotenoids are plant pigments that accumulate in human tissue (e.g. macula and skin) and can serve as biomarkers for diet quality; however, knowledge on skin and macular carotenoids in relation to cognition in children is limited. This study aimed to address this gap by assessing links between skin and macular carotenoids and academic achievement in school-aged children.Methods: Children 7-12 years old (n = 81) participated in a crosssectional study. Skin and macular carotenoids were measured with reflection spectroscopy and heterochromatic flicker photometry, respectively. Academic achievement was measured using Woodcock-Johnson IV (WJ-IV). Body Mass Index was calculated using height and weight measurements, demographic information was collected using a family demographics and pediatric health history questionnaire, and carotenoid intake was assessed using 7-day diet records.Results: Skin carotenoids were not related to macular pigment (r = 0.08, p = 0.22). Adjusting for age, sex, BMI percentile, household income, and total carotenoid consumption (mg/1000kcal), skin carotenoids were predictive of math (ß = 0.27, p = 0.02), broad math (ß = 0.36, p < 0.01) and math calculation (ß = 0.38, p < 0.01). Skin carotenoids displayed trending relationships with broad reading (ß = 0.23, p = 0.05) and reading fluency (ß = 0.22, p = 0.07). There were no significant associations between macular pigment and academic achievement (all ß's ≤ 0.07, all p's ≥ 0.56).Discussion: Skin carotenoids were positively associated with academic abilities in children, while macular carotenoids did not display this relationship. Future interventions examining prospective effects of changes in carotenoids in different tissues on childhood academic achievement are warranted.

3.
J Nutr ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971530

RESUMO

Dietary supplement use in the United States is widespread and increasing, especially among certain population groups, such as older Americans. The science surrounding dietary supplements has evolved substantially over the last few decades since their formal regulation in 1994. Much has been learned about the mechanisms of action of many dietary supplement ingredients, but the evidence on their health effects is still building. As is true of much nutrition research, there are many studies that point to health effects, but not all are at the level of scientific evidence (e.g., randomized controlled interventions), rigor, or quality needed for definitive statements of efficacy regarding clinical end points. New technologies and approaches are being applied to the science of dietary supplements, including nutrigenomics and microbiome analysis, data science, artificial intelligence (AI), and machine learning-all of which can elevate the science behind dietary supplements. Products can contain an array of bioactive compounds derived from foods as well as from medicinal plants, which creates enormous challenges in data collection and management. Clinical applications, particularly those aimed at providing personalized nutrition options for patients, have become more sophisticated as dietary supplements are incorporated increasingly into clinical practice and self-care. The goals of this article are to provide historical context for the regulation and science of dietary supplements, identify research resources, and suggest some future directions for science in this field.

