Quantitative Phosphoproteomics Analysis Reveals the Protective Mechanism of Chlorogenic Acid on Immunologically Stressed Broiler Meat Quality.

Modern poultry production is stressful for the birds, and this stress is recognized as a major cause of inferior meat quality. Chlorogenic acid (CGA), a plant phenolic acid, has excellent antioxidant and anti-inflammatory properties. The antioxidant capacity and phosphoproteomics of immunologically stressed broiler breast muscle were assessed to elucidate the mechanism of the beneficial effects of CGA on meat quality. Dietary CGA decreased drip and cooking loss, postmortem pH and antioxidant capacity of breast muscle from stressed broilers, and increased MyHC-I mRNA levels. Quantitative phosphoproteomics revealed that CGA supplementation downregulated the phosphorylation of myofibrillar proteins, glycolytic enzymes, and endoplasmic reticulum proteins involved in homeostasis, which contributed to improving the meat quality of broilers. Moreover, 14 phosphorylation sites (e.g., P13538-Ser1236 and F1NN63-Ser117) in 13 phosphoproteins were identified as key regulators of processes related to broiler meat quality. Together, these findings provide novel regulatory targets and nutritional strategies for improving the stressed broiler meat quality.

Effectiveness of traditional Chinese exercise in patients with fibromyalgia syndrome: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND OBJECTIVE: Fibromyalgia syndrome (FMS) is a common disorder characterized by heterogeneous symptoms that leads to decreased functioning, work productivity, and quality of life. Exercise has been recommended for fibromyalgia treatment. Traditional Chinese exercise (TCE), including Taichi, Qigong, Badunjin, Wuqinxi, etc., as a kind of mind-body exercise, plays an important role in alleviating symptoms of FMS. The objective of this study is to summarize the available evidence, through meta-analysis, on the pain relief, quality of life, sleep improvement, and emotion regulation of FMS in TCE. METHODS: Databases of PubMed, EMBASE, Cochrane library, Google scholar, CNKI, WANFANG DATA, VIP, etc. were used to search eligible studies that were published from the time of their inception to February 11, 2022, in English and Chinese. The included studies were divided into two groups: TCE group (experimental group) and control group. The Cochrane collaboration's tool was used to assess the risk of bias, and Revman5.4.1 software was used to synthesize and analyze the data. RESULTS: A total of 12 literatures were included in this study, which contained 781 patients, and 448 of them were included in the treatment group, 333 of others in control group. TCE significantly alleviated pain [SMD = -0.83, 95% CI (-1.15, -0.51), p < .00001], improved quality of life [SMD = -0.53, 95% CI (-0.86, -0.19), p = .002] and improved qualities of sleep [SMD = -0.41, 95% CI (-0.57, -0.24), p < .00001] and relieved depression [SMD = -0.40, 95% CI (-0.69, -0.10), p < .008]. CONCLUSION: TCE may be a way to reduce pain, improve the quality of life and sleep, and relieve depression for FMS, and it could be part of the FMS treatment.

Genome-wide interaction analysis of folate for colorectal cancer risk.

BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Glucosamine and Chondroitin Use and Mortality Among Adults in the United States from 1999 to 2014.

Introduction: Glucosamine and chondroitin are supplements that are often, but not always, used in combination for arthritis and joint pain. Multiple studies have suggested that glucosamine and chondroitin may be associated with reduced risk of several diseases, as well as all-cause, cancer- and respiratory disease-specific mortality. Methods: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to further evaluate the association between glucosamine and chondroitin with mortality. Participants include 38,021 adults, ages 20+ years and older, who completed the detailed NHANES between 1999 and 2014. Participants were followed for death through linkage with the National Death Index through the end of 2015, over which time 4905 deaths occurred. Adjusted hazard ratios (HRs) for overall and cause-specific mortality were estimated using Cox regression models. Results: Despite glucosamine and chondroitin use appearing to be inversely associated with mortality in the minimally adjusted models, no association was observed in multivariable models (glucosamine: HR = 1.02; 95% confidence interval [CI]: 0.86-1.21, chondroitin: HR = 1.04, 95% CI: 0.87-1.25). No association with cancer mortality or other mortality rate was observed after multivariable adjustment. There was a suggestive, nonsignificant inverse association for cardiovascular-specific mortality (glucosamine HR = 0.72; 95% CI: 0.46-1.15, chondroitin: HR = 0.76; 95% CI: 0.47-1.21). Conclusion: The lack of significant relationship between glucosamine and chondroitin use and all-cause or cause-specific mortality after adjusting extensively for multiple covariates in this nationally representative adult population was in contrast to prior literature. Given the limited power to explore the cause-specific mortality, future well-powered studies will be needed to better understand the potential association with cardiovascular-specific mortality.

