The impact of wounding and postharvest storage conditions on retention of soluble protein in sugar beet leaves.

Sugar beet leaves can be a viable and economically interesting source of high-quality protein for the food industry. We investigated how storage conditions and leaf wounding at harvest affect the content and quality of the soluble protein. After collection, leaves were either stored intact or shredded to mimic wounding induced by commercial leaf harvesters. Leaf material was stored in small volumes at different temperatures to assess leaf physiology or in larger volumes to assess temperature development at different locations in the bins. Protein degradation was more pronounced at higher storage temperatures. Wounding accelerated the degradation of soluble protein at all temperatures. Both wounding and storage at higher temperatures greatly stimulated respiration activity and heat production. At temperatures below 5°C, ribulose-1,5-biphosphate carboxylase oxygenase (RuBisCO) in intact leaves was preserved for up to 3 weeks. At temperatures of 30-40°C, RuBisCO degradation occurred within 48 h. Degradation was more pronounced in shredded leaves. In 0.8-m3 storage bins at ambient temperature, core temperatures rapidly increased, up to 25°C in intact leaves and up to 45°C in shredded leaves within 2-3 days. Immediate storage at 5°C greatly suppressed the temperature increase in intact but not in shredded leaves. The indirect effect of excessive wounding, that is, heat production, is discussed as the pivotal factor responsible for increased degradation of protein. For optimal retention of soluble protein levels and quality in harvested sugar beet leaves, it is advised to minimize wounding and to store the material at temperatures around -5°C. PRACTICAL APPLICATION: To preserve the soluble protein content and quality for at least 3 weeks, sugar beet leaves should be harvested with minimal wounding and stored at temperatures between 1 and 5°C. When aiming to store minimally wounded leaves in larger volumes, it must be ensured that the product temperature in the core of the biomass meets the temperature criterium or the cooling strategy must be adjusted. The principles of minimal wounding and low temperature storage are transferable to other leafy crops that are harvested for food protein.

[Interdisciplinary extremity board in the treatment of complex injuries]. / Interdisziplinäres Extremitäten-Board in der Behandlung von Komplexverletzungen.

BACKGROUND: Interdisciplinary case conferences are well-established in the field of oncology in order to provide the best possible treatment for patients with complex disease patterns which overlap several disciplines. METHODS: After studying the available literature the aims, indications, frequency, patient enrolment and documentation modalities, disciplines necessary to create the reconstruction plan and evaluation parameters of the board, were agreed in an interdisciplinary discussion among colleagues. The utilization of the extremity board and demographic features of the cases presented in the extremity board within the first 6 months were subsequently descriptively analyzed. RESULTS: The agreed primary aim of an extremity board is the timely and transparent preparation of a high-quality holistic reconstruction plan for optimized treatment of a challenging patient collective with complex injuries of the extremities. Decisive interfaces of an extremity board are the participation of interdisciplinary disciplines, established enrolment and documentation modalities and a longitudinal analysis of parameters of the acute medical treatment, the long-term function and quality of life of those affected. The patient collective so far mostly includes men under 40 years old with traumatic soft tissue defects and combined injuries. On average, reconstruction plans for 1-2 patients were approved in an interdisciplinary team per session. CONCLUSION: The extremity board serves as a platform for coordinated planning of treatment for patients with complex injuries. The limited personnel and time resources represent the greatest challenge for the successful implementation. The extremity board enables a high degree of interdisciplinary networking. The digital registration and documentation modality within the internal hospital documentation system is of utmost relevance. The preparation of the reconstruction plan is of decisive importance for the qualitative success of treatment and the restoration of function. The longitudinal analysis of appropriate parameters is imperative to measure the quality of treatment.

Robust and Highly Reproducible Generation of Cortical Brain Organoids for Modelling Brain Neuronal Senescence In Vitro.

Brain organoids are three-dimensional models of the developing human brain and provide a compelling, cutting-edge platform for disease modeling and large-scale genomic and drug screening. Due to the self-organizing nature of cells in brain organoids and the growing range of available protocols for their generation, issues with heterogeneity and variability between organoids have been identified. In this protocol paper, we describe a robust and replicable protocol that largely overcomes these issues and generates cortical organoids from neuroectodermal progenitors within 1 month, and that can be maintained for more than 1 year. This highly reproducible protocol can be easily carried out in a standard tissue culture room and results in organoids with a rich diversity of cell types typically found in the developing human cortex. Despite their early developmental make-up, neurons and other human brain cell types will start to exhibit the typical signs of senescence in neuronal cells after prolonged in vitro culture, making them a valuable and useful platform for studying aging-related neuronal processes. This protocol also outlines a method for detecting such senescent cells in cortical brain organoids using senescence-associated beta-galactosidase staining.

