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Aflatoxin contamination of maize is a threat to food security and public health for households that depend on farming in developing countries. The objective of this study was to determine levels of total aflatoxins in maize from farms adopting different artisanal aflatoxin control methods. A cross-sectional study was conducted with 315 maize farmers who provided maize samples for aflatoxin analysis and additional data on artisanal aflatoxin control methods applied at farm level. Maize grains were ground, and levels of aflatoxins were determined using competitive enzyme-linked immunosorbent assay. Data were analyzed by computing descriptive statistical measures, and binary logistic regression was used to determine the relationship between levels of aflatoxin in maize and artisanal control methods applied in different farms. Aflatoxin was detected in 98% of maize samples with a mean total aflatoxin level of 12.86 μg/kg which was above the maximum tolerable limits. There was a significant difference in total aflatoxin levels in maize obtained from farms which practiced minimum tillage compared to those practicing deep tillage (p = 0.015). Drying maize on bare ground had a higher likelihood of aflatoxin contamination than drying maize on tarpaulin (p = 0.005). One-third of maize samples had aflatoxin levels exceeding the set maximum limit, with maize samples from lowland areas having high proportions of aflatoxin-positive cases as compared to uplands. Artisanal aflatoxin control technologies such as land tillage, types of platforms for drying maize, and sources of maize seed significantly influence the level of aflatoxins in maize samples. We recommend targeted active surveillance for aflatoxins, continuous public education, and adoption of farm-level mitigation measures to reduce the impact of aflatoxin contamination in farming communities.

Communication campaigns are an accepted method for altering societal attitudes, increasing knowledge, and achieving social and behavioral change particularly within public health and the social sciences. The Image Gently(SM) campaign is a national education and awareness campaign in radiology designed to promote the need for and opportunities to decrease radiation to children when CT scans are indicated. In this article, the relatively new science of social marketing is reviewed and the theoretical basis for an effective communication campaign in radiology is discussed. Communication strategies are considered and the type of outcomes that should be measured are reviewed. This methodology has demonstrated that simple, straightforward safety messages on radiation protection targeted to medical professionals throughout the radiology community, utilizing multiple media, can affect awareness potentially leading to change in practice. [ABSTRACT FROM AUTHOR]

Most organizations planning to implement picture archiving and communications systems (PACS) are aware of the need to integrate the hospital information system (HIS) and radiology information system (RIS) with the PACS, yet few are acutely aware of the challenges associated with this requirement. This report highlights the results of collaborative efforts between Children's Hospital Medical Center-Cincinnati (CHMC) applications specialists with expertise in the HIS and CHMC information system, radiology staff familiar with the enterprise and radiology workflow and data flow requirements; and General Electric integration engineers familiar with the SMS HIS and RIS, and GE PACS. CHMC received Board approval, including full funding of the entire PACS project, in October 1998. An aggressive time frame for installation was established, as CHMC's PACS leadership committed to the selection, design, and implementation of PACS and computed radiography (CR) within 18 to 20 months. CHMC selected GE (Milwaukee, WI) as its PACS vendor in July 1999, and began its implementation in November 1999. We will present the four-stage integration process undertaken at CHMC: (1) planning the integration effort, (2) designing the Interface, (3) building the interface, and (4) testing the Interface. Copyright © 2000 by W.B. Saunders Company [ABSTRACT FROM AUTHOR]

TechStep was a technology-based trial, with a stepped care approach, to reduce sexual risks and increase PrEP uptake among transgender and gender expansive youth and young adults (15-24 years old). From October 2019 to September 2021, 254 participants were randomized into: 1) Text (n = 82), or 2) Webapp (n = 87), or 3) Control (n = 85). At the 3-month follow-up assessment, those randomized to Text and Webapp and did not demonstrate improvement on primary outcomes were re-randomized to receive virtual eCoaching (Text + or Webapp +), or to remain in their initial condition without eCoaching. Results showed no effect on condomless encounters at 6-month, the primary endpoint, when comparing the Webapp + (0.33 decrease; 95%CI: -0.01, 0.67, p-value = 0.057) or the Text + (0.27 decrease; 95%CI: -0.13, 0.68, p-value = 0.181) conditions to the Control condition. However, in secondary analyses, condomless encounters were significantly reduced for Text compared to Control. The rate of PrEP uptake was low for all study arms.Trial registration: Clinical Trials # NCT04000724 (registered June 26, 2019)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation and transcriptome sequencing (snmCT-seq) in frontal cortex from young adult and aged donors, we found widespread age- and sex-related variation in specific neuron types. The proportion of inhibitory SST- and VIP-expressing neurons was reduced in aged donors. Excitatory neurons had more profound age-related changes in their gene expression and DNA methylation than inhibitory cells. Hundreds of genes involved in synaptic activity, including EGR1, were less expressed in aged adults. Genes located in subtelomeric regions increased their expression with age and correlated with reduced telomere length. We further mapped cell-type-specific sex differences in gene expression and X-inactivation escape genes. Multi-omic single-nucleus epigenomes and transcriptomes provide new insight into the effects of age and sex on human neurons., Competing Interests: Declaration of interests J.R.E. serves on the scientific advisory board of Zymo Research Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Allele-specific methylation (ASM) is an epigenetic modification whereby one parental allele becomes methylated and the other unmethylated at a specific locus. ASM is most often driven by the presence of nearby heterozygous variants that influence methylation, but also occurs somatically in the context of genomic imprinting. In this study, we investigate ASM using publicly available single-cell reduced representation bisulfite sequencing (scRRBS) data on 608 B cells sampled from six healthy B cell samples and 1,230 cells from 11 chronic lymphocytic leukemia (CLL) samples. We developed a likelihood-based criterion to test whether a CpG exhibited ASM, based on the distributions of methylated and unmethylated reads both within and across cells. Applying our likelihood ratio test, 65,998 CpG sites exhibited ASM in healthy B cell samples according to a Bonferroni criterion (p < 8.4 × 10 -9 ), and 32,862 CpG sites exhibited ASM in CLL samples (p < 8.5 × 10 -9 ). We also called ASM at the sample level. To evaluate the accuracy of our method, we called heterozygous variants from the scRRBS data, which enabled variant-based calls of ASM within each cell. Comparing sample-level ASM calls to the variant-based measures of ASM, we observed a positive predictive value of 76%-100% across samples. We observed high concordance of ASM across samples and an overrepresentation of ASM in previously reported imprinted genes and genes with imprinting binding motifs. Our study demonstrates that single-cell bisulfite sequencing is a potentially powerful tool to investigate ASM, especially as studies expand to increase the number of samples and cells sequenced., Competing Interests: Declaration of interests The authors declare no competing financial interests., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human brain cell epigenomes by probing DNA methylation and chromatin conformation at single-cell resolution in 517 thousand cells (399 thousand neurons and 118 thousand non-neurons) from 46 regions of three adult male brains. We identified 188 cell types and characterized their molecular signatures. Integrative analyses revealed concordant changes in DNA methylation, chromatin accessibility, chromatin organization, and gene expression across cell types, cortical areas, and basal ganglia structures. We further developed single-cell methylation barcodes that reliably predict brain cell types using the methylation status of select genomic sites. This multimodal epigenomic brain cell atlas provides new insights into the complexity of cell-type-specific gene regulation in adult human brains.

Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), we explored open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveiled 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly a third of the cCREs demonstrated conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer's disease (AD), and major depression, and have developed deep learning models to predict the regulatory roles of noncoding risk variants in these disorders.

Cravings that precede loss of control (LOC) over food consumption present an opportunity for intervention in patients with the binge eating disorder (BED). In this pilot study, we used responsive deep brain stimulation (DBS) to record nucleus accumbens (NAc) electrophysiology during food cravings preceding LOC eating in two patients with BED and severe obesity (trial registration no. NCT03868670). Increased NAc low-frequency oscillations, prominent during food cravings, were used to guide DBS delivery. Over 6 months, we observed improved self-control of food intake and weight loss. These findings provide early support for restoring inhibitory control with electrophysiologically-guided NAc DBS. Further work with increased sample sizes is required to determine the scalability of this approach., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Laser photochemistry of pressed-pellet samples of polycyclic aromatic hydrocarbons (PAHs) produces covalently bonded dimers and some higher polymers. This chemistry was discovered initially via laser desorption time-of-flight mass spectrometry experiments, which produced masses ( m / z ) of 2M-2 and 2M-4 (where M is the monomer parent mass). Dimers are believed to be formed from photochemical dehydrogenation and radical polymerization chemistry in the desorption plume. Replication of these ablation conditions at higher throughput allowed PAH dimers of pyrene, perylene, and coronene to be produced and collected in milligram quantities. Differential sublimation provided purification of the dimers and elimination of residual monomers. The purified dimers were investigated with UV-visible, IR, and Raman spectroscopy, complemented by computational studies using density functional theory at the CAM-B3LYP/def2-TZV level. Calculations and predicted spectra were calibrated by comparison with the corresponding monomers and used to determine the lowest energy dimer structures. Infrared and Raman spectroscopy provided few distinctive signatures, but UV-visible spectra detected new transitions for each dimer. The comparison of simulated and experimental spectra allows determination of the most prevalent structures for the PAH dimers. The work presented here provides interesting insights into the spectroscopy of extended aromatic systems and a new strategy for the photochemical synthesis of large PAH dimers.

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by changes in cell composition that occur throughout disease pathogenesis, which includes the development of fibrosis in a subset of patients. DNA methylation (DNAm) is a plausible mechanism underlying these shifts, considering that DNAm profiles differ across tissues and cell types, and DNAm may play a role in cell-type differentiation. Previous work investigating the relationship between DNAm and fibrosis in NAFLD has been limited by sample size and the number of CpG sites interrogated., Results: Here, we performed an epigenome-wide analysis using Infinium MethylationEPIC array data from 325 individuals with NAFLD, including 119 with severe fibrosis and 206 with no histological evidence of fibrosis. After adjustment for latent confounders, we identified 7 CpG sites whose DNAm associated with fibrosis (p < 5.96 × 10 -8 ). Analysis of RNA-seq data collected from a subset of individuals (N = 56) revealed that gene expression at 288 genes associated with DNAm at one or more of the 7 fibrosis-related CpGs. DNAm-based estimates of cell-type proportions showed that estimated proportions of natural killer cells increased, while epithelial cell proportions decreased with disease stage. Finally, we used an elastic net regression model to assess DNAm as a biomarker of fibrotic stage and found that our model predicted fibrosis with a sensitivity of 0.93 and provided information beyond a model based solely on cell-type proportions., Conclusion: These findings are consistent with DNAm as a mechanism underpinning or marking fibrosis-related shifts in cell composition and demonstrate the potential of DNAm as a possible biomarker of NAFLD fibrosis., (© 2021. The Author(s).)

Background: Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB highlight the substantial role of epigenetic alterations. 5-hydroxymethylcytosine (5hmC) is a highly abundant cytosine modification in the developing cerebellum and is regulated by ten-eleven translocation (TET) enzymes., Results: We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened (SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes., Conclusions: These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.