Electroacupuncture alleviates pain after total knee arthroplasty through regulating neuroplasticity: A resting-state functional magnetic resonance imaging study.

INTRODUCTION: We aimed to evaluate the efficacy of electroacupuncture in relieving acute pain after total knee arthroplasty (TKA) and related mechanism. METHODS: In this randomized, single-blind, and sham-acupuncture controlled study. Forty patients with postoperative acute pain were recruited and randomly divided electroacupuncture group (n = 20) and sham-acupuncture group (n = 20) from November 2020 to October 2021. All patients received electroacupuncture or sham-acupuncture for 5 days after TKA. Their brain regions were scanned with resting-state functional magnetic resonance imaging before and after intervention. Pain was scaled. Another 40 matched healthy controls underwent scanning once. The amplitude of low-frequency fluctuation (ALFF) values was compared. Pearson's correlation analysis was utilized to explore the correlation of ALFF with clinical variables in patients after intervention. RESULTS: Compared with the HCs, patients with acute pain following TKA had significantly decreased ALFF value in right middle frontal gyrus, right supplementary motor area, bilateral precuneus, right calcarine fissure and surrounding cortex, and left triangular part of inferior frontal gyrus (false discovery rate corrected p < .05). Patients had higher ALFF value in bilateral precuneus, right cuneus, right angular gyrus, bilateral middle occipital gyrus, and left middle temporal gyrus after electroacupuncture (AlphaSim corrected p < .01). Correlation analysis revealed that the change (postoperative day 7 to postoperative day 3) of ALFF in bilateral precuneus were negatively correlated with the change of NRS scores (r = -0.706; p = .002; 95% CI = -0.890 to -0.323) in EA group. CONCLUSIONS: The functional activities of related brain regions decreased in patients with acute pain after TKA. The enhancement of the functional activity of precuneus may be the neurobiological mechanism of electroacupuncture in treating pain following TKA.

FHL3 promotes the formation of fast glycolytic muscle fibers by interacting with YY1 and muscle glycolytic metabolism.

The proportions of the various muscle fiber types are important in the regulation of skeletal muscle metabolism, as well as animal meat production. Four-and-a-half LIM domain protein 3 (FHL3) is highly expressed in fast glycolytic muscle fibers and differentially regulates the expression of myosin heavy chain (MyHC) isoforms at the cellular level. Whether FHL3 regulates the transformation of muscle fiber types in vivo and the regulatory mechanism is unclear. In this study, muscle-specific FHL3 transgenic mice were generated by random integration, and lentivirus-mediated gene knockdown or overexpression in muscles of mice or pigs was conducted. Functional analysis showed that overexpression of FHL3 in muscles significantly increased the proportion of fast-twitch myofibers and muscle mass but decreased muscle succinate dehydrogenase (SDH) activity and whole-body oxygen consumption. Lentivirus-mediated FHL3 knockdown in muscles significantly decreased muscle mass and the proportion of fast-twitch myofibers. Mechanistically, FHL3 directly interacted with the Yin yang 1 (YY1) DNA-binding domain, repressed the binding of YY1 to the fast glycolytic MyHC2b gene regulatory region, and thereby promoted MyHC2b expression. FHL3 also competed with EZH2 to bind the repression domain of YY1 and reduced H3K27me3 enrichment in the MyHC2b regulatory region. Moreover, FHL3 overexpression reduced glucose tolerance by affecting muscle glycolytic metabolism, and its mRNA expression in muscle was positively associated with hemoglobin A1c (HbA1c) in patients with type 2 diabetes. Therefore, FHL3 is a novel potential target gene for the treatment of muscle metabolism-related diseases and improvement of animal meat production.

