An atlas of protein-protein interactions across mouse tissues.

Cellular processes arise from the dynamic organization of proteins in networks of physical interactions. Mapping the interactome has therefore been a central objective of high-throughput biology. However, the dynamics of protein interactions across physiological contexts remain poorly understood. Here, we develop a quantitative proteomic approach combining protein correlation profiling with stable isotope labeling of mammals (PCP-SILAM) to map the interactomes of seven mouse tissues. The resulting maps provide a proteome-scale survey of interactome rewiring across mammalian tissues, revealing more than 125,000 unique interactions at a quality comparable to the highest-quality human screens. We identify systematic suppression of cross-talk between the evolutionarily ancient housekeeping interactome and younger, tissue-specific modules. Rewired proteins are tightly regulated by multiple cellular mechanisms and are implicated in disease. Our study opens up new avenues to uncover regulatory mechanisms that shape in vivo interactome responses to physiological and pathophysiological stimuli in mammalian systems.

Cross-sectional study of household solid fuel use and renal function in older adults in China.

BACKGROUND: Emerging evidence links outdoor air pollution and declined renal function but the relationship between household air pollution and renal function is not well understood. METHODS: Using cross-sectional data from the multi-provincial INTERMAP-China Prospective Study, we collected blood samples and questionnaire information on stove use and socio-demographic factors. We calculated estimated glomerular filtration rate (eGFR) from serum creatinine to assess renal function. Participants with eGFR <60 mL/min per 1.73 m2 were defined as having chronic kidney disease (CKD) in this analysis. Generalized estimating equations were used to estimate the association of household fuel with renal function and prevalent CKD in models adjusting for confounders. RESULTS: Among the 646 enrolled adults (40-79y; 56% female), one-third exclusively used clean fuel (gas and electric) cookstoves and 11% of northern China participants (n = 49 of 434) used only clean fuel heaters, whereas the rest used solid fuel. In multivariable models, use of solid fuel cookstoves was associated with 0.17 ml/min/1.73 m2 (95% CI: -0.30, 0.64) higher eGFR and 19% (0.86, 1.64) higher prevalence of CKD than exclusive clean fuel use. Greater intensity of solid fuel use was associated with 0.25 ml/min/1.73 m2 (-0.71, 0.21) lower eGFR per 5 stove-use years, though the confidence intervals included the null, while greater current intensity of indoor solid fuel use was associated with 1.02 (1.00, 1.04) higher prevalent CKD per 100 stove-use days per year. Larger associations between current solid fuel use and intensity of use with lower eGFR and prevalent CKD were observed among participants in southern China, those with hypertension or diabetes (eGFR only), and females (CKD only), through these groups had small sample sizes and some confidence intervals included the null. CONCLUSION: We found inconsistent evidence associating household solid fuel use and renal function in this cross-sectional study of peri-urban Chinese adults.

Plasma metabolites associated with cognitive function across race/ethnicities affirming the importance of healthy nutrition.

INTRODUCTION: We studied the replication and generalization of previously identified metabolites potentially associated with global cognitive function in multiple race/ethnicities and assessed the contribution of diet to these associations. METHODS: We tested metabolite-cognitive function associations in U.S.A. Hispanic/Latino adults (n = 2222) from the Community Health Study/ Study of Latinos (HCHS/SOL) and in European (n = 1365) and African (n = 478) Americans from the Atherosclerosis Risk In Communities (ARIC) Study. We applied Mendelian Randomization (MR) analyses to assess causal associations between the metabolites and cognitive function and between Mediterranean diet and cognitive function. RESULTS: Six metabolites were consistently associated with lower global cognitive function across all studies. Of these, four were sugar-related (e.g., ribitol). MR analyses provided weak evidence for a potential causal effect of ribitol on cognitive function and bi-directional effects of cognitive performance on diet. DISCUSSION: Several diet-related metabolites were associated with global cognitive function across studies with different race/ethnicities. HIGHLIGHTS: Metabolites associated with cognitive function in Puerto Rican adults were recently identified. We demonstrate the generalizability of these associations across diverse race/ethnicities. Most identified metabolites are related to sugars. Mendelian Randomization (MR) provides weak evidence for a causal effect of ribitol on cognitive function. Beta-cryptoxanthin and other metabolites highlight the importance of a healthy diet.

Balancing the Equation: A Natural History of Trimethylamine and Trimethylamine-N-oxide.