DNA methylation (DNAm) has a well-established association with age in many tissues, including peripheral blood mononuclear cells (PBMCs). Compared to DNAm, the closely related epigenetic modification known as DNA hydroxymethylation (DNAhm) was much more recently discovered in mammals. Preliminary investigations have observed a positive correlation between gene body DNAhm and cis-gene expression. While some of these studies have observed an association between age and global DNAhm, none have investigated region-specific age-related DNAhm in human blood samples. In this study, we investigated DNAhm and gene expression in PBMCs of 10 young and 10 old, healthy female volunteers. Thousands of regions were differentially hydroxymethylated in the old vs. young individuals in gene bodies, exonic regions, enhancers, and promoters. Consistent with previous work, we observed directional consistency between age-related differences in DNAhm and gene expression. Further, age-related DNAhm and genes with high levels of DNAhm were enriched for immune system processes which may support a role of age-related DNAhm in immunosenescence.

A healthy functioning immune system is critical to stave off infectious diseases, but as humans and other organisms age, their immune systems decline. As a result, diseases that were readily thwarted in early life pose nontrivial harm and can even be deadly in late life. Immunosenescence is defined as the general deterioration of the immune system with age, and it is characterized by functional changes in hematopoietic stem cells (HSCs) and specific blood cell types as well as changes in levels of numerous factors, particularly those involved in inflammation. Potential mechanisms underlying immunosenescence include epigenetic changes such as changes in DNA methylation (DNAm) and DNA hydroxymethylation (DNAhm) that occur with age. The purpose of this review is to describe what is currently known about the relationship between immunosenescence and the age-related changes to DNAm and DNAhm, and to discuss experimental approaches best suited to fill gaps in our understanding., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Understanding the relationships between health and aging is essential for delaying morbidity and maximizing independence in aging populations as life expectancies increase. Loss of cognitive function is a feared age-associated condition and growing public health concern. Alzheimer's disease (AD), the most common cause of dementia, has no curative therapies. Characterizing the relationships between risk factors, biomarkers, and AD progression is critical for the development of effective disease prediction, clinical intervention, and ultimately, disease prevention. The Emory Healthy Aging Study (EHAS) and the Emory Healthy Brain Study (EHBS), which is nested within EHAS, aim to further the understanding of healthy aging and the pathogenesis of age-related illnesses in well-characterized, community-based prospective cohorts and to identify biomarkers for the earliest manifestations of AD for the facilitation of preventative interventions. The EHAS is an innovative, longitudinal, web-based study enrolling English-speaking adults in the U.S. who agree to be contacted for future studies. Using validated instruments, the annual questionnaire enquires about demographics, socioeconomics, self-reported cognitive function, personal and family medical history, lifestyle, and psychosocial factors. Cognitive assessments are also obtained using an ambulatory device. Nested within EHAS, the EHBS is enrolling up to 2,500 EHAS participants, 50-75 years old, who do not have a diagnosis of AD, mild cognitive impairment, or any other memory disorder. EHBS in-person, biennial study visits, include neuropsychological testing, cardiovascular measures, retinal and brain imaging, biospecimen collection (blood, cerebrospinal fluid, gut microbiome), and other assessments. Since spring 2016, EHAS and EHBS have enrolled 12,500 and 863 participants with completed baseline assessments, respectively. Data and biospecimens from EHBS participants will support a broad range of AD biomarker discovery efforts, and follow-up of EHAS participants will enable assessment of self-reported cognitive trajectories and accumulation of incident cases of a variety of health conditions. The EHAS design supports the interval deployment of new study instruments and targeted sampling for ancillary studies. This project will increase our knowledge about healthy aging, improve our understanding of risk factors for cognitive impairment and dementias, support development of biomarkers, and facilitate studies of age-associated disorders including AD., (© 2019 S. Karger AG, Basel.)

Background: Pulmonary nodules in pediatric oncology patients can present a diagnostic and treatment dilemma. Imaging findings are often nonspecific and tissue diagnosis may be required for appropriate treatment. The smaller subpleural nodules may not be visualized and cannot be palpated during video-assisted thoracoscopic surgical (VATS) resection. Preoperative localization has been beneficial in obtaining an adequate pathological specimen., Objective: This study presents experience in a large pediatric hospital using CT-guided preoperative localization of pulmonary nodules combining two previously utilized techniques, hook wire and methylene blue blood patch localization., Materials and Methods: A search of the electronic medical record utilizing a medical record search application was performed to identify all patients who underwent preoperative lung nodule localization during a 12.5-year period (July 1999 through January 2012). A retrospective chart review of these patients was then performed. Pre- and postoperative imaging, interventional radiology procedural images and reports, surgical reports, and pathology reports were obtained and evaluated., Results: Thirty-five patients, with 40 nodules, who underwent preoperative CT-guided lung nodule localization were identified. Patients ranged in age from 8 months to 21 years. The pulmonary nodules ranged in size from 1.4 mm to 18 mm. Twelve nodules were localized using a Kopans breast lesion localization needle with hook wire, 4 were localized using a methylene blue blood patch, and 24 were localized using the combination of these two techniques. The technical success rate of all procedures was 100%. A pathological diagnosis was determined in 39 patients (97.5%). There were 6 (15.0%) minor complications and no major complications., Conclusion: CT-guided lung nodule localization using the combined techniques of methylene blue blood patch and hook wire is safe, technically feasible and successful in children. Using this combination of techniques will consistently yield a pathological diagnosis, is currently the preferred technique at our tertiary pediatric hospital and could be considered the new best practice.

