Neurocognitive outcomes in moderately preterm born adolescents.

BACKGROUND: Early preterm (EP) born children are at risk of neurocognitive impairments persisting into adulthood. Less is known about moderately to late (MLP) preterm born children, especially after early childhood. The aim of this study was to assess neurocognitive functioning of MLP adolescents regarding intelligence, executive and attentional functioning, compared with EP and full-term (FT) adolescents. METHODS: This study was part of the Longitudinal Preterm Outcome Project (LOLLIPOP), a large community-based observational cohort study. In total 294 children (81 EP, 130 MLP, and 83 FT) were tested at age 14 to 16 years, regarding intelligence, speed of processing, attention, and executive functions. We used the Dutch version of the Wechsler Intelligence Scale for Children-Third Edition-Dutch Version (WISC-III-NL), the Test of Everyday Attention for Children, and the Behavioural Assessment of the Dysexecutive Syndrome for Children. We assessed differences between preterm-born groups with the FT group as a reference. RESULTS: Compared to the FT group, MLP adolescents scored significantly lower on two subtasks of the WISC-III-NL, i.e. Similarities and Symbol Search. EP adolescents performed significantly lower on all neuropsychological tests than their FT peers, except for the subtask Vocabulary. The MLP adolescents scored in between FT and EP adolescents on all tasks, except for three WISC-III-NL subtasks. CONCLUSIONS: Neurocognitive outcomes of MLP adolescents fell mostly in between outcomes of their EP and FT peers. MLPs generally performed on a low-average to average level, and appeared susceptible to a variety of moderate neurodevelopmental problems at adolescent age, which deserves attention in clinical practice.

Healthy diets positively associated with health-related quality of life in children and adolescents from low socioeconomic areas: Findings from the Greek Food Aid Program, DIATROFI.

OBJECTIVES: To assess the relationship of diet with health-related quality of life (HRQoL) in vulnerable children and adolescents. METHODS: Data included 6583 children and adolescents (aged 3-18 years old) from the Greek Food-Aid DIATROFI Program in the 2015 to 2016 and 2017 to 2018 school years. HRQoL was measured with the Pediatric Quality of Life Inventory questionnaire and diet with food frequency questionnaires. The healthy plant-based diet index (hPDI), animal score, and dietary patterns were investigated. RESULTS: The hPDI and animal score were associated with good HRQoL (odds ratio [OR] [95% confidence interval], 10-unit increase: ORhPDI = 1.28 [1.05, 1.57], ORanimal = 1.51 [1.14, 2.00]) and physical (ORanimal = 1.62 [1.23, 2.13]), emotional (ORhPDI = 1.30 [1.07, 1.58], ORanimal = 1.41 [1.08, 1.85]) and school function (ORhPDI = 1.32 [1.09, 1.59], ORanimal = 1.46 [1.12, 1.89]). Dietary patterns of fruits, raw vegetables, and cheese were associated with good HRQoL (OR of 1-unit increase: 1.22 [1.13, 1.32]), and physical OR = 1.18 [1.09, 1.27]) and emotional function (OR = 1.09 [1.02, 1.18]). Starchy foods and sweetened beverages were associated with poor HRQoL (OR = 0.75 [0.63, 0.90]), and emotional (OR = 0.80 [0.68, 0.95]) and school function (OR = 0.72 [0.61, 0.85]). CONCLUSION: Healthy diets and dietary patterns were positively associated with the HRQoL of vulnerable children and adolescents, which may offer opportunities for prevention.

Gut feelings: the relations between depression, anxiety, psychotropic drugs and the gut microbiome.

The gut microbiome is involved in the bi-directional relationship of the gut - brain axis. As most studies of this relationship are small and do not account for use of psychotropic drugs (PTDs), we explored the relations of the gut microbiome with several internalizing disorders, while adjusting for PTDs and other relevant medications, in 7,656 Lifelines participants from the Northern Netherlands (5,522 controls and 491 participants with at least one internalizing disorder). Disorders included dysthymia, major depressive disorder (MDD), any depressive disorder (AnyDep: dysthymia or MDD), generalized anxiety disorder (GAD) and any anxiety disorder (AnyAnx: GAD, social phobia and panic disorder). Compared to controls, 17 species were associated with depressive disorders and 3 were associated with anxiety disorders. Around 90% of these associations remained significant (FDR <0.05) after adjustment for PTD use, suggesting that the disorders, not PTD use, drove these associations. Negative associations were observed for the butyrate-producing bacteria Ruminococcus bromii in participants with AnyDep and for Bifidobacterium bifidum in AnyAnx participants, along with many others. Tryptophan and glutamate synthesis modules and the 3,4-Dihydroxyphenylacetic acid synthesis module (related to dopamine metabolism) were negatively associated with MDD and/or dysthymia. After additional adjustment for functional gastrointestinal disorders and irritable bowel syndrome, these relations remained either statistically (FDR <0.05) or nominally (P < 0.05) significant. Overall, multiple bacterial species and functional modules were associated with internalizing disorders, including gut - brain relevant components, while associations to PTD use were moderate. These findings suggest that internalizing disorders rather than PTDs are associated with gut microbiome differences relative to controls.