Trimethylamine (TMA) and its N-oxide (TMAO) are ubiquitous in prokaryote and eukaryote organisms as well as in the environment, reflecting their fundamental importance in evolutionary biology, and their diverse biochemical functions. Both metabolites have multiple biological roles including cell-signaling. Much attention has focused on the significance of serum and urinary TMAO in cardiovascular disease risk, yet this is only one of the many facets of a deeper TMA-TMAO partnership that reflects the significance of these metabolites in multiple biological processes spanning animals, plants, bacteria, and fungi. We report on analytical methods for measuring TMA and TMAO and attempt to critically synthesize and map the global functions of TMA and TMAO in a systems biology framework.

Strategy for improved characterization of human metabolic phenotypes using a COmbined Multi-block Principal components Analysis with Statistical Spectroscopy (COMPASS).

MOTIVATION: Large-scale population omics data can provide insight into associations between gene-environment interactions and disease. However, existing dimension reduction modelling techniques are often inefficient for extracting detailed information from these complex datasets. RESULTS: Here, we present an interactive software pipeline for exploratory analyses of population-based nuclear magnetic resonance spectral data using a COmbined Multi-block Principal components Analysis with Statistical Spectroscopy (COMPASS) within the R-library hastaLaVista framework. Principal component analysis models are generated for a sequential series of spectral regions (blocks) to provide more granular detail defining sub-populations within the dataset. Molecular identification of key differentiating signals is subsequently achieved by implementing Statistical TOtal Correlation SpectroscopY on the full spectral data to define feature patterns. Finally, the distributions of cross-correlation of the reference patterns across the spectral dataset are used to provide population statistics for identifying underlying features arising from drug intake, latent diseases and diet. The COMPASS method thus provides an efficient semi-automated approach for screening population datasets. AVAILABILITY AND IMPLEMENTATION: Source code is available at https://github.com/cheminfo/COMPASS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Characterization and correction of the effects of hepatic iron on T1ρ relaxation in the liver at 3.0T.

PURPOSE: Quantitative T1ρ imaging is an emerging technique to assess the biochemical properties of tissues. In this paper, we report our observation that liver iron content (LIC) affects T1ρ quantification of the liver at 3.0T field strength and develop a method to correct the effect of LIC. THEORY AND METHODS: On-resonance R1ρ (1/T1ρ ) is mainly affected by the intrinsic R2 (1/T2 ), which is influenced by LIC. As on-resonance R1ρ is closely related to the Carr-Purcell-Meiboom-Gill (CPMG) R2 , and because the calibration between CPMG R2 and LIC has been reported at 1.5T, a correction method was proposed to correct the R2 contribution to the R1ρ . The correction coefficient was obtained from the calibration results and related transformed factors. To compensate for the difference between CPMG R2 and R1ρ , a scaling factor was determined using the values of CPMG R2 and R1ρ , obtained simultaneously from a single breath-hold from volunteers. The livers of 110 subjects were scanned to validate the correction method. RESULTS: LIC was significantly correlated with R1ρ in the liver. However, when the proposed correction method was applied to R1ρ , LIC and the iron-corrected R1ρ were not significantly correlated. CONCLUSION: LIC can affect T1ρ in the liver. We developed an iron-correction method for the quantification of T1ρ in the liver at 3.0T.

Quantitative Susceptibility Mapping of the Hippocampal Fimbria in Alzheimer's Disease.

