Quality of life in Brazilian obese adolescents: effects of a long-term multidisciplinary lifestyle therapy

Background  

Obesity has adverse physical, social, and economic consequences that can negatively affect quality of life (QOL). Thus the aim of this study was to verify the effects of a long-term multidisciplinary lifestyle intervention on QOL, body image, anxiety, depression and binge eating in obese adolescents.     

Discontinuation of Radiation Treatment among Medicaid‐Enrolled Women with Local and Regional Stage Breast Cancer

Abstract: For women with nonmetastatic breast cancer, radiation therapy is recommended as a necessary component of the breast conserving surgery (BCS) treatment option. The degree to which Medicaid‐enrolled women complete recommended radiation therapy protocols is not known. We evaluate radiation treatment completion rates for Medicaid enrollees aged 18–64 diagnosed with breast cancer. We determine clinical and socio‐demographic factors associated with not starting treatment, and with interruptions or not completing radiation treatment. Using data from the Washington State Cancer Registry linked to Medicaid enrollment and claims records, we identified Medicaid enrollees diagnosed with breast cancer from 1997 to 2003 who received BCS. Among the 402 women who met inclusion criteria, 105 (26%) did not receive any radiation. Factors significantly associated with not receiving radiation included in situ disease and non‐English as a primary language. Among those who received at least one radiation treatment, 65 (22%) failed to complete therapy and 71 (24%) patients had at least one 5 to 30 day gap in treatment. We found no significant predictors of interruptions in treatment or early discontinuation. A substantial proportion of Medicaid‐insured women who are eligible for radiation therapy following BCS either fail to receive any treatment, experience significant interruptions during therapy, or do not complete a minimum course of treatment. More effort is needed to ensure this vulnerable population receives adequate radiation following BCS.     

Relationship between nonalcoholic fatty liver disease prevalence and visceral fat in obese adolescents

BACKGROUND: Visceral adiposity is the major risk factor for paediatric nonalcoholic fatty liver disease. AIMS: Determine the prevalence of nonalcoholic fatty liver disease according to the visceral fat quartile. SUBJECTS: 181 obese adolescents including 113 girls (16.58+/-1.56 years) and 68 boys (16.87+/-1.62 years) were evaluated. METHODS: The inclusion criteria were obesity and post-pubertal stage of Tanner. Visceral fat of obese adolescents was distributed in quartiles after ultrasound nonalcoholic fatty liver disease diagnosis. RESULTS: Nonalcoholic fatty liver disease prevalence was 45.30%. It was observed that 62.07% and 76.47% of girls and boys with nonalcoholic fatty liver disease were found in the 4th quartile. In a multivariate logistic analysis it was observed that only visceral fat remained statistically significant, every 1cm increase in visceral fat was associated with a 1.97 fold (95% CI 1.06-3.66) in boys and 2.08 fold (95% CI 1.38-3.13) in girls increased risk to develop nonalcoholic fatty liver disease. Indeed it was verified a positive correlation between visceral fat, body mass index, insulin levels, homeostasis model assessment insulin resistance index and steatosis degree. CONCLUSIONS: Our findings suggested that the expansion of visceral fat was a determinant factor to increase nonalcoholic fatty liver disease prevalence and the visceral fat measured by ultrasound might be a good predictor to identify risk for nonalcoholic fatty liver disease in obese adolescents. It was confirmed by a stronger correlation between visceral fat and body mass index.     

A Novel Technique of Adjusting Segmentation Boundary Layers to Achieve Comparability of Retinal Thickness and Volumes between Spectral Domain and Time Domain Optical Coherence Tomography

Purpose. The quantitative assessment of retinal thickness and volume varies according to the optical coherence tomography (OCT) machine used due to differences in segmentation lines. We describe a novel method of adjusting the segmentation lines of spectral-domain OCT (SD-OCT) to enable comparison with time-domain OCT (TD-OCT), and assess factors affecting its accuracy. Methods. In a prospective study, SD-OCT (Spectralis OCT) and TD-OCT (Stratus OCT) were sequentially performed on 200 eyes of 100 healthy individuals. Central retinal thickness (CRT), central point thickness (CPT), and 1-mm volume of the Early Treatment Diabetic Retinopathy Study grid were compared between the two machines. The segmentation lines on SD-OCT were manually adjusted by a trained operator and the parameters compared again with TD-OCT. Results. The mean CRTs of Spectralis and Stratus were significantly different (268.2 μm vs. 193.9 μm, P < 0.001). After adjustment of segmentation lines, the mean adjusted Spectralis CRT was 197.3 μm, with the difference between SD-OCT and TD-OCT measurements decreasing from 74.3 μm to 3.4 μm (P < 0.001). The difference between the adjusted Spectralis and Stratus CRTs was smallest for high myopes (≤ -6.0 diopters [D]) compared with those with moderate and low myopia (1.5 μm vs. 3.5 μm and 4.6 μm, respectively; P < 0.001). Similar trends were obtained for central 1-mm volumes and CPT. Interoperator and intraoperator repeatability for adjustment of the segmentation lines were good, with an intraclass correlation of 0.99 for both. Conclusions. Manual adjustment of SD-OCT segmentation lines reliably achieves retinal thickness and volume measurements that are comparable to that of TD-OCT. This is valuable to allow comparisons in multicenter clinical trials where different OCT machines may be used.     

