117 research outputs found
Effective Weather Messaging: Applying the Bad News Response Model to Hurricane Warnings
Sweeny and Shepperd (2007, 2009) proposed the Bad News Response Model (BNRM), outlining three effective responses (i.e., Watchful Waiting, Active Change, Acceptance) as a function of the perceived controllability, likelihood, and severity of bad news. In the current study, we have adapted the BNRM, previously used in health-related scenarios, to explore the relationship between message content and responses in the context of hurricane warnings. Participants viewed hurricane warnings manipulated by severity (Category 1 vs. Category 5) and the inclusion of call-to-action statements (CTAs). The present study attempted to evaluate the effects of severity and controllability on participants’ engagement in desirable response types. We found that individuals chose Active Change more frequently when the severity was high. However, the situational factors did not significantly affect preferences for Watchful Waiting and Acceptance. The lack of significant severity and controllability effects were likely due, in part, to our small sample size, which severely underpowered the study. Also, individuals may have misinterpreted the intended manipulations. Thus, further research is necessary to provide more insight into the communication of weather, encourage appropriate preparations for approaching storms, and inform potential policy changes for weather reporting
Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease
OBJECTIVE:
To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines.
STUDY DESIGN:
This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention.
RESULTS:
There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications.
CONCLUSIONS:
More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management
In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis
Background & Aims
Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD.
Methods
We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system.
Results
Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001).
Conclusions
Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis
Twentyâ fiveâ year trajectories of insulin resistance and pancreatic βâ cell response and diabetes risk in nonalcoholic fatty liver disease
Background & AimsInsulin resistance is a risk marker for nonâ alcoholic fatty liver disease, and a risk factor for liver disease progression. We assessed temporal trajectories of insulin resistance and βâ cell response to serum glucose concentration throughout adulthood and their association with diabetes risk in nonâ alcoholic fatty liver disease.MethodsThree thousand and sixty participants from Coronary Artery Risk Development in Young Adults, a prospective biâ racial cohort of adults age 18â 30 years at baseline (1985â 1986; Y0) who completed up to 5 exams over 25 years and had fasting insulin and glucose measurement were included. At Y25 (2010â 2011), nonâ alcoholic fatty liver disease was assessed by noncontrast computed tomography after exclusion of other liver fat causes. Latent mixture modelling identified 25â year trajectories in homeostatic model assessment insulin resistance and βâ cell response homeostatic model assessmentâ β.ResultsThree distinct trajectories were identified, separately, for homeostatic model assessment insulin resistance (lowâ stable [47%]; moderateâ increasing [42%]; and highâ increasing [12%]) and homeostatic model assessmentâ β (lowâ decreasing [16%]; moderateâ decreasing [63%]; and highâ decreasing [21%]). Y25 nonâ alcoholic fatty liver disease prevalence was 24.5%. Among nonâ alcoholic fatty liver disease, highâ increasing homeostatic model assessment insulin resistance (referent: lowâ stable) was associated with greater prevalent (OR 95% CI = 8.0, 2.0â 31.9) and incident (OR = 10.5, 2.6â 32.8) diabetes after multivariable adjustment including Y0 or Y25 homeostatic model assessment insulin resistance. In contrast, nonâ alcoholic fatty liver disease participants with lowâ decreasing homeostatic model assessmentâ β (referent: highâ decreasing) had the highest odds of prevalent (OR = 14.1, 3.9â 50.9) and incident (OR = 10.3, 2.7â 39.3) diabetes.ConclusionTrajectories of insulin resistance and βâ cell response during young and middle adulthood are robustly associated with diabetes risk in nonâ alcoholic fatty liver disease. Thus, how persons with nonâ alcoholic fatty liver disease develop resistance to insulin provides important information about risk of diabetes in midlife above and beyond degree of insulin resistance at the time of nonâ alcoholic fatty liver disease assessment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146427/1/liv13747_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146427/2/liv13747.pd
It Starts with Us: Exploring Inclusive Pedagogies through Relational Learning Approaches among Library Workers
Chapter 43 the Vol. 2 of Exploring Inclusive & Equitable Pedagogies: Creating Space for All Learners.978-0-8389-3854-
Nε-lysine acetylation of the histone-like protein HBsu influences antibiotic survival and persistence in Bacillus subtilis
Nε-lysine acetylation is recognized as a prevalent post-translational modification (PTM) that regulates proteins across all three domains of life. In Bacillus subtilis, the histone-like protein HBsu is acetylated at seven sites, which regulates DNA compaction and the process of sporulation. In Mycobacteria, DNA compaction is a survival strategy in response antibiotic exposure. Acetylation of the HBsu ortholog HupB decondenses the chromosome to escape this drug-induced, non-growing state, and in addition, regulates the formation of drug-tolerant subpopulations by altering gene expression. We hypothesized that the acetylation of HBsu plays similar regulatory roles. First, we measured nucleoid area by fluorescence microscopy and in agreement, we found that wild-type cells compacted their nucleoids upon kanamycin exposure, but not exposure to tetracycline. We analyzed a collection of HBsu mutants that contain lysine substitutions that mimic the acetylated (glutamine) or unacetylated (arginine) forms of the protein. Our findings indicate that some level of acetylation is required at K3 for a proper response and K75 must be deacetylated. Next, we performed time-kill assays of wild-type and mutant strains in the presence of different antibiotics and found that interfering with HBsu acetylation led to faster killing rates. Finally, we examined the persistent subpopulation and found that altering the acetylation status of HBsu led to an increase in persister cell formation. In addition, we found that most of the deacetylation-mimic mutants, which have compacted nucleoids, were delayed in resuming growth following removal of the antibiotic, suggesting that acetylation is required to escape the persistent state. Together, this data adds an additional regulatory role for HBsu acetylation and further supports the existence of a histone-like code in bacteria
Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia
Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.</p
Increasing diversity, equity, and inclusion in the fields of nutrition and obesity: A roadmap to equity in academia
Research shows that a diverse faculty improves academic, clinical, and research outcomes in higher education. Despite that, persons in minority groups, usually categorized by race or ethnicity, are underrepresented in academia (URiA). The Nutrition Obesity Research Centers (NORCs), supported by the NIDDK, hosted workshops on five separate days in September and October 2020. NORCs convened these workshops to identify barriers and facilitators for diversity, equity, and inclusion (DEI) and provide specific recommendations to improve DEI within obesity and nutrition for individuals from URiA groups. Recognized experts on DEI presented each day, after which the NORCs conducted breakout sessions with key stakeholders who engage in nutrition and obesity research. The breakout session groups included early-career investigators, professional societies, and academic leadership. The consensus from the breakout sessions was that glaring inequities affect URiA in nutrition and obesity, particularly related to recruitment, retention, and advancement. Recommendations from the breakout sessions to improve DEI across the academe focused on six themes: (1) recruitment, (2) retention, (3) advancement, (4) intersectionality of multiple challenges (e.g., being Black and a woman), (5) funding agencies, and (6) implementation of strategies to address problems related to DEI
Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease
Background & aimsType 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.MethodsChildren with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.ResultsThis study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0-2.8]), associated with BMI z-score (HR, 1.8 [1.0-3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0-1.7]), and fibrosis stage (HR, 1.3 [1.0-1.5]).ConclusionsChildren with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed
Rare damaging CCR2 variants are associated with lower lifetime cardiovascular risk.
BACKGROUND: Previous work has shown a role of CCL2, a key chemokine governing monocyte trafficking, in atherosclerosis. However, it remains unknown whether targeting CCR2, the cognate receptor of CCL2, provides protection against human atherosclerotic cardiovascular disease. METHODS: Computationally predicted damaging or loss-of-function (REVEL > 0.5) variants within CCR2 were detected in whole-exome-sequencing data from 454,775 UK Biobank participants and tested for association with cardiovascular endpoints in gene-burden tests. Given the key role of CCR2 in monocyte mobilization, variants associated with lower monocyte count were prioritized for experimental validation. The response to CCL2 of human cells transfected with these variants was tested in migration and cAMP assays. Validated damaging variants were tested for association with cardiovascular endpoints, atherosclerosis burden, and vascular risk factors. Significant associations were replicated in six independent datasets (n = 1,062,595). RESULTS: Carriers of 45 predicted damaging or loss-of-function CCR2 variants (n = 787 individuals) were at lower risk of myocardial infarction and coronary artery disease. One of these variants (M249K, n = 585, 0.15% of European ancestry individuals) was associated with lower monocyte count and with both decreased downstream signaling and chemoattraction in response to CCL2. While M249K showed no association with conventional vascular risk factors, it was consistently associated with a lower risk of myocardial infarction (odds ratio [OR]: 0.66, 95% confidence interval [CI]: 0.54-0.81, p = 6.1 × 10-5) and coronary artery disease (OR: 0.74, 95%CI: 0.63-0.87, p = 2.9 × 10-4) in the UK Biobank and in six replication cohorts. In a phenome-wide association study, there was no evidence of a higher risk of infections among M249K carriers. CONCLUSIONS: Carriers of an experimentally confirmed damaging CCR2 variant are at a lower lifetime risk of myocardial infarction and coronary artery disease without carrying a higher risk of infections. Our findings provide genetic support for the translational potential of CCR2-targeting as an atheroprotective approach
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