Neutrophils suppress mucosal-associated invariant T cells in humans

Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that are abundant in mucosal tissues and the liver where they can respond rapidly to a broad range of riboflavin producing bacterial and fungal pathogens. Neutrophils, which are recruited early to sites of infection, play a nonredundant role in pathogen clearance and are crucial for controlling infection. The interaction of these two cell types is poorly studied. Here, we investigated both the effect of neutrophils on MAIT cell activation and the effect of activated MAIT cells on neutrophils. We show that neutrophils suppress the activation of MAIT cells by a cell-contact and hydrogen peroxide dependent mechanism. Moreover, highly activated MAIT cells were able to produce high levels of TNF-α that induced neutrophil death. We therefore provide evidence for a negative regulatory feedback mechanism in which neutrophils prevent overactivation of MAIT cells and, in turn, MAIT cells limit neutrophil survival.     

The influence of mental fatigue on brain activity: Evidence from a systematic review with meta-analyses

The occurrence of mental fatigue during tasks like driving a vehicle increases risk of injury or death. Changes in electroencephalographic (EEG) activity associated with mental fatigue has been frequently studied and considered a promising biomarker of mental fatigue. This is despite differences in methodologies and outcomes in prior research. A systematic review with meta-analyses was conducted to establish the influence of mental fatigue on EEG activity spectral bands, and to determine in which regions fatigue-related EEG spectral changes are likely to occur. A high-yield search strategy identified 21 studies meeting inclusion criteria for investigating the change in EEG spectral activity in non-diseased adults engaged in mentally fatiguing tasks. A medium effect size (using Cohen's g) of 0.68 (95%CI: 0.24–1.13) was found for increase in overall EEG activity following mental fatigue. Further examination of individual EEG spectral bands and regions using network meta-analyses indicated large increases in theta (g = 1.03; 95%CI: 0.79–1.60) and alpha bands (g = 0.85; 95%CI: 0.47–1.43), with small to moderate changes found in delta and beta bands. Central regions of the scalp showed largest change (g = 0.80; 95%CI: 0.46–1.21). Sub-group analyses indicated large increases in theta activity in frontal, central and posterior sites (all g > 1), with moderate changes in alpha activity in central and posterior sites. Findings have implications for fatigue monitoring and countermeasures with support for change in theta activity in frontal, central and posterior sites as a robust biomarker of mental fatigue and change in alpha wave activity considered a second line biomarker to account for individual variability.     

Experimental boundary conditions of reinstatement-induced return of fear in humans: Is reinstatement in humans what we think it is?

Experimental paradigms used to study reinstatement of fear in humans are characterized by procedural heterogeneity. Reinstatement protocols involve unexpected (re)-presentations of the unconditioned stimulus (USs) after fear extinction training. Here, we address the number of reinstatement USs administered as a potential boundary condition that may explain divergent findings in the field. A sample of 171 participants is exposed to a fear acquisition training, immediate extinction training, and reinstatement test experiment. Three groups differing in the number of reinstatement US are employed: one (n = 57) or four (n = 55) in experimental groups and zero (n = 59) in the control group. We adopt Bayesian statistical approaches beyond classical null hypothesis significance testing (NHST) to qualify evidence for or against this potential methodological boundary condition in reinstatement-induced return of fear. Startle potentiation to the reinstatement administration context was increased for the RI–US_one compared to the RI–US_zero group, supporting the role of context conditioning in reinstatement. This effect was weaker in the RI–US_four group. This, however, did not transfer to responding to conditioned stimuli during the return of fear-test: no evidence for an effect of the number of reinstatement USs (zero, one, four) was observed in behavioral or physiological measures. In sum, our results speak against the number of reinstatement USs as a potential boundary condition in experimentally induced return of fear in humans. This may challenge what we think we know about the reinstatement phenomenon in humans and call for critical reconsideration of paradigms as well as mechanisms that may underlie some reinstatement effects in the literature.     

Cantu syndrome: A longitudinal review of vascular findings in three individuals

Cantu syndrome is a rare autosomal dominant disorder caused by missense variants in ABCC9 and KCNJ8. It is characterized by hypertrichosis, neonatal macrosomia, coarse facial features, and skeletal anomalies. Reported cardiovascular anomalies include cardiomegaly, structural defects, collateral vessels, and rare report of arteriovenous malformation (AVM). Arterial dilation is reported in a few individuals including one with surgical intervention for a thoracic aortic aneurysm. The natural history of this aortopathy including the rate of progression or risk for dissection is unknown and longitudinal patient data is unavailable. We present data from vascular imaging in three individuals with genetically confirmed Cantu syndrome over 3 to 14 years of follow‐up. All patients had generally stable aortic dilation, which did not reach the surgical threshold, including one individual followed closely through pregnancy. In adulthood, one individual had a maximum ascending aortic measurement of 4.2 cm. Two pediatric patients had aortic root or ascending z‐scores of approximately +3. A large asymptomatic pelvic AVM was identified in one individual on head‐pelvis MRI. While the data reported in these individuals is reassuring regarding the risk for progressive disease, further data from additional individuals with Cantu syndrome is needed to best inform screening recommendations, improve understanding of dissection risk, and guide management.     

Obesity and COVID-19: The Two Sides of the Coin

The World Health Organization declared COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, a pandemic on March 12, 2020. COVID-19 is causing massive health problems and economic suffering around the world. The European Association for the Study of Obesity (EASO) promptly recognised the impact that the outbreak could have on people with obesity. On one side, emerging data suggest that obesity represents a risk factor for a more serious and complicated course of COVID-19 in adults. On the other side, the health emergency caused by the outbreak diverts attention from the prevention and care of non-communicable chronic diseases to communicable diseases. This might be particularly true for obesity, a chronic and relapsing disease frequently neglected and linked to significant bias and stigmatization. The Obesity Management Task Force (OMTF) of EASO contributes in this paper to highlighting the key aspects of these two sides of the coin and suggests some specific actions.     

Next‐generation sequencing for the diagnosis of MYH9‐RD: Predicting pathogenic variants

The heterogeneous manifestations of MYH9‐related disorder (MYH9‐RD), characterized by macrothrombocytopenia, Döhle‐like inclusion bodies in leukocytes, bleeding of variable severity with, in some cases, ear, eye, kidney, and liver involvement, make the diagnosis for these patients still challenging in clinical practice. We collected phenotypic data and analyzed the genetic variants in more than 3,000 patients with a bleeding or platelet disorder. Patients were enrolled in the BRIDGE‐BPD and ThromboGenomics Projects and their samples processed by high throughput sequencing (HTS). We identified 50 patients with a rare variant in MYH9. All patients had macrothrombocytes and all except two had thrombocytopenia. Some degree of bleeding diathesis was reported in 41 of the 50 patients. Eleven patients presented hearing impairment, three renal failure and two elevated liver enzymes. Among the 28 rare variants identified in MYH9, 12 were novel. HTS was instrumental in diagnosing 23 patients (46%). Our results confirm the clinical heterogeneity of MYH9‐RD and show that, in the presence of an unclassified platelet disorder with macrothrombocytes, MYH9‐RD should always be considered. A HTS‐based strategy is a reliable method to reach a conclusive diagnosis of MYH9‐RD in clinical practice.     

Associations of perceived prenatal stress and adverse pregnancy outcomes with perceived stress years after delivery

Archives of Women's Mental Health - Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal...