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Contains fulltext : 246727.pdf (Publisher’s version ) (Open Access) Background: This study assessed the course of fear of cancer recurrence (FCR) in patients newly diagnosed with head and neck cancer (HNC), identified FCR trajectories and factors associated with FCR trajectories. Methods: Six hundred and seventeen HNC patients from the NET-QUBIC cohort study completed the Cancer Worry Scale-6 at diagnosis, 3 and 6 months post-treatment. FCR trajectories were identified using Latent Class Growth Analysis. Associations were explored between FCR trajectories and baseline demographic and medical variables, coping and self-efficacy. Results: Overall, FCR decreased slightly between baseline and 3 months post-treatment and remained stable up to 6 months. Two FCR trajectories were identified: "high stable" (n = 125) and "low declining" (n = 492). Patients with high stable FCR were younger, reported more negative adjustment, passive coping, and reassuring thoughts, and less avoidance. Conclusions: The majority of HNC patients have low declining FCR after diagnosis, but one in five patients experience persistent high FCR up to 6 months post-treatment. 12 p.

© 2022 European Sleep Research Society.Studies describing paediatric sleep patterns are needed by taking culture into consideration. The aim of this study was to identify parent-reported sleep–wake patterns in young children and explore possible factors influencing sleep problems. The mothers of 2,434 young children enrolled from well-child outpatient clinics in Turkey completed an online survey including sociodemographic variables, Brief Infant Sleep Questionnaire, Edinburgh Postnatal Depression Scale and Generalised Anxiety Disorder scales. Overall, young children in Turkey go to bed late (10:00 p.m.), awaken twice per night for 30 min, and obtain 11.5 h of total sleep, showing no sex-specific differences. Distinct night-time sleep patterns emerged after 18 months of age. Importantly, although currently breastfed healthy children were 3.8-times less likely to sleep through the night, total sleep duration and exclusive breastfeeding duration were higher in children who were not sleeping through the night. Overall, bedsharing was identified in 11.5%, and only room sharing was reported in 52.9%. Parental perception of a child's sleep as problematic was 35.8%. Mothers with higher educational attainment were more likely to perceive their children's sleep as a problem. Maternal depressive and anxious symptoms and a history of excessive infant crying were the determinants predicting the likelihood of both parent-perceived sleep problems and poor sleepers. The present analysis of sleep structure in infancy and toddlerhood provides reference data for well-child visits. These findings highlight the importance of considering maternal anxiety, depression and behaviour management techniques to cope with fussy infants in addressing childhood behavioural sleep problems.

Background and Aims Crohn’s disease [CD] is characterised by a heterogeneous disease course. Patient stratification at diagnosis using clinical, serological, or genetic markers does not predict disease course sufficiently to facilitate clinical decision making. The current study aimed to investigate the additive predictive value of histopathological features to discriminate between a long-term mild and severe disease course. Methods Diagnostic biopsies from treatment-naïve CD patients with mild or severe disease courses in the first 10 years after diagnosis were reviewed by two gastrointestinal pathologists after developing a standardised form comprising 15 histopathological features. Multivariable logistic regression models were built to identify predictive features and compute receiver operating characteristic [ROC] curves. Models were internally validated using bootstrapping to obtain optimism-corrected performance estimates. Results In total, 817 biopsies from 137 patients [64 mild, 73 severe cases] were included. Using clinical baseline characteristics, disease course could only moderately be predicted (area under receiver operating characteristic curve [AUROC]: 0.738 [optimism 0.018], 95% confidence interval [CI] 0.65–0.83, sensitivity 83.6%, specificity 53.1%). When adding histopathological features, in colonic biopsies a combination of [1] basal plasmacytosis, [2] severe lymphocyte infiltration in lamina propria, [3] Paneth cell metaplasia, and [4] absence of ulcers were identified and resulted in significantly better prediction of a severe course (AUROC: 0.883 [optimism 0.033], 95% CI 0.82–0.94, sensitivity 80.4%, specificity 84.2%). Conclusions In this first study investigating the additive predictive value of histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improving stratification and facilitating clinical decision making.

© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.We evaluated the demographic features, etiologic risk factors, treatment strategies, and outcome of the infants and children with urolithiasis (UL). A retrospective multicenter study was conducted including 23 Pediatric Nephrology centers in Turkey. The medical records of 2513 children with UL were reviewed. One thousand, three hundred and four boys and 1209 girls (1.1:1) were reported. The mean age at diagnosis was 39.5 ± 35 months (0.4–231 months), and 1262 patients (50.2%) were in the first year of life (infants). Most of the cases with infantile UL were diagnosed incidentally. Microlithiasis (< 3 mm) was found in 794 patients (31.6%), and 64.5% of the patients with microlithiasis were infants. Stones were located in the pelvis-calyces in 63.2% (n: 1530) of the cases. The most common stone type was calcium oxalate (64.6%). Hypocitraturia was the most common metabolic risk factor (MRF) in children older than 12 months, but in infancy, hypercalciuria was more common. Fifty-five percent of the patients had received at least one medical treatment, mostly potassium citrate. At the end of a year’s follow-up, most of the patients with microlithiasis (85%) showed spontaneous remission. The rate of spontaneous stone resolution in infants was higher than in children. Spontaneous remission rate was higher in cases with MRF (− ) stones than in MRF (+) stones. However, remission rate with medical treatment was higher in cases with MRF (+) stones. This study represents the results of a large series of infants and children with UL and showed that there are several differences such as underlying metabolic and anatomic abnormalities, clinical course, and stone remission rates between infants and children with urinary stone disease.