Plasma fatty acid profiles: Relationships with sex, age, and state-reported heart disease mortality rates in the United States.

BACKGROUND: Fatty acids (FA) play an important role in health and heart disease risk. OBJECTIVE: We evaluated relationships of plasma FA levels, especially omega-3 FA, with sex, age, and reported heart disease mortality rates by state in a very large clinical population. METHODS: Plasma FA were measured by gas chromatography/mass spectrometry after lipid extraction in 1,169,621 fasting United States subjects grouped according to sex (56.2% female), age (<30, 30-<45, 45-<55, 55-<65, ≥65 years; median age 58.2 years), and state of residence. RESULTS: Plasma FA index values (median±interquartile range), expressed as a percent of total plasma FA, in all subjects were: saturated (14:0+16:0+18:0) 31.4±1.5%; monounsaturated (16:1n7-cis+18:1n9-cis) 21.3±2.2%; trans (16:1n7-trans+18:1n9-trans) 0.45±0.08%; omega-6 (18:2n6-cis+20:3n6+20:4n6) 42.5±3.0%; and omega-3 (20:5n3+22:6n3) 2.57±0.81%. The median eicosapentaenoic acid (EPA, 20:5n3) concentration was 22.1±9.7 µg/mL. Females had significantly (P<0.0001) higher omega-3 FA indices (+6.82%) than males. Subjects ≥65 years of age had a higher omega-3 FA index (+29.68%) and higher EPA levels (+57.05%) than subjects <30 years of age (P<0.00001). EPA concentrations and omega-3 FA indices were below overall median levels in most southern and midwestern states. State-reported heart disease mortality rates were inversely correlated with EPA levels (r=-0.504) and omega-3 FA indices (r=-0.570), and positively correlated with saturated FA indices (r=0.450), all P<0.01. CONCLUSION: In our large population, females, subjects ≥65 years, and those living in northeastern and western states had higher omega-3 fatty acid levels and lower saturated fatty acid levels than other subjects. Such changes were associated with lower state-wide heart disease death rates.

Additional Blue LED during Cultivation Induces Cold Tolerance in Tomato Fruit but Only to an Optimum.

Tomato is a chilling-sensitive fruit. The aim of this study is to examine the role of preharvest blue LED lighting (BL) to induce cold tolerance in 'Foundation' tomatoes. Blue and red supplemental LED light was applied to achieve either 0, 12 or 24% additional BL (0B, 12B and 24B). Mature green (MG) or red (R) tomatoes were harvested and cold stored at 4 °C for 0, 5, 10, 15 and 20 d, and then stored for 20 d at 20 °C (shelf life). Chilling injury (CI) indices, color and firmness, hydrogen peroxide, malondialdehyde, ascorbic acid and catalase activity were characterized. At harvest, R tomatoes cultivated at 12B were firmer and showed less coloration compared to fruit of other treatments. These fruits also showed higher loss of red color during cold storage and lower CI symptoms during shelf-life. MG tomatoes cultivated at 12B showed delayed coloring (non-chilled) and decreased weight loss (long cold stored) during shelf life compared to fruit in the other treatments. No effects of light treatments, both for MG and R tomatoes, were observed for the selected antioxidant capacity indicators. Improved cold tolerance for R tomatoes cultivated at 12B points to lycopene having higher scavenging activity at lower concentrations to mitigate chilling injury.

Human induced pluripotent stem cells generated from epilepsy patients for use as in vitro models for drug screening.

In this paper, we describe the generation and validation of human induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) from 6 epilepsy patients using a non-integrative Sendai virus vector. These human cellular models will enable patient-specific drug screening to improve outcomes for individuals with this disorder.

High Light Intensity Applied Shortly Before Harvest Improves Lettuce Nutritional Quality and Extends the Shelf Life.