BACKGROUND: The fimbria is a small white matter bundle that connects the hippocampus to the rest of the brain. Damage to the hippocampal gray matter is established in Alzheimer's disease (AD), but the hippocampal fimbrial status in the pathogenesis of AD is unclear. AD-related demyelination and iron deposition alter the diamagnetic and paramagnetic composition of tissues, which can be measured by quantitative susceptibility mapping (QSM). HYPOTHESIS: AD is associated with microstructural changes in the fimbria that might be detected by QSM. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: In all, 53 adults comprised of controls (n = 30), subjects with early stage AD (n = 13), and late stage AD (n = 10) who were classified according to their amyloid and tau status and presence of hippocampal atrophy. FIELD STRENGTH / SEQUENCE: 3T; 3D fast-field echo sequence for QSM analysis and 3D T1 -weighted MP-RAGE sequence for anatomical analysis. ASSESSMENT: Segmentation of the left hippocampal fimbria subfield was performed on T1 -weighted images and was applied to the coregistered QSM map for extraction of the mean, median, minimum, and maximum values of QSM. STATISTICAL TESTS: Group comparison of QSM values using analysis of variance (ANOVA) with post-hoc Tukey's test, accuracy of binary differentiation using receiver operating characteristic (ROC), and individual classification using discriminant analysis. RESULTS: QSMmean and QSMmedian values were significantly different among the three groups (P < 0.05) and showed a shifting from negative in the control group to positive in the AD group. The control and early AD subjects, who have normal hippocampal volumes, were differentiated by the QSMmean value (area under the curve [AUC] 0.744, P < 0.05) and the QSMmedian value (AUC 0.782, P < 0.05). Up to 76% of subjects (inclusive of 26 controls and six with early AD) were correctly classified using a model incorporating clinical and radiologic data. DATA CONCLUSION: The fimbria showed higher magnetic susceptibility in AD compared with controls. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Difference in ambient-personal exposure to PM2.5 and its inflammatory effect in local residents in urban and peri-urban Beijing, China: results of the AIRLESS project.

Measurement of ambient fine particulate matter (PM2.5) is often used as a proxy of personal exposure in epidemiological studies. However, the difference between personal and ambient exposure, and whether it biases the estimates of health effects remain unknown. Based on an epidemiological study (AIRLESS) and simultaneously launched intensive monitoring campaigns (APHH), we quantified and compared the personal and ambient exposure to PM2.5 and the related health impact among residents in Beijing, China. In total, 123 urban and 128 peri-urban non-smoking participants were recruited from two well-established cohorts in Beijing. During winter 2016 and summer 2017, each participant was instructed to carry a validated personal air monitor (PAM) to measure PM2.5 concentration at high spatiotemporal resolution for seven consecutive days in each season. Multiple inflammatory biomarkers were measured, including exhaled NO, blood monocytes counts and C-reactive protein. Linear mixed-effect models were used for the associations between exposure and health outcomes with adjustment for confounders. The average level of daily personal exposure to PM2.5 was consistently lower than using corresponding ambient concentration, and the difference is greater during the winter. The personal to ambient (P/A) ratio of exposure to PM2.5 exhibited an exponentially declining trend, and showed larger variations when ambient PM2.5 levels < 25 µg m-3. Personal exposure to PM2.5 was significantly associated with the increase in respiratory and systemic inflammatory biomarkers; however, the associations were weaker or became insignificant when ambient concentrations were used. Exposure to ambient PM2.5 might not be a good proxy to estimate the health effect of exposure to personal PM2.5.

Chemical Investigation of Household Solid Fuel Use and Outdoor Air Pollution Contributions to Personal PM2.5 Exposures.

In communities with household solid fuel use, transitioning to clean stoves/fuels often results in only moderate reductions in fine particulate matter (PM2.5) exposures; the chemical composition of those exposures may help explain why. We collected personal exposure (men and women) and outdoor PM2.5 samples in villages in three Chinese provinces (Shanxi, Beijing, and Guangxi) and measured chemical components, including water-soluble organic carbon (WSOC), ions, elements, and organic tracers. Source contributions from chemical mass balance modeling (biomass burning, coal combustion, vehicles, dust, and secondary inorganic aerosol) were similar between outdoor and personal PM2.5 samples. Principal component analysis of organic and inorganic components identified analogous sources, including a regional ambient source. Chemical components of PM2.5 exposures did not differ significantly by gender. Participants using coal had higher personal/outdoor (P/O) ratios of coal combustion tracers (picene, sulfate, As, and Pb) than those not using coal, but no such trend was observed for biomass burning tracers (levoglucosan, K+, WSOC). Picene and most levoglucosan P/O ratios exceeded 1 even among participants not using coal and biomass, respectively, indicating substantial indirect exposure to solid fuel emissions from other homes. Contributions of community-level emissions to exposures suggest that meaningful exposure reductions will likely require extensive fuel use changes within communities.

Association between egg intake and blood pressure in the USA: the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP).