Phosphatidylinositol 3-kinase-delta (PI3Kδ) signaling is critical for proliferation, survival, homing, and tissue retention of malignant B cells. Idelalisib, a selective oral inhibitor of PI3Kδ, has shown considerable single-agent activity in patients with heavily pretreated chronic lymphocytic leukemia (CLL). This study evaluated the safety and clinical activity of idelalisib in combination with bendamustine (IB) or rituximab (IR) or both (IBR) in patients with relapsed or refractory (R/R) CLL. Idelalisib was given continuously at 100 or 150 mg twice daily in combination with rituximab (375 mg/m 2 weekly × 8 doses), bendamustine (70 or 90 mg/m 2 , days 1 and 2 every 4 weeks × 6 cycles) or BR (rituximab, 375 mg/m 2 every 4 weeks and bendamustine, 70 mg/m 2 , days 1 and 2 every 4 weeks × 6 cycles). The primary endpoint was safety; secondary endpoints included overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Fifty-two patients (median age 64 years) with a median of 3 prior therapies were enrolled. ORR was 84.6% (89.5% IR group, 77.8% IB group, and 86.7% IBR group). The overall median PFS was 25.6 months, and median DOR was 26.6 months. The most common grade ≥3 adverse events (≥10% of patients) were pneumonia (19.2%), diarrhea (13.5%), and febrile neutropenia (17.3%). Idelalisib-based combination therapy with bendamustine and/or rituximab was highly active, resulting in durable tumor control in patients with heavily pretreated R/R CLL. However, its tolerability profile suggests that these regimens should be used cautiously in this patient population. ClinicalTrials.gov ID: NCT01088048., (Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: Peripherally inserted central catheters (PICCs) can lead to development of venous thrombosis and/or stenosis. The presence of venous thrombosis and/or stenosis may preclude children with chronic medical conditions from receiving lifesaving therapies, from hemodialysis in end-stage renal disease to total parenteral nutrition in short bowel syndrome. Several adult studies have found an association between PICCs and venous thrombosis and/or stenosis, but none has evaluated for this association in children., Objective: To determine the incidence of venous thrombosis and/or stenosis after PICC placement and identify factors that increase the risk of venous thrombosis and/or stenosis after PICC placement in children., Materials and Methods: We conducted a retrospective review of children ages 1-18 years with a PICC placed between January 2010 and July 2013 at our center, and included those who had at least one vascular imaging study of the ipsilateral extremity (Doppler ultrasound, venogram or MR angiogram) after PICC placement. Logistic regression was applied to determine risk factors for development of venous thrombosis and/or stenosis., Results: One thousand, one hundred and ten upper extremity PICCs were placed, with 703 PICCs in the right and 407 PICCs in the left. Eight hundred fifty-one imaging studies (609 Doppler ultrasounds, 193 contrast venograms and 49 MR angiograms) were performed in 376 patients. The incidence of venous thrombosis and/or stenosis in the imaged cohort was 26.3%. PICC laterality, insertion site, duration, patient height to PICC diameter ratio, and number of PICCs per patient were not associated with development of venous thrombosis and/or stenosis. Additionally, primary diagnosis and symptoms at the time of imaging did not predict findings of venous thrombosis and/or stenosis. However, patients exposed to non-PICC central venous catheters (CVC) were more likely to develop venous thrombosis and/or stenosis (odds ratio 1.95, 1.10-3.45)., Conclusion: More than a quarter of the vascular imaging studies performed in this study cohort showed previously unknown venous thrombosis and/or stenosis, irrespective of PICC laterality, insertion site, duration and size and the number of PICCs. A history of CVC was associated with a nearly two-fold increase in risk of venous thrombosis and/or stenosis after PICC placement. We suggest that PICCs and CVCs should be placed judiciously in all children, but especially in those with lifelong medical conditions who are more likely to incur direct consequences from limited vascular access.

Proteins that have existed for millions of years frequently contain repeats of functional domains within their primary structure, thereby improving their functional capacity. In the evolutionary young statherin protein contained within the in vivo-acquired enamel pellicle (AEP), we identified a single functional domain (DR9) located within the protein N-terminal portion that exhibits a higher affinity for hydroxyapatite and more efficient protection against enamel demineralization compared to other native statherin peptides. Thus, we tested the hypothesis that multiplication of functional domains of naturally occurring pellicle peptides amplifies protection against enamel demineralization. In addition, a specific amino acid sequence from histatin 3 (RR-14) was introduced to the hybrid peptides for further testing. Enamel specimens were sectioned to 150-µm thickness and randomly grouped as follows: DR9, DR9-DR9, DR9-RR14, statherin, histatin 1, or distilled water (control). After submersion for 2 h at 37°C, the specimens were placed in 2 mL demineralization solution for 12 d at 37°C. Upon sample removal, the remaining solution was subjected to colorimetric assays to determine the amount of calcium and phosphate released from each specimen. DR9-DR9 amplified protection against enamel demineralization when compared to single DR9 or statherin. Notably, the hybrid peptide DR9-RR14 demonstrated relatively strong protection when the antimicrobial property of these peptides was tested against Candida albicans and Streptococcus mutans. DR9-RR14 was able to maintain 50% of the antifungal activity compared with RR14 for C. albicans and similar values of S. mutans killing activity. This study has pioneered the functional exploration of the natural peptide constituents of the AEP and their evolution-inspired engineered peptides. The knowledge obtained here may provide a basis for the development of stable (proteinase-resistant) synthetic peptides for therapeutic use against dental caries, dental erosion, and/or oral candidiasis.