The effect of light intensity applied shortly before harvest on the nutritional quality, postharvest performance, and shelf life of loose-leaf lettuce (Lactuca sativa L. cv. Expertise RZ Salanova®) was investigated. Lettuce was grown either in a greenhouse with supplemental high-pressure sodium light (Experiment 1, EXP 1) or in a climate room under white LED light (Experiment 2, EXP 2). In both experiments full grown plants were transferred to a climate room for the End of Production (EoP) light treatments during the last week of cultivation. During EoP lighting plants were exposed to different intensities (0, 110, and 270 µmol m-2 s-1 in EXP 1; 50, 210, and 470 µmol m-2 s-1 in EXP 2) from white-red LEDs for 6 (EXP 2) or 7 days (EXP 1). Mature leaves were then harvested and stored in darkness at 10°C to study the postharvest performance. Changes in dry matter content, total ascorbic acid, and carbohydrates (including glucose, fructose sucrose, and starch) levels were determined during EoP lighting and during the subsequent shelf life as indicators of lettuce nutritional quality. Quality aspects (appearance, texture, and odor) were accessed during the shelf life as indicators of postharvest performance. In both experiments, high light intensities applied in EoP lighting increased dry matter percentage and contents of ascorbic acid (AsA) and carbohydrates at harvest and these increased levels were maintained during the shelf life. Increased light intensity in EoP treatment also extended the shelf life. The levels of AsA and carbohydrates at harvest correlated positively with the subsequent shelf life, indicating that the prolonged shelf life relies on the improved energy and antioxidant status of the crop at harvest.

Improved differentiation between primary lung cancer and pulmonary metastasis by combining dual-energy CT-derived biomarkers with conventional CT attenuation.

OBJECTIVES: To assess the clinical utility of dual-energy CT (DE-CT)-derived iodine concentration (IC) and effective Z (Zeff) in addition to conventional CT attenuation (HU) for the discrimination between primary lung cancer (LC) and pulmonary metastases (PM) from different primary malignancies. METHODS: DE-CT scans of 79 patients with LC (3 histopathologic subgroups) and 89 patients with PM (5 histopathologic subgroups) were evaluated. Quantitative IC, Zeff, and conventional HU values were extracted and normalized to the thoracic aorta. Differences between groups were assessed by pairwise Welch's t test. Correlation and linear regression analyses were used to examine the relationship of imaging parameters in LC and PM. Diagnostic accuracy was measured by the area under receiver operator characteristic curve (AUC) and validated based on resampling methods. RESULTS: Significant differences between subgroups of LC and PMs were noted for all imaging parameters, with the highest number of significant pairs for IC. In univariate analysis, only IC was a significant diagnostic feature for discriminating LC from PM (p = 0.03). All quantitative imaging parameters correlated significantly (p < 0.0001, respectively), with the highest correlation between IC and Zeff (r = 0.91), followed by IC and HU (r = 0.76) and Zeff and HU (r = 0.73). Diagnostic models combining IC or Zeff with HU (IC+HU: AUC = 0.73; Zeff+HU: AUC = 0.69; IC+Zeff+HU: AUC = 0.73) were not significantly different and outperformed individual parameters (IC: AUC = 0.57; Zeff: AUC = 0.57; HU: AUC = 0.55) in diagnostic accuracy (p < 0.05, respectively). CONCLUSION: DE-CT-derived IC or Zeff and conventional HU represent complementary imaging parameters, which, if used in combination, may improve the differentiation between LC and PM. KEY POINTS: • Individual quantitative imaging parameters derived from DE-CT (iodine concentration, effective Z) and conventional CT (HU) provide complementary diagnostic information for the differentiation of primary lung cancer and pulmonary metastases. • A combination of conventional HU and DE-CT parameters enhances the diagnostic utility of individual parameters.

Use of Human Induced Pluripotent Stem Cells and Kidney Organoids To Develop a Cysteamine/mTOR Inhibition Combination Therapy for Cystinosis.