Adapting an Undergraduate Summer Internship to a Virtual Format: Implementing a Mentored Cancer Research Experience to Meet Rising Demand for Flexible Learning Environments.

To meet the rising demand for flexible learning in data-driven health research, we adapted an in-person undergraduate research program (Quantitative Sciences Undergraduate Research Experience (QSURE)) to an all-virtual framework in summer 2020 and 2021. We used Web-conferencing and remote computing to implement virtual hands-on research training within a comprehensive cancer center. We designed the program to achieve research and career development goals: students completed faculty-mentored quantitative research projects and received education in the responsible conduct of research and practical skills, such as oral and written presentation. We assessed virtual program efficacy using pre- and post-program quantitative and qualitative student feedback. Eighteen students participated (nine each year); they reported high satisfaction with the virtual format. Compared with baseline, students reported improved perceived competence in quantitative skills and research knowledge post-program; these improvements were comparable to the in-person program. Defined benchmarks and consistent communication (with mentors, program directors, other students) were crucial to students' success; however, students noted challenges in building camaraderie online. With adequate resources, Web-based technology can be leveraged as an effective format for hands-on quantitative research training. Our framework can be tailored to an institution's needs, particularly those for which available resources better align with a virtual research program.

A dynamics model of neuron-astrocyte network accounting for febrile seizures.

Febrile seizure (FS) is a full-body convulsion caused by a high body temperature that affect young kids, however, how these most common of human seizures are generated by fever has not been known. One common observation is that cortical neurons become overexcited with abnormal running of sodium and potassium ions cross membrane in raised body temperature condition, Considering that astrocyte Kir4.1 channel play a critical role in maintaining extracellular homeostasis of ionic concentrations and electrochemical potentials of neurons by fast depletion of extracellular potassium ions, we examined here the potential role of temperature-dependent Kir4.1 channel in astrocytes in causing FS. We first built up a temperature-dependent computational model of the Kir4.1 channel in astrocytes and validated with experiments. We have then built up a neuron-astrocyte network and examine the role of the Kir4.1 channel in modulating neuronal firing dynamics as temperature increase. The numerical experiment demonstrated that the Kir4.1 channel function optimally in the body temperature around 37 °C in cleaning 'excessive' extracellular potassium ions during neuronal firing process, however, higher temperature deteriorates its cleaning function, while lower temperature slows down its cleaning efficiency. With the increase of temperature, neurons go through different stages of spiking dynamics from spontaneous slow oscillations, to tonic spiking, fast bursting oscillations, and eventually epileptic bursting. Thus, our study may provide a potential new mechanism that febrile seizures may be happened due to temperature-dependent functional disorders of Kir4.1 channel in astrocytes. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-021-09706-w.

Glucosamine Use and Risk of Colorectal Cancer: Results from UK Biobank.

BACKGROUND: Use of the dietary supplement glucosamine has been associated with reduced risk of colorectal cancer; however, it remains unclear if the association varies by screening status, time, and other factors. METHODS: We therefore evaluated these questions in UK Biobank. Multivariable-adjusted HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. RESULTS: No association was observed between use of glucosamine and risk of colorectal cancer overall (HR = 0.94; 95% CI, 0.85-1.04). However, the association varied by screening status (Pinteraction = 0.05), with an inverse association observed only among never-screened individuals (HR = 0.86; 95% CI, 0.76-0.98). When stratified by study time, an inverse association was observed in early follow-up among those entering the cohort in early years (2006-2008; HR = 0.80; 95% CI, 0.67-0.95). No heterogeneity was observed by age, sex, body mass index, smoking status, or use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: While there was no association between glucosamine use and colorectal cancer overall, the inverse association among never-screened individuals mirrors our observations in prior exploratory analyses of U.S. cohorts. The National Health Service Bowel Cancer Screening Program started in 2006 in England and was more widely implemented across the UK by 2009/2010. In line with this, we observed an inverse association limited to early follow-up in those surveyed from 2006 to 2008, before screening was widely implemented. IMPACT: These data suggest that unscreened individuals may benefit from use of glucosamine; however, further studies are needed to confirm the interplay of screening and timing.

