Effects of Normobaric Hypoxia on Oculomotor Dynamics of Aviator Students during a Simulated Flight Task

Hypoxia occurs when the body\u27s tissues are unable to obtain adequate oxygen supply and is the primary environmental factor present when pilots are exposed to increasing altitude levels. Hypoxia leads to impaired vision, cognition, and motor control function, which can negatively affect performance and become deadly if a pilot becomes incapacitated. Thus, objective identification of early-onset hypoxia is critical to increase the time of useful consciousness and prevent physiological episodes. Of the few studies utilizing eye-tracking, there is disagreement and mixed results concerning saccadic eye metrics as a means to measure and detect hypoxia. Therefore, the purpose of this study was to investigate saccadic velocity changes driven by acute normobaric hypoxia. Using a noninvasive infrared-based eye-tracking device, we recorded saccadic average peak velocity during flight tasks at simulated altitudes of 0 ft, 12,500 ft, and 19,000 ft. No changes were observed in saccadic average peak velocity among different altitude exposures. As time on task increased, saccadic average peak velocity decreased, suggesting that eye metrics can serve as an indicator of mental fatigue

Comparing estimates of physical activity in children across different cut-points and the associations with weight status

This study aimed to compare sedentary time (SED) and intensity-specific physical activity (PA) estimates and the associations of SED and PA with body mass index (BMI) and waist circumference (WC) using three different sets of cut-points in preschool-aged children. A total of 751 children (4.7 +/- 0.9 years, boys 52.7%) wore an ActiGraph GT3X+BT accelerometer on their hip for 7 days (24 h). Euclidean norm -1 G with negative values rounded to zero (ENMO) and activity counts from vertical axis (VACounts) and vector magnitude (VMCounts) were derived. Estimates of SED and light, moderate, vigorous, and moderate-to-vigorous PA (MVPA) were calculated for commonly used cut-points by Hildebrand et al., Butte et al., and Evenson et al. Furthermore, the prevalence of meeting the PA recommendation, 180 min/day of which at least 60 min/day being MVPA, were assessed for the cut-points. Multilevel mixed analysis was used to examine associations of SED and PA with BMI and WC. In accordance with the results, SED and PA intensity estimates differed largely across cut-points (i.e., SED = 22-341 min/day; light PA = 52-257 min/day; moderate PA = 5-18 min/day; vigorous PA = 7-17 min/day; MVPA = 13-35 min/day), and the prevalence of children meeting the PA recommendation varied from 4% to 70%. Associations of SED and PA with BMI or WC varied between the cut-points. Our results indicate that SED and PA estimates in preschool-aged children between studies using these cut-points are poorly comparable. Methods facilitating accelerometer-derived PA estimate comparison between studies are highly warranted.Peer reviewe

Ascending Growth is Associated with Offspring Adiposity in Pregnancies Complicated with Obesity or Gestational Diabetes

Context: Early growth is associated with childhood adiposity, but the influence of lifestyle remains unknown. Objective: This work aimed to investigate the association of growth profiles from high-risk pregnancies with adiposity at age 5 years, taking into account lifestyle and several antenatal/postnatal exposures. Methods: This prospective cohort study included 609 children born during the Finnish Gestational Diabetes Prevention Study (RADIEL), recruiting women with body mass index (BMI) greater than or equal to 30 and/or prior gestational diabetes mellitus (GDM) (2008-2013). Altogether 332 children attended the 5-year follow-up (2014-2017). Main outcome measures included growth profiles based on ponderal index (PI = weight/height(3)), investigated using latent class mixed models. Adiposity was assessed with anthropometrics and body composition (InBody720). Results: We identified 3 growth profiles: ascending (n = 82), intermediate (n = 351), and descending (n = 149). Children with ascending growth had a higher body fat percentage, ISO-BMI, and waist circumference (P Conclusion: Accelerated early growth was associated with higher adiposity in 5-year-old children from high-risk pregnancies, even when adjusted for lifestyle. Reducing cesarean deliveries and promoting breastfeeding may be beneficial for postnatal growth.Peer reviewe

Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria

Background: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. Methods: Cerebrospinal fuid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to CSF cytokine levels, acute and long-term neurologic complications, and long-term cogni‑ tive impairments. CSF kynurenine and KYNA from eight Swedish children without neurological or infectious disease admitted to Astrid Lindgren’s Children’s Hospital were quantifed and used for comparison. Results: Children with CM had signifcantly higher CSF concentration of kynurenine and KYNA than Swedish children (P \u3c 0.0001 for both), and CSF kynurenine and KYNA were positively correlated. In children with CM, CSF kynurenine and KYNA concentrations were associated with coma duration in children of all ages (P = 0.003 and 0.04, respec‑ tively), and CSF kynurenine concentrations were associated with worse overall cognition (P = 0.056) and attention (P = 0.003) at 12-month follow-up in children ≥5 years old. Conclusions: CSF KYNA and kynurenine are elevated in children with CM, indicating an inhibition of glutamatergic and cholinergic signaling. This inhibition may lead acutely to prolonged coma and long-term to impairment of atten‑ tion and cognition

The Application of New Molecular Methods in the Investigation of a Waterborne Outbreak of Norovirus in Denmark, 2012