DNA methylation (DNAm) is an important epigenetic process involved in the regulation of gene expression. While many studies have identified thousands of loci associated with age, few have differentiated between linear and non-linear DNAm trends with age. Non-linear trends could indicate early- or late-life gene regulatory processes. Using data from the Illumina 450K array on 336 human peripheral blood samples, we identified 21 CpG sites that associated with age (P<1.03E-7) and exhibited changing rates of DNAm change with age (P<1.94E-6). For 2 of these CpG sites (cg07955995 and cg22285878), DNAm increased with age at an increasing rate, indicating that differential DNAm was greatest among elderly individuals. We observed significant replication for both CpG sites (P<5.0E-8) in a second set of peripheral blood samples. In 8 of 9 additional data sets comprising samples of monocytes, T cell subtypes, and brain tissue, we observed a pattern directionally consistent with DNAm increasing with age at an increasing rate, which was nominally significant in the 3 largest data sets (4.3E-15

Purpose: Nocturia is associated with poor sleep quality; however, little is known about the relationship between nocturia and sleep quality across different workforce-relevant age groups of adults. This has implications for developing new treatment strategies that are well tolerated across populations., Methods: We conducted a cross-sectional study involving merged data from the 2005-2006 and 2007-2008 waves of the National Health and Nutrition Examination Survey. Participants responded to validated questions on nocturia frequency and sleep from the Functional Outcomes of Sleep Questionnaire General Productivity subscale (FOSQ-gp, range 1-4). Analyses included multivariable linear regression with stratification by gender to examine associations between nocturia frequency (higher worse) and the FOSQ-gp scores (lower scores indicating worse daytime function related to sleep disturbance)., Findings: Of 10,512 adults aged ≥20 years who completed the survey, 9148 (87%) had complete nocturia and FOSQ-gp data. The population age-adjusted prevalence of nocturia at least twice nightly was 21.1% among men and 26.6% among women (P < 0.001), and nocturia increased with age (P < 0.001). Compared with those with no or 1 episode of nocturia, those with nocturia at least twice nightly reported lower mean FOSQ-gp scores (3.65; 95% CI, 3.61-3.69 vs 3.19; 95% CI, 3.09-3.31 for men and 3.52; 95% CI, 3.48-3.56 vs 3.09; 95% CI, 3.02-3.16 for women). Older adults (aged >65 years) with greater nocturia frequency reported worse FOSQ-gp scores compared with younger adults with similar nocturia frequency (P < 0.001 among men and women)., Implications: In a population-based sample of community-dwelling men and women, the association between nocturia and worsened functional outcomes of sleep was greater among adults older than 65 years-a group more vulnerable to drug side effects, and in whom nocturia is typically multifactorial. Additionally, these analyses found that the association between nocturia and functional outcomes of sleep is stronger with increasing age among men. Effective treatment strategies that are well tolerated by older adults, such as multicomponent treatments that simultaneously address the combined effects of lower urinary tract and sleep dysfunction, are needed., Competing Interests: C.V.: no relevant disclosures C.F.: no relevant disclosures A.H.: no relevant disclosures T.J.: no relevant disclosures A.M.: no relevant disclosures, (Published by Elsevier Inc.)

Background: Peripherally inserted central catheter (PICC) is among the most common procedures performed in children in the hospital setting. PICC insertion can be simplified with the use of a sheathed needle as an alternative to the modified Seldinger technique., Objective: To retrospectively evaluate PICC placement for the technique used and the incidence of complications at a large pediatric tertiary care center., Materials and Methods: We retrospectively reviewed all PICC placements at a single institution over a 4-year period. We reviewed patient records for demographic data, PICC placement technique, catheter size and number of lumens, and the incidence of complications (i.e. multiple attempted puncture sites, phlebitis and vessel thrombosis). We analyzed complication rates between two placement techniques using a chi-square test., Results: We identified 8,816 successful PICC placements, 4,749 (53.9%) in males and 4,067 (46.1%) in females. The average age of the patients for which a line was placed was 5.6 years (range 1 day to 45 years). A direct sheathed needle puncture technique was used in 8,362 (94.9%) placements and a modified Seldinger technique was used in 454 (5.1%). Complications occurred in 312 (3.7%) of direct sheathed needle puncture placements versus 17 (3.7%) of modified Seldinger placements (P = 0.99). Multiple puncture sites were required in 175 (2.1%) attempted direct sheathed needle puncture placements compared with 8 (1.7%) attempted modified Seldinger placements (P = 0.63). Phlebitis occurred in 94 (1.1%) direct sheathed needle puncture lines versus 5 (1.1%) modified Seldinger placed lines (P = 0.96). Vessel thrombosis occurred in 43 (0.5%) direct sheathed needle puncture lines versus 4 (0.9%) modified Seldinger placed lines (P = 0.30)., Conclusion: The direct peel-away sheathed needle vessel puncture technique and the modified Seldinger technique used to place PICC lines in children have similar complication rates.

Background: Gaining access into non-dilated renal collecting systems for percutaneous nephrolithotripsy, particularly in patients with prohibitive body habitus and/or scoliosis, is often challenging using conventional techniques., Objective: To evaluate the feasibility of cone-beam CT for percutaneous nephrostomy placement for subsequent percutaneous nephrolithotripsy in children and adolescents., Materials and Methods: A retrospective review of percutaneous nephrostomy revealed use of cone-beam CT and 3-D guidance in 12 percutaneous nephrostomy procedures for 9 patients between 2006 and 2015. All cone-beam CT-guided percutaneous nephrostomies were for pre-lithotripsy access and all 12 were placed in non-dilated collecting systems., Results: Technical success was 100%. There were no complications., Conclusion: Cone-beam CT with 3-D guidance is a technically feasible technique for percutaneous nephrostomy in children and adolescents, specifically for nephrolithotripsy access in non-dilated collecting systems.