OBJECTIVES: To investigate associations of egg intake with blood pressure (BP) and the role of dietary variables and other macro- and micro-nutrients in the association. DESIGN: We used cross-sectional data for the USA as part of the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP). INTERMAP was surveyed between 1996 and 1999, including four 24-h dietary recalls, two 24-h urine collections and eight measurements of systolic BP and diastolic BP (SBP, DBP). Average egg intake (g/d) was calculated. Multivariable linear regression models were used to estimate the association between egg intake (per each 50 g/d or per quintile) and BP. The roles of dietary variables and other macro- and micro-nutrients in this association were also investigated. SETTING: In the USA. PARTICIPANTS: In total, 2195 US INTERMAP men and women aged 40-59 years. RESULTS: Participants were 50 % female, 54 % non-Hispanic White and 16 % non-Hispanic Black. Mean egg intake (sd) in men and women was 30·4(29·8) and 21·6(20·5) g/d, respectively. Adjusting for demographics, socio-economics, lifestyle and urinary Na:K excretion ratios, we found non-linear associations with BP in non-obese women (P-quadratic terms: 0·004 for SBP and 0·035 for DBP).The associations remained after adjusting for dietary variables, macro/micro nutrients or minerals. Dietary cholesterol was highly correlated with egg intake and may factor in the association. No association was found in obese women and in obese or non-obese men. CONCLUSION: Egg intake was non-linearly associated with SBP and DBP in non-obese women, but not in obese women or men. Underlying mechanisms require additional study regarding the role of obesity and sex.

Discordance in the Epithelial Cell-Dendritic Cell Major Histocompatibility Complex Class II Immunoproteome: Implications for Chlamydia Vaccine Development.

BACKGROUND: Chlamydia trachomatis and Chlamydia muridarum are intracellular bacterial pathogens of mucosal epithelial cells. CD4 T cells and major histocompatibility complex (MHC) class II molecules are essential for protective immunity against them. Antigens presented by dendritic cells (DCs) expand naive pathogen-specific T cells (inductive phase), whereas antigens presented by epithelial cells identify infected epithelial cells as targets during the effector phase. We previously showed that DCs infected by C trachomatis or C muridarum present epitopes from a limited spectrum of chlamydial proteins recognized by Chlamydia-specific CD4 T cells from immune mice. METHODS: We hypothesized that Chlamydia-infected DCs and epithelial cells present overlapping sets of Chlamydia-MHC class II epitopes to link inductive and effector phases to generate protective immunity. We tested that hypothesis by infecting an oviductal epithelial cell line with C muridarum, followed by immunoaffinity isolation and sequencing of MHC class I- and II-bound peptides. RESULTS: We identified 26 class I-bound and 4 class II-bound Chlamydia-derived peptides from infected epithelial cells. We were surprised to find that none of the epithelial cell class I- and class II-bound chlamydial peptides overlapped with peptides presented by DCs. CONCLUSIONS: We suggest the discordance between the DC and epithelial cell immunoproteomes has implications for delayed clearance of Chlamydia and design of a Chlamydia vaccine.

A Varroa destructor protein atlas reveals molecular underpinnings of developmental transitions and sexual differentiation.

Varroa destructor is the most economically damaging honey bee pest, weakening colonies by simultaneously parasitizing bees and transmitting harmful viruses. Despite these impacts on honey bee health, surprisingly little is known about its fundamental molecular biology. Here, we present a Varroa protein atlas crossing all major developmental stages (egg, protonymph, deutonymph, and adult) for both male and female mites as a web-based interactive tool (http://foster.nce.ubc.ca/varroa/index.html). We used intensity-based label-free quantitation to find 1,433 differentially expressed proteins across developmental stages. Enzymes for processing carbohydrates and amino acids were among many of these differences as well as proteins involved in cuticle formation. Lipid transport involving vitellogenin was the most significantly enriched biological process in the foundress (reproductive female) and young mites. In addition, we found that 101 proteins were sexually regulated and functional enrichment analysis suggests that chromatin remodeling may be a key feature of sex determination. In a proteogenomic effort, we identified 519 protein-coding regions, 301 of which were supported by two or more peptides and 169 of which were differentially expressed. Overall, this work provides a first-of-its-kind interrogation of the patterns of protein expression that govern the Varroa life cycle and the tools we have developed will support further research on this threatening honey bee pest.

Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry and Direct Infusion-High-Resolution Mass Spectrometry for Combined Exploratory and Targeted Metabolic Profiling of Human Urine.