4.
J Nutr ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38830472

RESUMO

BACKGROUND: Honey improves probiotic survival in vitro. However, if this effect translates to humans has not been investigated. OBJECTIVES: We aimed to determine effects of honey plus yogurt containing the probiotic Bifidobacterium animalis subsp. lactis DN-173 010/CNCM I-2494 (B. animalis) on intestinal transit time, probiotic enrichment, digestive health, mood, and cognition in adults. METHODS: Sixty-six healthy adults (34 female; 33.6 ± 9.8 y; 24.6 ± 3.0 kg/m2) in a crossover trial were randomly assigned to 2-wk yogurt conditions in a counterbalanced order with ≥4-wk washout: 1) Honey (HON): yogurt plus honey and 2) Negative Control (NC): heat-treated yogurt plus sugar. Of the participants, n = 62 completed the trial, and n = 37 (17 female; 32.0 ± 8.3 y; 25.0 ± 2.9 kg/m2) elected to enroll in a third condition (a nonrandomized study extension) after ≥4-wk washout with a reference Positive Control (PC): yogurt plus sugar. At baseline and end of each of the 3 conditions, intestinal transit time was measured with dye capsules; probiotic abundance with fecal DNA 16S sequencing; digestive health with symptom/function records, Bristol stool consistency, Gastrointestinal Tolerability, and Gastrointestinal Quality of Life Index; mood with Positive and Negative Affect Schedule-Short Form, Depression Anxiety Stress Scales-42, Patient-Reported Outcomes Measurement Information System questionnaires, and an emotional image task; and cognition with a spatial reconstruction task. Data were analyzed using linear mixed-effects models (LMMs) with significance at P ≤ 0.05. Baseline and end data were included in the LMM, with fixed effects being treatment, time, treatment by time interaction, and baseline covariate, and the random effect being the participant. RESULTS: B. animalis was enriched in HON (d = 3.54; P = 0.0002) compared to controls with linear discriminant analysis effect size. Intestinal transit time, gastrointestinal health, mood, and cognition did not differ between conditions (LMM: Ps > 0.05). CONCLUSIONS: Yogurt + honey enriched B. animalis but did not reduce intestinal transit time or have other functional gastrointestinal, mood, or cognitive effects in adults. This trial was registered at www. CLINICALTRIALS: gov as NCT04187950 and NCT04901390.

5.
Genome Res ; 34(4): 556-571, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38719473

RESUMO

H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich pericentromeric regions and also has key roles in repressing lineage-inappropriate protein-coding genes in differentiation and development. Here, we investigate the molecular consequences of heterochromatin loss in cells deficient in both SUV39H1 and SUV39H2 (Suv39DKO), the major mammalian histone methyltransferase enzymes that catalyze heterochromatic H3K9me3 deposition. We reveal a paradoxical repression of protein-coding genes in Suv39DKO cells, with these differentially expressed genes principally in euchromatic (Tn5-accessible, H3K4me3- and H3K27ac-marked) rather than heterochromatic (H3K9me3-marked) or polycomb (H3K27me3-marked) regions. Examination of the three-dimensional (3D) nucleome reveals that transcriptomic dysregulation occurs in euchromatic regions close to the nuclear periphery in 3D space. Moreover, this transcriptomic dysregulation is highly correlated with altered 3D genome organization in Suv39DKO cells. Together, our results suggest that the nuclear lamina-tethering of Suv39-dependent H3K9me3 domains provides an essential scaffold to support euchromatic genome organization and the maintenance of gene transcription for healthy cellular function.


Assuntos
Eucromatina , Heterocromatina , Histona-Lisina N-Metiltransferase , Histonas , Metiltransferases , Proteínas Repressoras , Transcrição Gênica , Eucromatina/metabolismo , Eucromatina/genética , Histonas/metabolismo , Histonas/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Heterocromatina/metabolismo , Heterocromatina/genética , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Animais , Camundongos , Humanos , Regulação da Expressão Gênica , Linhagem Celular
6.
Genome Biol Evol ; 16(7)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38753011

RESUMO

Understanding and predicting the relationships between genotype and phenotype is often challenging, largely due to the complex nature of eukaryotic gene regulation. A step towards this goal is to map how phenotypic diversity evolves through genomic changes that modify gene regulatory interactions. Using the Prairie Rattlesnake (Crotalus viridis) and related species, we integrate mRNA-seq, proteomic, ATAC-seq and whole-genome resequencing data to understand how specific evolutionary modifications to gene regulatory network components produce differences in venom gene expression. Through comparisons within and between species, we find a remarkably high degree of gene expression and regulatory network variation across even a shallow level of evolutionary divergence. We use these data to test hypotheses about the roles of specific trans-factors and cis-regulatory elements, how these roles may vary across venom genes and gene families, and how variation in regulatory systems drive diversity in venom phenotypes. Our results illustrate that differences in chromatin and genotype at regulatory elements play major roles in modulating expression. However, we also find that enhancer deletions, differences in transcription factor expression, and variation in activity of the insulator protein CTCF also likely impact venom phenotypes. Our findings provide insight into the diversity and gene-specificity of gene regulatory features and highlight the value of comparative studies to link gene regulatory network variation to phenotypic variation.


Assuntos
Venenos de Crotalídeos , Crotalus , Evolução Molecular , Animais , Crotalus/genética , Venenos de Crotalídeos/genética , Redes Reguladoras de Genes , Regulação da Expressão Gênica
7.
8.
Am J Med Qual ; 39(3): 123-130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38713600

RESUMO

Current maternal care recommendations in the United States focus on monitoring fetal development, management of pregnancy complications, and screening for behavioral health concerns. Often missing from these recommendations is support for patients experiencing socioeconomic or behavioral health challenges during pregnancy. A Pregnancy Medical Home (PMH) is a multidisciplinary maternal health care team with nurse navigators serving as patient advocates to improve the quality of care a patient receives and health outcomes for both mother and infant. Using bivariate comparisons between PMH patients and reference groups, as well as interviews with project team members and PMH graduates, this evaluation assessed the impact of a PMH at an academic medical university on patient care and birth outcomes. This PMH increased depression screenings during pregnancy and increased referrals to behavioral health care. This evaluation did not find improvements in maternal or infant birth outcomes. Interviews found notable successes and areas for program enhancement.


Assuntos
Serviços de Saúde Materna , Assistência Centrada no Paciente , Melhoria de Qualidade , Humanos , Gravidez , Feminino , Assistência Centrada no Paciente/organização & administração , Melhoria de Qualidade/organização & administração , Serviços de Saúde Materna/normas , Serviços de Saúde Materna/organização & administração , Adulto , Qualidade da Assistência à Saúde/organização & administração , Resultado da Gravidez , Estados Unidos , Equipe de Assistência ao Paciente/organização & administração , Complicações na Gravidez/terapia
9.
Gynecol Oncol Rep ; 53: 101397, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38694709

RESUMO

Objective: To assess gynecologic oncology patients' experiences with virtual prechemotherapy evaluation and determine preference for incorporating virtual visits into a chemotherapy schedule. Methods: From June-August 2023, a survey was distributed to patients with gynecologic malignancies who had both an in-person and virtual prechemotherapy visit at a tertiary comprehensive cancer center. Patient satisfaction and preference for incorporating virtual visits was elicited. Patients who preferred ≥ 50 % of prechemotherapy visits to be virtual were classified as "virtual-leaning" and those who preferred < 50 % virtual as "in-person-leaning." Results: Of 110 eligible patients, 93 agreed to participate and 73 completed the survey, yielding an overall 66.4% response rate and 78.5% (73/93) survey completion rate. Overall satisfaction with in-person and virtual visits were rated positively at similar rates (in-person 87.7%, virtual 87.2%). Sixty-four (88.4%) patients preferred some proportion of their visits to be virtual, 5 (7.0%) preferred no virtual care, and 4 (5.0%) had no preference. In a 6-cycle schedule of chemotherapy, the median number of preferred virtual visits was 3 (IQR 1.8-4.2). Forty-six (63.0%) patients were "virtual-leaning" and 23 (32.0%) were "in-person-leaning." When comparing groups, there was no difference in age, race, category of residence, commute, experience with technical difficulty, primary disease site, disease stage, number of prior chemotherapy cycles, or number of prior virtual visits. Conclusions: Most patients are highly satisfied with virtual visits and prefer virtual care to be included when undergoing chemotherapy. A hybrid model should be offered to gynecological cancer patients undergoing chemotherapy, with patient preference dictating the cadence of virtual visits.