Age and gender differences are prominent in the temperament literature, with the former particularly salient in infancy and the latter noted as early as the first year of life. This study represents a meta-analysis utilizing Infant Behavior Questionnaire-Revised (IBQ-R) data collected across multiple laboratories (N = 4438) to overcome limitations of smaller samples in elucidating links among temperament, age, and gender in early childhood. Algorithmic modeling techniques were leveraged to discern the extent to which the 14 IBQ-R subscale scores accurately classified participating children as boys (n = 2,298) and girls (n = 2,093), and into three age groups: youngest (< 24 weeks; n = 1,102), mid-range (24 to 48 weeks; n = 2,557), and oldest (> 48 weeks; n = 779). Additionally, simultaneous classification into age and gender categories was performed, providing an opportunity to consider the extent to which gender differences in temperament are informed by infant age. Results indicated that overall age group classification was more accurate than child gender models, suggesting that age-related changes are more salient than gender differences in early childhood with respect to temperament attributes. However, gender-based classification was superior in the oldest age group, suggesting temperament differences between boys and girls are accentuated with development. Fear emerged as the subscale contributing to accurate classifications most notably overall. This study leads infancy research and meta-analytic investigations more broadly in a new direction as a methodological demonstration, and also provides most optimal comparative data for the IBQ-R based on the largest and most representative dataset to date. National Institutes of Health [R01HL095606, R01HD082078, NIH R01 MH109692, R21 MH103627, R01 HD049878, R03 HD043057, 1P50 MH58922-01A1, 1P50 MH077928-01A1, 5R01HD080851-05, R01MH78033, 8P0GM103436, P20GM103436, 8P20GM103436, DK72996, M01RR10732]; Western Washington University [MFS 901, MFS 907] Published version MBE: R01HL095606, R01HD082078; National Institutes of Health https://www.nih.gov KPE, KB, & VL: NIH R01 MH109692; R21 MH103627 National Institutes of Health https://www.nih.gov MAB: R01 HD049878; R03 HD043057 National Institutes of Health https://www.nih.gov SG: 1P50 MH58922-01A1; 1P50 MH077928-01A1 National Institutes of Health https://www.nih.gov SS: 5R01HD080851-05 National Institutes of Health https://www.nih.gov AS: R01MH78033 National Institutes of Health https://www.nih.gov DL: 8P0GM103436; P20GM103436; 8P20GM103436 National Institutes of Health https://www.nih.gov TDRS: MFS 901; MFS 907 Western Washington University https://www.wwu.edu SAF: DK72996; M01RR10732 National Institutes of Health https://www.nih.gov None of the funders had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Human milk (HM) is the gold standard for the nutrition of infants. An important component of HM is human milk oligosaccharides (hMOs), which play an important role in gut microbiota colonization and gut immune barrier establishment, and thereby contribute to the maturation of the immune system in early life. Guiding these processes is important as disturbances have life-long health effects and can lead to the development of allergic diseases. Unfortunately, not all infants can be exclusively fed with HM. These infants are routinely fed with infant formulas that contain hMO analogs and other non-digestible carbohydrates (NDCs) to mimic the effects of hMOs. Currently, the hMO analogs 2'-fucosyllactose (2'-FL), galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS), and pectins are added to infant formulas; however, these NDCs cannot mimic all hMO functions and therefore new NDCs and NDC mixtures need to become available for specific groups of neonates like preterm and disease-prone neonates. In this review, we discuss human data on the beneficial effects of infant formula supplements such as the specific hMO analog 2'-FL and NDCs as well as their mechanism of effects like stimulation of microbiota development, maturation of different parts of the gut immune barrier and anti-pathogenic effects. Insights into the structure-specific mechanisms by which hMOs and NDCs exert their beneficial functions might contribute to the development of new tailored NDCs and NDC mixtures. We also describe the needs for new in vitro systems that can be used for research on hMOs and NDCs. The current data suggest that "tailored infant formulas" for infants of different ages and healthy statuses are needed to ensure a healthy development of the microbiota and the gut immune system of infants.

BACKGROUND & AIMS: Establishment of the gastrointestinal microbiota during infancy affects immune system development and oral tolerance induction. Perturbations in the microbiome during this period can contribute to development of immune-mediated diseases. We monitored microbiota maturation and associations with subsequent development of allergies in infants and children. METHODS: We collected 1453 stool samples, at 5, 13, 21, and 31weeks postpartum (infants), and once at school age (6-11 years), from 440 children (49.3% girls, 24.8% born by cesarean delivery; all children except for 6 were breastfed for varying durations; median 40 weeks; interquartile range, 30-53 weeks). Microbiota were analyzed by amplicon sequencing. Children were followed through 3 years of age for development of atopic dermatitis; data on allergic sensitization and asthma were collected when children were school age. RESULTS: Diversity of fecal microbiota, assessed by Shannon index, did not differ significantly among children from 5 through 13 weeks after birth, but thereafter gradually increased to 21 and 31 weeks. Most bacteria within the Bacteroidetes and Proteobacteria phyla were already present at 5 weeks after birth, whereas many bacteria of the Firmicutes phylum were acquired at later times in infancy. At school age, many new Actinobacteria, Firmicutes, and Bacteroidetes bacterial taxa emerged. The largest increase in microbial diversity occurred after 31 weeks. Vaginal, compared with cesarean delivery, was most strongly associated with an enrichment of Bacteroides species at 5 weeks through 31 weeks. From 13 weeks onward, diet became the most important determinant of microbiota composition; cessation of breast-feeding, rather than solid food introduction, was associated with changes. For example, Bifidobacteria, staphylococci, and streptococci significantly decreased on cessation of breastfeeding, whereas bacteria within the Lachnospiraceae family (Pseudobutyrivibrio, Lachnobacterium, Roseburia, and Blautia) increased. When we adjusted for confounding factors, we found fecal microbiota composition to be associated with development of atopic dermatitis, allergic sensitization, and asthma. Members of the Lachnospiraceae family, as well as the genera Faecalibacterium and Dialister, were associated with a reduced risk of atopy. CONCLUSIONS: In a longitudinal study of fecal microbiota of children from 5 weeks through 6 to 11 years, we tracked changes in diversity and composition associated with the development of allergies and asthma.

BACKGROUND AND OBJECTIVE: The purpose of this study is to determine whether patients, classified by their treating consultant in rehabilitation medicine as avoider or persister, show differences in a large set of detailed outcomes of actual, objectively measured daily physical behaviour.METHODS: In this explorative cross-sectional study, 16 patients were included; 9 patients were categorized as avoider and 7 patients as persister. Subjects wore the VitaMove activity monitor, a high-end accelerometry-based device that allowed automatic detection of a large set of body postures and motions. Physical behaviour was assessed in detail by total duration of body postures and motions as percentages of 24 hours, as well as by the number of sit-to-stand transfers, overall activity level, walking speed, and the distribution of bouts of physical activity and sedentary behaviour. Differences between groups were tested with the Mann Whitney U test.RESULTS: There were no significant differences between groups in any of the physical behaviour outcomes.CONCLUSIONS: Our study showed that activity-related behavioural style categorization by consultants in rehabilitation medicine is not expressed in objectively measured detailed outcomes of daily physical behaviour.

We studied the effect of duration of breastfeeding and history of prematurity on the duration of hospitalization in infants with lower respiratory tract infections (LRTI) because these may reflect the severity of illness as well as sizable direct and indirect healthcare costs. One hundred twenty-five patients (49 girls, 76 boys; aged 1-24 months) were hospitalized for LRTI during a period of 102 days and studied prospectively. We found a significant difference ( P = .045) between the durations of hospitalization of the 92 patients breastfed for at least six months, compared to the other group of 33 patients who were breastfed for less than six months. The durations of hospitalization among the groups with and without a history of prematurity were not statistically different ( P = .78). A history of breastfeeding for more than six months had significant effect on the duration of hospitalization, but this was not true for children with a history of preterm birth.

