Neural tracking in infancy predicts language development in children with and without family history of autism

During speech processing, neural activity in non-autistic adults and infants tracks the speech envelope. Recent research in adults indicates that this neural tracking relates to linguistic knowledge and may be reduced in autism. Such reduced tracking, if present already in infancy, could impede language development. In the current study, we focused on children with a family history of autism, who often show a delay in first language acquisition. We investigated whether differences in tracking of sung nursery rhymes during infancy relate to language development and autism symptoms in childhood. We assessed speech-brain coherence at either 10 or 14 months of age in a total of 22 infants with high likelihood of autism due to family history and 19 infants without family history of autism. We analyzed the relationship between speech-brain coherence in these infants and their vocabulary at 24 months as well as autism symptoms at 36 months. Our results showed significant speech-brain coherence in the 10- and 14-month-old infants. We found no evidence for a relationship between speech-brain coherence and later autism symptoms. Importantly, speech-brain coherence in the stressed syllable rate (1–3 Hz) predicted later vocabulary. Follow-up analyses showed evidence for a relationship between tracking and vocabulary only in 10-month-olds but not 14-month-olds and indicated possible differences between the likelihood groups. Thus, early tracking of sung nursery rhymes is related to language development in childhood

A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export

Abstract: Cholesterol import in mammalian cells is mediated by the LDL receptor pathway. Here, we perform a genome-wide CRISPR screen using an endogenous cholesterol reporter and identify >100 genes involved in LDL-cholesterol import. We characterise C18orf8 as a core subunit of the mammalian Mon1-Ccz1 guanidine exchange factor (GEF) for Rab7, required for complex stability and function. C18orf8-deficient cells lack Rab7 activation and show severe defects in late endosome morphology and endosomal LDL trafficking, resulting in cellular cholesterol deficiency. Unexpectedly, free cholesterol accumulates within swollen lysosomes, suggesting a critical defect in lysosomal cholesterol export. We find that active Rab7 interacts with the NPC1 cholesterol transporter and licenses lysosomal cholesterol export. This process is abolished in C18orf8-, Ccz1- and Mon1A/B-deficient cells and restored by a constitutively active Rab7. The trimeric Mon1-Ccz1-C18orf8 (MCC) GEF therefore plays a central role in cellular cholesterol homeostasis coordinating Rab7 activation, endosomal LDL trafficking and NPC1-dependent lysosomal cholesterol export

Interpretation of pre-morbid cardiac 3T MRI findings in overweight and hypertensive young adults

In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different body scales for indexation. We also aimed to explore the presence of myocardial fibrosis, fat and edema, and changes in cellular mass with extracellular volume (ECV), T(1) and T(2) tissue characteristics. We prospectively recruited 126 asymptomatic subjects (51% male) aged 27–41 years for 3T cardiac magnetic resonance imaging: 40 controls, 40 overweight, 17 hypertensive and 29 hypertensive overweight. Myocyte mass was calculated as (100%–ECV) * height(2.7)-indexed LVM. Absolute LVM was significantly increased in overweight, hypertensive and hypertensive overweight groups (104 ± 23, 109 ± 27, 112 ± 26 g) versus controls (87 ± 21 g), with similar volumes. Body surface area (BSA) indexation resulted in LVM normalization in overweights (48 ± 8 g/m(2)) versus controls (47 ± 9 g/m(2)), but not in hypertensives (55 ± 9 g/m(2)) and hypertensive overweights (52 ± 9 g/m(2)). BSA-indexation overly decreased volumes in overweight versus normal-weight (LV end-diastolic volume; 80 ± 14 versus 92 ± 13 ml/m(2)), where height(2.7)-indexation did not. All risk groups had lower ECV (23 ± 2%, 23 ± 2%, 23 ± 3%) than controls (25 ± 2%) (P = 0.006, P = 0.113, P = 0.039), indicating increased myocyte mass (16.9 ± 2.7, 16.5 ± 2.3, 18.1 ± 3.5 versus 14.0 ± 2.9 g/m(2.7)). Native T(1) values were similar. Lower T(2) values in the hypertensive overweight group related to heart rate. In conclusion, BSA-indexation masks hypertrophy and causes volume overcorrection in overweight subjects compared to controls, height(2.7)-indexation therefore seems advisable