10.
Nutr Res ; 126: 58-66, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615632

RESUMO

The Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) dietary pattern is associated with reduced cognitive decline and dementia risk. However, the nutrient features that distinguish the MIND from other patterns are unknown. We investigated the relationship between accordance to the MIND pattern and carotenoid intake (phytonutrients hypothesized to confer neuroprotection) relative to the Mediterranean, DASH, and Healthy Eating Index (HEI-2020). We hypothesized that MIND diet accordance would be a stronger predictor of carotenoid intake relative to other diet indices. A total of 396 adults (aged 19-82 years) completed the Dietary History Questionnaire to assess carotenoid intake and adherence to each diet index. Stepwise regressions with adjustment for covariates followed by the Meng's Z-test were used to compare correlation strength between each diet pattern and carotenoid. All diet patterns were positively associated with lutein and zeaxanthin, ß-carotene, α-carotene, and ß-cryptoxanthin (all ßs ≥0.38, Ps <.01). Effect size comparisons revealed that MIND accordance predicted a greater proportion of variance in lutein and zeaxanthin (all Zs ≥ 3.3, Ps < .001) and ß-carotene (all Zs ≥ 2.6, Ps < .01) relative to the Mediterranean, DASH, and HEI-2020. MIND accordance explained a greater proportion of variance in α-carotene (Z = 3.8, P < .001) and ß-cryptoxanthin (Z = 3.6, P < .001) relative to the HEI-2020. MIND diet accordance was disproportionately related to carotenoid intake, indicating the MIND index places greater emphasis on carotenoid-rich foods, particularly those containing lutein, zeaxanthin, and ß-carotene, relative to other diet indices. Future research is needed to define the role of these carotenoids in nutritional interventions for cognitive health.


Assuntos
Carotenoides , Dieta Saudável , Dieta Mediterrânea , Abordagens Dietéticas para Conter a Hipertensão , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Carotenoides/administração & dosagem , Adulto , Idoso de 80 Anos ou mais , Adulto Jovem , Luteína/administração & dosagem , Comportamento Alimentar , beta Caroteno/administração & dosagem , Dieta , Zeaxantinas/administração & dosagem , Padrões Dietéticos
11.
J Stroke Cerebrovasc Dis ; 33(7): 107732, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38657829

RESUMO

BACKGROUND: Young adults with stroke have distinct professional and social roles making them vulnerable to symptoms of post-stroke depression (PSD) and post-stroke anxiety (PSA). Prior reviews have examined the prevalence of anxiety and depression in stroke populations. However, there are a lack of studies that have focused on these conditions in young adults. OBJECTIVE: We performed a systematic review and meta-analysis of observational studies that reported on symptoms of PSD, PSA and comorbid PSD/PSA in young adults aged 18 to 55 years of age. METHODS: MEDLINE, EMBASE, SCOPUS and PsycINFO were searched for studies reporting the prevalence of symptoms of PSD and/or PSA in young adults with stroke from inception until June 23, 2023. We included studies that evaluated depression and/or anxiety symptoms with screening tools or interviews following ischemic or hemorrhagic stroke. Validated methods were employed to evaluate risk of bias. RESULTS: 4748 patients from twenty eligible studies were included. Among them, 2420 were also evaluated for symptoms of PSA while 847 participants were evaluated for both PSD and PSA symptoms. Sixteen studies were included in the random effects meta-analysis for PSD symptoms, with a pooled prevalence of 31 % (95 % CI 24-38 %). Pooled PSA symptom prevalence was 39 % (95 % CI 30-48 %) and comorbid PSD with PSA symptom prevalence was 25 % (95 % CI 12-39 %). Varying definitions of 'young adult', combinations of stroke subtypes, and methods to assess PSD and PSA contributed to high heterogeneity amongst studies. CONCLUSIONS: We identified high heterogeneity in studies investigating the prevalence of symptoms of PSD and PSA in young adults, emphasizing the importance of standardized approaches in future research to gain insight into the outcomes and prognosis of PSD and PSA symptoms following stroke in young adults. Larger longitudinal epidemiological studies as well as studies on tailored interventions are required to address the mental health needs of this important population. FUNDING: None.


