Gender Differences in Developing Biomarker-Based Major Depressive Disorder Diagnostics

The identification of biomarkers associated with major depressive disorder (MDD) holds great promise to develop an objective laboratory test. However, current biomarkers lack discriminative power due to the complex biological background, and not much is known about the influence of potential modifiers such as gender. We first performed a cross-sectional study on the discriminative power of biomarkers for MDD by investigating gender differences in biomarker levels. Out of 28 biomarkers, 21 biomarkers were significantly different between genders. Second, a novel statistical approach was applied to investigate the effect of gender on MDD disease classification using a panel of biomarkers. Eleven biomarkers were identified in men and eight in women, three of which were active in both genders. Gender stratification caused a (non-significant) increase of Area Under Curve (AUC) for men (AUC=0.806) and women (AUC=0.807) compared to non-stratification (AUC=0.739). In conclusion, we have shown that there are differences in biomarker levels between men and women which may impact accurate disease classification of MDD when gender is not taken into account

Fatigue in patients with chronic disease:results from the population-based Lifelines Cohort Study

(1) To evaluate the prevalence of severe and chronic fatigue in subjects with and without chronic disease; (2) to assess to which extent multi-morbidity contributes to severe and chronic fatigue; and (3) to identify predisposing and associated factors for severe and chronic fatigue and whether these are disease-specific, trans-diagnostic, or generic. The Dutch Lifelines cohort was used, including 78,363 subjects with (n = 31,039, 53 ± 12 years, 33% male) and without (n = 47,324, 48 ± 12 years, 46% male) ≥ 1 of 23 chronic diseases. Fatigue was assessed with the Checklist Individual Strength-Fatigue. Compared to participants without a chronic disease, a higher proportion of participants with ≥ 1 chronic disease were severely (23% versus 15%, p < 0.001) and chronically (17% versus 10%, p < 0.001) fatigued. The odds of having severe fatigue (OR [95% CI]) increased from 1.6 [1.5–1.7] with one chronic disease to 5.5 [4.5–6.7] with four chronic diseases; for chronic fatigue from 1.5 [1.5–1.6] to 4.9 [3.9–6.1]. Multiple trans-diagnostic predisposing and associated factors of fatigue were found, explaining 26% of variance in fatigue in chronic disease. Severe and chronic fatigue are highly prevalent in chronic diseases. Multi-morbidity increases the odds of having severe and chronic fatigue. Several trans-diagnostic factors were associated with fatigue, providing a rationale for a trans-diagnostic approach

Development of the Tilburg Pregnancy Distress Scale: the TPDS

Contains fulltext : 96807.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Pregnant women with high levels of stress, depression and/or anxiety are at increased risk for adverse perinatal outcomes and impaired neurologic and emotional development of the offspring. Pregnancy specific instruments to measure psychological functioning during gestation are scarce and do not define items based on in-depth interviews of pregnant and recently delivered women. The current study developed a pregnancy specific scale that measures psychological functioning using in-depth interviews. METHODS: Three focus groups were formed to discuss issues most relevant to pregnancy distress; 22 candidate items were derived for pilot testing (study I, n = 419) its psychometric properties by means of explorative factor analyses (EFA). This resulted in a 17-item TPDS which was further explored by confirmatory factor analyses (CFA) and concurrent and construct validity assessment (study II, n = 454). RESULTS: EFA in study I suggested a two component solution (negative affect (NA) and partner involvement (PI)). CFA in study II resulted in a higher order model of the NA subscale into three more subscales: NA regarding confinement, delivery and general health. TPDS, EPDS and GAD-7 were all significantly correlated. CONCLUSIONS: The TPDS constitutes a valid and user friendly instrument to assess pregnancy distress. In addition to its proven ability to pick up pregnancy specific negative affect it also includes an important sub-scale measuring perceived partner involvement

Developmental effects on sleep–wake patterns in infants receiving a cow’s milk-based infant formula with an added prebiotic blend: A Randomized Controlled Trial

