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Background A growing body of evidence has linked vitamin D deficiency to increased risk of cardiovascular disease. Vitamin D deficiency is also more common in African Americans for whom an increased cardiovascular disease risk exists. This study sought to test the hypothesis that 16 weeks of 60,000 IU monthly supplementation of oral vitamin D3 would improve flow-mediated dilation (FMD) in African Americans, whereas no change would be observed in the placebo group. Methods A randomized, double-blind, placebo-controlled clinical trial was conducted. Fifty-seven African-American adults were randomly assigned to either the placebo group or vitamin D group. Results Following 16 weeks of placebo (n = 23; mean age 31 α 2 years) or 60,000 IU monthly oral vitamin D3 (n = 22; mean age 29 α 2 years), serum concentrations of 25-hydroxyvitamin D (25(OH) D) increased from 38.2 α 3.0 to 48.7 α 3.2 nmol/l and 34.3 α 2.2 to 100.9 α 6.6 nmol/l, respectively. No changes in serum parathyroid hormone (PTH), serum calcium, or urine calcium/creatinine were observed following either treatment. Following 16 weeks of treatment, significant improvements in FMD were only observed in the vitamin D group (1.8 α 1.3%), whereas the placebo group had no change (−1.3 α 0.6%). Similarly, the vitamin D group exhibited an increase in absolute change in diameter (0.005 α 0.004 cm) and FMD/ shear (0.08 α 0.04 %/s−1, area under the curve (AUC) × 103) following treatment, whereas no change (−0.005 α 0.002 cm and −0.02 α 0.02 %/s−1, AUC, respectively) was observed following placebo. Conclusion Supplementation of 60,000 IU monthly oral vitamin D3 (~2,000 IU/ day) for 16 weeks is effective at improving vascular endothelial function in African-American adults. American Journal of Hypertension, advance online publication 10 February 2011; doi:10.1038/ajh.2011.12

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in older children. Pulmonary and extra-pulmonary symptoms associated with M. pneumoniae infection are reported. M. pneumoniae is mainly epidemic in Denmark with the recurrence every 4-7th year. Retrospectively, to describe the epidemiology and clinical features, in infants and children, during the M. pneumoniae epidemic in 2010 and 2011. All children under the age of 16 that were tested for M. pneumoniae during the period 01.02.2010-31.01.2012 were included. Medical charts, as well as radiological findings, were reviewed for all children with M. pneumoniae. A post-hoc analysis of viral co-infections was done on part of the cohort. 134 of 746 children were tested positive for M. pneumoniae by PCR or serology. Positive tests were found in 65% of children seven years and older, in 30% of 2-6-year-olds and 4% of infants (less than two years of age). Viral co-infection was found in 27% of the tested samples. The clinical presentation was a cough, asthma-like symptoms and low-grade fever. Extra-pulmonary symptoms were common and presented as nausea/vomiting by 33% of the children and skin manifestations by 25%. 84% of the children had a chest x-ray taken, and there were positive radiological findings in 94% of these. M. pneumoniae also affected infants and young children and symptoms were similar to infections with respiratory viruses, but severe LRTI were also seen. During an up-coming epidemic, assessment of extra-pulmonary manifestations can be helpful when diagnosing M. pneumoniae infections.

Background Genome-wide association studies found common variants in the fat mass and obesity-associated ( FTO ) gene associated with adiposity in Caucasians and Asians but the association was not confirmed in African populations. Association of FTO variants with insulin resistance and energy intake showed inconsistent results in previous studies. This study aimed to assess the influence of FTO variant rs9939609 on adiposity, insulin resistance, energy intake and physical activity in European - (EA) and African-American (AA) youth. Methods We conducted a cross-sectional study in EA and AA youths. One thousand, nine hundred and seventy-eight youths (48.2% EAs, 47.1% male, mean age 16.5 years) had measures of anthropometry. Percent body fat (%BF) was measured by dual-energy X-ray absorptiometry, visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) by magnetic resonance imaging. Energy intake and physical activity were based on self report from up to 7 24-hour recalls. Physical activity was also measured by accelerometry. Results FTO rs9939609 was significantly associated with body mass index (BMI) ( P = 0.01), weight ( P = 0.03) and waist circumference ( P = 0.04), with per-allele effects of 0.4 kg/m 2 , 1.3 kg and 0.8 cm, respectively. No significant association was found between rs9939609 and %BF, VAT, SAAT or insulin resistance ( P > 0.05), or between rs9939609 and energy intake or vigorous physical activity ( P > 0.05). No significant interactions of rs9939609 with ethnicity, gender, energy intake or physical activity were observed ( P > 0.05). Conclusions The FTO variant rs9939609 is modestly associated with BMI and waist circumference, but not with energy intake or physical activity. Moreover, these effects were similar for EAs and AAs. Improved understanding of the effect of the FTO variant will offer new insights into the etiology of excess adiposity.