A validated HPLC-MS/MS method for simultaneously analyzing curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetra-hydrocurcumin and piperine in human plasma, urine or feces.

Background: The spice curcumin is supposed to have many different beneficial health effects. To understand the complete pharmacokinetics of curcumin we need an analytical method to determine curcumin and its metabolites in human plasma, urine or feces. We have developed an HPLC-MS/MS method for the simultaneous analysis of curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and piperine in human plasma, urine or feces. Methods: Sample pretreatment involved a simple liquid-liquid extraction with tert-butyl methyl ether. Conjugated curcumin and analogs can be measured after enzymatic hydrolysis. Reversed-phase chromatography with a linear gradient of 50-95% methanol in 0.1% formic acid was used. Total run time is 15 min. The method was validated with regards to stability, specificity, sensitivity, linearity, accuracy, repeatability and reproducibility. The applicability of the method was tested using actual patients samples. Results: The LLOQ in plasma, urine and feces for curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and piperine ranged from 1 to 5 nM. Whereas all compounds could be quantified on a linear range between 2 and 400 nM. Plasma and feces recovery of curcumin was 97.1 ± 3.7% and 99.4 ± 16.2%, whereas urine showed a recovery of 57.1 ± 9.3%. All compounds had acceptable in-between day or between day variability in the different matrixes. Conclusion: A HPLC-MS/MS method was developed and validated for the simultaneous quantification of curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and piperine in human plasma, urine or feces. This method will aid in critically verifying the pharmacokinetics of curcumin made by supplement manufacturers and help us to provide insight in the claimed bioavailability of curcumin supplements.

Negative reviews online: an exploratory analysis of patient complaints about dental services in Western Australia.

OBJECTIVE: Rates of online reviews are continually increasing. Coinciding with this, is the beneficial abundance of subjective information that is now available to patients. Such information can be persuasive in selecting a healthcare provider. This analysis of one-and-two-star Google reviews received by dental practices within the Perth metropolitan region aims to identify common themes within dental practice complaints. METHODS: This mixed-methods study was conducted by gathering reviews from the 'Google review' feature, which have been published by users between 2013 and 2020. These data were then coded into recognised themes, and crucial quotes were selected and de-identified creating a narrative about the themes present which formed the qualitative component of this research. RESULTS: A total of 413 negative reviews were included in this study. From these, 1071 specific complaints were identified. Major themes identified included treatment issues, staffing, communication and professionalism, finance, and premise. Spread across these five themes were an additional thirty-eight subthemes. Overall, treatment was a primary concern for patients, making up 37.1% of the results. Within the subthemes 'treatment dissatisfaction (unspecified)' was also high, at 23.1%. CONCLUSION: This study identified the most common complaints received by dental clinics on Google review within the Perth metropolitan area. Further investigation is required to provide supplementary data regarding factors that may influence complaint rates and types, such as the socio-economic status of areas and geographical factors such as distance from the Perth metropolitan.

Child health, infant formula funding and South African health professionals: Eliminating conflict of interest.

Letters by Van Niekerk and Khan on article by Lake et al. (Lake L, Kroon M, Sanders D, et al. Child health, infant formula funding and South African health professionals: Eliminating conflict of interest. S Afr Med J 2019;109(12):902-906. https://doi.org/10.7196/SAMJ.2019.v109i12.14336); and response by Lake et al.

Child health, infant formula funding and South African health professionals: Eliminating conflict of interest.

Despite clear evidence of the benefits of exclusive and continued breastfeeding for children, women and society, far too few children in South Africa (SA) are breastfed. One of the major impediments to improving this situation is the continued and aggressive marketing of breastmilk substitutes (BMSs) and infiltration of the BMS industry into contexts with exposure to health professionals. In this article we, as academics, practitioners and child health advocates, describe contraventions of the regulations that protect breastfeeding in SA and argue that bold, proactive leadership to eliminate conflict of interest in respect of the BMS industry is urgently required, together with far greater investments in proven interventions to promote and support breastfeeding.