Background Few studies have evaluated nutritive effects of prebiotics on infant behavior state, physiology, or metabolic status. Methods In this double-blind randomized study, infants (n = 161) received cow’s milk-based infant formula (Control) or similar formula with an added prebiotic blend (polydextrose and galactooligosaccharides [PDX/GOS]) from 14–35 to 112 days of age. Infant wake behavior (crying/fussing, awake/content) and 24-h sleep–wake actograms were analyzed (Baseline, Days 70 and 112). Salivary cortisol was immunoassayed (Days 70 and 112). In a subset, exploratory stool 16S ribosomal RNA-sequencing was analyzed (Baseline, Day 112). Results One hundred and thirty-one infants completed the study. Average duration of crying/fussing episodes was similar at Baseline, significantly shorter for PDX/GOS vs. Control at Day 70, and the trajectory continued at Day 112. Latency to first and second nap was significantly longer for PDX/GOS vs. Control at Day 112. Cortisol awakening response was demonstrated at Days 70 and 112. Significant stool microbiome beta-diversity and individual taxa abundance differences were observed in the PDX/GOS group. Conclusions Results indicate faster consolidation of daytime waking state in infants receiving prebiotics and support home-based actigraphy to assess early sleep–wake patterns. A prebiotic effect on wake organization is consistent with influence on the gut–brain axis and warrants further investigation. Impact Few studies have evaluated nutritive effects of prebiotics on infant behavior state, cortisol awakening response, sleep–wake entrainment, and gut microbiome. Faster consolidation of daytime waking state was demonstrated in infants receiving a prebiotic blend in infant formula through ~4 months of age. Shorter episodes of crying were demonstrated at ~2 months of age (time point corresponding to age/developmental range associated with peak crying) in infants receiving formula with added prebiotics. Results support home-based actigraphy as a suitable method to assess early sleep–wake patterns. Prebiotic effect on wake organization is consistent with influence on the gut–brain axis and warrants further investigation

Severe loss of mechanical efficiency in COVID‐19 patients

Background: There is limited information about the impact of coronavirus disease (COVID-19) on the muscular dysfunction, despite the generalized weakness and fatigue that patients report after overcoming the acute phase of the infection. This study aimed to detect impaired muscle efficiency by evaluating delta efficiency (DE) in patients with COVID-19 compared with subjects with chronic obstructive pulmonary disease (COPD), ischaemic heart disease (IHD), and control group (CG). Methods: A total of 60 participants were assigned to four experimental groups: COVID-19, COPD, IHD, and CG (n = 15 each group). Incremental exercise tests in a cycle ergometer were performed to obtain peak oxygen uptake (VO2 peak). DE was obtained from the end of the first workload to the power output where the respiratory exchange ratio was 1. Results: A lower DE was detected in patients with COVID-19 and COPD compared with those in CG (P ≤ 0.033). However, no significant differences were observed among the experimental groups with diseases (P > 0.05). Lower VO2 peak, peak ventilation, peak power output, and total exercise time were observed in the groups with diseases than in the CG (P < 0.05). A higher VO2 , ventilation, and power output were detected in the CG compared with those in the groups with diseases at the first and second ventilatory threshold (P < 0.05). A higher power output was detected in the IHD group compared with those in the COVID-19 and COPD groups (P < 0.05) at the first and second ventilatory thresholds and when the respiratory exchange ratio was 1. A significant correlation (P < 0.001) was found between the VO2 peak and DE and between the peak power output and DE (P < 0.001). Conclusions: Patients with COVID-19 showed marked mechanical inefficiency similar to that observed in COPD and IHD patients. Patients with COVID-19 and COPD showed a significant decrease in power output compared to IHD during pedalling despite having similar response in VO2 at each intensity. Resistance training should be considered during the early phase of rehabilitation

Is consuming yoghurt associated with weight management outcomes? Results from a systematic review.

