Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

A Common Variant in the SETD7 Gene Predicts Serum Lycopene Concentrations

Dietary intake and higher serum concentrations of lycopene have been associated with lower incidence of prostate cancer and other chronic diseases. Identifying determinants of serum lycopene concentrations may thus have important public health implications. Prior studies have suggested that serum lycopene concentrations are under partial genetic control. The goal of this research was to identify genetic predictors of serum lycopene concentrations using the genome-wide association study (GWAS) approach among a sample of 441 Old Order Amish adults that consumed a controlled diet. Linear regression models were utilized to evaluate associations between genetic variants and serum concentrations of lycopene. Variant rs7680948 on chromosome 4, located in the intron region of the SETD7 gene, was significantly associated with serum lycopene concentrations (p = 3.41 × 10−9). Our findings also provided nominal support for the association previously noted between SCARB1 and serum lycopene concentrations, although with a different SNP (rs11057841) in the region. This study identified a novel locus associated with serum lycopene concentrations and our results raise a number of intriguing possibilities regarding the nature of the relationship between SETD7 and lycopene, both of which have been independently associated with prostate cancer. Further investigation into this relationship might help provide greater mechanistic understanding of these associations

The Founder: Dispositional Greed, Showbiz, and the Commercial Determinants of Health

Marketing unhealthy products by multinational corporations has caused considerable harm to individual health, collective wellbeing, and environmental sustainability. This is a growing threat to all societies and a significant contributor to the rising global burden of non-communicable diseases and early mortality. While there is growing consideration of the commercial determinants of health, this is largely focused on the methods by which unhealthy products are marketed and disseminated, including efforts to manipulate policy. Little attention has been paid to the underlying psychological traits and worldviews that are driving corporate greed. Here, we consider the role of “dispositional greed” in the commercial determinants of health with a focus on the historical attitudes and culture in the ultra-processed food industry—exemplified by “The Founder” of the McDonald’s franchise. We argue that greed and associated psychological constructs, such as social dominance orientation and collective narcissism, permeate the commercial determinants of health at a collective level. This includes how a culture of greed within organizations, and individual dispositional greed, can magnify and cluster at scale, perpetuated by social dominance orientation. We also consider the ways in which “showbiz” marketing specifically targets marginalized populations and vulnerable groups, including children—in ways that are justified, or even celebrated despite clear links to non-communicable diseases and increased mortality. Finally, we consider how greed and exploitative mindsets mirror cultural values and priorities, with trends for increasing collective narcissism at scale, recognizing that many of these attitudes are cultivated in early life. A healthier future will depend on navigating a path that balances material prosperity with physical and spiritual wellbeing. This will require cultural change that places higher value on kindness, reciprocity, and mutualistic values especially in early life, for more equitable flourishing

The Relationship between Gastrointestinal Health, Micronutrient Concentrations, and Autoimmunity: A Focus on the Thyroid

Currently, there is a lack of understanding of why many patients with thyroid dysfunction remain symptomatic despite being biochemically euthyroid. Gastrointestinal (GI) health is imperative for absorption of thyroid-specific nutrients as well as thyroid function directly. This comprehensive narrative review describes the impact of what the authors have conceptualized as the “nutrient–GI–thyroid axis”. Compelling evidence reveals how gastrointestinal health could be seen as the epicenter of thyroid-related care given that: (1) GI conditions can lower thyroid-specific nutrients; (2) GI care can improve status of thyroid-specific nutrients; (3) GI conditions are at least 45 times more common than hypothyroidism; (4) GI care can resolve symptoms thought to be from thyroid dysfunction; and (5) GI health can affect thyroid autoimmunity. A new appreciation for GI health could be the missing link to better nutrient status, thyroid status, and clinical care for those with thyroid dysfunction

Post-Operative Day Zero Discharge after Laparoscopic Appendectomy Does Not Worsen High-Yield Outcomes: A NSQIP Database Observational Study

Background: Post-operative day zero (POD-0) discharge after laparoscopic appendectomy for uncomplicated appendicitis has been studied primarily in single-center or pediatric studies. A larger study from a national sample addressing high-yield outcomes can update and supplement current literature and evaluate early discharge rates. Methods: This is a retrospective, observational National Surgical Quality Improvement (NSQIP) database study of laparoscopic appendectomies for uncomplicated appendicitis performed 2016–2019, with discharge POD-0 or post-operative day one (POD-1). Study outcomes included any or serious complication, unplanned readmission, and unplanned return to operating room (OR). Unadjusted outcomes comparisons were estimated via chi-square tests. Multivariate logistic regression models were constructed to adjust for potential confounders (sex, ethnicity, frailty, ASA score, tobacco use and diabetes). Results: A total of 25,629 patients were included in this analysis. More patients were discharged POD-1 (n = 15,229) than POD-0 (n = 10,440). Rate of any or serious complication was lower in patients discharged POD-0 than POD-1 (any complication: 2.0 vs. 2.8, p = 0.0002, serious complication: 1.4 vs. 2.1, p < 0.0001). Unplanned return to OR and unplanned readmission rates were not different between POD-0 and POD-1 discharged groups (p = 0.9 and p = 0.6, respectively). These findings were robust to adjustment for covariates in logistic regression modeling. Conclusions: This study found that unplanned readmission and other outcomes do not appear to be adversely affected by early discharge after laparoscopic appendectomy for uncomplicated appendicitis, confirming prior evidence on the topic in a large, national sample. It also found that early discharge does not appear to be used in most of these patients

