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Multi-criteria decision analysis (MCDA) is a decision aid frequently used in the field of forest management planning. It includes the evaluation of multiple criteria such as the production of timber and non-timber forest products and tangible as well as intangible values of ecosystem services (ES). Hence, it is beneficial compared to those methods that take a purely financial perspective. Accordingly, MCDA methods are increasingly popular in the wide field of sustainability assessment. Hybrid approaches allow aggregating MCDA and, potentially, other decision-making techniques to make use of their individual benefits and leading to a more holistic view of the actual consequences that come with certain decisions. This review is providing a comprehensive overview of hybrid approaches that are used in forest management planning. Today, the scientific world is facing increasing challenges regarding the evaluation of ES and the trade-offs between them, for example between provisioning and regulating services. As the preferences of multiple stakeholders are essential to improve the decision process in multi-purpose forestry, participatory and hybrid approaches turn out to be of particular importance. Accordingly, hybrid methods show great potential for becoming most relevant in future decision making. Based on the review presented here, the development of models for the use in planning processes should focus on participatory modeling and the consideration of uncertainty regarding available information.

Social anxiety disorder patients suffer from excessive anxious responses in social interaction leading to avoidance behavior and social impairment. Although the amygdala has a central role in perception and processing of threatening cues, little is known about the involved networks and corresponding dysfunctions in social anxiety. Therefore, this study aims to investigate the functional connectivity network of the amygdala in patients with social anxiety disorder and to identify regions that might influence amygdalar reactivity via modulatory pathways. Ten patients with anxiety disorders (social and/or panic) and 27 healthy controls underwent a facial emotion processing task as well as 6-min functional MRI at resting state. Individual voxel-wise functional connectivity maps were calculated using the amygdala as seed region. Group comparisons were done by random-effects analysis in SPM. Patients exhibited an amygdala hyperactivation during the emotional task and decreased functional coupling of the left amygdala with the medial orbitofrontal cortex and the posterior cingulate cortex/precuneus. The strength of this functional connectivity showed a negative association with the severity of state anxiety. In addition, an exploratory analysis revealed further reduced functional connectivity and a marked functional separation between the medial orbitofrontal and anterior cingulate cortices in the patient group. Our results suggest alterations within the amygdalar functional connectivity network in social anxiety disorder. Combined with the amygdalar hyperactivation our findings corroborate the proposed dysfunction of the fronto-amygdalar inhibition in anxiety disorders and indicate a modulatory influence of the anterior and posterior cingulate cortices on threat perception and processing. ►Resting state functional connectivity of amygdala in social anxiety disorder. ►Reduced amygdala connectivity with orbitofrontal and posterior cingulate cortices. ►Decreased coupling between orbitofrontal and anterior cingulate cortices.

Background Tuberous sclerosis complex (TSC) is a multisystem disease with prominent neurologic manifestations such as epilepsy, cognitive impairment and autism spectrum disorder. mTOR inhibitors have successfully been used to treat TSC-related manifestations in older children and adults. However, data on their safety and efficacy in infants and young children are scarce. The objective of this study is to assess the utility and safety of mTOR inhibitor treatment in TSC patients under the age of 2 years. Results A total of 17 children (median age at study inclusion 2.4 years, range 0–6; 12 males, 5 females) with TSC who received early mTOR inhibitor therapy were studied. mTOR inhibitor treatment was started at a median age of 5 months (range 0–19 months). Reasons for initiation of treatment were cardiac rhabdomyomas (6 cases), subependymal giant cell astrocytomas (SEGA, 5 cases), combination of cardiac rhabdomyomas and SEGA (1 case), refractory epilepsy (4 cases) and disabling congenital focal lymphedema (1 case). In all cases everolimus was used. Everolimus therapy was overall well tolerated. Adverse events were classified according to the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0). Grade 1–2 adverse events occurred in 12 patients and included mild transient stomatitis (2 cases), worsening of infantile acne (1 case), increases of serum cholesterol and triglycerides (4 cases), changes in serum phosphate levels (2 cases), increase of cholinesterase (2 cases), transient neutropenia (2 cases), transient anemia (1 case), transient lymphopenia (1 case) and recurrent infections (7 cases). No grade 3–4 adverse events were reported. Treatment is currently continued in 13/17 patients. Benefits were reported in 14/17 patients and included decrease of cardiac rhabdomyoma size and improvement of arrhythmia, decrease of SEGA size, reduction of seizure frequency and regression of congenital focal lymphedema. Despite everolimus therapy, two patients treated for intractable epilepsy are still experiencing seizures and another one treated for SEGA showed no volume reduction. Conclusion This retrospective multicenter study demonstrates that mTOR inhibitor treatment with everolimus is safe in TSC patients under the age of 2 years and shows beneficial effects on cardiac manifestations, SEGA size and early epilepsy.

