Epigenome-wide association study of asthma and wheeze characterizes loci within .

Background: To identify novel epigenetic markers of adolescent asthma and replicate findings in an independent cohort, then explore whether such markers are detectable at birth, predictive of early-life wheeze, and associated with gene expression in cord blood.

Methods: We performed epigenome-wide screening with recursive random forest feature selection and internal validation in the IOW birth cohort. We then tested whether we could replicate these findings in the independent cohort ALSPAC and followed-up our top finding with children of the IOW cohort.

Enhancing Student Learning in Removable Partial Denture Design by Using Virtual Three-Dimensional Models Versus Traditional Two-Dimensional Drawings: A Comparative Study.

Purpose: To compare the use of virtual 3D casts as an alternative to paper-based exercises in preclinical removable partial denture (RPD) design in terms of student outcomes (as evidenced by exercise evaluation scores), as well as student attitudes related to the 2 formats. The first hypothesis of this study is that virtual 3D digital models in the exercise will result in better student outcomes as evidenced by the final exercise score compared to the 2D drawings. The second hypothesis is that virtual 3D digital models in the exercise will result in greater student acceptance compared to the 2D drawings.

DNA methylation links prenatal smoking exposure to later life health outcomes in offspring.

Background: Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship.

Methods: We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring.

FCM Software Aids Extracellular Vesicle Light Scatter Standardization.

The study of extracellular vesicles (EVs) is a rapidly growing field due to their great potential in many areas of clinical medicine including diagnostics, prognostics, theranostics, and therapeutics. Flow cytometry is currently one of the most popular methods of analyzing EVs due to it being a high-throughput, multiparametric technique, that is readily available in the majority of research labs. Despite its wide use, few commercial flow cytometers are designed specifically for the detection of EVs.

Effect of gestational oily fish intake on the risk of allergy in children may be influenced by , expression and DNA methylation.

Background: Evidence suggests that prenatal exposure to long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease in children. LCPUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by the and genes. DNA methylation regulates gene activity and fatty acid supplementation could alter DNA methylation (DNA-M) at these genes.

Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns.

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip.

Thioflavin T Monitoring of Guanine Quadruplex Formation in the rs689-Dependent INS Intron 1.

The human proinsulin gene (INS) contains a thymine-to-adenine variant (rs689) located in the 3' splice site (3' ss) recognition motif of the first intron. The adenine at rs689 is strongly associated with type 1 diabetes. By weakening the polypyrimidine tract, the adenine allele reduces the efficiency of intron 1 splicing, which can be ameliorated by antisense oligonucleotides blocking a splicing silencer located upstream of the 3' ss.

Investigating the effect of discordant clinical and pathological diagnoses of complicated appendicitis on clinical outcomes.

Background: Following appendectomy, management is often guided by surgeon determination of whether the appendicitis is uncomplicated or complicated. Our objectives were to determine the incidence of discordance between intraoperative and pathological findings and determine effect on outcomes.

Methods: We performed a retrospective five-year cohort analysis of adults who underwent appendectomy for acute appendicitis.

Epigenome-wide association study of lung function level and its change.

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.

Mutation of the ATPase Domain of MutS Homolog-5 (MSH5) Reveals a Requirement for a Functional MutSγ Complex for All Crossovers in Mammalian Meiosis.

During meiosis, induction of DNA double strand breaks (DSB) leads to recombination between homologous chromosomes, resulting in crossovers (CO) and non-crossovers (NCO). In the mouse, only 10% of DSBs resolve as COs, mostly through a class I pathway dependent on MutSγ (MSH4/ MSH5) and MutLγ (MLH1/MLH3), the latter representing the ultimate marker of these CO events. A second Class II CO pathway accounts for only a few COs, but is not thought to involve MutSγ/ MutLγ, and is instead dependent on MUS81-EME1.

Distinguishing Wheezing Phenotypes from Infancy to Adolescence. A Pooled Analysis of Five Birth Cohorts.

Pooling data from multiple cohorts and extending the time frame across childhood should minimize study-specific effects, enabling better characterization of childhood wheezing. To analyze wheezing patterns from early childhood to adolescence using combined data from five birth cohorts. We used latent class analysis to derive wheeze phenotypes among 7,719 participants from five birth cohorts with complete report of wheeze at five time periods.