Postnatal screening and care for non-medical risk factors by preventive child healthcare in deprived and non-deprived neighbourhoods.

BACKGROUND: Children born in families with non-medical risk factors, such as deprivation, have higher odds of preterm birth (< 37 weeks of gestation) or being born small for gestational age (birth weight < 10th percentile). In addition, growing up they are at risk for growth and developmental problems. Preventive Child Healthcare (PCHC) monitors growth and development of babies and children. Early identification of children at risk could result in early interventions to prevent growth and developmental problems in later life. Therefore, we aimed to assess current practices in postnatal risk screening and care for non-medical risk factors and the collaboration with other healthcare professionals, in both deprived and non-deprived neighbourhoods in the Netherlands. METHODS: Eight out of ten invited PCHC organisations, from different areas in the Netherlands, consented to participate in this study. A questionnaire was designed and digitally distributed to professionals working at these organisations, where 370 physicians and nurses were employed. Data was collected between June and September 2016. Descriptive statistics, chi square tests and t-tests were applied. RESULTS: Eighty-nine questionnaires were eligible for analyses. Twenty percent of the respondents were working in a deprived neighbourhood and 70.8% of the respondents were employed as nurse. Most of them performed screening for non-medical risk factors in at least 50% of their consultations. PCHC professionals working in deprived neighbourhoods encountered significantly more often families with non-medical risk factors and experienced significantly more communication problems than their colleagues working in non-deprived neighbourhoods. 48.2% of the respondents were satisfied with the current form of postnatal risk screening in their organisation, whereas 41.2% felt a need for a structured postnatal risk assessment. Intensified collaboration is preferred with district-teams, general practitioners and midwifes, concerning clients with non-medical risk factors. CONCLUSION: This study shows that postnatal screening for non-medical risk factors is part of current PCHC practice, regardless the neighbourhood status they are deployed. PCHC professionals consider screening for non-medical risk factors as their responsibility. Consequently, they felt a need for a structured postnatal risk assessment and for an intensified collaboration with other healthcare professionals.

The validity of the 4-Skills Scan A double-validation study.

Adequate gross motor skills are an essential aspect of a child's healthy development. Where physical education (PE) is part of the primary school curriculum, a strong curriculum-based emphasis on evaluation and support of motor skill development in PE is apparent. Monitoring motor development is then a task for the PE teacher. To fulfill this task, teachers need adequate tools. The 4-Skills Scan is a quick and easily manageable gross motor skill instrument; however, its validity has never been assessed. Therefore, the purpose of this study was to assess the construct and concurrent validity of both 4-Skills Scans (version 2007 and version 2015). A total of 212 primary school children (6-12 years old) was requested to participate in both versions of the 4-Skills Scan. For assessing construct validity, children covered an obstacle course with video recordings for observation by an expert panel. For concurrent validity, a comparison was made with the M-ABC-2, by calculating Pearson correlations. Multivariable linear regression analyses were performed to determine the contribution of each subscale to the construct of gross motor skills, according to the M-ABC-2 and the expert panel. Correlations between the 4-Skills Scans and expert valuations were moderate, with coefficients of .47 (version 2007) and .46 (version 2015). Correlations between the 4-Skills Scans and the M-ABC-2 (gross) were moderate (.56) for version 2007 and high (.64) for version 2015. It is concluded that both versions of the 4-Skills Scans are satisfactory valid instruments for assessing gross motor skills during PE lessons.

Constitutive modelling of composite biopolymer networks.

The mechanical behaviour of biopolymer networks is to a large extent determined at a microstructural level where the characteristics of individual filaments and the interactions between them determine the response at a macroscopic level. Phenomena such as viscoelasticity and strain-hardening followed by strain-softening are observed experimentally in these networks, often due to microstructural changes (such as filament sliding, rupture and cross-link debonding). Further, composite structures can also be formed with vastly different mechanical properties as compared to the individual networks. In this present paper, we present a constitutive model presented in a continuum framework aimed at capturing these effects. Special care is taken to formulate thermodynamically consistent evolution laws for dissipative effects. This model, incorporating possible anisotropic network properties, is based on a strain energy function, split into an isochoric and a volumetric part. Generalisation to three dimensions is performed by numerical integration over the unit sphere. Model predictions indicate that the constitutive model is well able to predict the elastic and viscoelastic response of biological networks, and to an extent also composite structures.