The application of metabolic phenotyping to epidemiological studies involving thousands of biofluid samples presents a challenge for the selection of analytical platforms that meet the requirements of high-throughput precision analysis and cost-effectiveness. Here direct infusion-nanoelectrospray (DI-nESI) was compared with an ultra-performance liquid chromatography (UPLC)-high-resolution mass spectrometry (HRMS) method for metabolic profiling of an exemplary set of 132 human urine samples from a large epidemiological cohort. Both methods were developed and optimized to allow the simultaneous collection of high-resolution urinary metabolic profiles and quantitative data for a selected panel of 35 metabolites. The total run time for measuring the sample set in both polarities by UPLC-HRMS was 5 days compared with 9 h by DI-nESI-HRMS. To compare the classification ability of the two MS methods, we performed exploratory analysis of the full-scan HRMS profiles to detect sex-related differences in biochemical composition. Although metabolite identification is less specific in DI-nESI-HRMS, the significant features responsible for discrimination between sexes were mostly the same in both MS-based platforms. Using the quantitative data, we showed that 10 metabolites have strong correlation (Pearson's r > 0.9 and Passing-Bablok regression slope of 0.8-1.3) and good agreement assessed by Bland-Altman plots between UPLC-HRMS and DI-nESI-HRMS and thus can be measured using a cheaper and less sample- and time-consuming method. A further twenty metabolites showed acceptable correlation between the two methods with only five metabolites showing weak correlation (Pearson's  r < 0.4) and poor agreement due to the overestimation of the results by DI-nESI-HRMS.

Connectivity-based parcellation of the nucleus accumbens into core and shell portions for stereotactic target localization and alterations in each NAc subdivision in mTLE patients.

The nucleus accumbens (NAc), an important target of deep brain stimulation for some neuropsychiatric disorders, is thought to be involved in epileptogenesis, especially the shell portion. However, little is known about the exact parcellation within the NAc, and its structural abnormalities or connections alterations of each NAc subdivision in temporal lobe epilepsy (TLE) patients. Here, we used diffusion probabilistic tractography to subdivide the NAc into core and shell portions in individual TLE patients to guide stereotactic localization of NAc shell. The structural and connection abnormalities in each NAc subdivision in the groups were then estimated. We successfully segmented the NAc in 24 of 25 controls, 14 of 16 left TLE patients, and 14 of 18 right TLE patients. Both left and right TLE patients exhibited significantly decreased fractional anisotropy (FA) and increased radial diffusivity (RD) in the shell, while there was no significant alteration in the core. Moreover, relatively distinct structural connectivity of each NAc subdivision was demonstrated. More extensive connection abnormalities were detected in the NAc shell in TLE patients. Our results indicate that neuronal degeneration and damage caused by seizure mainly exists in NAc shell and provide anatomical evidence to support the role of NAc shell in epileptogenesis. Remarkably, those NAc shell tracts with increased connectivities in TLE patients were found decreased in FA, which indicates disruption of fiber integrity. This finding suggests the regeneration of aberrant connections, a compensatory and repair process ascribed to recurrent seizures that constitutes part of the characteristic changes in the epileptic network.

Quantitative intravoxel incoherent motion parameters derived from whole-tumor volume for assessing pathological complete response to neoadjuvant chemotherapy in locally advanced rectal cancer.

BACKGROUND: Many locally advanced rectal cancer (LARC) patients can benefit from neoadjuvant chemotherapy (NACT), with some achieving a pathological complete response (pCR). However, there is limited research reporting on the value of intravoxel incoherent motion (IVIM) in monitoring pCR in patients with LARC. PURPOSE: To identify whether IVIM parameters derived from whole-tumor volume (WTV) before and after NACT could accurately assess pCR in patients with LARC. STUDY TYPE: Prospective patient control study. POPULATION: Fifty-one patients with LARC before and after NACT, prior to surgery. FIELD STRENGTH/SEQUENCE: IVIM-diffusion imaging at 3T. ASSESSMENT: Apparent diffusion coefficient (ADC), slow diffusion coefficient (D), fast diffusion coefficient (D*), and perfusion-related diffusion fraction (f) values were obtained on diffusion-weighted magnetic resonance images (DW-MRI) using WTV methods and calculated using a biexponential model before and after NACT. STATISTICAL TESTS: DWI-derived ADC and IVIM-derived parameters and their percentage changes (ΔADC%, ΔD%, ΔD*%, and Δf%) were compared using independent-samples t-test and Mann-Whitney U-test between the pCR and non-pCR groups. The diagnostic performance of IVIM parameters and their percentage changes were evaluated using receiver operating characteristic curves. RESULTS: Compared with the non-pCR group, the pCR group exhibited significantly lower pre-ADCmean (P = 0.003) and pre-D values (P = 0.024), and significantly higher post-f (P = 0.002), ΔADCmean % (P = 0.002), ΔD% (P = 0.001), and Δf% values (P = 0.017). Receiver operating characteristic curves showed that the pre-D value had the best specificity (95.12%) and accuracy (86.27%) in predicting the pCR status, and ΔD% had the highest area under the curve (0.832) in assessing the pCR response to NACT. DATA CONCLUSIONS: The IVIM-derived D value is a promising tool in predicting the pCR status before therapy. The percentage changes in D values after therapy may help assess the pCR status prior to surgery. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.