The purpose of this study was to reduce pediatric doses while maintaining or improv-ing image quality scores without removing the grid from X-ray beam. This study was approved by the Institutional Animal Care and Use Committee. Three piglets (5, 14, and 20 kg) were imaged using six different selectable detector air kerma (Kair) per frame values (100%, 70%, 50%, 35%, 25%, 17.5%) with and without the grid. Number of distal branches visualized with diagnostic confidence relative to the injected vessel defined image quality score. Five pediatric interventional radiologists evaluated all images. Image quality score and piglet Kair were statistically compared using analysis of variance and receiver operating curve analysis to define the preferred dose setting and use of grid for a visibility of 2nd and 3rd order vessel branches. Grid removal reduced both dose to subject and imaging quality by 26%. Third order branches could only be visualized with the grid present; 100% detector Kair was required for smallest pig, while 70% detector Kair was adequate for the two larger pigs. Second order branches could be visualized with grid at 17.5% detector Kair for all three pig sizes. Without the grid, 50%, 35%, and 35% detector Kair were required for smallest to largest pig, respectively. Grid removal reduces both dose and image quality score. Image quality scores can be maintained with less dose to subject with the grid in the beam as opposed to removed. Smaller anatomy requires more dose to the detector to achieve the same image quality score.

Objective: As patients and information flow through the imaging process, value is added step-by-step when information is acquired, interpreted, and communicated back to the referring clinician. However, radiology information systems are often plagued with communication errors and delays. This article presents theories and recommends strategies to continuously improve communication in the complex environment of modern radiology., Conclusion: Communication theories, methods, and systems that have proven their effectiveness in other environments can serve as models for radiology.

There are a variety of available imaging modalities used for minimally invasive procedures in children, however, among the most frequently used is ultrasound (US). The advantages of US are vast and include real-time visualization, lack of ionizing radiation, and all-around versatility. US is also inexpensive, portable and widely available. In general US guided procedures in children have applications in nearly every aspect of medical therapy. Properly trained practitioners with US imaging experience and detailed knowledge of the relevant anatomy provide an invaluable service to the care of pediatric patients in many centers. This paper will discuss many of the image guided procedures that are performed in children and offer practical techniques from the collective experience of our practice at a large pediatric tertiary care center., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: We have previously shown that lymphopenia and monocytopenia at 2-3 months post-allogeneic haematopoietic cell transplant (HCT) is associated with poor survival in recipients of both myeloablative and reduced intensity conditioning regimens. It is not known whether the graft leukocyte content has a role in early lymphocyte and monocyte recovery following allogeneic T-cell replete peripheral blood HCT., Methods: Haematologic recovery data, including absolute lymphocyte and monocyte counts (ALC and AMC, respectively) at day +15, +30, +60, and +100, and outcomes data were pooled from two prior independent cohorts, and parameters were correlated with leukocyte graft content in those individuals receiving peripheral blood progenitor cell grafts. 216 consecutive patients from 2001-2010 were included in the analysis., Results: Neither infused allograft lymphocyte, monocyte, granulocyte, nor CD34+ cell number per kilogram recipient body weight correlated with haematologic recovery parameters or overall survival in this cohort. Prognostic factors for overall survival based on multivariate analysis were as expected from the results of the previous independent cohorts and included severity of chronic GVHD (p < 0.001), development of post-transplant relapse (p = 0.001), day +60 AMC > 0.3 x 10(9) cells/L (p = 0.0015), and day +100 ALC > 0.3 x 10(9) cells/L (p < 0.001). Low monocyte and lymphocyte counts at the day +60 and day +100 time points were significantly associated with acute GVHD and/or CMV viraemia., Conclusions: This study suggests that graft cell count does not influence post-transplant monocyte and lymphocyte recovery following T-cell replete allogeneic peripheral blood HCT. Post-transplant complications such as acute GVHD and/or CMV viraemia negatively influenced monocyte and lymphocyte recovery, and hence the survival. Further studies aimed at understanding the mechanisms behind sustained lymphopenia and monocytopenia post-transplant are needed.