Neural Tracking in Infancy Predicts Language Development in Children With and Without Family History of Autism

During speech processing, neural activity in non-autistic adults and infants tracks the speech envelope. Recent research in adults indicates that this neural tracking relates to linguistic knowledge and may be reduced in autism. Such reduced tracking, if present already in infancy, could impede language development. In the current study, we focused on children with a family history of autism, who often show a delay in first language acquisition. We investigated whether differences in tracking of sung nursery rhymes during infancy relate to language development and autism symptoms in childhood. We assessed speech-brain coherence at either 10 or 14 months of age in a total of 22 infants with high likelihood of autism due to family history and 19 infants without family history of autism. We analyzed the relationship between speech-brain coherence in these infants and their vocabulary at 24 months as well as autism symptoms at 36 months. Our results showed significant speech-brain coherence in the 10-and 14-month-old infants. We found no evidence for a relationship between speech-brain coherence and later autism symptoms. Importantly, speech-brain coherence in the stressed syllable rate (1–3 Hz) predicted later vocabulary. Follow-up analyses showed evidence for a relationship between tracking and vocabulary only in 10-month-olds but not in 14-month-olds and indicated possible differences between the likelihood groups. Thus, early tracking of sung nursery rhymes is related to language development in childhood

Comparison of two arthroscopic pump systems based on image quality

The effectiveness of arthroscopic pump systems has been investigated with either subjective measures or measures that were unrelated to the image quality. The goal of this study is to determine the performance of an automated pump in comparison to a gravity pump based on objective assessment of the quality of the arthroscopic view. Ten arthroscopic operations performed with a gravity pump and ten performed with an automated pump (FMS Duo system) were matched on duration of the surgery and shaver usage, type of operation, and surgical experience. Quality of the view was defined by means of the presence or absence of previously described definitions of disturbances (bleeding, turbidity, air bubbles, and loose fibrous tissue). The percentage of disturbances for all operations was assessed with a time-disturbance analysis of the recorded operations. The Mann–Whitney U test shows a significant difference in favor of the automated pump for the presence of turbidity only (Exact Sig. [2*(1-tailed Sig.)] = 0.015). Otherwise, no differences were determined (Exact Sig. [2*(1-tailed Sig.)] > 0.436). A new objective method is successfully applied to assess efficiency of pump systems based on the quality of the arthroscopic view. Important disturbances (bleeding, air bubbles, and loose fibrous tissue) are not reduced by an automated pump used in combination with a tourniquet. The most frequent disturbance turbidity is reduced by around 50%. It is questionable if this result justifies the use of an automated pump for straightforward arthroscopic knee surgeries using a tourniquet

Cardiovascular magnetic resonance native T-2 and T-2* quantitative values for cardiomyopathies and heart transplantations:a systematic review and meta-analysis

