Development of a transdiagnostic digital interactive application for eating disorders: psychometric properties, satisfaction, and perceptions on implementation in clinical practice.

BACKGROUND: Given limited availability of informed treatments for people affected by eating disorders (EDs), there has been increasing interest in developing self-administered, technology-based ED interventions. However, many available interventions are limited to a specific ED diagnosis or assume that participants are ready to change. We developed a digital self-help application (called ASTrA) that was explicitly designed to be transdiagnostic and to help increase motivation for change. The aim of the present study was to describe the development and examine the psychometric properties, user satisfaction and rated potentials for practical use of our application. METHODS: The content of our application was based on concepts derived from self-determination theory, the transtheoretical model of change, and cognitive theory. The application was developed by a multidisciplinary team of clinicians, researchers, staff members and individuals with lived ED experience, each being involved in all steps of the application's development. We tested validity, reliability, satisfaction and perceived feasibility for clinical implementation in an independent sample of 15 patients with an ED and 13 clinicians specialized in ED treatment. Psychometric properties were evaluated using descriptive statistics, correlations, content validity indices and intraclass coefficients. Differences in satisfaction ratings and perceived potential for clinical implementation of the application between clinicians and patients were examined using Mann-Whitney U tests. RESULTS: The digital application showed excellent validity (mean i-CVI: .93, range: .86-.96) and internal reliability (all Cronbach alpha's > .88). Patients and clinicians both considered the application acceptable, appropriate, and feasible for use in clinical practice. CONCLUSIONS: Findings suggest that our transdiagnostic interactive application has excellent psychometric properties. Furthermore, patients and clinicians alike were positive about the possible use of the application in clinical practice. The next step will be to investigate the application's effectiveness as an intervention to promote autonomous motivation and to facilitate remission in people on the waitlist for specialized ED treatment.

Mendelian randomization prioritizes abdominal adiposity as an independent causal factor for liver fat accumulation and cardiometabolic diseases.

Background: Observational studies have linked adiposity and especially abdominal adiposity to liver fat accumulation and non-alcoholic fatty liver disease. These traits are also associated with type 2 diabetes and coronary artery disease but the causal factor(s) underlying these associations remain unexplored. Methods: We used a multivariable Mendelian randomization study design to determine whether body mass index and waist circumference were causally associated with non-alcoholic fatty liver disease using publicly available genome-wide association study summary statistics of the UK Biobank (n = 461,460) and of non-alcoholic fatty liver disease (8434 cases and 770,180 control). A multivariable Mendelian randomization study design was also used to determine the respective causal contributions of waist circumference and liver fat (n = 32,858) to type 2 diabetes and coronary artery disease. Results: Using multivariable Mendelian randomization we show that waist circumference increase non-alcoholic fatty liver disease risk even when accounting for body mass index (odd ratio per 1-standard deviation increase = 2.35 95% CI = 1.31-4.22, p = 4.2e-03), but body mass index does not increase non-alcoholic fatty liver disease risk when accounting for waist circumference (0.86 95% CI = 0.54-1.38, p = 5.4e-01). In multivariable Mendelian randomization analyses accounting for liver fat, waist circumference remains strongly associated with both type 2 diabetes (3.27 95% CI = 2.89-3.69, p = 3.8e-80) and coronary artery disease (1.66 95% CI = 1.54-1.8, p = 3.4e-37). Conclusions: These results identify waist circumference as a strong, independent, and causal contributor to non-alcoholic fatty liver disease, type 2 diabetes and coronary artery disease, thereby highlighting the importance of assessing body fat distribution for the prediction and prevention of cardiometabolic diseases.

A trans-omic Mendelian randomization study of parental lifespan uncovers novel aging biology and therapeutic candidates for chronic diseases.

The study of parental lifespan has emerged as an innovative tool to advance aging biology and our understanding of the genetic architecture of human longevity and aging-associated diseases. Here, we leveraged summary statistics of a genome-wide association study including over one million parental lifespans to identify genetically regulated genes from the Genotype-Tissue Expression project. Through a combination of multi-tissue transcriptome-wide association analyses and genetic colocalization, we identified novel genes that may be associated with parental lifespan. Mendelian randomization (MR) analyses also identified circulating proteins and metabolites causally associated with parental lifespan and chronic diseases offering new drug repositioning opportunities such as those targeting apolipoprotein-B-containing lipoproteins. Liver expression of HP, the gene encoding haptoglobin, and plasma haptoglobin levels were causally linked with parental lifespan. Phenome-wide MR analyses were used to map genetically regulated genes, proteins and metabolites with other human traits as well as the disease-related phenome in the FinnGen cohorts (n = 135,638). Altogether, this study identified new candidate genes, circulating proteins and metabolites that may influence human aging as well as potential therapeutic targets for chronic diseases that warrant further investigation.

Glycerol-Based Dendrimer Nanocomposite Film as a Tunable pH-Sensor for Food Packaging.