Vitamin D deficiency is common and there exists a huge gap between recommended dietary vitamin D intakes and the poor vitamin D supply in the general population. While vitamin D is important for musculoskeletal health, there are accumulating data suggesting that vitamin D may also be important for fertility, pregnancy outcomes and lactation. Significant changes in vitamin D metabolism during pregnancy such as increased production of the “active vitamin D hormone” calcitriol support the important role of vitamin D in this setting. Observational studies show that vitamin D deficiency is a risk marker for reduced fertility and various adverse pregnancy outcomes and is associated with a low vitamin D content of breast milk. Meta-analyses of randomized controlled trials (RCTs) document that physiological vitamin D supplementation during pregnancy is safe and improves vitamin D and calcium status, thereby protecting skeletal health. Although certain RCTs and/or meta-analyses reported some other beneficial effects, it is still not clear whether vitamin D supplementation improves fertility or decreases the risk of adverse pregnancy outcomes such as low birth weight, pre-eclampsia and neonatal mortality, or reduces wheeze/asthma in the infants. Nevertheless, vitamin D supplementation in pregnant women is frequently required to achieve a sufficient vitamin D status as recommended by nutritional vitamin D guidelines. In this review, we provide an overview of systematic reviews, meta-analyses and large trials reporting clinical data on the role of vitamin D for fertility, pregnancy and lactation.

Background Ageing is characterised by physiological changes that can affect the nutrient availability and requirements. In particular, the status of vitamin D, cobalamin and folate has often been found to be critical in older people living in residential care. However, there is a lack of studies investigating the status of these nutrients in healthy and active home-dwelling elderly people. Methods The aim of this cross-sectional study was to assess the status of vitamin D based on serum concentrations of 25-hydroxycholecalciferol [25-(OH)D], cobalamin based on serum concentrations of holotranscobalamin (holoTC) and folate based on red blood cell (RBC) folate in unsupplemented, healthy and active German home-dwelling subjects ≥ 70 years of age (n = 134, mean ± SD: 75.8 ± 4.5 years). Dietary intake was assessed by 3-day food recalls. The study was conducted between March and November of 2021 (during the COVID-19 pandemic). Results The mean 25-(OH)D concentration was high at 85.1 ± 26.0 nmol/L, while the majority of women (92%) and men (94%) had 25-(OH)D concentrations ≥ 50 nmol/L. Less than 10% of men and women had 25-(OH)D concentrations < 50 nmol/L. The mean holoTC concentration was 88.9 ± 33.7 pmol/L (94.8 ± 34.6 pmol/L in women and 73.6 ± 25.6 in men). Only 8% of the women were cobalamin deficient (< 50 pmol/L holoTC) compared to 22% of the men. The mean RBC folate concentration was 831 ± 244 nmol/L, while the prevalence of folate deficiency was 10%. Linear regression analysis showed that only folate equivalent intake was associated with the relevant nutrient status marker. Conclusion Our findings suggest that healthy, independently living older people with high levels of education, physical activity, and health awareness are not necessarily at higher risk of vitamin D, folate and cobalamin deficiency. Further studies are needed to verify these findings and to identify lifestyle and dietary patterns that can predict adequate nutrient status for healthy ageing. Trial registration This study is officially recorded in the German Clinical Trials Register (DRKS00021302).

