Effect of antenatal milk expression education on lactation outcomes in birthing people with pre-pregnancy body mass index ≥ 25: Protocol for a randomized, controlled trial

Background: Birthing people with pre-pregnancy body mass indices (BMIs) ≥ 25 kg/m2, particularly those without prior breastfeeding experience, are at increased risk for suboptimal lactation outcomes. Antenatal milk expression (AME) may be one way to counteract the negative effects of early infant formula supplementation common in this population. Methods: This ongoing, randomized controlled trial in the United States evaluates the efficacy of a telelactation-delivered AME education intervention versus an attention control condition on lactation outcomes to 1 year postpartum among 280 nulliparous-to-primiparous, non-diabetic birthing people with pre-pregnancy BMI ≥ 25 kg/m2. The assigned study treatment is delivered via four weekly online video consultations between gestational weeks 37-40. Participants assigned to AME meet with study personnel and a lactation consultant to learn and practice AME. Instructions are provided for home practice of AME between study visits. Control group participants view videos on infant care/development at study visits. Participants complete emailed surveys at enrollment (340/7-366/7 gestational weeks) and 2 weeks, 6 weeks, 12 weeks, 6 months, and 12 months postpartum. Surveys assess lactation and infant feeding practices; breastfeeding self-efficacy, attitudes, and satisfaction; perception of insufficient milk; onset of lactogenesis-II; lactation support and problems; and reasons for breastfeeding cessation. Surveys also assess factors associated with lactation outcomes, including demographic characteristics, health problems, birth trauma, racial discrimination, and weight stigma. Health information and infant feeding data are abstracted from the pregnancy and birth center electronic health record. Milk samples are collected from the intervention group at each study visit and from both groups at each postpartum follow-up for future analyses. Qualitative interviews are conducted at 6 weeks postpartum to understand AME experiences. Primary outcomes of interest are breastfeeding exclusivity and breastfeeding self-efficacy scores at 2 weeks postpartum. Outcomes will be examined longitudinally with generalized linear mixed-effects modeling. Discussion: This is the first adequately powered trial evaluating the effectiveness of AME among U.S. birthing people and within a non-diabetic population with pre-pregnancy BMI ≥ 25 kg/m2. This study will also provide the first evidence of acceptability and effectiveness of telelactation-delivered AME. Trial registration: ClinicalTrials.gov: NCT04258709

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

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A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci

Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P < 5 × 10-8, including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P = 5.3 × 10 -21); 6p21.33 near HLA-C and MICA (rs9266772, P = 3.2 × 10 -12); 5p13.1 near PTGER4 (rs7720838, P = 8.2 × 10 -11); 2q33.1 in PLCL1 (rs10497813, P = 6.1 × 10-10), 3q28 in LPP (rs9860547, P = 1.2 × 10-9); 20q13.2 in NFATC2 (rs6021270, P = 6.9 × 10-9), 4q27 in ADAD1 (rs17388568, P = 3.9 × 10-8); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P = 4.8 × 10-8). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P = 1.7 × 10-12), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Web-based interventions for weight loss and weight maintenance among rural midlife and older women: protocol for a randomized controlled trial

Background: Weight loss is challenging and maintenance of weight loss is problematic among midlife and older rural women. Finding effective interventions using innovative delivery methods that can reach underserved and vulnerable populations of overweight and obese rural women is a public health challenge. Methods/Design: This Women Weigh-In for Wellness (The WWW study) randomized-controlled trial is designed to compare the effectiveness of theory-based behavior-change interventions using (1) website only, (2) website with peer-led support, or (3) website with professional email-counseling to facilitate initial weight loss (baseline to 6 months), guided continuing weight loss and maintenance (7-18 months) and self-directed weight maintenance (19-30 months) among rural women ages 45-69 with a BMI of 28-45. Recruitment efforts using local media will target 306 rural women who live within driving distance of a community college site where assessments will be conducted at baseline, 3, 6, 12, 18, 24 and 30 months by research nurses blinded to group assignments. Primary outcomes include changes in body weight, % weight loss, and eating and activity behavioral and biomarkers from baseline to each subsequent assessment. Secondary outcomes will be percentage of women achieving at least 5% and 10% weight loss without regain from baseline to 6, 18, and 30 months and achieving healthy eating and activity targets. Data analysis will use generalized estimating equations to analyze average change across groups and group differences in proportion of participants achieving target weight loss levels. Discussion: The Women Weigh-In for Wellness study compares innovative web-based alternatives for providing lifestyle behavior-change interventions for promoting weight loss and weight maintenance among rural women. If effective, such interventions would offer potential for reducing overweight and obesity among a vulnerable, hard-to-reach, population of rural women

Active Notch1 Confers a Transformed Phenotype to Primary Human Melanocytes

The importance of MAPK signaling in melanoma is underscored by the prevalence of activating mutations in N-Ras and B-Raf; yet, clinical development of inhibitors of this pathway has been largely ineffective, suggesting that alternative oncogenes may also promote melanoma. Notch is an interesting candidate that has only been correlated with melanoma development and progression; a thorough assessment of tumor-initiating effects of activated Notch on human melanocytes would clarify the mounting correlative evidence and perhaps identify a novel target for an otherwise untreatable disease. Analysis of a substantial panel of cell lines and patient lesions demonstrated that Notch activity is significantly higher in melanomas than their non-transformed counterparts. The use of a constitutively-active, truncated Notch transgene construct (N IC ) was exploited to determine if Notch activation is a ‘driving’ event in melanocytic transformation or instead a ‘passenger’ event associated with melanoma progression. N IC -infected melanocytes displayed increased proliferative capacity and biological features more reminiscent of melanoma such as dysregulated cell adhesion and migration. Gene expression analyses supported these observations and aided in the identification of MCAM, an adhesion molecule associated with acquisition of the malignant phenotype, as a direct target of Notch transactivation. N IC -positive melanocytes grew at clonal density, proliferated in limiting media conditions, and also exhibited anchorage-independent growth suggesting that Notch, alone, is a transforming oncogene in human melanocytes, a phenomenon not previously described for any melanoma oncogene; this new information yields valuable insight into the basic epidemiology of melanoma and launches a realm of possibilities for drug intervention in this deadly disease