Background and aimsBirth mode and other early life factors affect a newborn's microbial colonization with potential long-term health effects. Individual variations in early life gut microbiota development, especially their effects on the functional repertoire of microbiota, are still poorly characterized. This study aims to provide new insights into the gut microbiome developmental trajectories during the first year of life.MethodsOur study comprised 78 term infants sampled at 3 weeks, 3 months, 6 months, and 12 months (n = 280 total samples), and their mothers were sampled in late pregnancy (n = 50). Fecal DNA was subjected to shotgun metagenomic sequencing. Infant samples were studied for taxonomic and functional maturation, and maternal microbiota was used as a reference. Hierarchical clustering on taxonomic profiles was used to identify the main microbiota developmental trajectories in the infants, and their associations with perinatal and postnatal factors were assessed.ResultsIn line with previous studies, infant microbiota composition showed increased alpha diversity and decreased beta diversity by age, converging toward an adult-like profile. However, we did not observe an increase in functional alpha diversity, which was stable and comparable with the mother samples throughout all the sampling points. Using a de novo clustering approach, two main infant microbiota clusters driven by Bacteroidaceae and Clostridiaceae emerged at each time point. The clusters were associated with birth mode and their functions differed mainly in terms of biosynthetic and carbohydrate degradation pathways, some of which consistently differed between the clusters for all the time points. The longitudinal analysis indicated three main microbiota developmental trajectories, with the majority of the infants retaining their characteristic cluster until 1 year. As many as 40% of vaginally delivered infants were grouped with infants delivered by C-section due to their clear and persistent depletion in Bacteroides. Intrapartum antibiotics, any perinatal or postnatal factors, maternal microbiota composition, or other maternal factors did not explain the depletion in Bacteroides in the subset of vaginally born infants.ConclusionOur study provides an enhanced understanding of the compositional and functional early life gut microbiota trajectories, opening avenues for investigating elusive causes that influence non-typical microbiota development.

Objectives Research on typically developing (TD) children and those with neurodevelopmental disorders and genetic syndromes was targeted. Specifically, studies on autism spectrum disorder, Down syndrome, Rett syndrome, fragile X syndrome, cerebral palsy, Angelman syndrome, tuberous sclerosis complex, Williams-Beuren syndrome, Cri-du-chat syndrome, Prader-Willi syndrome, and West syndrome were searched. The objectives are to review observational and computational studies on the emergence of (pre-)babbling vocalisations and outline findings on acoustic characteristics of early verbal functions. Methods A comprehensive review of the literature was performed including observational and computational studies focusing on spontaneous infant vocalisations at the pre-babbling age of TD children, individuals with genetic or neurodevelopmental disorders. Results While there is substantial knowledge about early vocal development in TD infants, the pre-babbling phase in infants with neurodevelopmental and genetic syndromes is scarcely scrutinised. Related approaches, paradigms, and definitions vary substantially and insights into the onset and characteristics of early verbal functions in most above-mentioned disorders are missing. Most studies focused on acoustic low-level descriptors (e.g. fundamental frequency) which bore limited clinical relevance. This calls for computational approaches to analyse features of infant typical and atypical verbal development. Conclusions Pre-babbling vocalisations as precursor for future speech-language functions may reveal valuable signs for identifying infants at risk for atypical development. Observational studies should be complemented by computational approaches to enable in-depth understanding of the developing speech-language functions. By disentangling features of typical and atypical early verbal development, computational approaches may support clinical screening and evaluation.

We present a spectroscopic analysis of the most nearby Type I superluminous supernova (SLSN-I), SN 2018bsz. The photometric evolution of SN 2018bsz has several surprising features, including an unusual pre-peak plateau and evidence for rapid formation of dust greater than or similar to 200 d post-peak. We show here that the spectroscopic and polarimetric properties of SN 2018bsz are also unique. While its spectroscopic evolution closely resembles SLSNe-I, with early O II absorption and C II P Cygni profiles followed by Ca, Mg, Fe, and other O features, a multi-component H alpha profile appearing at similar to 30 d post-maximum is the most atypical. The H alpha is at first characterised by two emission components, one at similar to+3000 km s(-1) and a second at similar to - 7500 km s(-1), with a third, near-zero-velocity component appearing after a delay. The blue and central components can be described by Gaussian profiles of intermediate width (FWHM similar to 2000-6000 km s(-1)), but the red component is significantly broader (FWHM greater than or similar to 10000 km s(-1)) and Lorentzian. The blue H alpha component evolves towards a lower-velocity offset before abruptly fading at similar to + 100 d post-maximum brightness, concurrently with a light curve break. Multi-component profiles are observed in other hydrogen lines, including Pa beta, and in lines of Ca II and He I. Spectropolarimetry obtained before (10.2 d) and after (38.4 d) the appearance of the H lines shows a large shift on the Stokes Q - U plane consistent with SN 2018bsz undergoing radical changes in its projected geometry. Assuming the supernova is almost unpolarised at 10.2 d, the continuum polarisation at 38.4 d reaches P similar to 1.8%, implying an aspherical configuration. We propose that the observed evolution of SN 2018bsz can be explained by highly aspherical, possibly disk-like, circumstellar material (CSM) with several emitting regions. After the supernova explosion, the CSM is quickly overtaken by the ejecta, but as the photosphere starts to recede, the different CSM regions re-emerge, producing the peculiar line profiles. Based on the first appearance of H alpha, we can constrain the distance of the CSM to be less than similar to 6.5 x 10(15) cm (430 AU), or even lower (less than or similar to 87 AU) if the pre-peak plateau is related to an eruption that created the CSM. The presence of CSM has been inferred previously for other SLSNe-I, both directly and indirectly. However, it is not clear whether the rare properties of SN 2018bsz can be generalised for SLSNe-I, for example in the context of pulsational pair instability, or whether they are the result of an uncommon evolutionary path, possibly involving a binary companion., European Organisation for Astronomical Research in the Southern Hemisphere under ESO programme 2101.D-5023, Villum Fonden 19054, Science Foundation Ireland, European Commission, Royal Society of London, European Commission RS-EA/3471, Swedish Research Council, European Commission 2020-03330, National Agency for Research and Development (ANID)/Scholarship Program/Doctorado Nacional 2021 - 21211203, European Commission H2020-MSCA-IF-2018-842471, Ministry of Science and Innovation, Spain (MICINN), Agencia Estatal de Investigacion (AEI), European Social Fund (ESF) "Investing in your future" under the 2019 Ramon y Cajal program RYC2019-027683-I, Centro Superior de Investigaciones Cientificas (CSIC) 20215AT016, program Unidad de Excelencia Maria de Maeztu CEX2020-001058-M, EU Horizon 2020 research and innovation programme 101004719, European Research Council (ERC), European Commission 948381, Alan Turing Institute, GRAWITA/PRIN-MIUR project: "The new frontier of the Multi-Messenger Astrophysics: follow-up of electromagnetic transient counterparts of gravitational wave sources", HORIZON2020: AHEAD2020 871158 1103.D-0328 PID2020-115253GA-I00 HOSTFLOWS Swedish Research Council, European Research Council (ERC) European Commission 948381, HORIZON2020: AHEAD2020 871158 1103.D-0328 PID2020-115253GA-I00 HOSTFLOWS

A mixed-method study was undertaken to investigate factors affecting the transition to university of life sciences students at a research-intensive UK university. Questionnaire responses (N= 234) suggested that undergraduate students tended to agree that they had successfully transitioned to university level study in the first year. However, disproportionately more female students had a definite negative view of their success and this correlated with the lower first-year performance of female BSc Biological Sciences students. Focus groups with second-year female BSc Biological Sciences students revealed that they viewed transition as a period of great academic and social change. Through the lens of a transition model developed from Bean and Eaton’s model of student retention, it was seen that both academic and social self-efficacy were important in facilitating transition, and were greatly aided by academic and social relationships with peers and academics. The timing of self-reported successful transition varied between students, with some students not transitioning academically and/or socially until the second year. Recommendations are that student academic self-efficacy should be promoted through helping students gain the necessary academic toolkit. Tutorials, peer-led sessions together with more social events could increase social self-efficacy and warrants further research.