BACKGROUND: Mutations in CTNS-a gene encoding the cystine transporter cystinosin-cause the rare, autosomal, recessive, lysosomal-storage disease cystinosis. Research has also implicated cystinosin in modulating the mTORC1 pathway, which serves as a core regulator of cellular metabolism, proliferation, survival, and autophagy. In its severest form, cystinosis is characterized by cystine accumulation, renal proximal tubule dysfunction, and kidney failure. Because treatment with the cystine-depleting drug cysteamine only slows disease progression, there is an urgent need for better treatments. METHODS: To address a lack of good human-based cell culture models for studying cystinosis, we generated the first human induced pluripotent stem cell (iPSC) and kidney organoid models of the disorder. We used a variety of techniques to examine hallmarks of cystinosis-including cystine accumulation, lysosome size, the autophagy pathway, and apoptosis-and performed RNA sequencing on isogenic lines to identify differentially expressed genes in the cystinosis models compared with controls. RESULTS: Compared with controls, these cystinosis models exhibit elevated cystine levels, increased apoptosis, and defective basal autophagy. Cysteamine treatment ameliorates this phenotype, except for abnormalities in apoptosis and basal autophagy. We found that treatment with everolimus, an inhibitor of the mTOR pathway, reduces the number of large lysosomes, decreases apoptosis, and activates autophagy, but it does not rescue the defect in cystine loading. However, dual treatment of cystinotic iPSCs or kidney organoids with cysteamine and everolimus corrects all of the observed phenotypic abnormalities. CONCLUSIONS: These observations suggest that combination therapy with a cystine-depleting drug such as cysteamine and an mTOR pathway inhibitor such as everolimus has potential to improve treatment of cystinosis.

Vitamin D supplementation of 4000 IU daily and cardiac function in patients with advanced heart failure: The EVITA trial.

BACKGROUND: Data regarding the effects of vitamin D on cardiac function are inconclusive. METHODS: In a post-hoc analysis of the EVITA (Effect of vitamin D on mortality in heart failure) trial, we investigated whether a daily vitamin D3 supplement of 4000 IU for three years affects echocardiography parameters like left ventricular end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), and LV ejection fraction (LVEF) in patients with advanced heart failure (HF) and 25­hydroxyvitamin D levels <75 nmol/L. Of 400 patients enrolled, 199 were assigned to vitamin D and 201 to placebo. We assessed time × treatment interaction effects using linear mixed models and analyzed in subgroups vitamin D effects at 12 and 36 months post-randomization using analysis of covariance with adjustments for baseline values. RESULTS: At baseline, values of LVEDD, LVESD, and LVEF were 67.5 ±â€¯10.5 mm, 58.9 ±â€¯12.0 mm, and 30.47 ±â€¯10.2%, respectively. There were no time × treatment interaction effects on LV echocardiographic parameters in the entire study cohort, neither at 12 months nor at 36 months post-randomization (P-values > 0.05). However, in the subgroup of patients aged ≥50 years, vitamin D treatment was associated with an increase in LVEF of 2.73% (95%CI: 0.14 to 5.31%) at 12 months post-randomization (n = 311). The increase was slightly attenuated to 2.60% (95%CI: -2.47 to 7.67%) at 36 months post-randomization (n = 242). CONCLUSION: Our data indicate that vitamin D supplementation does not significantly improve cardiac function in all patients with advanced HF. However, vitamin D probably improves LV function in HF patients aged ≥50 years.

Targeted Diet Modification Reduces Multiple Sclerosis-like Disease in Adult Marmoset Monkeys from an Outbred Colony.

Experimental autoimmune encephalomyelitis (EAE) in common marmosets is a translationally relevant model of the chronic neurologic disease multiple sclerosis. Following the introduction of a new dietary supplement in our purpose-bred marmoset colony, the percentage of marmosets in which clinically evident EAE could be induced by sensitization against recombinant human myelin oligodendrocyte glycoprotein in IFA decreased from 100 to 65%. The reduced EAE susceptibility after the dietary change coincided with reduced Callitrichine herpesvirus 3 expression in the colony, an EBV-related γ1-herpesvirus associated with EAE. We then investigated, in a controlled study in marmoset twins, which disease-relevant parameters were affected by the dietary change. The selected twins had been raised on the new diet for at least 12 mo prior to the study. In twin siblings reverted to the original diet 8 wk prior to EAE induction, 100% disease prevalence (eight out of eight) was restored, whereas in siblings remaining on the new diet the EAE prevalence was 75% (six out of eight). Spinal cord demyelination, a classical hallmark of the disease, was significantly lower in new-diet monkeys than in monkeys reverted to the original diet. In new-diet monkeys, the proinflammatory T cell response to recombinant human myelin oligodendrocyte glycoprotein was significantly reduced, and RNA-sequencing revealed reduced apoptosis and enhanced myelination in the brain. Systematic typing of the marmoset gut microbiota using 16S rRNA sequencing demonstrated a unique, Bifidobacteria-dominated composition, which changed after disease induction. In conclusion, targeted dietary intervention exerts positive effects on EAE-related parameters in multiple compartments of the marmoset's gut-immune-CNS axis.

