The EAT-Lancet commission recently suggested that transformation to healthy diets by 2050 will require a reduction of at least 50% in consumption of foods such as red meat and sugar, and a doubling ...in the global consumption of fruits, vegetables, nuts, and legumes. A diet rich in plant-based foods and with fewer animal source foods confers both improved health and environmental benefits. Notably, the risk of vitamin B12 deficiency increases when consuming a diet low in animal products. Humans are dependent on animal foods such as dairy products, meat, fish and eggs. Vitamin B12 deficiency is common worldwide, especially in populations with low consumption of animal foods because of low socioeconomic status, ethical reasons, or because of their lifestyle (i.e., vegans). According to the European Food Safety Authoroty, the recommended adequate intake of vitamin B12 is 4.0 μg/d for adults, and vitamin B12 requirements are higher during pregnancy and lactation. Infants and children from deficient mothers and elderly people are at risk for vitamin B12 deficiency. Diagnosis of vitamin B12 deficiency is hampered by low specificity of available biomarkers, and there is no consensus yet regarding the optimal definition of low vitamin B12 status. In general, a combination of at least two biomarkers is recommended. Therefore, this review presents an overview of vitamin B12 biochemistry and its biomarkers. We further summarize current recommendations of vitamin B12 intake, and evidence on the associations of vitamin B12 intake from different nutrient-dense animal foods with vitamin B12 status markers. Finally, potential consequences of low vitamin B12 status on different health outcomes for pregnant women, infants and elderly are presented.
Aims
There are sex differences in the excess risk of diabetes‐associated cardiovascular disease. However, it is not clear whether these sex differences exist with regard to other complications like ...mental health aspects. Therefore, we investigated sex differences in the association of prediabetes and type 2 diabetes (T2D) with cognitive function, depression, and quality of life (QoL).
Materials and Methods
In a population‐based cross‐sectional cohort study (n = 7639; age 40–75 years, 50% women, 25% T2D), we estimated sex‐specific associations, and differences therein, of prediabetes and T2D (reference: normal glucose metabolism) with measures of cognitive function, depression, and physical and mental QoL. Sex differences were analysed using multiple regression models with interaction terms.
Results
In general, T2D, but not prediabetes, was associated with higher odds of cognitive impairment, major depressive disorder, and poorer QoL. The odds ratio (OR) of cognitive impairment associated with T2D was 1.29 (95% CI: 0.96–1.72) for women and 1.39 (1.10–1.75) for men. The OR of major depressive disorder associated with T2D was 1.19 (0.69–2.04) for women and 1.68 (1.02–2.75) for men. The mean difference of the physical QoL score (ranging from 0 to 100, with 100 indicating the best possible QoL) associated with T2D was −2.09 (−2.92 to −1.25) for women and −1.81 (−2.48 to −1.13) for men. The mean difference of the mental QoL score associated with T2D was −0.90 (−1.79 to −0.02) for women and −0.52 (−1.23 to 0.20) for men. There was no clear pattern of sex differences in the associations of either prediabetes or T2D with measures of cognitive function, depression, or QoL.
Conclusions
In general, T2D was associated with worse cognitive function, depression, and poorer QoL. The strength of these associations was similar among women and men.
The Muscle Insulin Sensitivity Index (MISI) has been developed to estimate muscle-specific insulin sensitivity based on oral glucose tolerance test (OGTT) data. To date, the score has been ...implemented with considerable variation in literature and initial positive evaluations were not reproduced in subsequent studies. In this study, we investigate the computation of MISI on oral OGTT data with differing sampling schedules and aim to standardise and improve its calculation. Seven time point OGTT data for 2631 individuals from the Maastricht Study and seven time point OGTT data combined with a hyperinsulinemic-euglycaemic clamp for 71 individuals from the PRESERVE Study were used to evaluate the performance of MISI. MISI was computed on subsets of OGTT data representing four and five time point sampling schedules to determine minimal requirements for accurate computation of the score. A modified MISI computed on cubic splines of the measured data, resulting in improved identification of glucose peak and nadir, was compared with the original method yielding an increased correlation (ρ = 0.576) with the clamp measurement of peripheral insulin sensitivity as compared to the original method (ρ = 0.513). Finally, a standalone MISI calculator was developed allowing for a standardised method of calculation using both the original and improved methods.
Use of very old donors in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk for graft dysfunction and worse long‐term results, especially for ...hepatitis C virus (HCV)‐positive recipients. This was a retrospective, single‐center review of primary, ABO‐compatible LT performed between 2001 and 2010. Recipients were stratified in four groups based on donor age (<60 years; 60–69 years; 70–79 years and ≥80 years) and their outcomes were compared. A total of 842 patients were included: 348 (41.3%) with donors <60 years; 176 (20.9%) with donors 60–69 years; 233 (27.7%) with donors 70–79 years and 85 (10.1%) with donors ≥80 years. There was no difference across groups in terms of early (≤30 days) graft loss, and graft survival at 1 and 5 years was 90.5% and 78.6% for grafts <60 years; 88.6% and 81.3% for grafts 60–69 years; 87.6% and 75.1% for grafts 70–79 years and 84.7% and 77.1% for grafts ≥80 years (p = 0.065). In the group ≥80 years, the 5‐year graft survival was lower for HCV‐positive versus HCV‐negative recipients (62.4% vs. 85.6%, p = 0.034). Based on our experience, grafts from donors ≥80 years may provide favorable results but require appropriate selection and allocation policies.