Calculating the predicted retinal thickness from spectral domain and time domain optical coherence tomography – comparison of different methods

Purpose

To compare the accuracy of different methods of calculating predicted central retinal thickness values in order to allow comparison between results of spectral-domain optical coherence tomography (SD-OCT) and time-domain OCT (TD-OCT) devices.

Methods

In a prospective cohort study, 100 consecutive healthy individuals without ocular disease underwent sequential scanning with SD-OCT (Spectralis OCT) and TD-OCT (Stratus OCT). A group of 60 eyes was used to generate the conversion equations, which were tested on the remaining 140 eyes. Four equations were used: 1. Mean difference between SD-OCT and TD-OCT; 2. Multiplying a ratio by the original retinal thickness; 3. Linear regression analysis using retinal thickness; and 4. Regression analysis using retinal thickness and spherical equivalent. All four methods were used to calculate predicted SD-OCT values from TD-OCT measurements, and vice versa.

Results

For all four equations, the predicted SD-OCT central retinal thickness values were similar to the actual SD-OCT, with mean difference ranging from 0.78 to 1.01 μm, and intraclass correlation coefficients >0.88. Both regression equations and mean difference showed greater accuracy, with variation between calculated and actual retinal thickness values ≤5 μm in 60 % of eyes. In contrast, the ratio method was less accurate, with 15.8 % of eyes showing differences >15 μm. Similar results were found for predicted TD-OCT values.

Conclusions

Several methods can be used to convert central retinal thickness values from SD-OCT to the predicted TD-OCT value, or vice versa, with high degrees of accuracy and reliability. These methods may allow comparison of OCT values from SD-OCT and TD-OCT devices in clinical trials and standard patient care.     

Crossover-active regions of the wheat genome are distinguished by DMC1, the chromosome axis,H3K27me3, and signatures of adaptation

The hexaploid bread wheat genome comprises over 16 gigabases of sequence across 21 chromosomes. Meiotic crossovers are highly polarized along the chromosomes, with elevation in the gene-dense distal regions and suppression in the Gypsy retrotransposon-dense centromere-proximal regions. We profiled the genomic landscapes of the meiotic recombinase DMC1 and the chromosome axis protein ASY1 in wheat and investigated their relationships with crossovers, chromatin state, and genetic diversity. DMC1 and ASY1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed strong co-enrichment in the distal, crossover-active regions of the wheat chromosomes. Distal ChIP-seq enrichment is consistent with spatiotemporally biased cytological immunolocalization of DMC1 and ASY1 close to the telomeres during meiotic prophase I. DMC1 and ASY1 ChIP-seq peaks show significant overlap with genes and transposable elements in the Mariner and Mutator superfamilies. However, DMC1 and ASY1 ChIP-seq peaks were detected along the length of each chromosome, including in low-crossover regions. At the fine scale, crossover elevation at DMC1 and ASY1 peaks and genes correlates with enrichment of the Polycomb histone modification H3K27me3. This indicates a role for facultative heterochromatin, coincident with high DMC1 and ASY1, in promoting crossovers in wheat and is reflected in distalized H3K27me3 enrichment observed via ChIP-seq and immunocytology. Genes with elevated crossover rates and high DMC1 and ASY1 ChIP-seq signals are overrepresented for defense-response and immunity annotations, have higher sequence polymorphism, and exhibit signatures of selection. Our findings are consistent with meiotic recombination promoting genetic diversity, shaping host–pathogen co-evolution, and accelerating adaptation by increasing the efficiency of selection.