Aim Infections in early childhood are common reasons to seek medical attention. This study compares the prevalence of infections, and the use of antibiotics and antipyretic-analgesics, in children from Finland, Estonia and Russian Karelia. Methods Children with a genetically increased risk for type 1 diabetes (N = 797) were observed from birth up to 3 years of age. Illnesses and medications were reported by parents continuously. All reported infections, antibiotics and antipyretic-analgesics were compared between Finland and Estonia, and to a lesser extent with Russian Karelia, due to poor study compliance. Results Compared with Estonians, Finns reported more infections during the first and second years of life. During the follow-up, Finnish children had 10 infections while Estonians only had 8 (p

This paper examined the association between friendship and academic networks and how the connections these networks have with academic performance and school misconduct differ when comparing three types of classrooms where students were grouped based on their academic ability (i.e., high-, low-, and mixed-ability). The sample was composed of 528 seventh to ninth graders (Mage = 15; 64.1% girls) from 12 classrooms (four in each category of ability grouping) across two waves in five schools in Chile. The effects of academic performance and school misconduct on receiving academic and friendship nominations were examined, as well as the interplay between academic and friendship relationships. Furthermore, the extent to which similarity in adolescents' academic performance and school misconduct contributed to the formation and maintenance of academic and friendship relationships was examined. Sex, socioeconomic status, and structural network features were also taken into account. Longitudinal social network analyses (RSiena) indicated that (1) in high-ability classrooms students chose high-achieving peers as academic partners; (2) in high-ability classrooms students avoided deviant peers (i.e., those high in school misconduct) as academic partners; and (3) academic relationships led to friendships, and vice versa, in both high- and low-ability classrooms. Whereas the interplay of friendship and academic relationships was similar in high- and low-ability classrooms, the formation and maintenance of academic networks unfolded differently in these two types of classrooms.

Background Little is known about changes in blood fatty acid compositions over time and the correlates of any changes in a general population. Objective The aim of this study was to estimate changes in 27 individual plasma phospholipid fatty acids and fatty acid groups over time, and to identify potential correlates of these changes. Methods Plasma phospholipid fatty acids were profiled at 3 time-points (1993–1997, 1998–2000, 2004–2011) among 722 participants in the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, UK. Linear regression models were used to estimate both 1) mean changes over time in 27 individual fatty acids and 8 prespecified fatty acid groups and 2) associations of changes in dietary and lifestyle factors with changes in the 8 fatty acid groups, mutually adjusted for dietary/lifestyle factors and other confounders. The prespecified fatty acid groups were odd-chain saturated fatty acids (SFAs), even-chain SFAs, very-long-chain SFAs, marine n–3 polyunsaturated fatty acids (PUFAs), plant n–3 PUFA, n–6 PUFAs, monounsaturated fatty acids (MUFAs), and trans-fatty acids (TFAs). Results Adjusted for confounders, fatty acid concentrations decreased for odd-chain SFAs (annual percentage difference in mol percentage: −0.63%), even-chain SFAs (−0.05%), n–6 PUFAs (−0.25%), and TFAs (−7.84%). In contrast, concentrations increased for marine n–3 PUFAs (1.28%) and MUFAs (0.45%), but there were no changes in very-long-chain SFAs or plant n–3 PUFA. Changes in fatty acid levels were associated with consumption of different food groups. For example, a mean 100 g/d increase in fatty fish intake was associated with a 19.3% greater annual increase in marine n–3 PUFAs. Conclusions Even-chain SFAs and TFAs declined and marine n–3 PUFAs increased over time. These changes were partially explained by changes in dietary habits, and could potentially help interpret associations of baseline fatty acid composition with future disease risk.

Environmental change and increasing levels of human activity are threats to marine mammals in the Arctic. Identifying marine mammal hotspots and areas of high species richness are essential to help guide management and conservation efforts. Herein, space use based on biotelemetric tracking devices deployed on 13 species (ringed seal Pusa hispida, bearded seal Erignathus barbatus, harbour seal Phoca vitulina, walrus Odobenus rosmarus, harp seal Pagophilus groenlandicus, hooded seal Cystophora cristata, polar bear Ursus maritimus, bowhead whale Balaena mysticetus, narwhal Monodon monoceros, white whale Delphinapterus leucas, blue whale Balaenoptera musculus, fin whale Balaenoptera physalus and humpback whale Megaptera novaeangliae; total = 585 individuals) in the Greenland and northern Barents Seas between 2005 and 2018 is reported. Getis-Ord Gi* hotspots were calculated for each species as well as all species combined, and areas of high species richness were identified for summer/autumn (Jun-Dec), winter/spring (Jan-May) and the entire year. The marginal ice zone (MIZ) of the Greenland Sea and northern Barents Sea, the waters surrounding the Svalbard Archipelago and a few Northeast Greenland coastal sites were identified as key marine mammal hotspots and areas of high species richness in this region. Individual hotspots identified areas important for most of the tagged animals, such as common resting, nursing, moulting and foraging areas. Location hotspots identified areas heavily used by segments of the tagged populations, including denning areas for polar bears and foraging areas. The hotspots identified herein are also important habitats for seabirds and fishes, and thus conservation and management measures targeting these regions would benefit multiple groups of Arctic animals.

Background Head and neck cancer (HNC) patients often suffer from distress attributed to their cancer diagnosis which may disturb their sleep. However, there is lack of research about poor sleep quality among newly diagnosed HNC patients. Therefore, our aim was to investigate the prevalence and the associated factors of poor sleep quality among HNC patients before starting treatment. Materials and methods A cross-sectional study was conducted using the baseline data from NET-QUBIC study, an ongoing multi-center cohort of HNC patients in the Netherlands. Poor sleep quality was defined as a Pittsburgh Sleep Quality Index (PSQI) total score of > 5. Risk factors examined were sociodemographic factors (age, sex, education level, living situation), clinical characteristics (HNC subsite, tumor stage, comorbidity, performance status), lifestyle factors, coping styles, and HNC symptoms. Results Among 560 HNC patients, 246 (44%) had poor sleep quality before start of treatment. Several factors were found to be significantly associated with poor sleep: younger age (odds ratio [OR] for each additional year 0.98, 95% CI 0.96–1.00), being female (OR 2.6, 95% CI 1.7–4.1), higher passive coping style (OR 1.18, 95% CI 1.09–1.28), more oral pain (OR 1.10, 95% CI 1.01–1.19), and less sexual interest and enjoyment (OR 1.13, 95% CI 1.06–1.20). Conclusion Poor sleep quality is highly prevalent among HNC patients before start of treatment. Early evaluation and tailored intervention to improve sleep quality are necessary to prepare these patients for HNC treatment and its consequences.