Purpose: To evaluate the technical feasibility and safety of percutaneous endovascular thrombolysis for extremity deep venous thrombosis (DVT) in children < 24 months old., Materials and Methods: A retrospective chart review of a clinical and imaging database was performed for pediatric patients who underwent endovascular therapy for DVT between January 2010 and July 2013. Indications, techniques, technical and clinical success, and complications were reviewed. Techniques for thrombolysis included catheter-directed therapy (CDT) using alteplase infusion via a multi-side hole catheter, mechanical thrombectomy, and angioplasty. Short-term outcomes were assessed using surgical and imaging follow-up examinations for patency of the targeted vessel. Patients included 11 children (mean age, 9 mo; range, 3 wk-23 mo) who consecutively underwent endovascular thrombolysis for upper extremity (n = 6) or lower extremity (n = 5) DVT. The most common indication was preservation of venous access for future cardiac surgery or medical therapy., Results: The most common risk factor was the presence of a central venous catheter (10 of 11 patients). All patients with upper extremity DVT had congenital heart disease. CDT and angioplasty were performed in all patients. Venous patency was established in all patients. A grade III (95%-100%) thrombolysis response was achieved in seven patients, and a grade II (50%-95%) thrombolysis response was achieved in four patients. A major complication of pulmonary embolism occurred in one patient with upper extremity thrombolysis and was managed by intravenous systemic alteplase and heparin. No recurrence of thrombosis was found on average follow-up of 11.8 months (range, 1-41 mo)., Conclusions: Percutaneous endovascular thrombolysis for extremity DVT is safe and technically feasible in children < 24 months old., (Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Iodinated and gadolinium contrast agents pose some risk for certain pediatric patients, including allergic-like reactions, contrast-induced nephropathy (CIN) and nephrogenic systemic fibrosis (NSF). Digital flat-panel detectors enhance image quality during angiography and might allow use of more dilute contrast material to decrease risk of complications that might be dose-dependent, such as CIN and NSF., Objective: To assess the maximum dilution factors for iodine- and gadolinium-based contrast agents suitable for vascular imaging with fluoroscopy and digital subtraction angiography (DSA) on digital flat-panel detectors in an animal model., Materials and Methods: We performed selective catheterization of the abdominal aorta, renal artery and common carotid artery on a rabbit. In each vessel we performed fluoroscopy and DSA during contrast material injection using iodinated and gadolinium contrast material at 100%, 80%, 50%, 33% and 20% dilutions. An image quality score (0 to 3) was assigned by each of eight evaluators. Intracorrelation coefficient, paired t-test, one-way repeated analysis of variance, Spearman correlation and receiver operating characteristic curve analysis were applied to the data., Results: Overall the image quality scores correlated linearly with dilution levels. For iodinated contrast material, the optimum cut-off level for DSA when a score of at least 2 is acceptable is above 33%; it is above 50% when a score of 3 is necessary. For gadolinium contrast material, the optimum cut-off for DSA images is above 50% when a score of at least 2 is acceptable and above 80% when a score of 3 is necessary., Conclusion: Knowledge of the relationship between image quality and contrast material dilution might allow a decrease in overall contrast load while maintaining appropriate image quality when using digital flat-panel detectors.

DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.

We have recently shown that lymphocyte and monocyte recovery by day +100 are associated with survival post myeloablative allogeneic hematopoietic transplant for acute leukemia. We hypothesized that lymphocyte and monocyte recovery would have a similar impact on survival in the reduced intensity setting. To test this hypothesis, we analyzed clinical data from 118 consecutive fludarabine/melphalan-conditioned patients by correlating peripheral blood absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) at days +15, +30, +60 and +100 with the outcomes. Multivariate analysis revealed that day +100 AMC (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.07-0.73, P=0.01) and mild chronic GVHD (RR 0.09, 95% CI 0.005-0.43, P=0.008) were independently associated with survival. To explore whether the patterns of lymphocyte and monocyte recovery had a prognostic value, we performed unsupervised hierarchical clustering on the studied hematopoietic parameters and identified three patient clusters, A-C. Patient clusters A and B both had improved OS compared with cluster C (77.8 months vs not reached vs 22.3 months, respectively, P<0.001). No patient in cluster C had a day +100 AMC >300. Both severe acute GVHD and relapse occurred more frequently in cluster C. Our data suggest that patients with low AMC by day +100 post fludarabine/melphalan-conditioned allogeneic hematopoietic SCT may be at risk for poor outcomes.

Many previous studies of immune reconstitution (IR) postallogeneic hematopoietic stem cell transplantation (HSCT) have focused on lymphocyte recovery. Recognizing that IR involves complex interactions between innate and adaptive immune networks, we hypothesized that patterns of both monocyte and lymphocyte recovery could provide additional prognostic information. To test our hypothesis, we analyzed data from 135 consecutive patients undergoing myeloablative allogeneic HSCT for acute myeloid (AML) and lymphoblastic leukemia (ALL) from 2001 to 2010. The absolute lymphocyte and monocyte counts (ALC and AMC, respectively) were determined longitudinally at days +15, +30, +60, and +100, and correlated with clinical outcomes. At the day +30 time point, both ALC and AMC >0.3 × 10(9) cells/L were strongly associated with improved survival (overall survival [OS] 29.6 months versus 5.4 months, P = .006 and 25.3 months versus 5.1 months, P = .01 respectively), a pattern that generally continued through the day +100 evaluation. Multivariate analysis revealed the following independent prognostic factors: early disease status at transplantation, the development of chronic GVHD, the day +30 AMC, day +100 AMC, and day +100 ALC. To further explore whether any inherent patterns in the timing of lymphocyte and monocyte recovery had prognostic value post-HSCT, we performed unsupervised hierarchical clustering on the longitudinal hematopoietic parameters studied in this cohort. Four clusters of patients were identified: clusters A-D. Patient clusters B and D both demonstrated improved ALC and AMC recovery at the day +60 and day +100 time points and had significantly improved OS compared with clusters A and C (57.8 months versus 19.7 and 4.4 months, respectively, P < .001). Our data suggest that patients with poor lymphocyte and monocyte recovery beyond the day +60 time points may be at risk for poorer outcomes, and that further investigation into lymphoid/myeloid interactions in developing individualized immunotherapy is warranted., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Although use of inferior vena cava (IVC) filters for prophylaxis against pulmonary embolism (PE) is well reported in adults, long-term studies in children are lacking. We performed retrospective review of imaging and clinical database of IVC filters for the last 12 years. Thirty-five patients (mean age: 15.5 y) underwent filter placement and/or retrieval. Indications for placement were contraindication to anticoagulation with known deep venous thrombosis (DVT) (18) or high risk of venous thromboembolism (5), recurrent DVT despite anticoagulation (1), and prophylaxis before endovascular thrombolysis (8). All filter placements were technically successful without any complications. Filter retrieval was successful in 15 of 19 attempted (79%) at a mean of 42 days. Two complications occurred during retrieval: IVC stenosis successfully treated with angioplasty and contained IVC perforation. Endothelialization of filter prevented retrieval in 4 patients. Mean follow-up was 29.3 months. No patients had IVC thrombosis, breakthrough pulmonary embolism, filter fracture, or embolism. Two patients had recurrent DVT. Our results indicate that IVC filters can be successfully placed and retrieved in children with minimal procedural complications; follow-up demonstrates acceptable complication rate owing to presence of filters. Prophylactic IVC filter placement may be considered before endovascular thrombolysis for lower extremity DVT. Retrievable filters should be used in children for appropriate indications.

