The Cues and Care Trial: A randomized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight infants

Abstract Background Very low birthweight infants are at risk for deficits in cognitive and language development, as well as attention and behaviour problems. Maternal sensitive behaviour (i.e. awareness of infant cues and appropriate responsiveness to those cues) in interaction with her very low birthweight infant is associated with better outcomes in these domains; however, maternal anxiety interferes with the mother's ability to interact sensitively with her very low birthweight infant. There is a need for brief, cost-effective and timely interventions that address both maternal psychological distress and interactive behaviour. The Cues and Care trial is a randomized controlled trial of an intervention designed to reduce maternal anxiety and promote sensitive interaction in mothers of very low birthweight infants. Methods and design Mothers of singleton infants born at weights below 1500 g are recruited in the neonatal intensive care units of 2 tertiary care hospitals, and are randomly assigned to the experimental (Cues) intervention or to an attention control (Care) condition. The Cues intervention teaches mothers to attend to their own physiological, cognitive, and emotional cues that signal anxiety and worry, and to use cognitive-behavioural strategies to reduce distress. Mothers are also taught to understand infant cues and to respond sensitively to those cues. Mothers in the Care group receive general information about infant care. Both groups have 6 contacts with a trained intervener; 5 of the 6 sessions take place during the infant's hospitalization, and the sixth contact occurs after discharge, in the participant mother's home. The primary outcome is maternal symptoms of anxiety, assessed via self-report questionnaire immediately post-intervention. Secondary outcomes include maternal sensitive behaviour, maternal symptoms of posttraumatic stress, and infant development at 6 months corrected age. Discussion The Cues and Care trial will provide important information on the efficacy of a brief, skills-based intervention to reduce anxiety and increase sensitivity in mothers of very low birthweight infants. A brief intervention of this nature may be more readily implemented as part of standard neonatal intensive care than broad-based, multi-component interventions. By intervening early, we aim to optimize developmental outcomes in these high risk infants. Trial Registration Current Controlled Trials ISRCTN00918472 The Cues and Care Trial: A randomized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight infant

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

We performed a multistage genome-wide association study (GWAS) including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT; per-allele odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.74–0.84; P = 3.0×10−12), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2; OR = 1.46; 95% CI = 1.30–1.65; P = 1.1×10−10), rs9581943 at 13q12.2 (PDX1; OR = 1.15; 95% CI = 1.10–1.20; P = 2.4×10−9), and rs16986825 at 22q12.1 (ZNRF3; OR = 1.18; 95% CI = 1.12–1.25; P = 1.2×10−8). An independent signal was identified in exon 2 of TERT at the established region 5p15.33 (rs2736098; OR = 0.80; 95% CI = 0.76–0.85; P = 9.8×10−14). We also identified a locus at 8q24.21 (rs1561927; P = 1.3×10−7) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study has identified multiple new susceptibility alleles for pancreatic cancer worthy of follow-up studies

Reducing the tendency to self-handicap: The effect of self-affirmation

Self-handicapping, the creating or claiming of obstacles to one\u27s performance to influence explanations given for subsequent outcomes, has been shown to have a host of attitudinal and behavioral consequences. Given the wide ranging impact of self-handicapping, it is important to understand the conditions under which self-handicapping is more or less likely to occur. Accordingly, the present study tested the hypothesis that people will be less likely to engage in self-handicapping if they have previously engaged in self-affirmation. The results of this study found that self-affirmation was more effective in reducing self-handicapping behavior when individuals experienced non-contingent success than when they experience contingent success. Theoretical contributions to the self-handicapping and self-affirmation literatures are discussed, as are practical implications. © 2005 Elsevier Inc. All rights reserved

Common and Divergent Features of T Cells from Blood, Gut, and Genital Tract of Antiretroviral Therapy-Treated HIV+ Women.

T cells residing in mucosal tissues play important roles in homeostasis and defense against microbial pathogens. The gut and female reproductive tract (FRT) are both tolerogenic environments, but they differ in the kinds of foreign Ags they need to tolerate. How these different environments influence the properties of their T cells is poorly understood, but important for understanding women's health. We recruited antiretroviral therapy-suppressed women living with HIV who donated, within one visit, blood and tissue samples from the ileum, colon, rectosigmoid, endometrium, endocervix, and ectocervix. With these samples, we conducted 36-parameter cytometry by time of flight phenotyping of T cells. Although gut and FRT T cells shared features discriminating them from their blood counterparts, they also harbored features distinguishing them from one another. These included increased proportions of CD69+ T resident memory cells of the T effector memory phenotype, as well as preferential coexpression of CD69 and CD103, on the gut-derived cells. In contrast, CD69+CD103+ T resident memory CD8+ T cells from FRT, but not those from gut, preferentially expressed PD1. We further determined that a recently described population of CXCR4+ T inflammatory mucosal cells differentially expressed multiple other chemokine receptors relative to their blood counterparts. Our findings suggest that T cells resident in different tolerogenic mucosal sites take on distinct properties

Tissue-specific differences in HIV DNA levels and mechanisms that govern HIV transcription in blood, gut, genital tract and liver in ART-treated women.

IntroductionSex-specific differences affect multiple aspects of HIV infection, yet few studies have quantified HIV levels in tissues from women. Since an HIV functional cure will likely require a major reduction of infected cells from most tissues, we measured total and intact HIV DNA and the HIV transcription profile in blood, gut, genital tract and liver from HIV-positive antiretroviral therapy (ART) -treated women.MethodsPeripheral blood mononuclear cells (PBMC) and biopsies from the gastrointestinal (ileum, colon, rectosigmoid +/- liver) and genital (ectocervix, endocervix and endometrium) tracts were collected from 6 ART-treated (HIV RNA < 200 copies/mL) women. HIV DNA (total and intact) and levels of read-through, initiated (total), 5'elongated, polyadenylated and multiply spliced HIV transcripts were measured by droplet digital PCR. Immunophenotyping of cells was performed using Cytometry by time of flight (CyTOF).ResultsWe detected total HIV DNA in all tissues and intact HIV DNA in blood, ileum, colon, rectosigmoid and ectocervix. Initiated HIV transcripts per provirus were higher in PBMC and endometrium than in ileum, colon, rectosigmoid, ectocervix or endocervix, and higher in the rectum than either ileum or colon. 5'Elongated HIV transcripts per provirus were comparable in PBMC and endometrium, but higher than in gut or cervical samples. Polyadenylated and multiply spliced HIV transcripts were detected in PBMC (6/6 and 3/6 individuals respectively), but rarely in the tissues.ConclusionsThese results suggest tissue-specific differences in the mechanisms that govern HIV expression, with lower HIV transcription in most tissues than blood. Therapies aimed at disrupting latency, such as latency-reversing or latency-silencing agents, will be required to penetrate into multiple tissues and target different blocks to HIV transcription