In December 2012, an outbreak of acute gastrointestinal illness occurred in a geographical distinct area in Denmark covering 368 households. A combined microbiological, epidemiological and environmental investigation was initiated to understand the outbreak magnitude, pathogen(s) and vehicle in order to control the outbreak. Norovirus GII.4 New Orleans 2009 variant was detected in 15 of 17 individual stool samples from 14 households. Norovirus genomic material from water samples was detected and quantified and sequencing of longer parts of the viral capsid region (>1000 nt) were applied to patient and water samples. All five purposely selected water samples tested positive for norovirus GII in levels up to 1.8×10(4) genomic units per 200 ml. Identical norovirus sequences were found in all 5 sequenced stool samples and 1 sequenced water sample, a second sequenced water sample showed 1 nt (<0.1%) difference. In a cohort study, including 256 participants, cases were defined as residents of the area experiencing diarrhoea or vomiting onset on 12-14 December 2012. We found an attack rate of 51%. Being a case was associated with drinking tap-water on 12-13 December (relative risk = 6.0, 95%CI: 1.6-22) and a dose-response relation for the mean glasses of tap-water consumed was observed. Environmental investigations suggested contamination from a sewage pipe to the drinking water due to fall in pressure during water supply system renovations. The combined microbiological, epidemiological and environmental investigations strongly indicates the outbreak was caused by norovirus contamination of the water supply system

Correction of a urea cycle defect after ex vivo gene editing of human hepatocytes

Ornithine transcarbamylase deficiency (OTCD) is a monogenic disease of ammonia metabolism in hepatocytes. Severe disease is frequently treated by orthotopic liver transplantation. An attractive approach is the correction of a patient's own cells to regenerate the liver with gene-repaired hepatocytes. This study investigates the efficacy and safety of ex vivo correction of primary human hepatocytes. Hepatocytes isolated from an OTCD patient were genetically corrected ex vivo, through the deletion of a mutant intronic splicing site achieving editing efficiencies >60% and the restoration of the urea cycle in vitro. The corrected hepatocytes were transplanted into the liver of FRGN mice and repopulated to high levels (>80%). Animals transplanted and liver repopulated with genetically edited patient hepatocytes displayed normal ammonia, enhanced clearance of an ammonia challenge and OTC enzyme activity, as well as lower urinary orotic acid when compared to mice repopulated with unedited patient hepatocytes. Gene expression was shown to be similar between mice transplanted with unedited or edited patient hepatocytes. Finally, a genome-wide screening by performing CIRCLE-seq and deep sequencing of >70 potential off-targets revealed no unspecific editing. Overall analysis of disease phenotype, gene expression, and possible off-target editing indicated that the gene editing of a severe genetic liver disease was safe and effective. Keywords: CRISPR; FRGN; ex vivo; genome editing; hepatocyte transplantation; liver-humanized mouse; primary hepatocytes; urea cycle disorder

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Practical steps needed to achieve impact of the WHO 2019 movement behaviour guidelines for children under the age of 5 : the SUNRISE Study Europe Group evaluation

The World Health Organisation (WHO) guidelines for the ‘24-h movement behaviours’1 (physical activity (PA), sedentary behaviour (SB) including screen time, and sleep) in the under-5s were published in April 2019 (Supplementary Figure S1).2 The guidelines were developed as a response to the childhood obesity pandemic,2 to help ensure that under-5s have healthy levels of PA, screen time, and sleep. Evidence review and synthesis showed that these behaviours influenced a wide range of other outcomes, with substantial short-term and long-term consequences (e.g., cognitive, social and emotional development; language development; cardiometabolic health; bone and skeletal health; motor development; physical fitness; growth; and wellbeing).2 Five years later, it is now appropriate to test whether key actions in response to these guidelines were taken across Europe, and to consider ways of increasing the impact of the WHO Guidelines across Europe in the next 5 years. Therefore, the SUNRISE Study Europe Group considered three tests to examine if European public health policy and clinical practice were sufficiently responsive to the WHO Guidelines: (1) Do European nations have national guidelines for the movement behaviours in the under-5s or have they adopted/adapted the WHO Guidelines? (2) Do they have adequate surveillance of the movement behaviours in these age groups? (3) Do they have specific movement behaviour policies for children under-5

Sex differential in mortality trends of old-aged Danes: a nation wide study of age, period and cohort effects

Objective Over the last half century the mortality rates in Denmark for females above age 80 have declined dramatically whereas the decline for males have been modest, resulting in a change in sex-ratio for centenarians from 2 to 5. Here we investigate whether this mortality pattern is mainly explained by period effects, cohort effects or both. This can provide clues for where to search for causes behind the changes in sex differential in mortality seen in many Western countries during the last decades. Methods Age-period-cohort study of mortality for all Danish women and men aged 79–98 during the period 1949–2006. Outcome measures Relative risks for deaths and second order differences for exploration of the nonlinear variation. Results Both the overall trends in mortality differences and the fluctuations in mortality for both men and women were better explained by period effects than by cohort effects. The observed rates were better described by the age, period and cohort model than by other models. Conclusions Our results suggest that causes for both the overall increased difference in mortality and the short term fluctuations in mortality rates are primarily to be found in the period dimension. Cohort effects on the mortality of the oldest Danish women and men played a significant but minor role compared to period effects