The quantification of big pools of diverse molecules provides important insights on brain function, but is often restricted to a limited number of observations, which impairs integration with other modalities. To resolve this issue, a method allowing for the prediction of mRNA expression in the entire brain based on microarray data provided in the Allen Human Brain Atlas was developed. Microarray data of 3702 samples from 6 brain donors was registered to MNI and cortical surface space using FreeSurfer. For each of 18,686 genes, spatial dependence of transcription was assessed using variogram modelling. Variogram models were employed in Gaussian process regression to calculate best linear unbiased predictions for gene expression at all locations represented in well-established imaging atlases for cortex, subcortical structures and cerebellum. For validation, predicted whole-brain transcription of the HTR1A gene was correlated with [carbonyl-11C]WAY-100635 positron emission tomography data collected from 30 healthy subjects. Prediction results showed minimal bias ranging within ±0.016 (cortical surface), ±0.12 (subcortical regions) and ±0.14 (cerebellum) in units of log2 expression intensity for all genes. Across genes, the correlation of predicted and observed mRNA expression in leave-one-out cross-validation correlated with the strength of spatial dependence (cortical surface: r = 0.91, subcortical regions: r = 0.85, cerebellum: r = 0.84). 816 out of 18,686 genes exhibited a high spatial dependence accounting for more than 50% of variance in the difference of gene expression on the cortical surface. In subcortical regions and cerebellum, different sets of genes were implicated by high spatially structured variability. For the serotonin 1A receptor, correlation between PET binding potentials and predicted comprehensive mRNA expression was markedly higher (Spearman ρ = 0.72 for cortical surface, ρ = 0.84 for subcortical regions) than correlation of PET and discrete samples only (ρ = 0.55 and ρ = 0.63, respectively). Prediction of mRNA expression in the entire human brain allows for intuitive visualization of gene transcription and seamless integration in multimodal analysis without bias arising from non-uniform distribution of available samples. Extension of this methodology promises to facilitate translation of omics research and enable investigation of human brain function at a systems level. •Comprehensive mRNA expression atlases in MNI and surface space for each gene.•Gaussian process regression corrects bias from non-uniform distribution of samples.•Improved correlation with PET data shown for the serotonin 1A receptor.•Models of spatial dependence vary across brain structures for each gene.•High spatially structured variability indicates relevant topology of transcription.

Morning chronotypes are associated with healthier metabolic profiles and lifestyles compared to evening chronotypes. However, limited research examined the relationship between chronotype, dietary intake, and metabolic health using accurate measures such as food records. This cross-sectional study aimed to investigate the association between chronotype, dietary intake, and metabolic health markers in a cohort of Ukrainian individuals. Chronotypes were determined using the Morningness-Eveningness Questionnaire (MEQ) in 110 healthy to obese individuals (30–75 years) without type 2 diabetes. Dietary intake was derived from weighed seven days food diaries, anthropometrics and blood markers of glucose and lipid metabolism were measured. Morning chronotypes were significantly older and exhibited distinct dietary patterns, including lower intake of fat and animal protein and higher intake of carbohydrates when compared to evening chronotypes (p < 0.01). Higher MEQ scores, reflecting a tendency toward a morning chronotype, were associated with lower BMI, waist circumference, fasting triglycerides, and glucose (p < 0.05). Further, being of morning chronotype predicted better overall metabolic health. These associations remained significant after adjusting for confounders. The findings suggest that morning chronotypes have a different dietary pattern characterized by a more balanced diet and favorable metabolic profile. Synchronizing daily routines with morning preferences could positively influence metabolic health.

Advances in high-throughput DNA sequencing have propelled research into the human microbiome and its link to metabolic health. We explore microbiome analysis methods, specifically emphasizing metabolomics, how dietary choices impact the production of microbial metabolites, providing an overview of studies examining the connection between enterotypes and diet, and thus, improvement of personalized dietary recommendations. Acetate, propionate, and butyrate constitute more than 95% of the collective pool of short-chain fatty acids. Conflicting data on acetate’s effects may result from its dynamic signaling, which can vary depending on physiological conditions and metabolic phenotypes. Human studies suggest that propionate has overall anti-obesity effects due to its well-documented chemistry, cellular signaling mechanisms, and various clinical benefits. Butyrate, similar to propionate, has the ability to reduce obesity by stimulating the release of appetite-suppressing hormones and promoting the synthesis of leptin. Tryptophan affects systemic hormone secretion, with indole stimulating the release of GLP-1, which impacts insulin secretion, appetite suppression, and gastric emptying. Bile acids, synthesized from cholesterol in the liver and subsequently modified by gut bacteria, play an essential role in the digestion and absorption of dietary fats and fat-soluble vitamins, but they also interact directly with intestinal microbiota and their metabolites. One study using statistical methods identified primarily two groupings of enterotypes Bacteroides and Ruminococcus. The Prevotella-dominated enterotype, P-type, in humans correlates with vegetarians, high-fiber and carbohydrate-rich diets, and traditional diets. Conversely, individuals who consume diets rich in animal fats and proteins, typical in Western-style diets, often exhibit the Bacteroides-dominated, B-type, enterotype. The P-type showcases efficient hydrolytic enzymes for plant fiber degradation but has limited lipid and protein fermentation capacity. Conversely, the B-type features specialized enzymes tailored for the degradation of animal-derived carbohydrates and proteins, showcasing an enhanced saccharolytic and proteolytic potential. Generally, models excel at predictions but often struggle to fully elucidate why certain substances yield varied responses. These studies provide valuable insights into the potential for personalized dietary recommendations based on enterotypes.