Use of T1 relaxation time in rotating frame (T1 ρ) and apparent diffusion coefficient to estimate cerebral stroke evolution.

BACKGROUND: The major factor for the appropriate treatment strategies for ischemia patients is its onset timing. PURPOSE/HYPOTHESIS: To study to evaluate the diagnostic accuracy of T1 relaxation time in a rotating frame (T1 ρ) and apparent diffusion coefficient (ADC) from MRI to estimate ischemia stages. STUDY TYPE: Prospective. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: In all, 73 patients (49 males, aged 29-78 years and 24 females, aged 22-94 years) with ischemia were prospectively imaged with T1 ρ and diffusion MRI during the postischemic period. FIELD STRENGTH/SEQUENCE: 3T/T1 ρ and diffusion-weighted imaging (DWI). ASSESSMENT: Ischemic parenchyma included tissue with elevated signal areas on DWI and correlative hypointense areas on ADC maps. STATISTICAL TESTS: The sensitivity of variables to ischemia time was quantified by analyzing the respective correlations of these values with onset time. RESULTS: ΔT1 ρ (ipsilateral-contralateral differences in T1 ρ) (R2 = 0.956) and T1 ρipsi (ipsilateral ischemia T1 ρ values) (R2 = 0.941) were elevated in all ischemic lesions; these values increased linearly as a function of time, unlike ΔADC (ipsilateral-contralateral differences in ADC) (R2 = -0.410) and ADCipsi (ipsilateral ischemia ADC values) (R2 = 0.550). ΔT1 ρ and T1 ρipsi were significantly different between all stages (P < 0.01), except the acute and hyperacute stages (P = 0.589 for ΔT1 ρ, P = 0.290 for T1 ρipsi , respectively), but ΔADC and ADCipsi only between the late subacute and early subacute stages (P < 0.01) and the late subacute and chronic stages (P < 0.01). DATA CONCLUSION: These data suggest that T1 ρ can provide estimates for the ischemic time in patients. T1 ρ has the potential to outperform diffusion for single-timepoint examination because the T1 ρ change during strokes is positive and linear. If patients with suspected stroke are scanned by MRI within the appropriate timeframe, T1 ρ may provide tools for evaluating stroke onset, potentially aiding in treatment strategies. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1247-1254.

Integrating dynamic contrast-enhanced magnetic resonance imaging and diffusion kurtosis imaging for neoadjuvant chemotherapy assessment of nasopharyngeal carcinoma.