Detecting dispersed duplications in high-throughput sequencing data using a database-free approach.

MOTIVATION: Dispersed duplications (DDs) such as transposon element insertions and copy number variations are ubiquitous in the human genome. They have attracted the interest of biologists as well as medical researchers due to their role in both evolution and disease. The efforts of discovering DDs in high-throughput sequencing data are currently dominated by database-oriented approaches that require pre-existing knowledge of the DD elements to be detected. RESULTS: We present DD_DETECTION, a database-free approach to finding DD events in high-throughput sequencing data. DD_DETECTION is able to detect DDs purely from paired-end read alignments. We show in a comparative study that this method is able to compete with database-oriented approaches in recovering validated transposon insertion events. We also experimentally validate the predictions of DD_DETECTION on a human DNA sample, showing that it can find not only duplicated elements present in common databases but also DDs of novel type. AVAILABILITY AND IMPLEMENTATION: The software presented in this article is open source and available from https://bitbucket.org/mkroon/dd_detection.

Modelling of cross-linked actin networks - Influence of geometrical parameters and cross-link compliance.

A major structural component of the cell is the actin cytoskeleton, in which actin subunits are polymerised into actin filaments. These networks can be cross-linked by various types of ABPs (Actin Binding Proteins), such as Filamin A. In this paper, the passive response of cross-linked actin filament networks is evaluated, by use of a numerical and continuum network model. For the numerical model, the influence of filament length, statistical dispersion, cross-link compliance (including that representative of Filamin A) and boundary conditions on the mechanical response is evaluated and compared to experimental results. It is found that the introduction of statistical dispersion of filament lengths has a significant influence on the computed results, reducing the network stiffness by several orders of magnitude. Actin networks have previously been shown to have a characteristic transition from an initial bending-dominated to a stretching-dominated regime at larger strains, and the cross-link compliance is shown to shift this transition. The continuum network model, a modified eight-chain polymer model, is evaluated and shown to predict experimental results reasonably well, although a single set of parameters cannot be found to predict the characteristic dependence of filament length for different types of cross-links. Given the vast diversity of cross-linking proteins, the dependence of mechanical response on cross-link compliance signifies the importance of incorporating it properly in models to understand the roles of different types of actin networks and their respective tasks in the cell.

Melanocyte antigen-specific antibodies cannot be used as markers for recent disease activity in patients with vitiligo.

BACKGROUND: Objective parameters to assess disease activity in non-segmental vitiligo are lacking. Melanocyte antigen-specific antibodies are frequently found in the sera of patients with vitiligo and the presence of these antibodies may correlate with disease activity. OBJECTIVE: To investigate the relationship between melanocyte antigen-specific antibodies and recent disease activity in patients with vitiligo and to evaluate the potential usefulness of this objective parameter in daily clinical practice. METHODS: The prevalence of tyrosinase, melanoma antigen recognized by T-cells-1 (MART1), melanin-concentrating hormone receptor-1 (MCHR1), gp100 and tyrosine hydroxylase (TH) antibodies was evaluated in 21 patients with non-segmental vitiligo and in 20 healthy controls. RESULTS: In 21 patients, nine (42.8%) showed antibody responses against tyrosinase, MART1, MCHR1, gp100 or TH. No antibody responses were found in the 20 controls. No correlation was found between the presence of antibodies and recent disease activity or other clinical characteristics such as age, gender, extension and duration of vitiligo. CONCLUSIONS: In this study, 42.8% of the vitiligo patients showed an antibody response to melanocyte antigen-specific antigens. However, the presence of antibodies against melanocytes did not correlate with recent disease activity or other relevant disease parameters, and for the moment screening for these antibodies in individual patients does not appear to be clinically relevant.

A chemo-mechanical constitutive model for transiently cross-linked actin networks and a theoretical assessment of their viscoelastic behaviour.

Biological materials can undergo large deformations and also show viscoelastic behaviour. One such material is the network of actin filaments found in biological cells, giving the cell much of its mechanical stiffness. A theory for predicting the relaxation behaviour of actin networks cross-linked with the cross-linker α-actinin is proposed. The constitutive model is based on a continuum approach involving a neo-Hookean material model, modified in terms of concentration of chemically activated cross-links. The chemical model builds on work done by Spiros (Doctoral thesis, University of British Columbia, Vancouver, Canada, 1998) and has been modified to respond to mechanical stress experienced by the network. The deformation is split into a viscous and elastic part, and a thermodynamically motivated rate equation is assigned for the evolution of viscous deformation. The model predictions were evaluated for stress relaxation tests at different levels of strain and found to be in good agreement with experimental results for actin networks cross-linked with α-actinin.

