Macronutrient intake and frailty: the Rotterdam Study

Purpose: To investigate the longitudinal association between the macronutrient composition of the diet and frailty. Methods: Data were obtained from 5205 Dutch middle-aged and older adults participating in the Rotterdam Study. Frailty was measured using a frailty index based on the accumulation of 38 health-related deficits, score between 0 and 100, and a higher score indicating more frailty. Frailty was assessed at baseline and 11 years later (range of 23 years). Macronutrient intake was assessed using food-frequency questionnaires. The association between macronutrients and frailty over time was evaluated using multivariable linear regression, adjusted for the frailty index at baseline, energy intake, and other relevant confounders. All analyses were performed in strata of BMI. Results: Median frailty index score was 13.8 points (IQR 9.6; 19.1) at baseline and increased by a median of 2.3 points (IQR − 2.0; 7.6) after 11 years. Overall, we found no significant associations between intake of carbohydrates or fat and frailty over time. We did observe a significant positive association between an iso-energetic intake of 10 g protein and frailty over time (β 0.31 (95% CI 0.06; 0.55)) which was mainly driven by animal protein (β 0.31 (95% CI 0.07; 0.56)). It did not depend on whether it was substituted fat or carbohydrates. Conclusions: Our findings suggest that a reduction in the intake of animal protein may improve the overall health status over time in a relatively healthy population. More research is needed on the optimal macronutrient composition of the diet and frailty in more vulnerable populations

Magnetic resonance imaging evidence for subclinical joint bleeding in a Dutch population of people with severe hemophilia on prophylaxis

Background: Previous studies suggest that subclinical bleeding occurs in persons with hemophilia. Objectives: The aim of this study was to investigate whether patients with lifelong access to prophylaxis showed signs of previous subclinical bleeding on magnetic resonance imaging (MRI) in joints without a history of joint bleeding. Methods: This single-center cross-sectional study included persons with severe hemophilia A on prophylaxis, aged 16 to 33 years, with lifetime bleeding records available. Per participant, 1 index joint without a history of joint bleeding was evaluated with 3-Tesla MRI, including hemosiderin sensitive sequences. MRI scans were reviewed according to the International Prophylaxis Study Group (IPSG) additive MRI scale (range, 0-17/joint). Hemosiderin deposits with/without synovial hypertrophy were considered signs of previous subclinical bleeding. Additionally, physical examination was performed, followed by ultrasound examination according to the Hemophilia Early Arthropathy Detection with Ultrasound protocol. Results: In 43 patients with a median age of 23.5 years, 43 joints (16 elbows, 13 knees, 14 ankles) without reported bleeds were evaluated with MRI. The median IPSG MRI score was 1 (range, 0-9). Signs of previous subclinical bleeding were observed in 7 of 43 joints (16%; 95% CI, 7-30): 7 of 7 joints showed hemosiderin deposits, with concomitant synovial hypertrophy in 2 of 7 joints. MRI changes were accompanied by swelling and ultrasound-detected synovial hypertrophy in 1 ankle only. None of the other joints showed abnormalities at physical examination and ultrasound. Conclusion: In this study, 16% of the joints without reported bleeds showed signs of previous subclinical bleeding, providing evidence for subclinical bleeding in people with severe hemophilia with lifelong access to prophylaxis

Update of the CHIP (CT in Head Injury Patients) decision rule for patients with minor head injury based on a multicenter consecutive case series