Background: The clinical application of cardiovascular magnetic resonance (CMR) T2 and T2* mapping is currently limited as ranges for healthy and cardiac diseases are poorly defined. In this meta-analysis we aimed to determine the weighted mean of T2 and T2* mapping values in patients with myocardial infarction (MI), heart transplantation, non-ischemic cardiomyopathies (NICM) and hypertension, and the standardized mean difference (SMD) of each population with healthy controls. Additionally, the variation of mapping outcomes between studies was investigated. Methods: The PRISMA guidelines were followed after literature searches on PubMed and Embase. Studies reporting CMR T2 or T2* values measured in patients were included. The SMD was calculated using a random effects model and a meta-regression analysis was performed for populations with sufficient published data. Results: One hundred fifty-four studies, including 13,804 patient and 4392 control measurements, were included. T2 values were higher in patients with MI, heart transplantation, sarcoidosis, systemic lupus erythematosus, amyloidosis, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and myocarditis (SMD of 2.17, 1.05, 0.87, 1.39, 1.62, 1.95, 1.90 and 1.33, respectively, P < 0.01) compared with controls. T2 values in iron overload patients (SMD =-0.54, P = 0.30) and Anderson-Fabry disease patients (SMD = 0.52, P = 0.17) did both not differ from controls. T2* values were lower in patients with MI and iron overload (SMD of-1.99 and-2.39, respectively, P < 0.01) compared with controls. T2* values in HCM patients (SMD =-0.61, P = 0.22), DCM patients (SMD =-0.54, P = 0.06) and hypertension patients (SMD =-1.46, P = 0.10) did not differ from controls. Multiple CMR acquisition and patient demographic factors were assessed as significant covariates, thereby influencing the mapping outcomes and causing variation between studies. Conclusions: The clinical utility of T2 and T2* mapping to distinguish affected myocardium in patients with cardiomyopathies or heart transplantation from healthy myocardium seemed to be confirmed based on this meta-analysis. Nevertheless, variation of mapping values between studies complicates comparison with external values and therefore require local healthy reference values to clinically interpret quantitative values. Furthermore, disease differentiation seems limited, since changes in T2 and T2* values of most cardiomyopathies are similar

Cardiac Alterations on 3T MRI in Young Adults With Sedentary Lifestyle-Related Risk Factors

BACKGROUND: Young adult populations with the sedentary lifestyle-related risk factors overweight, hypertension, and type 2 diabetes (T2D) are growing, and associated cardiac alterations could overlap early findings in non-ischemic cardiomyopathy on cardiovascular MRI. We aimed to investigate cardiac morphology, function, and tissue characteristics for these cardiovascular risk factors. METHODS: Non-athletic non-smoking asymptomatic adults aged 18–45 years were prospectively recruited and underwent 3Tesla cardiac MRI. Multivariate linear regression was performed to investigate independent associations of risk factor-related parameters with cardiac MRI values. RESULTS: We included 311 adults (age, 32 ± 7 years; men, 49%). Of them, 220 subjects had one or multiple risk factors, while 91 subjects were free of risk factors. For overweight, increased body mass index (per SD = 5.3 kg/m(2)) was associated with increased left ventricular (LV) mass (+7.3 g), biventricular higher end-diastolic (LV, +8.6 ml), and stroke volumes (SV; +5.0 ml), higher native T(1) (+7.3 ms), and lower extracellular volume (ECV, −0.38%), whereas the higher waist-hip ratio was associated with lower biventricular volumes. Regarding hypertension, increased systolic blood pressure (per SD = 14 mmHg) was associated with increased LV mass (+6.9 g), higher LV ejection fraction (EF; +1.0%), and lower ECV (−0.48%), whereas increased diastolic blood pressure was associated with lower LV EF. In T2D, increased HbA1c (per SD = 9.0 mmol/mol) was associated with increased LV mass (+2.2 g), higher right ventricular end-diastolic volume (+3.2 ml), and higher ECV (+0.27%). Increased heart rate was linked with decreased LV mass, lower biventricular volumes, and lower T(2) values. CONCLUSIONS: Young asymptomatic adults with overweight, hypertension, and T2D show subclinical alterations in cardiac morphology, function, and tissue characteristics. These alterations should be considered in cardiac MRI-based clinical decision making

The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER

Human cytomegalovirus uses an E3 ubiquitin ligase to divert MHC I molecules into the ER-associated degradation pathway for destruction

Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits

Funder: H2020 European Research Council; doi: http://dx.doi.org/10.13039/100010663Funder: Research Foundation FlandersFunder: Universiteit Gent; doi: http://dx.doi.org/10.13039/501100004385Funder: Marguerite-Marie DelacroixFunder: Autistica; doi: http://dx.doi.org/10.13039/100011706Funder: Riksbankens Jubileumsfond; doi: http://dx.doi.org/10.13039/501100004472; Grant(s): NHS14-1802:1Funder: K.F. Hein FondsFunder: Scott Family Junior Research FellowshipAbstract: Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years