Proinflammatory Diet Is Associated With Increased Risk of Fecal Incontinence Among Older Women: Prospective Results From the Nurses' Health Study.

Fecal incontinence (FI) is a debilitating gastrointestinal disorder with a devastating impact on quality of life, particularly on older women, partly because of unique risk factors including parity and menopause. Therefore, identifying modifiable factors, such as diet, are crucial for developing effective prevention strategies for FI among those at risk. We previously found higher dietary fiber intake was associated with lower FI risk, providing the first population-based data to connect diet and FI prevention.

Association of animal and plant protein intakes with biomarkers of insulin and insulin-like growth factor axis.

Background & Aims: Insulin and insulin-like growth factor (IGF)-1 signaling is a proposed mechanism linking dietary protein and major chronic diseases. However, it is unclear whether animal and plant proteins are associated with biomarkers of insulin and IGF axis.

Methods: We analyzed a total of 14,709 participants from Nurses' Health Study and Health Professionals Follow-up Study who had provided a blood sample.

Healthy lifestyle index and risk of pancreatic cancer in the Women's Health Initiative.

Purpose: Lifestyle factors such as smoking, alcohol, body weight, physical activity, and diet quality have been associated with the risk of pancreatic cancer. However, studies of their combined association in women are limited.

Methods: Data on smoking habits, alcohol intake, diet composition, recreational physical activity, body weight, and waist circumference, obtained at recruitment for 136,945 postmenopausal women (aged 50-79 years) participating in the Women's Health Initiative study, were categorized separately, with higher scores for each variable assigned to the categories representing healthier behaviors.

The Isocaloric Substitution of Plant-Based and Animal-Based Protein in Relation to Aging-Related Health Outcomes: A Systematic Review.

Plant-based and animal-based protein intake have differential effects on various aging-related health outcomes, but less is known about the health effect of isocaloric substitution of plant-based and animal-based protein. This systematic review summarized current evidence of the isocaloric substitutional effect of plant-based and animal-based protein on aging-related health outcomes. PubMed and Embase databases were searched for epidemiologic observational studies published in English up to 15 March 2021.

Analgesic Use and Circulating Estrogens, Androgens, and Their Metabolites in the Women's Health Initiative Observational Study.

Unlabelled: Though studies have observed inverse associations between use of analgesics (aspirin, NSAIDs, and acetaminophen) and the risk of several cancers, the potential biological mechanisms underlying these associations are unclear. We investigated the relationship between analgesic use and serum concentrations of estrogens, androgens, and their metabolites among postmenopausal women to provide insights on whether analgesic use might influence endogenous hormone levels, which could in turn influence hormone-related cancer risk. The study included 1,860 postmenopausal women from two case-control studies nested within the Women's Health Initiative Observational Study.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and Colorectal Cancer Survival.

Background: Patients with cancer are recommended to follow cancer prevention guidelines due to inadequate evidence for specific recommendations for cancer survivors.

Methods: We examined whether diet and lifestyle scores measuring adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention guidelines were associated with colorectal cancer-specific and overall mortality among 1,491 patients with colorectal cancer in two prospective cohorts. Cox proportional hazards regression models were used to calculate the multivariable-adjusted HRs and 95% confidence intervals (CI).

Low-Fat Dietary Modification and Risk of Ductal Carcinoma of the Breast in the Women's Health Initiative Dietary Modification Trial.

Background: Results of observational studies of the association between dietary fat and risk of invasive breast cancer have been inconsistent. In the Women's Health Initiative dietary modification (DM) randomized trial designed to lower fat intake, the intervention was not associated with a statistically significant reduction of overall breast cancer risk. However, the DM association with risk of ductal carcinoma (DCIS) of the breast, a putative breast cancer precursor, has not been reported.

Association between weight cycling and risk of kidney cancer: a prospective cohort study and meta-analysis of observational studies.

Purpose: Weight cycling is common in populations. However, it is unclear whether frequency and magnitude of weight cycling is associated with kidney cancer risk, independent of body mass index (BMI).

Methods: A prospective cohort study followed 85,562 participants from Health Professionals Follow-up Study and Nurses' Health Study (1992-2014).

Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors.

Background & Aims: Recent increasing trends in early-onset colorectal cancer (CRC) strongly supports that early-life diet is involved in CRC development. However, data are lacking on the relationship with high sugar intake during early life.

Methods: We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses' Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015.

Physical activity and all-cause and cause-specific mortality: assessing the impact of reverse causation and measurement error in two large prospective cohorts.

Most cohort studies have only a single physical activity (PA) measure and are thus susceptible to reverse causation and measurement error. Few studies have examined the impact of these potential biases on the association between PA and mortality. A total of 133,819 participants from Nurses' Health Study and Health Professionals Follow-up Study (1986-2014) reported PA through biennial questionnaires.

New Horizons: Emerging Therapies and Targets in Thyroid Cancer.

The treatment of patients with progressive metastatic follicular cell-derived and medullary thyroid cancers that do not respond to standard therapeutic modalities presents a therapeutic challenge. As a deeper understanding of the molecular drivers for these tumors has occurred and more potent and specific compounds are developed, the number of Food and Drug Administration (FDA)-approved treatments for thyroid cancer has expanded. In addition, with the advent of disease-agnostic target-directed FDA approvals an ever-broadening number of therapeutic options are available for clinicians and patients.

Insulin-related dietary indices predict 24-h urinary C-peptide in adult men.

The dietary insulin index directly estimates the postprandial insulin secretion potential of foods, whereas the empirical dietary index for hyperinsulinaemia (EDIH) assesses the insulinaemic potential of usual diets based on fasting plasma C-peptide, and is primarily reflective of insulin resistance. It is unknown whether these insulin-related indices are predictive of an integrated measure of insulin secretion. We conducted a cross-sectional analysis that included 293 non-diabetic men with 24-h urinary C-peptide data from the Men's Lifestyle Validation Study.

Insulinemic Potential of Lifestyle Is Inversely Associated with Leukocyte Mitochondrial DNA Copy Number in US White Adults.

Background: Poor lifestyles have been linked to insulin insensitivity/hyperinsulinemia, which may contribute to downstream changes such as inflammation and oxidative damage and the development of chronic diseases. As a biomarker of intracellular oxidative stress, leukocyte mitochondrial DNA copy number (mtDNA-CN) has been related to lifestyle factors including diet and weight. No epidemiologic study has examined the relation between combined insulinemic potential of lifestyle and mtDNA-CN.

The Mediterranean diet, plasma metabolome, and cardiovascular disease risk.

Aims: To investigate whether metabolic signature composed of multiple plasma metabolites can be used to characterize adherence and metabolic response to the Mediterranean diet and whether such a metabolic signature is associated with cardiovascular disease (CVD) risk.

Methods And Results: Our primary study cohort included 1859 participants from the Spanish PREDIMED trial, and validation cohorts included 6868 participants from the US Nurses' Health Studies I and II, and Health Professionals Follow-up Study (NHS/HPFS). Adherence to the Mediterranean diet was assessed using a validated Mediterranean Diet Adherence Screener (MEDAS), and plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry.

Dietary Inflammatory Potential and Risk of Crohn's Disease and Ulcerative Colitis.

Background & Aims: Inflammation is a potential mechanism through which diet modulates the onset of inflammatory bowel disease. We analyzed data from 3 large prospective cohorts to determine the effects of dietary inflammatory potential on the risk of developing Crohn's disease (CD) and ulcerative colitis (UC).

Methods: We collected data from 166,903 women and 41,931 men in the Nurses' Health Study (1984-2014), Nurses' Health Study II (1991-2015), and Health Professionals Follow-up Study (1986-2012).

Associations of C-reactive protein and fibrinogen with mortality from all-causes, cardiovascular disease and cancer among U.S. adults.