Assuntos
Ansiedade , Depressão , Acidente Vascular Cerebral , Humanos , Prevalência , Depressão/epidemiologia , Depressão/diagnóstico , Depressão/psicologia , Adulto , Ansiedade/epidemiologia , Ansiedade/diagnóstico , Ansiedade/psicologia , Adulto Jovem , Feminino , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/complicações , Masculino , Adolescente , Fatores de Risco , Pessoa de Meia-Idade , Fatores Etários , Comorbidade , Estudos Observacionais como Assunto , Medição de Risco , Prognóstico , AVC Isquêmico/epidemiologia , AVC Isquêmico/diagnóstico , AVC Isquêmico/psicologia
12.
JAMA Netw Open ; 7(4): e248747, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687479

RESUMO

Importance: Area-level measures of sociodemographic disadvantage may be associated with racial and ethnic disparities with respect to receipt of treatment for metastatic renal cell carcinoma (mRCC) but have not been investigated previously, to our knowledge. Objective: To assess the association between area-level measures of social vulnerability and racial and ethnic disparities in the treatment of US Medicare beneficiaries with mRCC from 2015 through 2019. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries older than 65 years who were diagnosed with mRCC from January 2015 through December 2019 and were enrolled in fee-for-service Medicare Parts A, B, and D from 1 year before through 1 year after presumed diagnosis or until death. Data were analyzed from November 22, 2022, through January 26, 2024. Exposures: Five different county-level measures of disadvantage and 4 zip code-level measures of vulnerability or deprivation and segregation were used to dichotomize whether an individual resided in the most vulnerable quartile according to each metric. Patient-level factors included age, race and ethnicity, sex, diagnosis year, comorbidities, frailty, Medicare and Medicaid dual enrollment eligibility, and Medicare Part D low-income subsidy (LIS). Main Outcomes and Measures: The main outcomes were receipt and type of systemic therapy (oral anticancer agent or immunotherapy from 2 months before to 1 year after diagnosis of mRCC) as a function of patient and area-level characteristics. Multivariable regression analyses were used to adjust for patient factors, and odds ratios (ORs) from logistic regression and relative risk ratios (RRRs) from multinomial logistic regression are reported. Results: The sample included 15 407 patients (mean [SD] age, 75.6 [6.8] years), of whom 9360 (60.8%) were men; 6931 (45.0%), older than 75 years; 93 (0.6%), American Indian or Alaska Native; 257 (1.7%), Asian or Pacific Islander; 757 (4.9%), Hispanic; 1017 (6.6%), non-Hispanic Black; 12 966 (84.2%), non-Hispanic White; 121 (0.8%), other; and 196 (1.3%), unknown. Overall, 8317 patients (54.0%) received some type of systemic therapy. After adjusting for individual factors, no county or zip code-level measures of social vulnerability, deprivation, or segregation were associated with disparities in treatment. In contrast, patient-level factors, including female sex (OR, 0.78; 95% CI, 0.73-0.84) and LIS (OR, 0.48; 95% CI, 0.36-0.65), were associated with lack of treatment, with particularly limited access to immunotherapy for patients with LIS (RRR, 0.25; 95% CI, 0.14-0.43). Associations between individual-level factors and treatment in multivariable analysis were not mediated by the addition of area-level metrics. Disparities by race and ethnicity were consistently and only observed within the most vulnerable areas, as indicated by the top quartile of each vulnerability deprivation index. Conclusions and Relevance: In this cohort study of older Medicare patients diagnosed with mRCC, individual-level demographics, including race and ethnicity, sex, and income, were associated with receipt of systemic therapy, whereas area-level measures were not. However, individual-level racial and ethnic disparities were largely limited to socially vulnerable areas, suggesting that efforts to improve racial and ethnic disparities may be most effective when targeted to socially vulnerable areas.