Anthropogenic enhancements to production of highly oxygenated molecules from autoxidation.

Atmospheric oxidation of natural and anthropogenic volatile organic compounds (VOCs) leads to secondary organic aerosol (SOA), which constitutes a major and often dominant component of atmospheric fine particulate matter (PM). Recent work demonstrates that rapid autoxidation of organic peroxy radicals (RO) formed during VOC oxidation results in highly oxygenated organic molecules (HOM) that efficiently form SOA. As NO emissions decrease, the chemical regime of the atmosphere changes to one in which RO autoxidation becomes increasingly important, potentially increasing PM, while oxidant availability driving RO formation rates simultaneously declines, possibly slowing regional PM formation.

Morphological and Molecular Analysis of Australian Earwigs (Dermaptera) Points to Unique Species and Regional Endemism in the Anisolabididae Family.

Dermaptera (earwigs) from the Anisolabididae family may be important for pest control but their taxonomy and status in Australia is poorly studied. Here we used taxonomic information to assess the diversity of southern Australian Anisolabididae and then applied barcodes as well as additional gene fragments (mitochondrial and nuclear) to corroborate classification and assess the monophyly of the putative genera. Anisolabididae morphospecies fell into two genera, Fieber and Burr, based on paramere morphology.

Different definitions of atopic dermatitis: impact on prevalence estimates and associated risk factors.

Background: There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD), and no uniform clinical definition.

Objectives: To investigate to what extent operational definitions of AD cause fluctuation in the prevalence estimates and the associated risk factors.

Methods: We first reviewed the operational definitions of AD used in the literature.

The Interdependence of Motor and Social Skill Development: Influence on Participation.

Participation is a major outcome area for physical therapists serving young children with disabilities. Contemporary models of disability such as the International Classification of Function, developmental theories such as the system perspective, and evidence-based early childhood practices recognize the interdependence of developmental domains, and suggest that change in 1 area of development influences change in another. Physical therapy provided in naturally occurring activities and routines, considered the preferred service delivery method, promotes participation of young children with disabilities.

The impact of a General Practitioner-led community paediatric allergy clinic: A service evaluation.

Background: The NHS is not meeting the nation's allergy needs. There are insufficient allergy specialists, with variable care across the country. General practitioners (GPs) are lacking in allergy training.

DNA methylation and allergic sensitizations: A genome-scale longitudinal study during adolescence.

Background: The presence of allergic sensitization has a major influence on the development and course of common childhood conditions such as asthma and rhinitis. The etiology of allergic sensitization is poorly understood, and its underlying biological mechanisms are not well established. Several studies showed that DNA methylation (DNAm) at some CpGs is associated with allergic sensitization.

Gorillas have been infected with the HERV-K (HML-2) endogenous retrovirus much more recently than humans and chimpanzees.

Human endogenous retrovirus-K (HERV-K) human mouse mammary tumor virus-like 2 (HML-2) is the most recently active endogenous retrovirus group in humans, and the only group with human-specific proviruses. HML-2 expression is associated with cancer and other diseases, but extensive searches have failed to reveal any replication-competent proviruses in humans. However, HML-2 proviruses are found throughout the catarrhine primates, and it is possible that they continue to infect some species today.

Epigenome-wide meta-analysis of DNA methylation and childhood asthma.

Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis.

Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma.

Automated Synthesis Protocol of Sequence-Defined Oligo-Urethane-Amides Using Thiolactone Chemistry.

An automated, iterative protocol for the synthesis of multifunctional, sequence-defined oligo-urethane-amides using thiolactone chemistry is reported. Here, sequenced functionalization of the backbone is easily introduced using commercially available primary amines. The chemistry is carried out on solid phase using different supports for better optimization of the synthetic protocol and in order to demonstrate the versatility of the approach.

Evaluation of intraductal delivery of poly(ethylene glycol)-doxorubicin conjugate nanocarriers for the treatment of ductal carcinoma in situ (DCIS)-like lesions in rats.

Ductal carcinoma in situ is the most commonly diagnosed early stage breast cancer. The efficacy of intraductally delivered poly(ethylene glycol)-doxorubicin (PEG-DOX) nanocarriers, composed of one or more DOX conjugated to various PEG polymers, was investigated in an orthotopic ductal carcinoma in situ-like rat model. In vitro cytotoxicity was evaluated against 13762 Mat B III cells using MTT assay.