Vitamin D supplementation and bone turnover in advanced heart failure: the EVITA trial.

Low vitamin D status is common in patients with heart failure and may influence bone health. A daily vitamin D dose of 4000 IU (moderately high dose) for 3 years had however no effect on parameters of bone metabolism, even in patients with very low vitamin D status. INTRODUCTION: Low vitamin D status is common in patients with heart failure (HF) and has been related to disturbed bone turnover. The present study investigated the effect of a daily vitamin D3 dose of 4000 IU on bone turnover markers (BTMs) in patients with advanced HF and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L. METHODS: In this pre-specified secondary analysis of a randomized controlled trial, we assessed in 158 male HF patients (vitamin D group: n = 80; placebo group: n = 78) between-group differences in calciotropic hormones (25OHD, 1,25-dihydroxyvitamin D [1,25(OH)2D], intact parathyroid hormone [iPTH]), and BTMs (cross-linked C-telopeptide of type I collagen, bone-specific alkaline phosphatase, undercarboxylated osteocalcin). Comparisons were performed at the end of a 3-year vitamin D supplementation period with adjustments for baseline values. RESULTS: Compared with placebo, vitamin D increased 25OHD on average by 54.3 nmol/L. At study termination, 25OHD and 1,25(OH)2D were significantly higher (P < 0.001 and P = 0.007, respectively), whereas iPTH tended to be lower in the vitamin D group than in the placebo group (P = 0.083). BTMs were initially within their reference ranges and did not differ significantly between groups at study termination, neither in the entire study cohort nor when data analysis was restricted to the subgroup of patients with initial 25OHD concentrations < 30 nmol/L (n = 54) or to patients with initial hyperparathyroidism (n = 65) (all P values > 0.05). CONCLUSIONS: A daily vitamin D3 dose of 4000 IU did not influence BTMs. Data indicate that vitamin D supplementation will not lower bone turnover in male patients with heart failure.

Prevalence of high-risk human papillomavirus infection and cancer gene mutations in nonmalignant tonsils.

OBJECTIVES: To analyze the prevalence of high-risk HPV (human papillomavirus) and genetic alterations in nonmalignant tonsils. METHODS: We collected benign fresh tonsillar tissue specimens from 477 patients undergoing tonsillectomy because of chronic tonsillitis or tonsillar hypertrophy in 2012 (Group A, n=237) and in 2015 (Group B, n=240). Luminex xMAP technique served to detect E6/E7 DNA from 16 different high-risk HPV types. Tonsillar DNA and peripheral blood leukocyte DNA from the infected individuals were analyzed using Nimblegen SeqCap EZ Comprehensive Cancer Design panel. The panel targets 578 different genes that are relevant in carcinogenesis. HPV negative tonsillar specimens from age- and gender matched individuals were used as controls. All specimens harboring high-risk HPV were analyzed using fluorescence in situ hybridization (FISH). RESULTS: Five of 477 (1.0%) patients tested positive for the following HPV types: HPV16 (two cases), HPV52 (one case), HPV66 (one case), HPV52 and HPV68 (coinfection, one case). FISH analyses showed that the appearance of HPV in specimens infected with HPV 16 was episomal. Benign tonsils infected with high-risk HPV harbored mutations in EP300, NF1, PIK3CA, and RB1 which are considered relevant in the development of HPV-associated head and neck squamous cell carcinoma (SCC). CONCLUSIONS: The prevalence of high-risk HPV in nonmalignant tonsils is low. High-risk HPV positive tonsils harbored mutations in genes that are commonly altered in HPV-associated head and neck SCC. The role of these mutations in tonsillar carcinogenesis is an interesting target for future research.

Randomized supplementation of 4000 IU vitamin D3 daily vs placebo on the prevalence of anemia in advanced heart failure: the EVITA trial.