ObjectiveThe first year response to growth hormone (GH) treatment is related to the total height gain in GH treated children, but an individual poor first year response is a weak predictor of a poor total GH effect in GH deficient (GHD) children. We investigated whether an underwhelming growth response after 2 years might be a better predictor of poor adult height (AH) outcome after GH treatment in GHD children.Design and methodsHeight data of GHD children treated with GH for at least 4 consecutive years of which at least two prepubertal and who attained (near) (n)AH were retrieved from the Belgian Register for GH treated children (n = 110, 63% boys). In ROC analyses, the change in height (ΔHt) SDS after the first and second GH treatment years were tested as predictors of poor AH outcome defined as: (1) nAH SDS ResultsEleven percent of the cohort had a total ΔHt SDS 70%. First-year ΔHt SDS ConclusionIn GHD children the growth response after 2 prepubertal years of GH treatment did not meaningfully improve the prediction of poor AH outcome after GH treatment compared to first-year growth response parameters. Therefore, the decision to re-evaluate the diagnosis or adapt the GH dose in case of poor response after 1 year should not be postponed for another year.

Human milk (HM) is the gold standard for the nutrition of infants. An important component of HM is human milk oligosaccharides (hMOs), which play an important role in gut microbiota colonization and gut immune barrier establishment, and thereby contribute to the maturation of the immune system in early life. Guiding these processes is important as disturbances have life-long health effects and can lead to the development of allergic diseases. Unfortunately, not all infants can be exclusively fed with HM. These infants are routinely fed with infant formulas that contain hMO analogs and other non-digestible carbohydrates (NDCs) to mimic the effects of hMOs. Currently, the hMO analogs 2'-fucosyllactose (2'-FL), galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS), and pectins are added to infant formulas; however, these NDCs cannot mimic all hMO functions and therefore new NDCs and NDC mixtures need to become available for specific groups of neonates like preterm and disease-prone neonates. In this review, we discuss human data on the beneficial effects of infant formula supplements such as the specific hMO analog 2'-FL and NDCs as well as their mechanism of effects like stimulation of microbiota development, maturation of different parts of the gut immune barrier and anti-pathogenic effects. Insights into the structure-specific mechanisms by which hMOs and NDCs exert their beneficial functions might contribute to the development of new tailored NDCs and NDC mixtures. We also describe the needs for new in vitro systems that can be used for research on hMOs and NDCs. The current data suggest that "tailored infant formulas" for infants of different ages and healthy statuses are needed to ensure a healthy development of the microbiota and the gut immune system of infants.

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (? 3 months; VEBNE) and early (4–15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ? 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort. © 2020, The Author(s)., Marga und Walter Boll-Stiftung Universität zu Köln, UoC Bundesministerium für Bildung und Forschung, BMBF: 01GM1903, 01GM1515 PKD Foundation, PKDF European Paediatric Neurology Society, EPNS, We thank the German Society for Pediatric Nephrology (GPN) and the ESCAPE Network for their support. ML was supported by grants of the GPN, the European Society for Paediatric Nephrology (ESPN), the German PKD foundation, the Koeln Fortune program, the GEROK program of the Medical Faculty of University of Cologne, and the Marga and Walter Boll-Foundation. FS and ML are supported by the the German Federal Ministry of Research and Education (BMBF grant 01GM1515 and 01GM1903). KB was supported by the Koeln Fortune program of the Medical Faculty of University of Cologne and the Marga and Walter Boll-Foundation. This work was generated within the European Reference Network for Rare Kidney Disorders (ERKNet). Open Access funding provided by Projekt DEAL.

Background Human rhinoviruses (HRVs), human enteroviruses (HEVs) and human parechoviruses (HPeVs) have been linked to acute otitis media (AOM). We evaluated this association in a prospective birth cohort setting. Methods A total of 324 healthy infants were followed up from birth to age 3 years. Nasal swab samples were collected at age 3, 6, 12, 18, 24, and 36 months and screened for HRV and HEV using real-time reverse-transcription quantitative polymerase chain reaction. Stool samples were collected monthly and analyzed for HRV, HEV, and HPeV. AOM episodes diagnosed by physicians were reported by parents in a diary. The association of viruses with AOM was analyzed using generalized estimation equations, and their relative contributions using population-attributable risk percentages. Results A clear association was found between AOM episodes and simultaneous detection of HEV (adjusted odds ratio for the detection of virus in stools, 2.04; 95% confidence interval, 1.06–3.91) and HRV (1.54; 1.04–2.30). HPeV showed a similar, yet nonsignificant trend (adjusted odds ratio, 1.44; 95% confidence interval, .81–2.56). HRV and HEV showed higher population-attributable risk percentages (25% and 20%) than HPeV (11%). Conclusions HEVs and HRVs may contribute to the development of AOM in a relatively large proportion of cases.

Background Clostridium perfringens forms part of the human gut microbiota and has been associated with life-threatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains. Methods C. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis. Results 29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis, whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B, netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC. Conclusions Approximately a third of preterm infants are colonised 3 weeks after birth with toxin gene-carrying C. perfringens. We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens. Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC. Trial registration clinicaltrials.govNCT01102738, registered 13th April 2010.

The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant's microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed “settler types”, based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/ or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children's cohorts based on settler types may reveal group effects that might otherwise be masked.

To foster lifelong learning skills, we need new didactic approaches with aligned assessment methods. Therefore, we investigated whether the outcomes of a project assignment show a different relation to learning strategies than a longitudinal knowledge-based assessment. We studied learning strategies of first year students of medicine and biomedical sciences (n = 248) and performed hierarchical regression analyses for the learning strategies and grades of the longitudinal knowledge-based test and project assignment. Scores of students, measured with the Motivated Strategies for Learning Questionnaire (Likert scale 1-7), were relatively low for critical thinking (3.53), compared to rehearsal (4.40), elaboration (4.82), organisation (4.69) and metacognitive self-regulation (4.33). Knowledge based tests showed a significant relation to elaboration (p

Several factors affect gut microbiota development in early life, among which breastfeeding plays a key role. We followed 24 mother-infant pairs to investigate the associations between concentrations of selected human milk oligosaccharides (HMOs) in breastmilk, infant faeces, and the faecal microbiota composition in healthy, breastfed infants at two, six and 12 weeks of age. Lactation duration had a significant effect on breastmilk HMO content, which decreased with time, except for 3-fucosyllactose (3FL) and Lacto-N-fucopentaose III (LNFP III). We confirmed that microbiota composition was strongly influenced by infant age and was associated with mode of delivery and breastmilk LNFP III concentration at two weeks, with infant sex, delivery mode, and concentrations of 3′sialyllactose (3′SL) in milk at six weeks, and infant sex and Lacto-N-hexaose (LNH) in milk at 12 weeks of age. Correlations between levels of individual breastmilk HMOs and relative abundance of OTUs found in infant faeces, including the most predominant Bifidobacterium OTUs, were weak and varied with age. The faecal concentration of HMOs decreased with age and were strongly and negatively correlated with relative abundance of OTUs within genera Bifidobacterium, Parabacteroides, Escherichia-Shigella, Bacteroides, Actinomyces, Veillonella, Lachnospiraceae Incertae Sedis, and Erysipelotrichaceae Incertae Sedis, indicating the likely importance of these taxa for HMO metabolism in vivo.