The authors illustrate their experience with use of octogenarian donors for liver transplantation, highlighting the risk factors for graft loss and showing that accurate donor evaluation and appropriate donor‐to‐recipient matching are key to favorable long‐term results. See editorial by Lai et al on page 1962.
Aims/hypothesis
The associations of sitting, standing, physical activity and sleep with cardiometabolic health and glycaemic control markers are interrelated. We aimed to identify 24 h time-use ...compositions associated with optimal metabolic and glycaemic control and determine whether these varied by diabetes status.
Methods
Thigh-worn activPAL data from 2388 participants aged 40–75 years (48.7% female; mean age 60.1 SD = 8.1 years;
n
=684 with type 2 diabetes) in The Maastricht Study were examined. Compositional isometric log ratios were generated from mean 24 h time use (sitting, standing, light-intensity physical activity LPA, moderate-to-vigorous physical activity MVPA and sleeping) and regressed with outcomes of waist circumference, fasting plasma glucose (FPG), 2 h plasma glucose, HbA
1c
, the Matsuda index expressed as
z
scores, and with a clustered cardiometabolic risk score. Overall analyses were adjusted for demographics, smoking, dietary intake and diabetes status, and interaction by diabetes status was examined separately. The estimated difference when substituting 30 min of one behaviour with another was determined with isotemporal substitution. To identify optimal time use, all combinations of 24 h compositions possible within the study footprint (1st–99th percentile of each behaviour) were investigated to determine those cross-sectionally associated with the most-optimal outcome (top 5%) for each outcome measure.
Results
Compositions lower in sitting time and with greater standing time, physical activity and sleeping had the most beneficial associations with outcomes. Associations were stronger in participants with type 2 diabetes (
p
<0.05 for interactions), with larger estimated benefits for waist circumference, FPG and HbA
1c
when sitting was replaced by LPA or MVPA in those with type 2 diabetes vs the overall sample. The mean (range) optimal compositions of 24 h time use, considering all outcomes, were 6 h (range 5 h 40 min–7 h 10 min) for sitting, 5 h 10 min (4 h 10 min–6 h 10 min) for standing, 2 h 10 min (2 h–2 h 20 min) for LPA, 2 h 10 min (1 h 40 min–2 h 20 min) for MVPA and 8 h 20 min (7 h 30 min–9 h) for sleeping.
Conclusions/interpretation
Shorter sitting time and more time spent standing, undergoing physical activity and sleeping are associated with preferable cardiometabolic health. The substitutions of behavioural time use were significantly stronger in their associations with glycaemic control in those with type 2 diabetes compared with those with normoglycaemic metabolism, especially when sitting time was balanced with greater physical activity.
Graphical Abstract
While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. ...Accelerometer‐derived (activPAL3) 6‐ or 7‐day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.4% Type 2 diabetes mellitus (T2DM)). Multivariable regression models examined associations between stepping metrics (average step count, and time spent slower and faster paced stepping) with arterial stiffness (measured as carotid–femoral pulse wave velocity (cfPWV)), and several indices of microvascular health (heat‐induced skin hyperemia, retinal vessel reactivity and diameter), adjusting for confounders and moderators. PA pattern metrics were added to the regression models to identify associations with vascular health beyond that of stepping metrics. Analyses were stratified by T2DM status if an interaction effect was present. Average step count and time spent faster paced stepping was associated with better vascular health, and the association was stronger in those with compared to those without T2DM. In fully adjusted models a higher step count inter‐daily stability was associated with a higher (worse) cfPWV in those without T2DM (std β = 0.04, p = 0.007) and retinal venular diameter in the whole cohort (std β = 0.07, p = 0.002). A higher within‐day variability in faster paced stepping was associated with a lower (worse) heat‐induced skin hyperemia in those with T2DM (std β = −0.31, p = 0.008). Above and beyond PA volume, the daily and weekly patterns in which PA was accumulated were additionally associated with improved macro‐ and microvascular health, which may have implications for the prevention of vascular disease.
•Normalizing images with respect to healthy prostate tissue is optimal.•Histogram-based normalization should be used otherwise.•Over 87% of radiomic features drastically change after ...normalization.•Improper normalization is worse than no normalization.
The variance in intensities of MRI scans is a fundamental impediment for quantitative MRI analysis. Intensity values are not only highly dependent on acquisition parameters, but also on the subject and body region being scanned. This warrants the need for image normalization techniques to ensure that intensity values are consistent within tissues across different subjects and visits. Many intensity normalization methods have been developed and proven successful for the analysis of brain pathologies, but evaluation of these methods for images of the prostate region is lagging.