Vitamin B12 Supplementation and Vitamin B12 Blood Serum Levels: Evaluation of Effect Modification by Gender and Smoking Status.

Research suggests that high intake of supplemental vitamin B12 may be associated with increased risk of cancer, with some evidence that this association may vary by gender and smoking status. This investigation evaluates if similar patterns in association are observed for data for 11,757 adults from the National Health and Nutrition Examination Survey (1999-2006). Survey-weighted multivariable-adjusted linear regression was used to evaluate the association between regular B12 supplement use and log-transformed serum B12 levels. Persons taking vitamin B12 through a multivitamin/multimineral (MVMM) had a median supplemental intake of 12 mcg/day (Q1: 6, Q3: 25), compared to 100 mcg/day (Q1: 22, Q3: 500) for persons reporting supplemental B12 intake through a MVMM-exclusive source. MVMM users had a geometric mean serum B12 26% (95% CI: 23%-30%) higher than nonusers, whereas MVMM-exclusive users' geometric mean was 61% (95% CI: 53%-70%) higher than nonusers (p-trend < 0.001). Although a positive trend (p-trend < 0.001) was observed for both men and women, the association was stronger among women (p-interaction < 0.001). No interaction was observed for smoking status (p-interaction = 0.45). B12 supplementation is associated with higher levels of serum B12, with significant interaction by gender but not smoking. Further work is needed to better understand the interplay of B12 and gender.

Comparison of efficacy and safety of traditional Chinese patent medicine in the treatment of vitiligo in children or adults: A protocol for systematic review and network meta-analysis.

BACKGROUND: Vitiligo is a common depigmented skin disease in children or adults, which usually causes considerable psychological burden to life and work for the reason that it affects appearance. The conventional therapies, including external 308 nm excimer laser therapy along with oral administration of western medicine, are associated with distinct disadvantages. Notably, traditional Chinese patent medicine (TCPM) exerts a vital part in treating vitiligo. Currently, no existing research has examined the effectiveness and safety of different TCPMs in treating vitiligo among either child or adult patients. As a result, the present network meta-analysis was carried out for the systematic comparison of the effectiveness of different TCPMs in treating vitiligo. METHODS: The electronic databases, like PubMed, Web of Science, EMBASE, The Cochrane Library, Chinese Scientific Journals Database, China National Knowledge Infrastructure, Wanfang database and China BioMedical Literature, were searched systemically by 2 reviewers independently from inception to August 2020 to identify relevant randomized controlled trial (RCTs) according to our study inclusion criteria. In data extraction, risk of bias among those enrolled articles was also detected. Besides, the Bayesian network meta-analysis method was utilized to evaluate the evidence and data collected. This adopted the STATA and Win BUGS software for analysis. RESULTS: The present work assessed the safety and efficacy of different TCPMs in treating vitiligo among child or adult patients. CONCLUSION: Our findings can shed precious lights on applying TCPMs in clinic and help the clinicians to formulate the efficient diagnostic and therapeutic strategies. ETHICS AND DISSEMINATION: No ethical approval was needed in this study. INPLASY REGISTRATION NUMBER: INPLASY2020120050.

Glucosamine and Chondroitin Use in Relation to C-Reactive Protein Concentration: Results by Supplement Form, Formulation, and Dose.