Assuntos
Carcinoma de Células Renais , Disparidades em Assistência à Saúde , Neoplasias Renais , Medicare , Humanos , Masculino , Feminino , Idoso , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/etnologia , Estados Unidos , Estudos Retrospectivos , Medicare/estatística & dados numéricos , Neoplasias Renais/terapia , Neoplasias Renais/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Idoso de 80 Anos ou mais , Vulnerabilidade Social , Populações Vulneráveis/estatística & dados numéricos , Fatores Socioeconômicos
13.
Skin Res Technol ; 30(4): e13675, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38558144

RESUMO

AIMS: This research assessed the safety of aqueous ozone (AO) on human skin after multiple exposures for up to 40 hours. METHODS AND RESULTS: Full thickness recombinant human skin (EpiDerm FT, EFT-400) was exposed to AO for 7 seconds per minute for the first 6 minutes of each hour, repeated hourly over four time periods (4, 10, 20 and 40 hours). An MTT assay assessed viability of skin cells after exposure, compared to incubator control, negative control and vehicle control (distilled water). No significant difference in tissue viability was found between the AO condition and any of the control conditions through 20 hours of exposures. At 40 hours of exposure, tissue viability was lower in the AO group when compared with negative control (p = 0.030) but not the other controls. CONCLUSIONS: The current study supports further consideration of repeated application of AO on human skin, such as for hand hygiene. IMPACT STATEMENT: The present research is the first well-controlled in vitro study assessing the cytotoxicity of repeated exposures of AO on a full-thickness human skin model. This information helps to inform the evaluation of AO as a potential alternative for hand and wound antisepsis.


Assuntos
Higiene das Mãos , Ozônio , Humanos , Ozônio/toxicidade , Pele , Epiderme , Água
14.
Mol Cancer Res ; 22(6): 515-523, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38546397

RESUMO

The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA. IMPLICATIONS: PIGA somatic mutation in duodenal tumors from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.


Assuntos
Polipose Adenomatosa do Colo , Neoplasias Duodenais , Glicosilfosfatidilinositóis , Mutação , Humanos , Glicosilfosfatidilinositóis/metabolismo , Glicosilfosfatidilinositóis/genética , Neoplasias Duodenais/genética , Neoplasias Duodenais/metabolismo , Neoplasias Duodenais/patologia , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/metabolismo , Polipose Adenomatosa do Colo/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Carcinogênese/genética , Masculino , Feminino
15.
iScience ; 27(3): 109124, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38455978

RESUMO

Dysregulation of normal transcription factor activity is a common driver of disease. Therefore, the detection of aberrant transcription factor activity is important to understand disease pathogenesis. We have developed Priori, a method to predict transcription factor activity from RNA sequencing data. Priori has two key advantages over existing methods. First, Priori utilizes literature-supported regulatory information to identify transcription factor-target gene relationships. It then applies linear models to determine the impact of transcription factor regulation on the expression of its target genes. Second, results from a third-party benchmarking pipeline reveals that Priori detects aberrant activity from 124 single-gene perturbation experiments with higher sensitivity and specificity than 11 other methods. We applied Priori and other top-performing methods to predict transcription factor activity from two large primary patient datasets. Our work demonstrates that Priori uniquely discovered significant determinants of survival in breast cancer and identified mediators of drug response in leukemia.