The literature on first-year study success has identified a host of factors that may affect a student’s chances of succeeding, ranging from personal circumstances to educational environment. One of the factors that often emerges in this context is (non-)attendance of classes, lectures and tutorials. Intuitively, one would expect this to be all the more important in programmes that employ a student-centred and interactive approach to learning, such as problem-based learning. Interestingly, there is little dedicated research that looks into the importance of (non-)attendance in such a learning environment. This article addresses this gap in the literature by looking at the effect of (non-)attendance on the study success of three cohorts of Maastricht University’s Bachelor in European Studies (annual intake of 325–350 students). Controlling for a range of factors, we find that attendance matters for several measures of study success and also for the committed and participating student.

Introduction: The transition from pre-dialysis chronic kidney disease (CKD) to post-dialysis start is a critical period associated with high patient mortality and increased hospital admissions. Little is known about the trends of key clinical and laboratory parameters through this time of transition to start dialysis. Methods: De-identified data including demographics, vital signs, lab results, and eGFR from the Fresenius Medical Care-CKD Registry were analyzed to determine trends in clinical and laboratory parameters through the time of transition from 12 months pre-dialysis start to 12months post-dialysis start. Trends in key clinical and laboratory parameters associated with cardiovascular, nutritional, mineral metabolism and inflammatory domains were examined in association with the transition to dialysis start and first year dialysis survival. Findings: All parameters show divergence for patients who survive vs. do not survive the first year of dialysis. Of note, during pre-dialysis CKD the absolute systolic blood pressure (SBP) level is lower and the slope for SBP decline is significantly steeper for patients who do not survive the first year on dialysis. Discussion: This study uniquely demonstrates the trajectories of key parameters though the transition from pre-dialysis to post-dialysis start. Significant differences are noted in the pre-dialysis period for patients who survive vs. those who do not survive the first year of dialysis. Early recognition of adverse trends in the pre-dialysis period may create opportunity to intervene to improve early dialysis outcomes.

Background: In typical development, postural adjustments during reaching change in the second half of infancy, including increasing rates of direction-specific adjustments. These changes are absent or different in infants at risk of cerebral palsy (CP). To discover whether these changes are related to acquisition of independent walking, we studied postural adjustments during reaching in infants before and after they learned to walk.Methods: Ten typically developing (TD) infants and 11 infants at very high risk (VHR) of CP were assessed before and after they learned to walk. Reaching movements were elicited during supported sitting, while surface electromyography was recorded of arm, neck, and trunk muscles. Percentages of direction-specific adjustments (first level of control), and recruitment patterns and anticipatory activation (second level of control) were calculated.Results: In both groups, postural adjustments during reaching were similar before and after acquisition of independent walking. Direction-specificity increased with age in typically developing infants but not in VHR-infants.Conclusion: Increasing age rather than the transition to independent walking is associated with increasing direction-specificity of TD-infants during reaching while sitting, while infants at very high risk of CP show no increase in direction-specificity, suggesting that they gradually grow into a postural deficit.

Objective: To evaluate dispositional coping strategies as predictors for changes in well-being after 1 year in older patients with cancer (OCP) and 2 control groups. Methods: OCP were compared with 2 control groups: middle-aged patients with cancer (MCP) (aging effect) and older patients without cancer (ONC) (cancer effect). Patients were interviewed shortly after a cancer diagnosis and 1 year later. Dispositional coping was measured with the Short Utrecht Coping List. For well-being, we considered psychological well-being (depression, loneliness, distress) and physical health (fatigue, ADL, IADL). Logistic regression analyses were performed to study baseline coping as predictor for subsequent well-being while controlling for important baseline covariates. Results: A total of 1245 patients were included in the analysis at baseline: 263 OCP, 590 ONC, and 392 MCP. Overall, active tackling was employed most often. With the exception of palliative reacting, OCP utilized each coping strategy less frequently than MCP. At 1-year follow-up, 833 patients (66.9%) were interviewed. Active coping strategies (active tackling and seeking social support) predicted subsequent well-being only in MCP. Avoidance coping strategies did not predict well-being in any of the patient groups. Palliative reacting predicted distress in OCP; depression and dependency for ADL in MCP. Conclusions: Coping strategies influence subsequent well-being in patients with cancer, but the impact is different in the age groups. Palliative reacting was the only coping strategy that predicted well-being (ie, distress) in OCP and is therefore, especially in this population, a target for coping skill interventions.

Natural Killer (NK) cells contribute to HIV control in adults, but HLA-B-mediated T-cell activity has a more substantial impact on disease outcome. However, the HLA-B molecules influencing immune control in adults have less impact on paediatric infection. To investigate the contribution NK cells make to immune control, we studied >300 children living with HIV followed over two decades in South Africa. In children, HLA-B alleles associated with adult protection or disease-susceptibility did not have significant effects, whereas Bw4 (p = 0.003) and low HLA-A expression (p = 0.002) alleles were strongly associated with immunological and viral control. In a comparator adult cohort, Bw4 and HLA-A expression contributions to HIV disease outcome were dwarfed by those of protective and disease-susceptible HLA-B molecules. We next investigated the immunophenotype and effector functions of NK cells in a subset of these children using flow cytometry. Slow progression and better plasma viraemic control were also associated with high frequencies of less terminally differentiated NKG2A+NKp46+CD56dim NK cells strongly responsive to cytokine stimulation and linked with the immunogenetic signature identified. Future studies are indicated to determine whether this signature associated with immune control in early life directly facilitates functional cure in children., Author summary In adults, immune control of HIV is strongly influenced by antiviral CD8+ T-cell responses restricted by ‘protective’ HLA class I molecules, such as HLA-B*57, and by ‘disease-susceptible’ HLA class I molecules such as HLA-B*58:02. By contrast, Natural Killer (NK) cells responses make a smaller, albeit significant, contribution. In this study, we evaluate in children living with HIV the contribution of NK cell responses to immune control of HIV, in an age group where HIV-specific CD8+ T-cell responses have less impact on disease outcome. A cohort of >300 therapy-naïve children living with HIV shows that a genetic signature favouring a KIR-education on NK cells is associated with slow progression and better viraemic control. Consistent with this, we observed control of HIV viraemia and lower total HIV DNA levels among children was associated with a less differentiated NKG2A+NKp46+ CD56dim NK cell population that functionally was highly responsive to cytokine stimulation. Thus, the study identifies a signature that can impact future therapeutic strategies to achieve remission in children.