BACKGROUND: Yoghurt is part of the diet of many people worldwide and is commonly recognised as a 'health food'. Epidemiological studies suggest that yoghurt may be useful as part of weight management programs. In the absence of comprehensive systematic reviews, this systematic review investigated the effect of yoghurt consumption by apparently healthy adults on weight-related outcomes. METHODS: An extensive literature search was undertaken, as part of a wider scoping review, to identify yoghurt studies. A total of 13 631 records were assessed for their relevance to weight-related outcomes. RESULTS: Twenty-two publications were eligible according to the review protocol. Cohort studies (n=6) and cross-sectional studies (n=7) all showed a correlation between yoghurt and lower or improved body weight/composition. Six randomised controlled trials (RCTs) and one controlled trial had various limitations, including small size and short duration. One RCT showed significant effects of yoghurt on weight loss, but was confounded by differences in calcium intake. One trial showed nonsignificant weight gain and the remaining five trials showed nonsignificant weight losses that were greater in yoghurt consumers. CONCLUSIONS: Yoghurt consumption is associated with lower body mass index, lower body weight/weight gain, smaller waist circumference and lower body fat in epidemiological studies. RCTs suggest weight reduction effects, but do not permit determination of a cause-effect relationship. Well-controlled, adequately powered trials in research and community settings appear likely to identify a modest but beneficial effect of yoghurt consumption for prevention of weight gain and management of obesity. The ready availability of yoghurt (a nutrient-dense food) and its ease of introduction to most diets suggests that educating the public to eat yoghurt as part of a balanced and healthy diet may potentially contribute to improved public health. Future carefully designed RCTs could provide proof of principle and large community-based studies could determine the practical impact of yoghurt on body weight/composition

PRegnancy Outcomes after a Maternity Intervention for Stressful EmotionS (PROMISES): study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There is ample evidence from observational prospective studies that maternal depression or anxiety during pregnancy is a risk factor for adverse psychosocial outcomes in the offspring. However, to date no previous study has demonstrated that treatment of depressive or anxious symptoms in pregnancy actually could prevent psychosocial problems in children. Preventing psychosocial problems in children will eventually bring down the huge public health burden of mental disease. The main objective of this study is to assess the effects of cognitive behavioural therapy in pregnant women with symptoms of anxiety or depression on the child's development as well as behavioural and emotional problems. In addition, we aim to study its effects on the child's development, maternal mental health, and neonatal outcomes, as well as the cost-effectiveness of cognitive behavioural therapy relative to usual care.</p> <p>Methods/design</p> <p>We will include 300 women with at least moderate levels of anxiety or depression at the end of the first trimester of pregnancy. By including 300 women we will be able to demonstrate effect sizes of 0.35 or over on the total problems scale of the child behavioural checklist 1.5-5 with alpha 5% and power (1-beta) 80%.</p> <p>Women in the intervention arm are offered 10-14 individual cognitive behavioural therapy sessions, 6-10 sessions during pregnancy and 4-8 sessions after delivery (once a week). Women in the control group receive care as usual.</p> <p>Primary outcome is behavioural/emotional problems at 1.5 years of age as assessed by the total problems scale of the child behaviour checklist 1.5 - 5 years.</p> <p>Secondary outcomes will be mental, psychomotor and behavioural development of the child at age 18 months according to the Bayley scales, maternal anxiety and depression during pregnancy and postpartum, and neonatal outcomes such as birth weight, gestational age and Apgar score, health care consumption and general health status (economic evaluation).</p> <p>Trial Registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2242">NTR2242</a></p

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition

A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration.

NAD metabolism regulates diverse biological processes, including ageing, circadian rhythm and axon survival. Axons depend on the activity of the central enzyme in NAD biosynthesis, nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2), for their maintenance and degenerate rapidly when this activity is lost. However, whether axon survival is regulated by the supply of NAD or by another action of this enzyme remains unclear. Here we show that the nucleotide precursor of NAD, nicotinamide mononucleotide (NMN), accumulates after nerve injury and promotes axon degeneration. Inhibitors of NMN-synthesising enzyme NAMPT confer robust morphological and functional protection of injured axons and synapses despite lowering NAD. Exogenous NMN abolishes this protection, suggesting that NMN accumulation within axons after NMNAT2 degradation could promote degeneration. Ectopic expression of NMN deamidase, a bacterial NMN-scavenging enzyme, prolongs survival of injured axons, providing genetic evidence to support such a mechanism. NMN rises prior to degeneration and both the NAMPT inhibitor FK866 and the axon protective protein Wld(S) prevent this rise. These data indicate that the mechanism by which NMNAT and the related Wld(S) protein promote axon survival is by limiting NMN accumulation. They indicate a novel physiological function for NMN in mammals and reveal an unexpected link between new strategies for cancer chemotherapy and the treatment of axonopathies