The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial

BackgroundClinical evidence on the use of cannabidiol (CBD) for sleep remains limited. Even fewer studies have tested the comparative effectiveness of cannabinoid formulations found within CBD products used for sleep or how they compare to other complementary therapies such as melatonin.MethodsParticipants (N = 1,793 adults experiencing symptoms of sleep disturbance) were randomly assigned to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15 mg CBD or 5 mg melatonin, alone or in combination with minor cannabinoids. Sleep disturbance was assessed over a period of 5 weeks (baseline week and 4 weeks of product use) using Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A, administered via weekly online surveys. A linear mixed-effects regression model was used to assess the differences in the change in sleep disturbance through time between each active product arm and CBD isolate.ResultsAll formulations exhibited a favorable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in sleep disturbance (p &lt; 0.001 in within-group comparisons). Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality. There were no significant differences in effect, however, between 15 mg CBD isolate and formulations containing 15 mg CBD and 15 mg cannabinol (CBN), alone or in combination with 5 mg cannabichromene (CBC). There were also no significant differences in effect between 15 mg CBD isolate and formulations containing 5 mg melatonin, alone or in combination with 15 mg CBD and 15 mg CBN.ConclusionsOur findings suggest that chronic use of a low dose of CBD is safe and could improve sleep quality, though these effects do not exceed that of 5 mg melatonin. Moreover, the addition of low doses of CBN and CBC may not improve the effect of formulations containing CBD or melatonin isolate

International ResearchKit App for women with menstrual pain: Development, Access, and Engagement

Background: Primary dysmenorrhea is a common condition in women of reproductive age. A previous app-based study undertaken by our group demonstrated that a smartphone app supporting self-acupressure introduced by a health care professional can reduce menstrual pain. Objective: This study aims to evaluate whether a specific smartphone app is effective in reducing menstrual pain in 18- to 34-year-old women with primary dysmenorrhea in a self-care setting. One group of women has access to the full-featured study app and will be compared with 2 control groups who have access to fewer app features. Here, we report the trial design, app development, user access, and engagement. Methods: On the basis of the practical implications of the previous app-based study, we revised and reengineered the study app and included the ResearchKit (Apple Inc) framework. Behavior change techniques (BCTs) were implemented in the app and validated by expert ratings. User access was estimated by assessing recruitment progress over time. User evolution and baseline survey respondent rate were assessed to evaluate user engagement. Results: The development of the study app for a 3-armed randomized controlled trial required a multidisciplinary team. The app is accessible for the target population free of charge via the Apple App Store. In Germany, within 9 months, the app was downloaded 1458 times and 328 study participants were recruited using it without external advertising. A total of 98.27% (5157/5248) of the app-based baseline questions were answered. The correct classification of BCTs used in the app required psychological expertise. Conclusions: Conducting an innovative app study requires multidisciplinary effort. Easy access and engagement with such an app can be achieved by recruitment via the App Store. Future research is needed to investigate the determinants of user engagement, optimal BCT application, and potential clinical and self-care scenarios for app use. Trial registration: ClinicalTrials.gov NCT03432611; https://clinicaltrials.gov/ct2/show/NCT03432611 (Archived by WebCite at http://www.webcitation.org/75LLAcnCQ)

A Common Variant in the SETD7 Gene Predicts Serum Lycopene Concentrations

Dietary intake and higher serum concentrations of lycopene have been associated with lower incidence of prostate cancer and other chronic diseases. Identifying determinants of serum lycopene concentrations may thus have important public health implications. Prior studies have suggested that serum lycopene concentrations are under partial genetic control. The goal of this research was to identify genetic predictors of serum lycopene concentrations using the genome-wide association study (GWAS) approach among a sample of 441 Old Order Amish adults that consumed a controlled diet. Linear regression models were utilized to evaluate associations between genetic variants and serum concentrations of lycopene. Variant rs7680948 on chromosome 4, located in the intron region of the SETD7 gene, was significantly associated with serum lycopene concentrations (p = 3.41 × 10−9). Our findings also provided nominal support for the association previously noted between SCARB1 and serum lycopene concentrations, although with a different SNP (rs11057841) in the region. This study identified a novel locus associated with serum lycopene concentrations and our results raise a number of intriguing possibilities regarding the nature of the relationship between SETD7 and lycopene, both of which have been independently associated with prostate cancer. Further investigation into this relationship might help provide greater mechanistic understanding of these associations

Rating of Included Trials on the Efficacy-Effectiveness Spectrum : development of a new tool for systematic reviews

Funding: This work was supported by the National Institutes of Health National Center for Complementary and Integrative Health (R24 AT001293)Peer reviewedPostprin