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that emerged during the COVID-19 pandemic. Although recognized as an immune-mediated condition, the pathogenesis remains unresolved. Furthermore, the absence of a diagnostic test can lead to delayed immunotherapy. Using state-of-the-art mass-spectrometry proteomics, assisted by artificial intelligence (AI), we aimed to identify a diagnostic signature for MIS-C and to gain insights into disease mechanisms. We identified a highly specific 4-protein diagnostic signature in children with MIS-C. Furthermore, we identified seven clusters that differed between MIS-C and controls, indicating an interplay between apolipoproteins, immune response proteins, coagulation factors, platelet function, and the complement cascade. These intricate protein patterns indicated MIS-C as an immunometabolic condition with global hypercoagulability. Our findings emphasize the potential of AI-assisted proteomics as a powerful and unbiased tool for assessing disease pathogenesis and suggesting avenues for future interventions and impact on pediatric disease trajectories through early diagnosis. Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children.

There is a considerable burden of children being hospitalized due to infectious diseases worldwide. The COVID-19 pandemic provided a unique opportunity to examine effects of worldwide efforts to control spread of infection. We aimed to investigate overall age-specific hospitalizations due to viral and bacterial infections and diseases triggered by respiratory tract infections during and after lockdown. This nationwide register–based observational study included children from 29 days to 17 years old hospitalized in all Danish pediatric emergency departments during the years 2015–2021. Main outcomes were ICD-10 diagnoses for infectious diseases and infection triggered illnesses. Fluctuations in hospitalization events were explored using figures with weekly events per 100,000. Total events followed a predictable pattern during 2015–2019. In 2020–2021, there was a drop in hospital encounters after lockdowns and surge after reopenings. In 2021, there was a surge of hospital encounters in the late summer due to respiratory syncytial virus infections and asthmatic bronchitis mostly in infants from 29 days to 2 years. For the infectious diseases, there was a dramatic decrease in events after lockdowns and immediate increase in cases that followed the same pattern of previous years after reopenings. Bacterial infections, like urinary tract infections, sepsis, and meningitis followed a steady pattern throughout all calendar-years. Conclusions : Nationwide efforts to minimize infectious disease spread like lockdowns have a preventative and period lasting effect but reopenings/reunions result in surges of infectious diseases. This might be due to children not getting immunized steadily thereby increasing the pool of possible hosts for potential viral infections. What is Known: •  There is a seasonal fluctuation in viral/respiratory infections in children with higher infection rates in the winter and lower rates in the  summer. • RSV infection is a major source of concern. What is New: •  Major lockdowns and reopenings disrupt the seasonal fluctuations which can result in high surges  in infections that increases the burden of children emergency departments and the risk of serious complications.

PurposeThe risk of developing asthma-like symptoms and asthma in childhood is influenced by genetics, environmental exposures, prenatal and early postnatal events, and their interactions. The cohort name refers to vitamins A and D, and nitric oxide (NO) spelt backwards and this cohort profile paper aims to present the data collection and aim of the cohort.The overall aim when establishing this cohort was to investigate if childhood lung function can be traced back to early neonatal lung function and fractional exhaled NO (FeNO) and investigate prenatal and postnatal risk factors including maternal and neonatal vitamin A and D levels in preterm and term born children.ParticipantsOne thousand five hundred women and their babies born at Nordsjaellands Hospital in Denmark from 2013 to 2014 were included in the AD-ON research biobank prior to birth.Neonates from the AD-ON research biobank, admitted to the Neonatal Intensive Care Unit at Nordsjaellands Hospital, were included in the AD-ON neonatal cohort. The neonatal cohort consisted of 149 neonates hereof 63 preterm and 86 term born. The children in the cohort have been invited to follow-up visits at age 1 and 6 years.Findings to datePublished data from this cohort includes a validated and clinically applicable method to measure FeNO in neonates. We found an age-specific pattern of association between respiratory symptoms at age 1 and neonatal FeNO in preterm children. Moreover, we found that the respiratory symptoms risk was associated with postnatal factors (Respiratory Syncytial Virus infection and parental smoking) in preterm infants and prenatal factors (parental asthma and maternal infection during pregnancy) in term born infants.Future plansIn the future, the children will be examined continuously with 3-year to 5-year intervals until the age of 18. Lung function, allergy tests, environmental exposure measurements and questionnaires will be collected at each follow-up visit.