Background: Earlier reviews indicated that in many countries adults, children and adolescents consume on an average less polyunsaturated fatty acids (PUFAs) than recommended by the Food and Agriculture Organisation/World Health Organisation. Summary: The intake of total and individual n-3 and n-6 PUFAs in European infants, children, adolescents, elderly and pregnant/lactating women was evaluated systematically. Results: The evaluations were done against recommendations of the European Food Safety Authority. Key Messages: Fifty-three studies from 17 different European countries reported an intake of total n-3 and n-6 PUFAs and/or individual n-3 or n-6 PUFAs in at least one of the specific population groups: 10 in pregnant women, 4 in lactating women, 3 in infants 6-12 months, 6 in children 1-3 years, 11 in children 4-9 years, 8 in adolescents 10-18 years and 11 in elderly >65 years. Mean linoleic acid intake was within the recommendation (4 energy percentage [E%]) in 52% of the countries, with inadequate intakes more likely in lactating women, adolescents and elderly. Mean alpha-linolenic acid intake was within the recommendation (0.5 E%) in 77% of the countries. In 26% of the countries, mean eicosapentaenoic acid and/or docosahexaenoic acid intake was as recommended. These results indicate that intake of n-3 and n-6 PUFAs may be suboptimal in specific population groups in Europe. (C) 2017 S. Karger AG, Basel

Several studies have reported that intestinal microbial colonization patterns differ between non-allergic and allergic infants. However, the microbial signature underlying the pathogenesis of allergies remains unclear. We aim to gain insight into the development of the intestinal microbiota of healthy infants and infants who develop allergy in early life, and identify potential microbiota biomarkers of later allergic disease. Using a case-control design in a Chinese sub-cohort of a Singaporean birth cohort (GUSTO), we utilized 16S rRNA gene sequencing to assess intestinal microbial composition and diversity of 21 allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and correlated the microbiota with allergy at ages 18 and 36 months. Pronounced differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. The intestine of healthy infants was colonised with higher abundance of commensal Bifidobacterium. Conversely, Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B) ratio (above the population median K/B ratio) at age 3 months had an odds ratio of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46 – 55.50) compared to those with low K/B ratio. This study demonstrated a relationship between the ratio of genera Klebsiella and Bifidobacterium during early infancy and development of paediatric allergy in childhood. Our study postulates that an elevated Klebsiella/Bifidobacterium ratio in early infancy could be a potential indicator of an increased risk of allergy development. This line of research might enable future intervention strategies in early life to prevent or treat allergy. Our study provides new insights into microbial signatures associated with childhood allergy, in particular, suggests that an elevated Klebsiella/Bifidobacterium ratio could be a potential early-life microbiota biomarker of allergic disease.

BACKGROUND: Pet and dampness or mould exposure are considered risk factors for asthma and sensitization. It is unclear whether timing of exposure to these factors is differentially associated with asthma risk and sensitization in adolescence.OBJECTIVE: We investigated the role of timing of pet and dampness or mould exposure in asthma and sensitization in adolescence. Understanding this role is essential to build targeted prevention strategies.METHODS: We used data from 1871 participants of the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. Residential exposure to pets, dampness or mould was assessed by repeated parental questionnaires. We used asthma data from the 17-year questionnaire and sensitization data from the 16-year medical examination. We characterized timing using longitudinal exposure patterns from pregnancy till age 17 using longitudinal latent class growth modelling. We used logistic regression models to analyse associations of exposure patterns with asthma at age 17 and sensitization at age 16.RESULTS: For none of the time windows, exposure to pets and dampness or mould was associated with asthma at age 17, but a lower sensitization risk at age 16 was suggested, for example the odds ratio (95% confidence interval) for sensitization was 0.63 (0.35-1.11) and 0.69 (0.44-1.08) for early life and persistently high pet exposure, respectively, compared with very low exposure. An inverse association was also suggested for sensitization and moderate early childhood dampness or mould exposure (0.71 [0.42-1.19]).CONCLUSION AND CLINICAL RELEVANCE: Different timing of pet and dampness or mould exposure was not associated with asthma, but lower risk of sensitization in adolescence was suggested, which could be partly attributable to reversed causation. Current findings are not sufficient to recommend pet avoidance to prevent allergic disease. More prospective studies are needed to obtain insights that can be used in clinical practice.

Melatonin is a circadian regulatory hormone with neuroprotective properties. We have previously demonstrated the association of the genetic variant rs12506228 near the melatonin receptor 1A gene (MTNR1A) with intolerance to shift‐work. Furthermore, this variant has been connected to Alzheimer's disease. Because of the previously suggested role of melatonin signalling in foetal neurocognitive and sleep development, we studied here the association of rs12506228 with early development. The study sample comprised 8‐month‐old infants from the Finnish CHILD‐SLEEP birth cohort (n = 1,301). Parental questionnaires assessed socioemotional, communication and motor development, as well as sleep length and night awakenings. The A allele of rs12506228 showed an association with slower socioemotional (p = .025) and communication (p = .0098) development, but no direct association with sleep. However, the association of the Finnish seasons with infant sleep length interacted with rs12506228. Taken together, rs12506228 near MTNR1A, which has been previously linked to adult and elderly traits, is shown here to associate with slower early cognitive development. In addition, these results suggest that the darker seasons associate with longer infant sleep time, but only in the absence of the rs12506228 AA genotype. Because the risk allele has been connected to fewer brain MT1 melatonin receptors, these associations may reflect the influence of decreased melatonin signalling in early development.

Human milk represents a source of bacteria for the initial establishment of the oral (and gut) microbiomes in the breastfed infant, however, the origin of bacteria in human milk remains largely unknown. While some evidence points towards a possible endogenous enteromammary route, other authors have suggested that bacteria in human milk are contaminants from the skin or the breastfed infant mouth. In this work 16S rRNA sequencing and bacterial culturing and isolation was performed to analyze the microbiota on maternal precolostrum samples, collected from pregnant women before delivery, and on oral samples collected from the corresponding infants. The structure of both ecosystems demonstrated a high proportion of taxa consistently shared among ecosystems, Streptococcus spp. and Staphylococcus spp. being the most abundant. Whole genome sequencing on those isolates that, belonging to the same species, were isolated from both the maternal and infant samples in the same mother-infant pair, evidenced that in 8 out of 10 pairs both isolates were >99.9% identical at nucleotide level. The presence of typical oral bacteria in precolostrum before contact with the newborn indicates that they are not a contamination from the infant, and suggests that at least some oral bacteria reach the infant’s mouth through breastfeeding., This research was supported by grant AGL2016-75476-R. LR was funded by grant 624773 (FP-7-PEOPLE-2013IEF, European Commission) and is currently supported by the Juan de la Cierva Postdoctoral Trainee Program of the Spanish Ministry of Economy and Competitiveness (MINECO; IJCI-2015-23196).

This study was the first to longitudinally explore the extent to which early temperament and sensory processing were of predictive value for cognitive development and Autism Spectrum Disorder (ASD) symptomatology in a sample of preterm children (N = 50, 22 girls, mean gestational age 27 weeks). At the corrected ages of 10, 18, and 24 months, sensory processing and temperament were assessed, as were cognitive development and ASD symptoms at 36 months. Better cognitive development was predicted by fewer hospitalisation days at birth and by lower Activity Level at 18 months. Temperamental subscales of Negative Affect showed associations with both parent-reported and observational measures of ASD symptomatology, whereas sensory processing only had predictive value for parent-reported symptoms of ASD. The usefulness of temperament and sensory processing for prediction of ASD symptom severity and cognitive outcomes became clear in the second year of life. The results indicate that this area of research is worth additional investigation in the extreme and very preterm population, to explore in further detail whether these two concepts might be able to provide information about which preterms are more likely to develop ASD or cognitive impairments.

