Sleep-Related Breathing Disorders and Lower Urinary Tract Dysfunction in Children and Adolescents: A Scoping Review.

Aims: Sleep disordered breathing (SDB), lower urinary tract dysfunction (LUTD), and enuresis (NE) are common in children and adolescents and have serious consequences, especially on social and emotional development. Even though much is known about the association between SDB and NE among adults, the number of articles in children and adolescents is limited. Therefore, the aim of the present scoping review was to map out the current knowledge about SDB and LUTD in children and adolescents.

De novo DNA-based catch bonds.

All primary chemical interactions weaken under mechanical stress, which imposes fundamental mechanical limits on the materials constructed from them. Biological materials combine plasticity with strength, for which nature has evolved a unique solution-catch bonds, supramolecular interactions that strengthen under tension. Biological catch bonds use force-gated conformational switches to convert weak bonds into strong ones.

SI-PET-RAFT in flow: improved control over polymer brush growth.

Surface-initiated photoinduced electron transfer-reversible addition-fragmentation chain transfer (SI-PET-RAFT) provides a light-dependent tool to synthesize polymer brushes on different surfaces that tolerates oxygen and water, and does not require a metal catalyst. Here we introduce improved control over SI-PET-RAFT polymerizations continuous flow conditions. We confirm the composition and topological structure of the brushes by X-ray photoelectron spectroscopy, ellipsometry, and AFM.

Clinical benefits and economic cost-savings of remote electrical neuromodulation (REN) for migraine prevention.

Aims: Assess the clinical benefits and associated direct and indirect cost-savings from Remote Electrical Neuromodulation (REN) for migraine prevention.

Methods: REN, a prescribed, wearable, FDA-cleared neuromodulation-device for acute and/or preventive treatment of migraine, recently demonstrated efficacy for migraine prevention when used every-other-day, in a prospective, randomized, double-blind, placebo-controlled, multi-center study. Following baseline (4-weeks), subjects underwent treatment with REN or placebo (8-weeks), and electronically reported migraine symptoms and acute treatments daily.

Single-Molecule Force Spectroscopy of a Tetraaryl Succinonitrile Mechanophore.

Fluorescent damage reporters that use mechanochemical activation of a covalent bond to elicit an optical signal are emerging tools in material mechanics as a means to access the nanoscale distribution of forces inside materials under stress. A promising class of damage reporters are tetraaryl succinonitriles (TASN), whose mechanical activation results in stable fluorescent radical species. However, in-depth insights into the molecular mechanics of TASN activation are absent, precluding their use as quantitative mechanoprobes.

Optical tweezer measurements of asymptotic nonlinearities in complex fluids.

This article presents micro-medium-amplitude oscillatory shear (μMAOS), a method to measure the frequency-dependent micromechanical properties of soft materials in the asymptotically nonlinear regime using optical tweezers. We have developed a theoretical framework to extract these nonlinear mechanical properties of the material from experimental measurements and also proposed a physical interpretation of the third-order nonlinearities measured in single-tone oscillatory tests. We validate the method using a well-characterized surfactant solution of wormlike micelles, and subsequently employ this technique to demonstrate that the cytoplasm of a living cell undergoes strain softening and shear thinning when locally subjected to weakly nonlinear oscillatory deformations.

Bundled payments for chronic diseases increased health care expenditure in the Netherlands, especially for multimorbid patients.

Bundled payments aim to stimulate the integration of healthcare services and ultimately reduce healthcare expenditure growth through improved quality of care. The Netherlands introduced bundled payments for chronic diseases in 2010 by reimbursing providers annually for a bundle of primary care services related to COPD, Diabetes, or Vascular Risk Management. We aimed to assess the long-term effects of these bundled payments on healthcare expenditure.

From trials to clinical practice: Temporal trends in the coverage of specialized allied health services for Parkinson's disease.

Background And Purpose: To determine how the coverage of specialized allied health services for patients with Parkinson's disease (PD) has developed in the Netherlands since the publication of trials that demonstrated cost-effectiveness.

Methods: We used healthcare expenditure-based data on all insured individuals in the Netherlands to determine the annual proportion of patients with PD who received either specialized or generic allied health services (physiotherapy, occupational therapy, speech-language therapy) in 2 calendar years separated by a 5-year interval (2012 and 2017). Specialized allied health services were delivered through the ParkinsonNet approach, which encompassed professional training and concentration of care among specifically trained professionals.

Allosteric pathway selection in templated assembly.

Assembling large numbers of molecular building blocks into functional nanostructures is no trivial task. It relies on guiding building blocks through complex energy landscapes shaped by synergistic and antagonistic supramolecular interactions. In nature, the use of molecular templates is a potent strategy to navigate the process to the desired structure with high fidelity.

Disease variants alter transcription factor levels and methylation of their binding sites.

Most disease-associated genetic variants are noncoding, making it challenging to design experiments to understand their functional consequences. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer the downstream effects of disease-associated variants, but most of these variants remain unexplained. The analysis of DNA methylation, a key component of the epigenome, offers highly complementary data on the regulatory potential of genomic regions.