Objectives: Glucosamine and chondroitin supplements have been associated with reduced inflammation, as measured by C-reactive protein (CRP). It is unclear if associations vary by formulation (glucosamine alone vs. glucosamine+chondroitin), form (glucosamine hydrochloride vs. glucosamine sulfate), or dose. Design, Subjects, Setting, Location: The authors evaluated these questions using cross-sectional data collected between 1999 and 2010 on 21,917 US adults, surveyed as part of the National Health and Nutrition Examination Survey (NHANES). Exposures: Glucosamine and chondroitin use was assessed during an in-home interview; exposures include supplement formulation, form, and dose. Outcome/Analysis: CRP was measured using blood collected at interview. Survey-weighted linear regression was used to evaluate the multivariable-adjusted association between exposures and log-transformed CRP. Results: In early years (1999-2004), use of glucosamine (ratio = 0.87; 95% confidence interval [CI] = 0.79-0.96) and chondroitin (ratio = 0.83; 95% CI = 0.72-0.95) was associated with reduced CRP. However, associations significantly varied by calendar time (p-interaction = 0.04 and p-interaction = 0.01, respectively), with associations nonsignificant in later years (ratio = 1.09; 95% CI = 0.94-1.28 and ratio = 1.16; 95% CI = 0.99-1.35, respectively). Consequently, all analyses have been stratified by calendar time. Associations did not significantly differ by formulation in either set of years; however, significant associations were observed for combined use of glucosamine+chondroitin (ratioearly = 0.82; 95% CI = 0.72-0.95; ratiolate = 1.16; 1.00-1.35), but not glucosamine alone. Associations also did not significantly differ by supplement form. Even so, a significant inverse association was observed only for glucosamine sulfate in the early years (ratio = 0.78; 95% CI = 0.64-0.95); no significant association was observed for glucosamine hydrochloride. No significant trends were observed by dose. Conclusions: Although a significant inverse association was observed for glucosamine and chondroitin and CRP in early years, this association did not hold in later years. This pattern held for combined use of glucosamine+chondroitin as well as glucosamine sulfate, although associations did not significantly vary by supplement form, formulation, or dose. Further study is needed to better understand these associations in the context of calendar time.

Activatable NIR-II Plasmonic Nanotheranostics for Efficient Photoacoustic Imaging and Photothermal Cancer Therapy.

Precise manipulation of optical properties through the structure-evolution of plasmonic nanoparticles is of great interest in biomedical fields including bioimaging and phototherapy. However, previous success has been limited to fixed assembled structures or visible-NIR-I absorption. Here, an activatable NIR-II plasmonic theranostics system based on silica-encapsulated self-assembled gold nanochains (AuNCs@SiO2 ) for accurate tumor diagnosis and effective treatment is reported. This transformable chain structure breaks through the traditional molecular imaging window, whose absorption can be redshifted from the visible to the NIR-II region owing to the fusion between adjacent gold nanoparticles in the restricted local space of AuNCs@SiO2 triggered by the high H2 O2 level in the tumor microenvironment (TME), leading to the generation of a new string-like structure with strong NIR-II absorption, which is further confirmed by finite-difference-time-domain (FDTD) simulation. With the TME-activated characteristics, AuNCs@SiO2 exhibits excellent properties for photoacoustic imaging and a high photothermal conversion efficiency of 82.2% at 1064 nm leading to severe cell death and remarkable tumor growth inhibition in vivo. These prominent intelligent TME-responsive features of AuNCs@SiO2 may open up a new avenue to explore optical regulated nano-platform for intelligent, accurate, and noninvasive theranostics in NIR-II window.