The prevalence of thyroid disease in patients with vitiligo: a systematic review.

BACKGROUND: Thyroid disease has been suggested to be associated with vitiligo. However, the outcomes of prevalence studies on thyroid disease in vitiligo vary widely. OBJECTIVES: To summarize and critically appraise current evidence of the prevalence of thyroid diseases in vitiligo. METHODS: A systematic review was performed searching the electronic databases OVID MEDLINE, OVID EMBASE and PubMed. Guidelines for the critical appraisal of studies on prevalence of a health problem were adapted to evaluate the methodological quality of the included studies. Results were analysed in a meta-analysis with a risk ratio (RR). RESULTS: Forty-eight studies published between 1968 and 2012 met the inclusion criteria. Most of the studies (50%) were of fair methodological quality, whereas 18 studies (38%) were of poor quality and six studies (12%) were of good quality. Thyroid disease, autoimmune thyroid disease and presence of thyroid-specific autoantibodies showed a mean prevalence of, respectively, 15·1%, 14·3% and 20·8% in patients with vitiligo and an RR of, respectively, 1·9, 2·5 and 5·2 (all statistically significant). This review shows an increased prevalence and an increased risk of (autoimmune) thyroid disease in patients with vitiligo compared with nonvitiligo. This risk seems to increase with age. CONCLUSIONS: Clinicians should be aware of this increased risk in patients with vitiligo and should be attentive for symptoms of thyroid disease. To make recommendations on screening for thyroid disease in patients with vitiligo future research of good methodological quality, including differentiation of vitiligo types and the use of standardized outcome measures, is needed.

Low yield of routine screening for thyroid dysfunction in asymptomatic patients with vitiligo.

BACKGROUND: Nonsegmental vitiligo is considered to be an autoimmune disease and is known to be associated with other autoimmune diseases, particularly affecting the thyroid. Screening patients with nonsegmental vitiligo for thyroid function and for the presence of thyroid autoantibodies has been recommended. OBJECTIVE: To investigate the prevalence of thyroid dysfunction and thyroid peroxidase-specific (TPO) antibodies in a large cohort of patients with nonsegmental vitiligo in order to help decide whether routine screening is justified. METHODS: A total of 434 adults with nonsegmental vitiligo who were referred to our institute were enrolled. Thyroid function and anti-TPO antibody titres were assessed in those patients who had no history of thyroid disease or recent thyroid screening. RESULTS: Forty-three patients had already been diagnosed with thyroid dysfunction, and in 27 patients the general practitioner had performed a thyroid function test with negative results <3months previously. In these patients, thyroid function assessment was not repeated. The remaining 364 patients were screened for thyroid dysfunction. Overt hypothyroidism was newly diagnosed in three (0·8%) patients; subclinical disease was found in 10 (2·7%) patients and increased levels of TPO antibodies, without thyroid disease, were found in 49 (13·5%) patients. An elevated risk for thyroid disease was found among older women and in women with a positive family history of thyroid disease. CONCLUSION: The overall prevalence of thyroid dysfunction in adult patients with nonsegmental vitiligo was higher than reported in the general population. However, the number of newly diagnosed cases with overt and subclinical thyroid dysfunction in our population was low. Most patients had already been diagnosed by their general practitioner and had symptoms indicative for thyroid disease. Thyroid disease was found predominantly among older women and in subjects with a positive family history of thyroid disease. Thyroid screening including anti-TPO antibodies is advisable in these high-risk subpopulations.

Optimal length of smooth muscle assessed by a microstructurally and statistically based constitutive model.

Smooth muscle exhibits an optimal length at which it is able to generate a maximum amount of force. In this study, the optimal length is assessed by use of a microstructurally and statistically based constitutive model for smooth muscle. The model is based on the sliding filament theory, and a modified version of Hill's mechanical model was adopted. It was conjectured, that a variation in the overlap in the actomyosin contractile units together with a statistical dispersion in the size of the dense bodies are responsible for the optimal length characteristics. The influence of contractile unit length, dense body size and dense body compliance was investigated, and the model was fully able to predict experimental data. The results indicate that the compliance of the dense bodies does not contribute significantly to the total compliance of the contractile apparatus.