OBJECTIVE: To update the existing CHIP (CT in Head Injury Patients) decision rule for detection of (intra)cranial findings in adult patients following minor head injury (MHI).METHODS: The study is a prospective multicenter cohort study in the Netherlands. Consecutive MHI patients of 16 years and older were included. Primary outcome was any (intra)cranial traumatic finding on computed tomography (CT). Secondary outcomes were any potential neurosurgical lesion and neurosurgical intervention. The CHIP model was validated and subsequently updated and revised. Diagnostic performance was assessed by calculating the c-statistic.RESULTS: Among 4557 included patients 3742 received a CT (82%). In 383 patients (8.4%) a traumatic finding was present on CT. A potential neurosurgical lesion was found in 73 patients (1.6%) with 26 (0.6%) patients that actually had neurosurgery or died as a result of traumatic brain injury. The original CHIP underestimated the risk of traumatic (intra)cranial findings in low-predicted-risk groups, while in high-predicted-risk groups the risk was overestimated. The c-statistic of the original CHIP model was 0.72 (95% CI 0.69-0.74) and it would have missed two potential neurosurgical lesions and one patient that underwent neurosurgery. The updated model performed similar to the original model regarding traumatic (intra)cranial findings (c-statistic 0.77 95% CI 0.74-0.79, after crossvalidation c-statistic 0.73). The updated CHIP had the same CT rate as the original CHIP (75%) and a similar sensitivity (92 versus 93%) and specificity (both 27%) for any traumatic (intra)cranial finding. However, the updated CHIP would not have missed any (potential) neurosurgical lesions and had a higher sensitivity for (potential) neurosurgical lesions or death as a result of traumatic brain injury (100% versus 96%).CONCLUSIONS: Use of the updated CHIP decision rule is a good alternative to current decision rules for patients with MHI. In contrast to the original CHIP the update identified all patients with (potential) neurosurgical lesions without increasing CT rate.</p

Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands

Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and depletes pre-existing memory lymphocytes, causing immune amnesia. A measles outbreak in the Dutch Orthodox Prote

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

Study of Spin and Decay-Plane Correlations of W Bosons in the e+e- -> W+W- Process at LEP

Data collected at LEP at centre-of-mass energies \sqrt(s) = 189 - 209 GeV are used to study correlations of the spin of W bosons using e+e- -> W+W- -> lnqq~ events. Spin correlations are favoured by data, and found to agree with the Standard Model predictions. In addition, correlations between the W-boson decay planes are studied in e+e- -> W+W- -> lnqq~ and e+e- -> W+W- -> qq~qq~ events. Decay-plane correlations, consistent with zero and with the Standard Model predictions, are measured

Measurement of W Polarisation at LEP

The three different helicity states of W bosons produced in the reaction e+ e- -> W+ W- -> l nu q q~ at LEP are studied using leptonic and hadronic W decays. Data at centre-of-mass energies \sqrt s = 183-209 GeV are used to measure the polarisation of W bosons, and its dependence on the W boson production angle. The fraction of longitudinally polarised W bosons is measured to be 0.218 \pm 0.027 \pm 0.016 where the first uncertainty is statistical and the second systematic, in agreement with the Standard Model expectation

Ultrarelativistic sources in nonlinear electrodynamics

The fields of rapidly moving sources are studied within nonlinear electrodynamics by boosting the fields of sources at rest. As a consequence of the ultrarelativistic limit the delta-like electromagnetic shock waves are found. The character of the field within the shock depends on the theory of nonlinear electrodynamics considered. In particular, we obtain the field of an ultrarelativistic charge in the Born-Infeld theory.Comment: 10 pages, 3 figure

Search for Anomalous Couplings in the Higgs Sector at LEP

Anomalous couplings of the Higgs boson are searched for through the processes e^+ e^- -> H gamma, e^+ e^- -> e^+ e^- H and e^+ e^- -> HZ. The mass range 70 GeV < m_H < 190 GeV is explored using 602 pb^-1 of integrated luminosity collected with the L3 detector at LEP at centre-of-mass energies sqrt(s)=189-209 GeV. The Higgs decay channels H -> ffbar, H -> gamma gamma, H -> Z\gamma and H -> WW^(*) are considered and no evidence is found for anomalous Higgs production or decay. Limits on the anomalous couplings d, db, Delta(g1z), Delta(kappa_gamma) and xi^2 are derived as well as limits on the H -> gamma gamma and H -> Z gamma decay rates

Measurement of W Polarisation at LEP

The three different helicity states of W bosons produced in the reaction e+ e- -> W+ W- -> l nu q q~ at LEP are studied using leptonic and hadronic W decays. Data at centre-of-mass energies \sqrt s = 183-209 GeV are used to measure the polarisation of W bosons, and its dependence on the W boson production angle. The fraction of longitudinally polarised W bosons is measured to be 0.218 \pm 0.027 \pm 0.016 where the first uncertainty is statistical and the second systematic, in agreement with the Standard Model expectation