Comparative efficacy and safety of traditional Chinese medicine for lipodermatosclerosis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Lipodermatosclerosis (LDS) is a severe skin change accompanied by the development of chronic venous disease of the lower extremities. Its main clinical manifestations are erythema, induration, hyperpigmentation, and rough and thickened skin. It may also eventually lead to refractory ulcers, skin necrosis and even cancer. Conventional treatment methods mainly include the intake of oral anabolic hormones or androgen and pressure therapy. However, patients often refuse due to their drug resistance and intolerance. As a clinical irreplaceable treatment method for LDS, traditional Chinese medicine (TCM) has not been compared of the safety and effectiveness so far. Therefore, we cannot wait to use a method to compare the efficacy of TCM for LDS systematically, such as network meta-analysis (NMA). METHODS: We will retrieve the relevant Chinese and English databases comprehensively. All the randomized controlled trials of TCM for LDS from January 2015 to September 2020 will be included. Under the guidance of inclusion criteria, 2 researchers will screen the literature, then assess the risk of bias and extract data. We will use Bayesian NMA to evaluate all available evidence in STATA 14.0 and WinBUGS software. RESULTS: This study will use Bayesian NMA to evaluate the efficacy and safety of TCM for LDS. CONCLUSION: This study provide a reliable theoretical basis for the clinical application of TCM in the treatment of LDS, and contribute to the formulation of treatment guidelines for LDS.

Glucosamine and Chondroitin Supplements and Risk of Colorectal Adenoma and Serrated Polyp.

BACKGROUND: Studies have shown an inverse association between use of glucosamine and chondroitin supplements and colorectal cancer risk. However, the association with the precursor lesion, colorectal adenoma and serrated polyp, has not been examined. METHODS: Analyses include 43,163 persons from the Nurses' Health Study (NHS), Health Professionals Follow-up Study (HPFS), and NHS2 who reported on glucosamine/chondroitin use in 2002 and who subsequently underwent ≥1 lower gastrointestinal endoscopy. By 2012, 5,715 conventional (2,016 high-risk) adenomas were detected, as were 4,954 serrated polyps. Multivariable logistic regression for clustered data was used to calculate OR and 95% confidence intervals (CI). RESULTS: Glucosamine/chondroitin use was inversely associated with high risk and any conventional adenoma in NHS and HPFS: in the pooled multivariable-adjusted model, glucosamine + chondroitin use at baseline was associated with a 26% (OR = 0.74; 95% CI, 0.60-0.90; P heterogeneity = 0.23) and a 10% (OR = 0.90; 95% CI, 0.81-0.99; P heterogeneity = 0.36) lower risk of high-risk adenoma and overall conventional adenoma, respectively. However, no association was observed in NHS2, a study of younger women (high-risk adenoma: OR = 1.09; 95% CI, 0.82-1.45; overall conventional adenoma: OR = 1.00; 95% CI, 0.86-1.17), and effect estimates pooled across all three studies were not significant (high-risk: OR = 0.83; 95% CI, 0.63-1.10; P heterogeneity = 0.03; overall conventional adenoma: OR = 0.93; 95% CI, 0.85-1.02; P heterogeneity = 0.31). No associations were observed for serrated polyps. CONCLUSIONS: Glucosamine/chondroitin use was associated with lower risks of high-risk and overall conventional adenoma in older adults; however, this association did not hold in younger women, or for serrated polyps. IMPACT: Our study suggests that glucosamine and chondroitin may act on early colorectal carcinogenesis in older adults.

Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.

BACKGROUND: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. METHODS: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. RESULTS: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. CONCLUSIONS: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. IMPACT: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

Use of dietary supplements in relation to urinary phthalate metabolite concentrations: Results from the National Health and Nutrition Examination Survey.