BACKGROUND: Low 25-hydroxyvitamin D (25OHD) levels (< 75 nmol/l) are inversely associated with anemia prevalence. Since anemia and low 25OHD levels are common in patients with heart failure (HF), we aimed to investigate whether vitamin D supplementation can reduce anemia prevalence in advanced HF. METHODS: EVITA (Effect of Vitamin D on Mortality in Heart Failure) is a randomized, placebo-controlled clinical trial in patients with initial 25OHD levels < 75 nmol/l. Participants received either 4000 IU vitamin D3 daily or a matching placebo for 36 months. A total of 172 patients (vitamin D group: n = 85; placebo group: n = 87) were investigated in this pre-specified secondary data analysis. Hemoglobin (Hb) and other hematological parameters were measured at baseline and study termination. Assessment of between-group differences in anemia prevalence and Hb concentrations was performed at study termination, while adjusting for baseline differences. RESULTS: In the vitamin D and placebo group, baseline proportions of patients with anemia (Hb < 12.0 g/dL in females and < 13.0 g/dL in males) were 17.2% and 10.6%, respectively (P = 0.19). At study termination, the proportion of patients with anemia in the vitamin D and placebo groups was 32.2% and 31.8%, respectively (P > 0.99). There was no between-group difference in change in the Hb concentrations (- 0.04 g/dL [95%CI:-0.53 to 0.45 g/dL]; P = 0.87). Results regarding anemia risk and Hb concentrations were similar in the subgroup of patients with chronic kidney disease (vitamin D group: n = 26; placebo group: n = 23). Moreover, results did not differ substantially when data analysis was restricted to patients with deficient baseline 25OHD levels. CONCLUSIONS: A daily vitamin D supplement of 4000 IU did not reduce anemia prevalence in patients with advanced HF. Data challenge the clinical relevance of vitamin D supplementation to increase Hb levels. TRIAL REGISTRATION: The study was registered at EudraCT (No. 2010-020793-42) and clinicaltrials.gov ( NCT01326650 ).

Association Between Concentrations of Hemoglobin Determined by Fecal Immunochemical Tests and Long-term Development of Advanced Colorectal Neoplasia.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening using quantitative fecal immunochemical tests (FITs) is rapidly gaining ground worldwide. FITs are invariably used in a dichotomous manner using pre-specified cut-off values. To optimize FIT-based screening programs, we investigated the association between fecal hemoglobin (fHb) concentrations below the FIT cut-off value and later development of colorectal advanced neoplasia (AN). METHODS: We analyzed data collected from a population-based study of 9561 average-risk subjects (50-74 years old) in the Netherlands who were offered 4 rounds of FIT screening for CRC from November 2006 through December 2014. We analyzed data from 7663 participants screened at least once and found to have a negative FIT result at baseline (below the cut-off value of 10 µg Hb/ g feces). Participants were followed for a median of 4.7 years (interquartile range, 2.0-6.1 years); CRCs diagnosed outside the screening program were identified from the Dutch Comprehensive Cancer Centre database. Hazard ratios for AN were determined using Cox proportional hazard regression analyses. Logistic regression techniques were used to calculate risks of AN after consecutive fHb concentrations below the cut-off value. RESULTS: After 8 years of follow-up, participants with baseline concentrations of 8-10 µg fHb/g had a higher cumulative incidence of AN (33%) than participants with 0 µg fHb/g (5%) (P < .001). Multi-variate hazard ratios increased from 1.2 for subjects with concentrations of 0-2 µg fHb/g to 8.2 for subjects with concentrations of 8-10 µg fHb/g (P < .001). Participants with 2 consecutive fHb concentrations of 8 µg Hb/g had a 14-fold increase in risk of AN compared with participants with 2 consecutive fHb concentrations of 0 µg Hb/g (P < .001). CONCLUSIONS: In a population-based study of average-risk individuals with a FIT result below the cut-off value, we associated baseline concentrations of 8-10 µg fHb/g with an increased risk of AN compared with baseline concentrations of 0 µg fHb/g. Baseline and consecutive fHb concentrations are independent predictors for incident AN. This information might be used in designing personalized strategies for population-based CRC screening and reduce unnecessary repeat tests. Trialregister.nl no: first round, NTR1096; second round and additional invitees, NTR1512.

Higher dietary cholesterol and ω-3 fatty acid intakes are associated with a lower success rate of Helicobacter pylori eradication therapy in Japan.

