A Deep Intronic PKHD1 Variant Identified by SpliceAI in a Deceased Neonate With Autosomal Recessive Polycystic Kidney Disease.

The etiologies of newborn deaths in neonatal intensive care units usually remain unknown, even after genetic testing. Whole-genome sequencing, combined with artificial intelligence-based methods for predicting the effects of non-coding variants, provide an avenue for resolving these deaths. Using one such method, SpliceAI, we identified a maternally inherited deep intronic PKHD1 splice variant (chr6:52030169T>C), in trans with a pathogenic missense variant (p.Thr36Met), in a newborn who died of autosomal recessive polycystic kidney disease at age 2 days. We validated the deep intronic variant's impact in maternal urine-derived cells expressing PKHD1. Reverse transcription polymerase chain reaction followed by Sanger sequencing showed that the variant causes inclusion of 147bp of the canonical intron between exons 29 and 30 of PKHD1 into the mRNA, including a premature stop codon. Allele-specific expression analysis at a heterozygous site in the mother showed that the mutant allele completely suppresses canonical splicing. In an unrelated healthy control, there was no evidence of transcripts including the novel splice junction. We returned a diagnostic report to the parents, who underwent in vitro embryo selection.

The Buddy Benefit: Increasing the Effectiveness of an Employee-Targeted Weight-Loss Program.

It is well known that significant others (particularly romantic partners) can influence people's weight management efforts. However, what constitutes effective support-and from which type of individual (e.g., romantic partner, family member, friend)-is unclear. Thus, framed by confirmation theory, we assessed the effectiveness and types of communication of a weight-loss "buddy" through reports of 704 individuals enrolled in a 15-week synchronous online weight-loss program. Roughly 54% of participants chose buddies; and those who did lost more weight and waist inches than those who were involved in the program without buddy support. We also found that a combination of high accepting and high challenging messages from buddies was associated with the greatest decrease in body mass index (BMI) as well as the greatest reduction in waist size. Furthermore, the support by romantic partners paralleled support by other types of buddies. Having a supportive buddy who was not a romantic partner was just as effective as turning to a romantic partner for assistance. This study underscores the important role of a buddy in supporting weight-loss program involvement and encourages individuals to consider enlisting the help of a buddy, as opposed to losing weight alone, in order to maximize weight management effectiveness.

Mindfulness Approaches and Weight Loss, Weight Maintenance, and Weight Regain.

PURPOSE OF REVIEW: There is an urgent need for effective weight management techniques, as more than one third of US adults are overweight or obese. Recommendations for weight loss include a combination of reducing caloric intake, increasing physical activity, and behavior modification. Behavior modification includes mindful eating or eating with awareness. The purpose of this review was to summarize the literature and examine the impact of mindful eating on weight management. RECENT FINDINGS: The practice of mindful eating has been applied to the reduction of food cravings, portion control, body mass index, and body weight. Past reviews evaluating the relationship between mindfulness and weight management did not focus on change in mindful eating as the primary outcome or mindful eating as a measured variable. This review demonstrates strong support for inclusion of mindful eating as a component of weight management programs and may provide substantial benefit to the treatment of overweight and obesity.

Using synchronous distance education to deliver a weight loss intervention: A randomized trial.

OBJECTIVE: To implement a randomized trial to evaluate the effectiveness of a weight loss program delivered using synchronous distance education compared with a wait-list control group with 6-month follow-up. METHODS: Adults with a body mass index (BMI) ≥25 were randomized to the intervention (n = 42) or wait-list control group (n = 38). The intervention group participated in a synchronous, online, 15-week weight loss program; weight loss was the primary outcome. Secondary measures included height, BMI, and confidence in ability to be physically active and eat healthy. Assessments occurred at three and four time points in the intervention and control group, respectively. RESULTS: Participants who completed the program lost significantly more weight (1.8 kg) than those in the wait-list control group (0.25 kg) at week 15 [F(1,61) = 6.19, P = 0.02] and had a greater reduction in BMI (0.71 vs. 0.14 kg/m(2) ), [F(1,61) = 7.45, P = 0.01]. There were no significant differences between the intervention and the wait-list control groups for change in confidence in ability to be physically active or eat healthy. Weight loss was maintained at 6 months. CONCLUSIONS: Use of synchronous distance education is a promising approach for weight loss. The results of this study will help to inform future research that employs Web-based interventions.