16.
J Nutr ; 154(3): 866-874, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38219862

RESUMO

BACKGROUND: Bifidobacterium animalis ssp. lactis DN-173 010/CNCM I-2494 (B. animalis) is a probiotic strain commonly added to yogurt. Yogurt and honey are a popular culinary pairing. Honey improves bifidobacteria survival in vitro. However, probiotic survival in yogurt with honey during in vitro digestion has not been investigated. OBJECTIVES: The study aimed to evaluate the effects of different honey varietals and concentrations on B. animalis survivability in yogurt through in vitro digestion. METHODS: Yogurt with honey or control-treated samples underwent in vitro simulated oral, gastric, and intestinal digestion. B. animalis cells were enumerated on de Man Rogosa and Sharpe (MRS) medium followed by an overlay with a modified selective MRS medium; all underwent anaerobic incubation. B. animalis were enumerated predigestion and after oral, gastric, and intestinal digestion. There were 2 study phases: Phase 1 tested 4 honey varietals at 20% wt/wt per 170 g yogurt, and Phase 2 tested 7 dosages of clover honey (20, 14, 10, 9, 8, 6, and 4% wt/wt) per 170 g yogurt. RESULTS: Similar B. animalis counts were observed between all treatments after oral and gastric digestion (<1 Log colony forming units (CFU)/g probiotic reduction). Higher B. animalis survivability was observed in yogurt with clover honey after exposure to simulated intestinal fluids (∼3.5 Log CFU/g reduction; P < 0.05) compared to all control treatments (∼5.5 Log CFU/g reduction; P < 0.05). Yogurt with 10-20% wt/wt clover honey increased B. animalis survivability after simulated in vitro digestion (≤ ∼4.7 Log CFU/g survival; P < 0.05). CONCLUSIONS: Yogurt with added honey improves probiotic survivability during in vitro digestion. The effective dose of clover honey in yogurt was 10-20% wt/wt per serving (1-2 tablespoons per 170 g yogurt) for increased probiotic survivability during in vitro digestion.


Assuntos
Bifidobacterium animalis , Mel , Probióticos , Humanos , Iogurte/microbiologia , Bifidobacterium , Probióticos/uso terapêutico , Digestão
17.
Horm Behav ; 157: 105452, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37977023

RESUMO

Social hierarchies are a prevalent feature of all animal groups, and an individual's rank within the group can significantly affect their overall health, typically at the greatest expense of the lowest-ranked individuals, or omegas. These subjects have been shown to exhibit various stress-related phenotypes, such as increased hypothalamic-pituitary axis activity and increased amygdalar corticotropin-releasing factor levels compared to higher-ranked subjects. However, these findings have been primarily characterized in males and in models requiring exhibition of severe aggression. The goals of the current study, therefore, were to characterize the formation and maintenance of social hierarchies using the tube test and palatable liquid competition in same-sex groups of male and female C57BL/6 J mice. We also aimed to examine the effects of tube test-determined social rank on plasma and hypothalamic oxytocin and vasopressin levels, peptides with established roles in social behaviors and the stress response. Lastly, we assessed the effects of environmental enrichment and length of testing on the measures outlined above. Overall, we demonstrated that males and females develop social hierarchies and that these hierarchies can be determined using the tube test. While we were unable to establish a consistent connection between peptide levels and social rank, we observed transient changes in these peptides reflecting complex interactions between social rank, sex, environment, and length of testing. We also found that many male and female omegas began to exhibit passive coping behavior after repeated tube test losses, demonstrating the potential of this assay to serve as a model of chronic, mild psychosocial stress.


Assuntos
Hierarquia Social , Comportamento Social , Humanos , Animais , Camundongos , Masculino , Feminino , Camundongos Endogâmicos C57BL , Agressão/fisiologia , Hipotálamo
18.
J Nutr ; 154(1): 271-283, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37949114