Contains fulltext : 201327.pdf (Publisher’s version ) (Open Access) Gastrointestinal (GI) microbiota composition differs between breastfed and formula-fed infants. Today's infant formulas are often fortified with prebiotics to better mimic properties of human milk with respect to its effect on GI microbiota composition and function. We used Illumina HiSeq sequencing of PCR-amplified 16S rRNA gene fragments to investigate the composition of faecal microbiota in 2-12 week old infants receiving either breastmilk, infant formulas fortified with prebiotics, or mixed feeding. We compared these results with results from infants fed traditional formulas used in the Netherlands in 2002-2003, which contained no added prebiotics. We showed that today's formulas supplemented with either scGOS (0.24-0.50 g/100 ml) or scGOS and lcFOS (at a 9:1 ratio; total 0.6 g/100 ml) had a strong bifidogenic effect as compared to traditional formulas, and they also resulted in altered patterns of microbial colonisation within the developing infant gastrointestinal tract. We identified three microbial states (or developmental stages) in the first 12 weeks of life, with a gradual transition pattern towards a bifidobacteria dominated state. In infants receiving only fortified formulas, this transition towards the bifidobacteria dominated state was accelerated, whereas in infants receiving mixed feeding the transition was delayed, as compared to exclusively breastfed infants. 13 p.

Background Peritoneal dialysis (PD) starters generally have a better outcome compared with hemodialysis (HD) starters, perhaps related to treatment characteristics or case mix. We previously showed that pre- and post-dialysis start clinical parameter trajectories are related to outcomes. The aim of this study was to investigate these trajectories in PD and HD starters. Methods This retrospective observational study analyzing data from the Fresenius Medical Care–chronic kidney disease (CKD) Registry from January 2009 to March 2018 examines trends in key clinical parameters through the transition period covering 12 months before to 12 months after dialysis start in 8,088 HD and 1,015 PD starters. Results Hemodialysis starters differed from PD starters by a significantly greater decline in estimated glomerular filtration rate (eGFR) slope (-0.64 vs -0.45 mL/min/1.73 m2/month) before and higher eGFR (9.85 vs 7.84 mL/min/1.73 m2) at dialysis start. Relatedly, differences in phosphorus (0.07 vs 0.05 mg/dL/month) and hemoglobin (-0.08 vs -0.01 g/dL/month) slopes before the transition to dialysis therapy were observed. After dialysis start, HD starters experienced a greater increase in albumin (0.01 vs 0 g/dL/month) whereas PD starters experienced a decline in serum sodium and higher white blood cell counts compared with HD starters. Conclusion For nephrology practice CKD patients, HD and PD starters appear clinically comparable in the year before dialysis start although HD starters exhibit a more rapid pre-dialytic eGFR decline. Ideally, studies comparing incident HD and PD outcomes should also consider CKD eGFR trajectories. In the first dialysis year, divergence occurs in albumin, white blood cell count, sodium and hemoglobin trends, which may be partly treatment-related.

Background Acquiring a traumatic injury constitutes a severe life change for the survivor, but also for the surrounding family. The paradigm of helping the family has primarily been on psychosocial interventions targeting caregivers. However, interventions including both survivor and caregivers should be an essential part of treatment, as the whole family’s functional level and mental health can be affected. The current study protocol presents a manualized family intervention for families living with traumatic injury to the brain (TBI) or spinal cord (tSCI). The objectives are to investigate if the intervention improves quality of life (QoL) and decreases burden. It is hypothesized that the family intervention improves problem-solving strategies and family dynamics, which will reduce the burden. This may improve the caregivers’ mental health, which will improve the support to the survivor and QoL. Methods The study is an interventional, two-arm, randomized controlled trial. During a 2-year period, a total of 132 families will be included. Participants will be recruited from East-Denmark. Inclusion criteria are (1) TBI or tSCI, (2) ≥ 18 years of age, (3) ≥ 6 months to ≤ 2 years since discharge from hospital, (4) ability to understand and read Danish, (5) cognitive abilities that enable participation, and (6) a minimum of one family member actively involved in the survivor’s life. Exclusion criteria are (1) active substance abuse, (2) aphasia, (3) prior neurologic or psychiatric diagnose, and (4) history of violence. Within each disease group, families will be allocated randomly to participate in an intervention or a control group with a ratio 1:1. The intervention groups receive the family intervention consisting of eight sessions of 90 min duration. Families in the control groups receive 2 h of psychoeducation. All participants complete questionnaires on QoL, self-perceived burden, family dynamics, problem-solving strategies, mental health, and resilience at pre-intervention, post-intervention, and 6-month follow up. Conclusion If the intervention is found to have effect, the study will contribute with novel knowledge on the use of a manual-based intervention including the entire family. This would be of clinical interest and would help families living with the consequences of TBI or tSCI. Trials registration ClinicalTrials.gov, NCT03814876. Retrospectively registered on 24 January 2019.

Introduction: Hospital of diagnosis is shown to have an impact on the probability of undergoing a resection in different types of gastrointestinal cancer. The aim of this study was to investigate the inter-hospital variation in resection rates and its impact on survival among patients with non-metastatic colon cancer.Methods: All patients diagnosed with non-metastatic colon cancer between 2009 and 2014 were selected from the Netherlands Cancer Registry. Multilevel logistic regression was used to examine the variation in resection rates among hospitals. The effect of variation in surgical resection on overall survival was assessed using Cox regression analyses. Relative survival was used as an estimate for disease-specific survival.Results: 38164 patients, treated in 95 different hospitals, were included in the analysis. After adjustments, resection rates varied between hospitals from 88 to 99%. This variation increased among patients older than 75 years, from 79 to 98%. Crude overall 5-year survival was 64%. After adjustment, no significant difference in overall or relative survival between hospitals with higher and lower resection rates was observed.Conclusion: Resection rates are important to consider when interpreting hospital outcomes. There is a significant variation in resection rates in patients with non-metastatic colon cancer among hospitals in the Netherlands. This variation increases in the elderly. No significant effect on survival was found. This could imply that undertreatment may play a role as well as that some patients might not benefit from surgery. (C) 2019 Published by Elsevier Ltd.

Publisher Copyright: © 2018, The Author(s). The infant gut microbiota has a high abundance of antibiotic resistance genes (ARGs) compared to adults, even in the absence of antibiotic exposure. Here we study potential sources of infant gut ARGs by performing metagenomic sequencing of breast milk, as well as infant and maternal gut microbiomes. We find that fecal ARG and mobile genetic element (MGE) profiles of infants are more similar to those of their own mothers than to those of unrelated mothers. MGEs in mothers' breast milk are also shared with their own infants. Termination of breastfeeding and intrapartum antibiotic prophylaxis of mothers, which have the potential to affect microbial community composition, are associated with higher abundances of specific ARGs, the composition of which is largely shaped by bacterial phylogeny in the infant gut. Our results suggest that infants inherit the legacy of past antibiotic consumption of their mothers via transmission of genes, but microbiota composition still strongly impacts the overall resistance load.