BACKGROUND: Since neoadjuvant chemotherapy (NAC) has proven a benefit for locally advanced nasopharyngeal carcinoma (NPC), early response evaluation after chemotherapy is important to implement individualized therapy for NPC in the era of precision medicine. PURPOSE: To determine the combined and independent contribution between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion kurtosis imaging (DKI) in the early monitoring of NAC response for NPC. STUDY TYPE: Prospective. POPULATION: Fifty-three locally advanced NPC patients. FIELD STRENGTH/SEQUENCE: Four examinations before and at 4, 20, and 40 days after NAC initiation were performed at 3T MRI including DCE-MRI and DKI (b values = 0, 500, 1000, 1500 s/mm2 ). ASSESSMENT: DCE-MRI parameters (Ktrans [the volume transfer constant of Gd-DTPA], kep [rate constant], νe [the extracellular volume fraction of the imaged tissue], and νp [the blood volume fraction]) and DKI parameters (Dapp [apparent diffusion for non-Gaussian distribution] and Kapp [apparent kurtosis coefficient]) were analyzed using dedicated software. STATISTICAL TESTS: MRI parameters and their corresponding changes were compared between responders and nonresponders after one or two NAC cycles treatment using independent-samples Student's t-test or Mann-Whitney U-test depending on the normality contribution test and then followed by logistic regression and receiver operating characteristic curve (ROC) analyses. RESULTS: The responder group (RG) patients presented significantly higher mean Ktrans and Dapp values at baseline and larger Δ K ( 0 - 4 ) trans , Δvp(0-4) , and ΔDapp(0-4) values after either one or two NAC cycles compared with the nonresponder group (NRG) patients (all P < 0.05). ROC analyses demonstrated the higher diagnostic accuracy of combined DCE-MRI and DKI model to distinguish nonresponders from responders after two NAC cycles than using DCE-MRI (0.987 vs. 0.872, P = 0.033) or DKI (0.987 vs. 0.898, P = 0.047) alone. DATA CONCLUSION: Combined DCE-MRI and DKI models had higher diagnostic accuracy for NAC assessment compared with either model used independently. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1208-1216.

Nutrient profiling and adherence to components of the UK national dietary guidelines association with metabolic risk factors for CVD and diabetes: Airwave Health Monitoring Study.

CVD is the leading cause of death worldwide. Diet is a key modifiable component in the development of CVD. No official UK diet quality index exists for use in UK nutritional epidemiological studies. The aims of this study are to: (i) develop a diet quality index based on components of UK dietary reference values (DRV) and (ii) determine the association between the index, the existing UK nutrient profile (NP) model and a comprehensive range of cardiometabolic risk markers among a British adult population. A cross-sectional analysis was conducted using data from the Airwave Health Monitoring Study (n 5848). Dietary intake was measured by 7-d food diary and metabolic risk using waist circumference, BMI, blood lipid profile, glycated Hb (HbA1c) and blood pressure measurements. Diet quality was assessed using the novel DRV index and NP model. Associations between diet and cardiometabolic risk were analysed via multivariate linear models and logistic regression. A two-point increase in NP score was associated with total cholesterol (ß -0·33 mmol/l, P<0·0001) and HbA1c (ß -0·01 %, P<0·0001). A two-point increase in DRV score was associated with waist circumference (ß -0·56 cm, P<0·0001), BMI (ß -0·15 kg/m2, P<0·0001), total cholesterol (ß -0·06 mmol/l, P<0·0001) and HbA1c (ß -0·02 %, P=0·002). A one-point increase in DRV score was associated with type 2 diabetes (T2D) (OR 0·94, P=0·01) and obesity (OR 0·95, P<0·0001). The DRV index is associated with overall diet quality and risk factors for CVD and T2D, supporting its application in nutritional epidemiological studies investigating CVD risk in a UK population.

Associations of High-Density Lipoprotein Particle and High-Density Lipoprotein Cholesterol With Alcohol Intake, Smoking, and Body Mass Index　- The INTERLIPID Study.

BACKGROUND: Recently, high-density lipoprotein particles (HDL-P) have been found to be more strongly inversely associated with coronary artery disease (CAD) risk than their counterpart, HDL cholesterol (HDL-C). Given that lifestyle is among the first targets in CAD prevention, we compared the associations of HDL-P and HDL-C with selected lifestyle factors. Methods and Results: We examined 789 Japanese participants of the INTERLIPID Study: men (n=386) and women (n=403) aged 40-59 years in 1996-1998. Participants treated for dyslipidemias were excluded. Lifestyle factors included alcohol intake, smoking amount, and body mass index (BMI). Multivariable linear regression was used for cross-sectional analyses of these factors with HDL-P, HDL-C, HDL-P size subclasses (small, medium and large) and mean HDL-P size. In men, higher alcohol intake was associated with higher HDL-P and higher HDL-C. The associations of alcohol, however, were strongest with HDL-P. A higher smoking amount tended to be associated with lower HDL-P and HDL-C. In contrast, BMI was not associated with HDL-P, but was strongly inversely associated with HDL-C. While alcohol intake favored larger mean HDL-P size, smoking and BMI favored a lipid profile with smaller HDL-P subclasses and overall smaller mean HDL-P size. Similar, but generally weaker results were observed in women. CONCLUSIONS: Although both HDL-P and HDL-C are parameters of HDL, they have different associations with alcohol, smoking and BMI.