Hierarchical galaxy formation is the model whereby massive galaxies form from an assembly of smaller units 1 . The most massive objects therefore form last. The model succeeds in describing the clustering of galaxies 2 , but the evolutionary history of massive galaxies, as revealed by their visible stars and gas, is not accurately predicted. Near-infrared observations (which allow us to measure the stellar masses of high-redshift galaxies 3 ) and deep multi-colour images indicate that a large fraction of the stars in massive galaxies form in the first 5 Gyr (refs 4–7 ), but uncertainties remain owing to the lack of spectra to confirm the redshifts (which are estimated from the colours) and the role of obscuration by dust. Here we report the results of a spectroscopic redshift survey that probes the most massive and quiescent galaxies back to an era only 3 Gyr after the Big Bang. We find that at least two-thirds of massive galaxies have appeared since this era, but also that a significant fraction of them are already in place in the early Universe.

Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.

Developing acceptable medicines for children is a complicated task. Several factors must be considered, including age, physiology, texture preference, formulation, and legal framework among others. In the development of new paediatric medicines, these factors are assessed. However, for older medicines, e.g., prednisolone, acceptability is still a challenge. This study was an open-label randomised three-arm cross-over study investigating different formulations of prednisolone (crushed tablets, whole tablets, and oral solution) in paediatric patients with asthma and asthma-like symptoms. Participants were randomised into two different formulations on two consecutive days. For each formulation, the child or caregiver was asked to evaluate acceptability using a modified five-point Wong Baker Face scale. An analysis of variance (ANOVA) model was used to test for significance. For the 41 children, included mean age was 4.7 years (SD ± 3.6), and mean weight was 21 kg (SD ± 10.8). Sixty-one percent were boys. The participants were divided accordingly into three age groups: 6 to 23 months (N = 11), 2 to 5 years (N = 14), and 6–11 years (N = 16). The overall acceptability was low, with only 23 out of 71 scores rating the treatment either 1 or 2 (32%). The ANOVA test showed a significant difference in acceptability score between crushed tablets and whole tablets (p < 0.003). The mean acceptability score for the crushed tablet was the least favourable at 3.9 compared to oral solution (3.1), oro-dispersible tablet (2.8), and whole tablets (2.4). This is problematic in long-term treatment and for the youngest children who cannot swallow tablets. The improvement of age-appropriate and acceptable formulations is necessary.

Because the development of healthy bodies during the years of growth has life-long health consequences, it is important to understand the early influences of diet and physical activity (PA). One way to generate hypotheses concerning such influences is to conduct cross-sectional studies of how diet and PA are related to different components of body composition. The subjects were 660 black and white adolescents. Total body bone mineral content (BMC) was measured with dual-energy X-ray absorptiometry; free-living diet and PA were assessed with 4-7 separate 24-h recalls. The main dietary variables investigated were: total energy intake, macronutrient distribution (%), dairy servings, vitamin D, and calcium. The main PA variables were hours of moderate PA (3-6 METs) and vigorous PA (>6 METs). BMC was higher in blacks than in whites (P<0.01) and it increased more in boys than in girls (age by sex interaction) as age increased (P<0.01). After adjustment for age, race and sex, higher levels of BMC were associated with higher levels of energy intake, dairy servings, calcium, vitamin D, and vigorous PA (all P 's<0.05). In the multivariable model, significant and independent proportions of the variance in BMC were explained by race, the age by sex interaction, calcium, and vigorous PA (all P 's<0.01). When height was used as the outcome variable, similar diet results were obtained; however, there was a sex by vigorous PA interaction, such that vigorous PA was associated with height only in the girls. These data are consistent with the hypothesis that the bone mass and height of growing youths are positively influenced by higher dietary intake of energy and dairy foods, along with sufficient amounts of vigorous PA. This hypothesis needs to be tested in randomized controlled trials.