Image-guided transrectal drainage is an effective treatment option for many deep pelvic abscesses in children. Currently, a variety of imaging and catheter techniques are used to access and drain these abscesses. The present report describes an approach for introducing the transrectal catheter by using transabdominal ultrasound guidance to direct transrectal advancement of an Amplatz dilator with coaxial placement of the metal cannula and inner trocar from a pigtail catheter set, followed by placement of the pigtail catheter via Seldinger technique. This approach eliminates some of the limitations of other transrectal techniques. The present report describes a single-institutional experience with this technique in 13 patients., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Objective: Communication of acute or critical results between the radiology department and referring clinicians has been a deficiency of many radiology departments. The failure to perform or document these communications can lead to poor patient care, patient safety issues, medical-legal issues, and complaints from referring clinicians. To mitigate these factors, a communication and documentation tool was created and incorporated into our departmental customer service program. This article will describe the implementation of a comprehensive customer service program in a hospital-based radiology department., Materials and Methods: A comprehensive customer service program was created in the radiology department. Customer service representatives were hired to answer the telephone calls to the radiology reading rooms and to help convey radiology results. The radiologists, referring clinicians, and customer service representatives were then linked via a novel workflow management system. This workflow management system provided tools to help facilitate the communication needs of each group. The number of studies with results conveyed was recorded from the implementation of the workflow management system., Results: Between the implementation of the workflow management system on August 1, 2005, and June 1, 2009, 116,844 radiology results were conveyed to the referring clinicians and documented in the system. This accounts for more than 14% of the 828,516 radiology cases performed in this time frame., Conclusion: We have been successful in creating a comprehensive customer service program to convey and document communication of radiology results. This program has been widely used by the ordering clinicians as well as radiologists since its inception.

In the United States, teleradiology using an external service to provide preliminary or final medical image interpretation is an increasingly necessary component of radiology services, especially for smaller institutions or practices. This review aims to provide a background history to the current teleradiology services provided and also addresses the limitations and issues involved in organising such a service.

As the capability of medical imaging equipment improves, and relatively new modalities such as cone beam CT with guidance becomes more widely available, the range and complexity of image guided orthopedic procedures continues to expand. Challenges include the predictable technical and anatomic issues, as well as the complex operational and political issues associated with moving and integrating an interventional radiology service into the traditional operating room environment.

The Alliance for Radiation Safety in Pediatric Imaging is an organization of over 45 international professional societies and agencies with the goal of promoting radiation safety for children. The Alliance, through the Image Gently campaign, uses social marketing techniques and critical partnerships with vendors, government agencies, and not-for-profit organizations, to advocate best practices in radiation use and safety. Advocacies include improving education regarding radiation risk to patients from medical imaging for radiologists, technologists, and referring physicians; promoting standardization of dose measurements and display across vendor equipment; and improving medical literacy for parents.

We describe a method of exchanging a blocked nasojejunal (NJ) tube involving the use of a percutaneous transluminal angioplasty balloon to rupture the tube, followed by insertion of a guidewire through this rupture to create a guide for subsequent placement of a modified NJ tube. We used this technique in a child with a critical need for an NJ tube, in whom routine guidewire exchange was not feasible because of tube obstruction as well as the patient's anatomic abnormalities. This technique might also be useful for other patients in whom standard techniques are ineffective.

Whereas adipose tissue possesses a local renin-angiotensin system, the synthesis and regulated release of renin has not been addressed. To that end, we utilized differentiating 3T3-L1 cells and analyzed renin expression and secretion. Renin mRNA expression and protein enzymatic activity were not detectable in preadipocytes. However, upon differentiation, renin mRNA and both intracellular and extracellular renin activity were upregulated. In differentiated adipocytes, forskolin treatment resulted in a 28-fold increase in renin mRNA, whereas TNFalpha treatment decreased renin mRNA fourfold. IL-6, insulin, and angiotensin (Ang) II were without effect. In contrast, forskolin and TNFalpha each increased renin protein secretion 12- and sevenfold, respectively. Although both forskolin and TNFalpha induce lipolysis in adipocytes, fatty acids, prostaglandin E(2), and lipopolysaccharide had no effect on renin mRNA or secretion. To evaluate the mechanism(s) by which forskolin and/or TNFalpha are able to regulate renin secretion, a general lipase inhibitor (E600) and PKA inhibitor (H89) were used. Both inhibitors attenuated forskolin-induced renin release, whereas they had no effect on TNFalpha-regulated secretion. In contrast, E600 potentiated forskolin-stimulated renin mRNA levels, whereas H89 had no effect. Neither inhibitor had any influence on TNFalpha regulation of renin mRNA. Relative to lean controls, renin expression was reduced 78% in the epididymal adipose tissue of obese male C57Bl/6J mice, consistent with TNFalpha-mediated downregulation of renin mRNA in the culture system. In conclusion, the expression and secretion of renin are regulated under a complex series of hormonal and metabolic determinants in mature 3T3-L1 adipocytes.