BACKGROUND: Research suggests that dietary supplements may be a source of exposure to phthalates, given that diethyl phthalate (DEP) or di-n-butyl phthalate (DBP) can be components of coatings that facilitate extended release or encapsulate dietary supplements. METHODS: Using nationally representative data on a population of 12,281 adults ages 20 y + surveyed between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES), we evaluated the association between dietary supplement use in relation to urinary phthalate metabolites of DEP (monoethyl phthalate, MEP) and DBP (mono-n-butyl phthalate, MBP). We examined associations pertaining to regular use of multivitamin/multimineral (MVMM) supplements, as well as regular use of any other non-MVMM supplement products, the number of non-MVMM supplement products used, as well as individual supplements potentially containing phthalates (exclusive of MVMM). For each urinary phthalate metabolite, results are presented as the minimally-adjusted and multivariable-adjusted ratio, comparing the geometric mean among users to non-users. RESULTS: In multivariable models, we observed a significant positive association between regular use of MVMM use and MEP, with persons using MVMM supplements having 11% higher geometric mean MEP than non-users (Ratio: 1.11; 95% CI: 1.04-1.20); no association was observed for MVMM in relation to MBP. No other significant multivariable-adjusted associations were observed, although power was limited in analyses of individual supplements. Associations did not markedly vary by gender; however, the associations of garlic supplement use with MEP and MBP varied by calendar time, with statistically significant positive associations observed in later years. CONCLUSIONS: A modest significant association was observed between MVMM use and MEP. No other significant associations were observed in our overall multivariable models. Follow-up on the positive association observed between garlic and urinary phthalate metabolite concentrations observed in later years in a well-powered, prospective study would further clarify study findings.

Trends in Dietary Supplement Use Among US Adults From 1999-2012.

Importance: Dietary supplements are commonly used by US adults; yet, little is known about recent trends in supplement use. Objective: To report trends in dietary supplement use among US adults. Design, Setting, and Participants: Serial cross-sectional study using nationally representative data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2012. Participants include noninstitutionalized adults residing in the United States, surveyed over 7 continuous 2-year cycles (sample size per cycle, 4863 to 6213). Exposures: Calendar time, as represented by NHANES cycle. Main Outcomes and Measures: In an in-home interview, participants were queried on use of supplements in the preceding 30 days to estimate the prevalence of use within each NHANES cycle, and trends were evaluated across cycles. Outcomes included use of any supplements; use of multivitamins/multiminerals (MVMM; defined as a product containing ≥10 vitamins and/or minerals); and use of individual vitamins, minerals, and nonvitamin, nonmineral supplements. Data were analyzed overall and by population subgroup (including age, sex, race/ethnicity, and educational status), and were weighted to be nationally representative. Results: A total of 37 958 adults were included in the study (weighted mean age, 46.4 years; women, 52.0% ), with an overall response rate of 74%. Overall, the use of supplements remained stable between 1999 and 2012, with 52% of US adults reporting use of any supplements in 2011-2012 (P for trend = .19). This trend varied by population subgroup. Use of MVMM decreased, with 37% reporting use of MVMM in 1999-2000 and 31% reporting use in 2011-2012 (difference, -5.7% [95% CI, -8.6% to -2.7%], P for trend < .001). Vitamin D supplementation from sources other than MVMM increased from 5.1% to 19% (difference, 14% [95% CI, 12% to 17%], P for trend < .001) and use of fish oil supplements increased from 1.3% to 12% (difference, 11% [95% CI, 9.1% to 12%], P for trend < .001) over the study period, whereas use of a number of other supplements decreased. Conclusions and Relevance: Among adults in the United States, overall use of dietary supplements remained stable from 1999-2012, use of MVMM decreased, and trends in use of individual supplements varied and were heterogeneous by population subgroups.

Vitamin D supplement improved testicular function in diabetic rats.

This study was designed to investigate the role that 1,25(OH)2D3 plays against testicular lesion in diabetic rats and try to find its possible mechanism of the steroidogenesis and the spermatogenesis. In diabetic rats, prolonged hyperglycemia evaluated inflammatory cytokines, damaged sperm production function and redox balance, diminished serum testosterone. After treated with 1,25(OH)2D3 at two different doses respectively for 12 months, all the alternations were effectively normalized. 1,25(OH)2D3 showed inhibitory effect on excessive inflammatory biomarkers and adjusted the expression reproductive genes and testicular androgen synthesis. It also upregulated Bcl-2 expression, decreased Bax and COX-2 expression and inhibited active caspase cascade (caspase 8 and caspase 3), which may preserved the testicular cells under diabetic condition. It revealed that vitamin D supplement may protect the cells through suppressing inflammation factors and alleviating cell apoptotic death, as well as upregulating the expression of genes related to reproductive and testosterone synthesis.