Large amounts of food are wasted during the food supply chain. This loss is in part due to consumer confusion over dates on food packages that can indicate a variety of quality indicators in the product (e.g., expiration date, "best by" date, "sell by" dates, etc.). To reduce this food loss, much research has been focused on the films that offer simple and easily manipulated indication systems to detect food spoilage. However, these materials are usually hydrophilic biopolymers that can detect the food spoilage in a wide pH range but do not provide highly sensitive real-time measurements. In this work, a glycerol-based nanocomposite core-shell latex film was synthesized to create a responsive packaging material that can provide real-time pH detection of food with high sensitivity. First, the pH-responsive dendrimer comonomer was synthesized from glycerol and diamine. Then, the nanoencapsulation polymerization process via miniemulsion was conducted to form a core-shell structure with tunable nanoshell thickness for a sensible pH-responsive release (<0.5 pH change). Next, the flexible film encapsulated a color-indicative dye that provided highly sensitive and visible color changes as both the pH dropped and the time elapsed in the food. This film also provided a barrier to water and heat and resisted deformation. Ultimately, this nanocomposite flexible film pending a pH sensor has the potential as an intelligent food packaging material for a universal, accurate, easy-to-use, and real-time food spoilage monitoring system to reduce food waste.

Comparing steady-state to unsteady-state respiration rate measurement methods for design of modified atmosphere packaging of grape tomatoes and blueberries with microperforations.

Designing modified atmosphere packages (MAPs) for fresh produce requires respiration rate (RR) data. A steady-state (SS) approach is widely used but is expensive, tedious, and time-consuming. Unsteady-state (USS) methods mitigate shortcomings of the SS approach, but comparisons between the two approaches have not been done to verify the design outcomes of MAPs, especially those with microperforations. RR measurement methods for grape tomatoes and blueberries were compared. Data were then used to design microperforated MAP packages to compare predicted design specifications created from RR data with observed shelf life. Results show that the USS method provides similar magnitudes of RR and predicts similar numbers of perforations as the SS method. Observations of packages produced using 100 µm perforations, using measured respiration data, suggest that both methods underestimated what might have been deemed correct by about one microperforation. PRACTICAL APPLICATION: Designing packaging for fresh produce requires the knowledge of produce respiration. Steady-state methods are conceptually simple, but time-consuming. Unsteady-state methods are rapid. This work compares methods on design of packages.

Association of Long-term Exposure to Elevated Lipoprotein(a) Levels With Parental Life Span, Chronic Disease-Free Survival, and Mortality Risk: A Mendelian Randomization Analysis.

Importance: Elevated lipoprotein(a) (Lp[a]) levels are associated with atherosclerotic cardiovascular diseases. The association between high Lp(a) levels and human longevity phenotypes is, however, controversial. Objective: To examine whether genetically determined Lp(a) levels are associated with parental life span and chronic disease-free survival (health span) and the association between Lp(a) levels and long-term, all-cause mortality risk. Design, Setting, and Participants: In this genetic association study, cross-sectional mendelian randomization (UK Biobank [2006-2010] and LifeGen Consortium) and prospective analyses (European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk [1993-1997, with patients followed up to 2016]) were conducted using individual-level data on 139 362 participants. The association between a weighted genetic risk score of 26 independent single-nucleotide polymorphisms at the LPA locus on parental life span using individual participant data from the UK Biobank, as well as with summary statistics of a genome-wide association study of more than 1 million life spans (UK Biobank and LifeGen), were examined. The association between these single-nucleotide polymorphisms and the age at the end of the health span was tested using summary statistics of a previous genome-wide association study in the UK Biobank. The association between Lp(a) levels and all-cause mortality in the EPIC-Norfolk study was also investigated. Data were analyzed from December 2018 to December 2019. Exposures: Genetically determined and measured Lp(a) levels. Main Outcomes and Measures: Parental life span, health span, and all-cause mortality. Results: In 139 362 white British participants (mean [SD] age, 62.8 [3.9] years; 52% women) from the UK Biobank, increases in the genetic risk score (weighted for a 50-mg/dL increase in Lp[a] levels) were inversely associated with a high parental life span (odds ratio, 0.92; 95% CI, 0.89-0.94; P = 2.7 × 10-8). Using the Egger-mendelian randomization method, a negative association between LPA single-nucleotide polymorphisms and parental life span (mean [SD] Egger-mendelian randomization slope, -0.0019 [0.0002]; P = 2.22 × 10-18) and health span (-0.0019 [0.0003]; P = 3.00 × 10-13) was noted. In 18 720 participants from EPIC-Norfolk (5686 cases), the mortality risk for those with Lp(a) levels equal to or above the 95th percentile was equivalent to being 1.5 years older in chronologic age (ß coefficient [SE], 0.194 [0.064]). Conclusions and Relevance: The results of this study suggest a potential causal effect of absolute Lp(a) levels on human longevity as defined by parental life span, health span, and all-cause mortality. The results also provide a rationale for trials of Lp(a)-lowering therapy in individuals with high Lp(a) levels.

Spontaneous reduction of multiple pregnancy: incidence and effect on outcome.

OBJECTIVE: Our objective was to determine the incidence of spontaneous reduction in multiple pregnancies during the first 12 gestational weeks and determine the outcome of the surviving fetuses. STUDY DESIGN: Analysis of prospectively collected ultrasound and birth information on 709 multiple and 5962 singleton pregnancies conceived at a private infertility clinic. RESULTS: Spontaneous reduction of one or more gestational sacs and or embryos occurred before the 12th week of gestation in 36% of twin (95% CI, 32%-40%), 53% of triplet (95% CI, 44%-61%), and 65% of quadruplet (95% CI, 46%-85%) pregnancies. Reduction was less frequent after ovulation induction than after spontaneous ovulation. In general, pregnancy duration and birth weight were inversely related to the initial gestational sac number irrespective of the final birth number. CONCLUSIONS: More than 50% of patients with 3 or more gestational sacs had spontaneous reduction before 12 weeks. The surviving fetuses weighed less and were born earlier than unreduced pregnancies with the same initial number of fetuses.