Meiosis is a germ-line cell division whereby chromosomes undergo DNA replication followed by two rounds of segregation, producing gametes required for sexual reproduction (Villeneuve and Hillers 2001). Homologous chromosomes pair and recombine, yielding crossovers or noncrossovers (Hunter 2015). Crossovers are required for balanced segregation at the first division and generate genetic diversity. Recombination is initiated during early prophase I, when chromosomes undergo DNA double-strand breaks (DSBs) catalyzed by SPO11 enzymes (Keeney et al. 2014). DMC1 and RAD51 recombinases bind single-stranded DNA at each DSB end and promote strand invasion of homologous DNA (Hunter 2015). In plants and mammals, a minority of strand invasion events mature into crossovers (∼3%–10% of DSBs) (Cole et al. 2010; Mercier et al. 2015), with most dissociated via anticrossover pathways (Hunter 2015).Meiotic recombination is orchestrated by the assembly of a proteinaceous axis, which underpins meiotic chromosome architecture in eukaryotes (Zickler and Kleckner 1999). Sister chromatids are organized as linear arrays of chromatin loops connected to the axis (Zickler and Kleckner 1999). In plants, the chromosome axis includes the HORMA domain protein ASY1 and its interacting partners ASY3 and ASY4, which promote DMC1-mediated interhomolog synapsis and recombination (Armstrong et al. 2002; Sanchez-Moran et al. 2007; Ferdous et al. 2012; Chambon et al. 2018). As prophase I progresses, the synaptonemal complex is installed between the axes of homologous chromosomes, promoting crossover maturation (Zickler and Kleckner 1999).Crossovers exert a powerful influence on eukaryotic genetic variation and genome evolution (Barton and Charlesworth 1998) and are an essential plant-breeding tool. However, significant heterogeneity in crossover rates occurs along chromosomes, which can impede crop improvement (Taagen et al. 2020). Selection for useful variation can cause hitchhiking of deleterious alleles via linkage drag in low-recombination regions (Hill and Robertson 1966). This is particularly pronounced in bread wheat (Triticum aestivum), as crossovers concentrate in distal regions (Saintenac et al. 2009; Choulet et al. 2014). For example, 82% of crossovers on Chromosome 3B occur within 19% of its physical length (Darrier et al. 2017). Bread wheat is an allohexaploid, comprising homoeologous A, B, and D subgenomes of seven chromosomes each (2n = 6x = 42, AABBDD) (Marcussen et al. 2014). Wheat chromosomes are large (473–830 Mb), with high transposable element (TE) content, and comprise one of the most complex assembled genomes (IWGSC 2018).Pronounced compartmentalization of features occurs along the wheat chromosomes. For example, crossover rate, gene density, and euchromatic (H3K4me3, H3K9ac, and H3K27ac) and facultative heterochromatic (H3K27me3) marks increase toward the telomeres, whereas Gypsy LTR retrotransposon density and constitutive heterochromatic marks (H3K9me2 and CG- and CHG-context DNA methylation) increase toward the centromeres (Choulet et al. 2014; IWGSC 2018; Li et al. 2019). Gene function, chromatin state, and expression breadth across tissues are also stratified (Ramírez-González et al. 2018). Genes with broad expression, high H3K36me3 and H3K9ac levels, and “housekeeping” functions are located predominantly in the low-recombination interstitial and centromere-proximal regions (R2 and C compartments), whereas those with tissue-specific expression, high H3K27me3 levels, and functions in development and response to environmental stimuli are enriched in the high-recombination distal regions (R1 and R3 compartments) (IWGSC 2018; Ramírez-González et al. 2018).Chromatin state significantly influences recombination in plant genomes. For example, meiotic DSB hotspots in Arabidopsis and maize are located in nucleosome-depleted regions (NDRs) associated with genes and specific transposon families (He et al. 2017; Choi et al. 2018). Furthermore, Arabidopsis crossover hotspots can be suppressed via RNA-directed DNA methylation (Yelina et al. 2015), and mutants with reduced non-CG DNA methylation show increased pericentromeric SPO11-1-oligonucleotides and crossovers (Underwood et al. 2018). Large tracts of the crossover-suppressed compartments of the wheat genome are marked by constitutive heterochromatin (IWGSC 2018; Li et al. 2019; Concia et al. 2020). Additionally, H3K27me2 associates with crossover suppression in wheat, despite distal enrichment (Liu et al. 2021). However, fine-scale relationships between chromatin, meiotic recombination, axis occupancy, and sequence variation in wheat remain incompletely understood.As DMC1 marks an early stage in meiotic recombination, and the axis protein ASY1 promotes synapsis and recombination, we sought to profile their localization in wheat using ChIP-seq. This allowed us to investigate the genetic and epigenetic features that associate with meiotic DSBs and axis occupancy. DMC1 binding and axis occupancy are necessary, but not sufficient, for repair of meiotic DSBs as crossovers. We therefore aimed to identify properties that distinguish crossover-active DMC1 and ASY1 ChIP-seq peaks and genes by examining chromatin state and genetic variation across crossover-rate gradients.     

Pressure wave fidelity in catheter introducers.

Pressure waveform fidelity was examined in two sizes of the Bard catheter introducer. The purpose of this endeavor was to determine whether accurate blood pressure measurements could be achieved directly via the catheter introducers. The introducers were incorporated into a mock circulatory system for the study. The effects of supporting dilators and catheters within the introducer sheath during pressure measurements were also considered. Parameters used to explain pressure waveform response within the catheter introducers included the damping coefficient and the natural frequency of the catheter introducer, and the effects of impedance mismatching between the transducer and the mock circulatory system. Overall, the pressure measurements obtained from the catheter introducer were distorted. Mean pressure levels measured in the introducers were up to 15 mmHg higher than the true mean pressure. The distortion in the pressure measurements can be attributed for the most part to impedance mismatching. In sum, the pressure measurements obtained from catheter introducer-manometer systems should be used only referentially, and not as an absolute standard.