RESUMO

BACKGROUND: Undigested components of the human diet affect the composition and function of the microorganisms present in the gastrointestinal tract. Techniques like metagenomic analyses allow researchers to study functional capacity, thus revealing the potential of using metagenomic data for developing objective biomarkers of food intake. OBJECTIVES: As a continuation of our previous work using 16S and metabolomic datasets, we aimed to utilize a computationally intensive, multivariate, machine-learning approach to identify fecal KEGG (Kyoto encyclopedia of genes and genomes) Orthology (KO) categories as biomarkers that accurately classify food intake. METHODS: Data were aggregated from 5 controlled feeding studies that studied the individual impact of almonds, avocados, broccoli, walnuts, barley, and oats on the adult gastrointestinal microbiota. Deoxyribonucleic acid from preintervention and postintervention fecal samples underwent shotgun genomic sequencing. After preprocessing, sequences were aligned and functionally annotated with Double Index AlignMent Of Next-generation sequencing Data v2.0.11.149 and MEtaGenome ANalyzer v6.12.2, respectively. After the count normalization, the log of the fold change ratio for resulting KOs between pre- and postintervention of the treatment group against its corresponding control was utilized to conduct differential abundance analysis. Differentially abundant KOs were used to train machine-learning models examining potential biomarkers in both single-food and multi-food models. RESULTS: We identified differentially abundant KOs in the almond (n = 54), broccoli (n = 2474), and walnut (n = 732) groups (q < 0.20), which demonstrated classification accuracies of 80%, 87%, and 86% for the almond, broccoli, and walnut groups using a random forest model to classify food intake into each food group's respective treatment and control arms, respectively. The mixed-food random forest achieved 81% accuracy. CONCLUSIONS: Our findings reveal promise in utilizing fecal metagenomics to objectively complement self-reported measures of food intake. Future research on various foods and dietary patterns will expand these exploratory analyses for eventual use in feeding study compliance and clinical settings.


Assuntos
Microbioma Gastrointestinal , Juglans , Adulto , Humanos , Metagenoma , Dieta , Fezes , Biomarcadores , Ingestão de Alimentos , Metagenômica/métodos
19.
Cancer Res Commun ; 4(1): 55-64, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38108490

RESUMO

Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.S. sites. Differences in four pain scores at study enrollment by race were investigated. Cox proportional hazards models and joint longitudinal survival models were fit for each of the scale scores to estimate HRs and 95% confidence intervals (CI) for the association with all-cause mortality. The cohort included 879 individuals (20% self-identifying as Black) enrolled at 38 U.S. sites. Black participants had worse pain at baseline compared with White participants, most notably a higher average pain rating (mean 3.1 vs. 2.2 on a 10-point scale). For each pain scale, higher pain was associated with higher mortality after adjusting for measures of disease burden, particularly for severe bone pain compared with no pain (HR, 2.47; 95% CI: 1.44-4.22). The association between pain and all-cause mortality was stronger for participants with castration-resistant prostate cancer compared with those with metastatic hormone-sensitive prostate cancer and was similar among Black and White participants. Overall, Black participants reported worse pain than White participants, and more severe pain was associated with higher mortality independent of clinical covariates for all pain scales. SIGNIFICANCE: Black participants with advanced prostate cancer reported worse pain than White participants, and more pain was associated with worse survival. More holistic clinical assessments of pain in this population are needed to determine the factors upon which to intervene to improve quality of life and survivorship, particularly for Black individuals.


Assuntos
Dor do Câncer , Neoplasias da Próstata , Humanos , Masculino , Negro ou Afro-Americano , Estudos Prospectivos , Neoplasias da Próstata/complicações , Qualidade de Vida , Estados Unidos/epidemiologia , Brancos , Taxa de Sobrevida
20.
Cortex ; 172: 14-37, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38154375

RESUMO

In behavioral, cognitive, and social sciences, reaction time measures are an important source of information. However, analyses on reaction time data are affected by researchers' analytical choices and the order in which these choices are applied. The results of a systematic literature review, presented in this paper, revealed that the justification for and order in which analytical choices are conducted are rarely reported, leading to difficulty in reproducing results and interpreting mixed findings. To address this methodological shortcoming, we created a checklist on reporting reaction time pre-processing to make these decisions more explicit, improve transparency, and thus, promote best practices within the field. The importance of the pre-processing checklist was additionally supported by an expert consensus survey and a multiverse analysis. Consequently, we appeal for maximal transparency on all methods applied and offer a checklist to improve replicability and reproducibility of studies that use reaction time measures.

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