In this paper, we compare four different normalization methods on 49 T2-w scans of prostate cancer patients: 1) the well-established histogram normalization, 2) the generalized scale normalization, 3) an extension of generalized scale normalization called generalized ball-scale normalization, and 4) a custom normalization based on healthy prostate tissue intensities. The methods are compared qualitatively and quantitatively in terms of behaviors of intensity distributions as well as impact on radiomic features.
Our findings suggest that normalization based on prior knowledge of the healthy prostate tissue intensities may be the most effective way of acquiring the desired properties of normalized images. In addition, the histogram normalization method outperform the generalized scale and generalized ball-scale methods which have proven superior for other body regions.
Dendritic cells (DCs) are central in maintaining the intricate balance between immunity and tolerance by orchestrating adaptive immune responses. Being the most potent antigen presenting cells, DCs ...are capable of educating naïve T cells into a wide variety of effector cells ranging from immunogenic CD4(+) T helper cells and cytotoxic CD8(+) T cells to tolerogenic regulatory T cells. This education is based on three fundamental signals. Signal I, which is mediated by antigen/major histocompatibility complexes binding to antigen-specific T cell receptors, guarantees antigen specificity. The co-stimulatory signal II, mediated by B7 family molecules, is crucial for the expansion of the antigen-specific T cells. The final step is T cell polarization by signal III, which is conveyed by DC-derived cytokines and determines the effector functions of the emerging T cell. Although co-stimulation is widely recognized to result from the engagement of T cell-derived CD28 with DC-expressed B7 molecules (CD80/CD86), other co-stimulatory pathways have been identified. These pathways can be divided into two groups based on their impact on primed T cells. Whereas pathways delivering activatory signals to T cells are termed co-stimulatory pathways, pathways delivering tolerogenic signals to T cells are termed co-inhibitory pathways. In this review, we discuss how the nature of DC-derived signal II determines the quality of ensuing T cell responses and eventually promoting either immunity or tolerance. A thorough understanding of this process is instrumental in determining the underlying mechanism of disorders demonstrating distorted immunity/tolerance balance, and would help innovating new therapeutic approaches for such disorders.
A
bstract
The quantum interference between the decays of entangled neutral kaons is studied in the process
ϕ
→ K
S
K
L
→
π
+
π
−
π
+
π
−
, which exhibits the characteristic Einstein-Podolsky-Rosen ...correlations that prevent both kaons to decay into
π
+
π
−
at the same time. This constitutes a very powerful tool for testing at the utmost precision the quantum coherence of the entangled kaon pair state, and to search for tiny decoherence and
CPT
violation effects, which may be justified in a quantum gravity framework.
The analysed data sample was collected with the KLOE detector at DAΦNE, the Frascati
ϕ
-factory, and corresponds to an integrated luminosity of about 1.7 fb
−
1
, i.e. to about 1
.
7 × 10
9
ϕ
→ K
S
K
L
decays produced. From the fit of the observed ∆
t
distribution, being ∆
t
the difference of the kaon decay times, the decoherence and
CPT
violation parameters of various phenomenological models are measured with a largely improved accuracy with respect to previous analyses.
The results are consistent with no deviation from quantum mechanics and
CPT
symmetry, while for some parameters the precision reaches the interesting level at which — in the most optimistic scenarios — quantum gravity effects might show up. They provide the most stringent limits up to date on the considered models.
Aims/hypothesis
Type 2 diabetes is a highly heterogeneous disease for which new subgroups (‘clusters’) have been proposed based on disease severity: moderate age-related diabetes (MARD), moderate ...obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD) and severe insulin-resistant diabetes (SIRD). It is unknown how disease severity is reflected in terms of quality of life in these clusters. Therefore, we aimed to investigate the cluster characteristics and cluster-wise evolution of quality of life in the previously defined clusters of type 2 diabetes.
Methods
We included individuals with type 2 diabetes from the Maastricht Study, who were allocated to clusters based on a nearest centroid approach. We used logistic regression to evaluate the cluster-wise association with diabetes-related complications. We plotted the evolution of HbA
1c
levels over time and used Kaplan–Meier curves and Cox regression to evaluate the cluster-wise time to reach adequate glycaemic control. Quality of life based on the Short Form 36 (SF-36) was also plotted over time and adjusted for age and sex using generalised estimating equations. The follow-up time was 7 years. Analyses were performed separately for people with newly diagnosed and already diagnosed type 2 diabetes.
Results
We included 127 newly diagnosed and 585 already diagnosed individuals. Already diagnosed people in the SIDD cluster were less likely to reach glycaemic control than people in the other clusters, with an HR compared with MARD of 0.31 (95% CI 0.22, 0.43). There were few differences in the mental component score of the SF-36 in both newly and already diagnosed individuals. In both groups, the MARD cluster had a higher physical component score of the SF-36 than the other clusters, and the MOD cluster scored similarly to the SIDD and SIRD clusters.
Conclusions/interpretation
Disease severity suggested by the clusters of type 2 diabetes is not entirely reflected in quality of life. In particular, the MOD cluster does not appear to be moderate in terms of quality of life. Use of the suggested cluster names in practice should be carefully considered, as the non-neutral nomenclature may affect disease perception in individuals with type 2 diabetes and their healthcare providers.
Graphical Abstract
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