The highly diverse serotonergic system with at least 16 different receptor subtypes is implicated in the pathophysiology of most neuropsychiatric disorders including affective and anxiety disorders, obsessive compulsive disorder, post-traumatic stress disorder, eating disorders, sleep disturbance, attention deficit/hyperactivity disorder, drug addiction, suicidal behavior, schizophrenia, Alzheimer, etc. Alterations of the interplay between various pre- and postsynaptic receptor subtypes might be involved in the pathogenesis of these disorders. However, there is a lack of comprehensive in vivo values using standardized procedures. In the current PET study we quantified 3 receptor subtypes, including the major inhibitory (5‐HT1A and 5‐HT1B) and excitatory (5‐HT2A) receptors, and the transporter (5‐HTT) in the brain of healthy human subjects to provide a database of standard values. PET scans were performed on 95 healthy subjects (age=28.0±6.9years; 59% males) using the selective radioligands [carbonyl-11C]WAY-100635, [11C]P943, [18F]altanserin and [11C]DASB, respectively. A standard template in MNI stereotactic space served for region of interest delineation. This template follows two anatomical parcellation schemes: 1) Brodmann areas including 41 regions and 2) AAL (automated anatomical labeling) including 52 regions. Standard values (mean, SD, and range) for each receptor and region are presented. Mean cortical and subcortical binding potential (BP) values were in good agreement with previously published human in vivo and post-mortem data. By means of linear equations, PET binding potentials were translated to post-mortem binding (provided in pmol/g), yielding 5.89pmol/g (5‐HT1A), 23.5pmol/g (5‐HT1B), 31.44pmol/g (5‐HT2A), and 11.33pmol/g (5‐HTT) being equivalent to the BP of 1, respectively. Furthermore, we computed individual voxel-wise maps with BP values and generated average tracer-specific whole-brain binding maps. This knowledge might improve our interpretation of the alterations taking place in the serotonergic system during neuropsychiatric disorders. ► In vivo quantification of 5-HT 1A, 1B, 2A and 5-HTT in 95 healthy subjects ► PET radioligands [carbonyl-11C]WAY-100635, [11C]P943, [18F]altanserin and [11C]DASB ► Using a standard template in MNI space, a total of 93 ROIs were analyzed. ► The mean, SD and range of binding potentials (BPs) are provided. ► Using linear equations, in vivo PET BP was compared to post-mortem protein density.

•Assess the interrelation of brain glucose metabolism & functional connections.•Whole-brain functional input explains glucose metabolism of target region.•Functional input reflects non-oxidative, on-demand metabolism of synaptic signaling.•Shift to higher network integration during task performance.•Decreased segregation of brain networks in the elderly. The human brain is characterized by interacting large-scale functional networks fueled by glucose metabolism. Since former studies could not sufficiently clarify how these functional connections shape glucose metabolism, we aimed to provide a neurophysiologically-based approach. 51 healthy volunteers underwent simultaneous PET/MRI to obtain BOLD functional connectivity and [18F]FDG glucose metabolism. These multimodal imaging proxies of fMRI and PET were combined in a whole-brain extension of metabolic connectivity mapping. Specifically, functional connectivity of all brain regions were used as input to explain glucose metabolism of a given target region. This enabled the modeling of postsynaptic energy demands by incoming signals from distinct brain regions. Functional connectivity input explained a substantial part of metabolic demands but with pronounced regional variations (34 - 76%). During cognitive task performance this multimodal association revealed a shift to higher network integration compared to resting state. In healthy aging, a dedifferentiation (decreased segregated/modular structure of the brain) of brain networks during rest was observed. Furthermore, by including data from mRNA maps, [11C]UCB-J synaptic density and aerobic glycolysis (oxygen-to-glucose index from PET data), we show that whole-brain functional input reflects non-oxidative, on-demand metabolism of synaptic signaling. The metabolically-derived directionality of functional inputs further marked them as top-down predictions. In addition, the approach uncovered formerly hidden networks with superior efficiency through metabolically informed network partitioning. Applying multimodal imaging, we decipher a crucial part of the metabolic and neurophysiological basis of functional connections in the brain as interregional on-demand synaptic signaling fueled by anaerobic metabolism. The observed task- and age-related effects indicate promising future applications to characterize human brain function and clinical alterations.