Background:Helicobacter pylori infection is a known risk factor for duodenal ulcers, gastritis, and gastric cancer. The eradication of H. pylori is successful in treating these disorders; however, the success rate of eradication therapy is declining. There may be an interaction with nutrient intake to account for this decline.Objective: We investigated the influence of food and nutrient intake on H. pylori eradication therapy.Design: In this study, 4014 subjects underwent endoscopy, were tested for serum antibodies to H. pylori (2046 positive; 51.0%), and had their food intake assessed with the use of a food-frequency questionnaire (FFQ). Of the positive subjects, endoscopies showed that 389 (19.0%) had gastritis and/or duodenal ulcers and were also positive for a 13C-urea breath test (UBT). These 389 subjects received 1-wk H. pylori eradication therapy with lansoprazole, amoxicillin, and clarithromycin and a second UBT 8 wk after treatment. Complete demographic characteristics, serum lipid, insulin, glycated hemoglobin, C-reactive protein (CRP), and creatinine concentrations as well as complete FFQs were available for 352 subjects. Multivariate logistic regression analyses were performed to determine factors that were associated with successful H. pylori eradication therapy.Results: The success rate of eradication therapy was 60.4% (235 of 389). Factors associated with the failure of eradication therapy included increased age (P = 0.02), higher CRP concentrations (P < 0.01), higher dietary cholesterol (P < 0.01) or egg intake (P < 0.01), higher ω-3 (n-3) fatty acid (P = 0.02) or fish intake (P = 0.01), and higher vitamin D intake (P = 0.02). Moreover, the higher vitamin D intake was strongly linked to higher fish intake. A limitation of the study is that we did not assess the antibiotic resistance of H. pyloriConclusions: Our results indicate that higher egg and fish intake may be negatively correlated with successful H. pylori eradication therapy in H. pylori-positive subjects with gastritis and/or duodenal ulcers.

Simultaneous dual-contrast multi-phase liver imaging using spectral photon-counting computed tomography: a proof-of-concept study.

BACKGROUND: To assess the feasibility of dual-contrast spectral photon-counting computed tomography (SPCCT) for liver imaging. METHODS: We present an SPCCT in-silico study for simultaneous mapping of the complementary distribution in the liver of two contrast agents (CAs) subsequently intravenously injected: a gadolinium-based contrast agent and an iodine-based contrast agent. Four types of simulated liver lesions with a characteristic arterial and portal venous pattern (haemangioma, hepatocellular carcinoma, cyst, and metastasis) are presented. A material decomposition was performed to reconstruct quantitative iodine and gadolinium maps. Finally, a multi-dimensional classification algorithm for automatic lesion detection is presented. RESULTS: Our simulations showed that with a single-scan SPCCT and an adapted contrast injection protocol, it was possible to reconstruct contrast-enhanced images of the liver with arterial distribution of the iodine-based CA and portal venous phase of the gadolinium-based CA. The characteristic patterns of contrast enhancement were visible in all liver lesions. The approach allowed for an automatic detection and classification of liver lesions using a multi-dimensional analysis. CONCLUSIONS: Dual-contrast SPCCT should be able to visualise the characteristic arterial and portal venous enhancement with a single scan, allowing for an automatic lesion detection and characterisation, with a reduced radiation exposure.

Dietary phosphate supplement does not rescue skeletal phenotype in a mouse model for craniometaphyseal dysplasia.

BACKGROUND: Mutations in the human progressive ankylosis gene (ANKH; Mus musculus ortholog Ank) have been identified as cause for craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. We previously reported a knock-in (KI) mouse model (Ank KI/KI) for CMD and showed transiently lower serum phosphate (Pi) as well as significantly higher mRNA levels of fibroblast growth factor 23 (Fgf23) in Ank KI/KI mice. FGF23 is secreted by bone and acts in kidney to promote Pi wasting which leads to lower serum Pi levels. Here, we examined whether increasing the Pi level can partially rescue the CMD-like skeletal phenotype by feeding Ank +/+ and Ank KI/KI mice with high Pi (1.7 %) diet from birth for 6 weeks. We studied the Pi metabolism in Ank KI/KI mice and CMD patients by examining the Pi regulators FGF23 and parathyroid hormone (PTH). RESULTS: High Pi diet did not correct CMD-like features, including massive jawbone, increased endosteal and periosteal perimeters and extensive trabeculation of femurs in Ank KI/KI mice shown by computed microtomography (µCT). This unexpected negative result is, however, consistent with normal serum/plasma levels of the intact/active form of FGF23 and PTH in Ank KI/KI mice and in CMD patients. In addition, FGF23 protein expression was unexpectedly normal in Ank KI/KI femoral cortical bone as shown by immunohistochemistry despite increased mRNA levels for Fgf23. Renal expression of genes involved in the FGF23 bone-kidney axis, including mFgfr1, mKlotho, mNpt2a, mCyp24a1 and m1αOHase, were comparable between Ank +/+ and Ank KI/KI mice as shown by quantitative real-time PCR. Different from normal FGF23 and PTH, serum 25-hydroxyvitamin D was significantly lower in Ank KI/KI mice and vitamin D insufficiency was found in four out of seven CMD patients. CONCLUSIONS: Our data suggests that FGF23 signaling and Pi metabolism are not significantly affected in CMD and transiently low Pi level is not a major contributor to CMD.

Effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular disease risk factors: a randomized clinical trial.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the primary omega-3 fatty acids in fish oil, have been shown to reduce cardiovascular disease (CVD) risk. OBJECTIVE: This study aimed to examine the independent effects of EPA and DHA on lipid and apolipoprotein levels, as well as on inflammatory biomarkers of CVD risk, using doses often used in the general population. DESIGN: A blinded, randomized 6-week trial was performed in 121 healthy, normolipidemic subjects who received olive oil placebo 6g/d, EPA 600mg/d, EPA 1800mg/d, or DHA 600mg/d. The EPA was derived from genetically modified yeast. RESULTS: The subjects tolerated the supplements well with no safety issues; and the expected treatment-specific increases in plasma EPA and DHA levels were observed. Compared to placebo, the DHA group had significant decreases in postprandial triglyceride (TG) concentrations (-20%, -52.2mg/dL, P=0.03), significant increases in fasting and postprandial low-density lipoprotein cholesterol (LDL-C) (+18.4%, 17.1mg/dL, P=0.001), with no significant changes in inflammatory biomarkers. No significant effects were observed in the EPA 600mg/d group. The high-dose EPA group had significant decreases in lipoprotein-associated phospholipase A2 concentrations (Lp-PLA2) (-14.1%, -21.4ng/mL, P=0.003). CONCLUSIONS: The beneficial effects of EPA 1800mg/d on CVD risk reduction may relate in part to the lowering of Lp-PLA2 without adversely affecting LDL-C. In contrast, DHA decreased postprandial TG, but raised LDL-C. Our observations indicate that these dietary fatty acids have divergent effects on cardiovascular risk markers.

Calciotropic and phosphaturic hormones in heart failure.

AIMS: Despite adherence to evidence-based guidelines, heart failure [HF] still results in 5-year mortality rates of 50%, indicating a need to implement additional preventive/intervention strategies. This review summarizes data on alterations in the calciotropic and phosphaturic hormones 1,25-dihydroxyvitamin D [1,25(OH)2D] and fibroblast growth factors-23 [FGF-23] in HF and discusses non-pharmacological measures for targeting these hormones. DATA SYNTHESIS: The role of 1,25(OH)2D in the regulation of calcium and phosphate homeostasis is central. 1,25(OH)2D also plays a pivotal role in cardiac function, but is downregulated by FGF-23. There is accumulating evidence from epidemiological data that HF is associated with decreased circulating 1,25(OH)2D and elevated FGF-23 levels. In patients with failing hearts, very low 1,25(OH)2D and extremely high FGF-23 levels have been reported. Experimental data support the assumption that vitamin D deficiency and high serum phosphate/FGF-23 levels increase the risk of HF. This review provides a hypothesis of how vitamin D deficiency, high calcium/phosphorus intake, physical inactivity, and age-related renal impairment may all contribute to HF by adversely affecting calcium- and phosphate-regulating hormones. Several case series in infants and a meta-analysis of randomized controlled trials in adults have already reported successful treatment of or a significant risk reduction in HF by vitamin D supplements. The association of calcium/phosphorus intake, physical activity, or renal function with calciotropic/phosphaturic hormones and HF is however less well documented. CONCLUSIONS: More attention should be paid in future to the association of circulating 1,25(OH)2D and FGF-23 levels with HF and to (non-pharmacological) measures for targeting these calciotropic/phosphaturic hormones.