Identification of context-dependent expression quantitative trait loci in whole blood.

Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations. Knowledge of the context that determines the nature and strength of eQTLs may help identify cell types relevant to pathophysiology and the regulatory networks underlying disease.

Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms.

Background: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages.

Results: Here, we report on the large-scale identification of 6366 age-related variably methylated positions (aVMPs) identified in 3295 whole blood DNA methylation profiles, 2044 of which have a matching RNA-seq gene expression profile.

Blood lipids influence DNA methylation in circulating cells.

Background: Cells can be primed by external stimuli to obtain a long-term epigenetic memory. We hypothesize that long-term exposure to elevated blood lipids can prime circulating immune cells through changes in DNA methylation, a process that may contribute to the development of atherosclerosis. To interrogate the causal relationship between triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels and genome-wide DNA methylation while excluding confounding and pleiotropy, we perform a stepwise Mendelian randomization analysis in whole blood of 3296 individuals.

Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

Background And Aims: Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history.

Determining the quality and complexity of next-generation sequencing data without a reference genome.

We describe an open-source kPAL package that facilitates an alignment-free assessment of the quality and comparability of sequencing datasets by analyzing k-mer frequencies. We show that kPAL can detect technical artefacts such as high duplication rates, library chimeras, contamination and differences in library preparation protocols. kPAL also successfully captures the complexity and diversity of microbiomes and provides a powerful means to study changes in microbial communities.

Exome sequencing of germline DNA from non-BRCA1/2 familial breast cancer cases selected on the basis of aCGH tumor profiling.

The bulk of familial breast cancer risk (∼70%) cannot be explained by mutations in the known predisposition genes, primarily BRCA1 and BRCA2. Underlying genetic heterogeneity in these cases is the probable explanation for the failure of all attempts to identify further high-risk alleles. While exome sequencing of non-BRCA1/2 breast cancer cases is a promising strategy to detect new high-risk genes, rational approaches to the rigorous pre-selection of cases are needed to reduce heterogeneity.

Directed adenovirus evolution using engineered mutator viral polymerases.

Adenoviruses (Ads) are the most frequently used viruses for oncolytic and gene therapy purposes. Most Ad-based vectors have been generated through rational design. Although this led to significant vector improvements, it is often hampered by an insufficient understanding of Ad's intricate functions and interactions.

Experiences with array-based sequence capture; toward clinical applications.

Although sequencing of a human genome gradually becomes an option, zooming in on the region of interest remains attractive and cost saving. We performed array-based sequence capture using 385K Roche NimbleGen, Inc. arrays to zoom in on the protein-coding and immediate intron-flanking sequences of 112 genes, potentially involved in mental retardation and congenital malformation.

Genome-wide assessment of differential roles for p300 and CBP in transcription regulation.

Despite high levels of homology, transcription coactivators p300 and CREB binding protein (CBP) are both indispensable during embryogenesis. They are largely known to regulate the same genes. To identify genes preferentially regulated by p300 or CBP, we performed an extensive genome-wide survey using the ChIP-seq on cell-cycle synchronized cells.

Deep sequencing to reveal new variants in pooled DNA samples.

We evaluated massive parallel sequencing and long-range PCR (LRP) for rare variant detection and allele frequency estimation in pooled DNA samples. Exons 2 to 16 of the MUTYH gene were analyzed in breast cancer patients with Illumina's (Solexa) technology. From a pool of 287 genomic DNA samples we generated a single LRP product, while the same LRP was performed on 88 individual samples and the resulting products then pooled.

CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes.

Background: The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments.

Results: We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes.

Developing access to number magnitude: a study of the SNARC effect in 7- to 9-year-olds.

The SNARC (spatial-numerical association of response codes) effect refers to the finding that small numbers facilitate left responses, whereas larger numbers facilitate right responses. The development of this spatial association was studied in 7-, 8-, and 9-year-olds, as well as in adults, using a task where number magnitude was essential to perform the task and another task where number magnitude was irrelevant. When number magnitude was essential, a SNARC effect was found in all age groups.

Upside-down transfer of porcine keratinocytes from a porous, synthetic dressing to experimental full-thickness wounds.

Currently, the use of cultured epithelial autografts as an alternative to split-thickness skin autografts for coverage of full-thickness wounds is limited due to fragility of the sheet and variability in the outcome of healing. This could be circumvented by the transfer of proliferating keratinocytes, instead of differentiated sheets, to the wound bed and the "in vivo" regeneration of epidermis. The aim of this study was to achieve re-epithelialization on experimental full-thickness wounds in the pig using a porous, synthetic carrier seeded with proliferating keratinocytes.

Uveitis referral pattern in a Midwest University Eye Center.

We determined the referral pattern and visual prognosis for patients with uveitis at a tertiary university eye center in the Midwestern U.S. over a five-year period.