C-reactive protein (CRP) and fibrinogen are associated with an increased risk of death with suggested differences by gender, diet quality and race/ethnicity. However, the current evidence is limited. We used data including 8646 men and 9880 women from the National Health and Nutrition Examination Survey (NHANES) Linked Morality cohort (1999-2011) to investigate the associations of CRP and fibrinogen with mortality overall and by gender, race/ethnicity and diet quality.

Dietary Intake of Branched-Chain Amino Acids and Risk of Colorectal Cancer.

Branched-chain amino acids (BCAA) are essential amino acids, and emerging evidence suggests that BCAAs may mediate pathways related to cancer progression, possibly due to their involvement in insulin metabolism. We investigated the association between dietary intake of BCAAs with colorectal cancer risk in three prospective cohorts: the Nurses' Health Study I [(NHS), number of participants () at baseline = 77,017], NHS II ( = 92,984), and the Health Professionals Follow-up Study [(HPFS) = 47,255]. Validated food frequency questionnaires were administered every 4 years and follow-up questionnaires on lifestyle biennially.

Cells isolated from residual intracranial tumors after treatment express iPSC genes and possess neural lineage differentiation plasticity.

Background: The goal of this study is to identify and characterize treatment resistant tumor initiating cells (TRTICs) using orthotopic xenografts.

Methods: TRTICs were enriched from GBM cell lines using mouse xenografts treated with fractionated doses of radiation and temozolomide. TRTICs were characterized by neurosphere clonogenicity and self-renewal, serial xenotransplantation, differentiation potential, and mRNA & miRNA transcriptomic profiling.

Diagnostic and Prognostic Significance of Methionine Uptake and Methionine Positron Emission Tomography Imaging in Gliomas.

The present most common image diagnostic tracer in clinical practice for glioma is F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for brain tumors diagnosis and prognosis. PET is a promising molecular imaging technique, which provides real-time information on the metabolic behavior of the tracer. The diffusive nature of glioblastoma (GBM) and heterogeneity often make the radiographic detection by FDG-PET inaccurate, and there is no gold standard.

Lack of Constitutively Active DNA Repair Sensitizes Glioblastomas to Akt Inhibition and Induces Synthetic Lethality with Radiation Treatment in a p53-Dependent Manner.

Treatment refractory glioblastoma (GBM) remains a major clinical problem globally, and targeted therapies in GBM have not been promising to date. The Cancer Genome Atlas integrative analysis of GBM reported the striking finding of genetic alterations in the p53 and PI3K pathways in more than 80% of GBMs. Given the role of these pathways in making cell-fate decisions and responding to genotoxic stress, we investigated the reliance of these two pathways in mediating radiation resistance.

NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability.

To identify potential molecular hubs that regulate oncogenic kinases and target them to improve treatment outcomes for glioblastoma patients. Data mining of The Cancer Genome Atlas datasets identified nicotinamide-N-methyl transferase (NNMT) as a prognostic marker for glioblastoma, an enzyme linked to the reorganization of the methylome. We tested our hypothesis that NNMT plays a crucial role by modulating protein methylation, leading to inactivation of tumor suppressors and activation of oncogenes.

Methionine and Kynurenine Activate Oncogenic Kinases in Glioblastoma, and Methionine Deprivation Compromises Proliferation.

Purpose: We employed a metabolomics-based approach with the goal to better understand the molecular signatures of glioblastoma cells and tissues, with an aim toward identifying potential targetable biomarkers for developing more effective and novel therapies.

Experimental Design: We used liquid chromatography coupled with mass spectrometry (LC-MS/Q-TOF and LC-MS/QQQ) for the discovery and validation of metabolites from primary and established glioblastoma cells, glioblastoma tissues, and normal human astrocytes.

Results: We identified tryptophan, methionine, kynurenine, and 5-methylthioadenosine as differentially regulated metabolites (DRM) in glioblastoma cells compared with normal human astrocytes (NHAs).