Using synchronous distance-education technology to deliver a weight management intervention.

OBJECTIVE: To compare the effectiveness of online delivery of a weight management program using synchronous (real-time), distance-education technology to in-person delivery. METHODS: Synchronous, distance-education technology was used to conduct weekly sessions for participants with a live instructor. Program effectiveness was indicated by changes in weight, body mass index (BMI), waist circumference, and confidence in ability to eat healthy and be physically active. RESULTS: Online class participants (n = 398) had significantly greater reductions in BMI, weight, and waist circumference than in-person class participants (n = 1,313). Physical activity confidence increased more for in-person than online class participants. There was no difference for healthy eating confidence. CONCLUSIONS AND IMPLICATIONS: This project demonstrates the feasibility of using synchronous distance-education technology to deliver a weight management program. Synchronous online delivery could be employed with no loss to improvements in BMI, weight, and waist circumference.

Delivering a behavior-change weight management program to teachers and state employees in North Carolina.

PURPOSE: To ascertain the effectiveness of a behavior-change weight management program offered to teachers and state employees in North Carolina (NC). DESIGN: Fifteen-week weight management program with premeasures and postmeasures. SETTING: State agencies and public K-12 schools in five NC counties. SUBJECTS: A total of 2574 NC state employees enrolled in 141 classes. INTERVENTION: Eat Smart, Move More, Weigh Less (ESMMWL) is a 15-week weight management program delivered by trained instructors. Lessons inform, empower, and motivate participants to live mindfully as they make choices about eating and physical activity. MEASURES: Height, weight, body mass index (BMI), waist circumference, blood pressure, confidence in ability to eat healthy and be physically active, changes in eating, and physical activity behaviors. ANALYSIS: Descriptive statistics, t-tests, χ(2) tests, and analyses of variance. RESULTS: Data are reported for 1341 participants in ESMMWL who completed the program, submitted an evaluation, and had not participated in the program in the past; 89% were female and mean age was 48.8 years. Average BMI and waist circumference decreased significantly. Confidence in eating healthfully and being physically active increased significantly. The percentage of participants with a BMI < 30 kg/m(2) increased from 40% to 45% and those with a normal blood pressure increased from 23% to 32.5%. Participants reported being more mindful of what and how much they ate (92%), being more mindful of how much daily physical activity they got (88%), and eating fewer calories (87.3%). CONCLUSION: This project demonstrated the feasibility of implementing a behavior change-based weight management program at the worksite to achieve positive outcomes related to weight, blood pressure, healthy eating, and physical activity behaviors. Programs such as this have the potential to provide health care cost savings.

Effects of a behavior-based weight management program delivered through a state cooperative extension and local public health department network, North Carolina, 2008-2009.

INTRODUCTION: Eat Smart, Move More, Weigh Less (ESMMWL) is an adult weight management program developed in response to North Carolina Obesity Plan recommendations to make weight management interventions accessible to underserved populations. ESMMWL was designed to be delivered through the North Carolina Cooperative Extension and North Carolina Division of Public Health. Program coursework included content on evidence-based eating and physical activity behaviors and incorporated mindful eating concepts. The objectives of this study were to describe participant changes in weight and behaviors and to document the effectiveness of the program. METHODS: In this prospective pilot study, courses were delivered and data collected from January 2008 through June 2009. Instructors provided feedback about implementation. For participants, height, weight, and waist circumference were measured at baseline and completion. Participants completed a questionnaire about changes in their eating and physical activity behaviors, changes in their confidence to engage in weight management behaviors, and their satisfaction with the course. RESULTS: Seventy-nine instructors delivered 101 ESMMWL courses in 48 North Carolina counties. Most of the 1,162 completers were white women. Approximately 83% reported moving toward or attaining their goal. The average weight loss was 8.4 lb. Approximately 92% reported an increase in confidence to eat healthfully, and 82% reported an increase in confidence to be physically active. Instructors made suggestions for program standardization. CONCLUSION: This study demonstrated the effectiveness, diffusion, and implementation of a theoretically based weight management program through a state extension and local public health department network. Study of the sustainability of changes in eating and physical activity behaviors is needed.