Understanding self-management behaviors in symptomatic adults with uncertain etiology using an illness perceptions framework

The self-management behaviors of individuals with medical conditions that have an unknown etiology have not been studied. This study assesses the relationship between illness perceptions and various illness self-management behaviors in patients undergoing clinical genomic sequencing to identify a genetic cause for their condition. Hierarchical linear regression, Poisson linear regression, and logistic regression were used to assess the effect of illness perceptions (i.e., perceived consequences, timeline, personal control, treatment control, identity, concern, understanding, emotional impact, and causal beliefs as measured by the Brief Illness Perceptions Questionnaire) on healthcare use, prescription medication use, and doctor recommended supplement use, respectively (n = 200). Analyses revealed that (1) illness identity beliefs were positively associated with healthcare use (β =.20, p =.04), (2) both treatment control beliefs (B =.03, p =.02) and genetic causal beliefs (B =.17, p =.049) were positively associated with prescription medication use, and (3) both timeline beliefs (OR =1.23, p =.02) and emotional impact (OR =1.20, p =.02) were positively associated with doctor recommended supplement use. These findings can be used to inform the development of guidelines for treating patients who are seeking a genetic diagnosis for their illness

Patient hopes for diagnostic genomic sequencing: roles of uncertainty and social status

For patients with unexplained or undiagnosed conditions, genomic sequencing offers the hope of resolving unanswered questions. With the growth of clinical genomic sequencing, understanding factors that shape patients' hope for information could have important implications for developing patient education guidelines. Based on the goal-directed theory of hope, we investigated illness uncertainty as a form of motivation and subjective social status as a form of perceived resources to predict the amount and kinds of information that adult patients (N=191) and parents of pediatric patients (N=79) hoped to receive from diagnostic sequencing results. Participants were part of a larger longitudinal study on clinical genomic sequencing, but the current study focuses on their hopes for diagnostic sequencing results. Hopes for information were assessed through close-ended and open-ended responses. Findings from mixed methods analyses indicated that although patients and parents hoped to learn multiple kinds of information from diagnostic sequencing results, their hopes appeared to be influenced by their illness uncertainty and perceptions of their social and economic resources. These findings suggest that patients' illness uncertainty and perceived resources could be useful avenues for discussing patient hopes and educating patients about strengths and limitations of genomic sequencing

Protective Effects of C-Type Natriuretic Peptide on Linear Growth and Articular Cartilage Integrity in a Mouse Model of Inflammatory Arthritis

Objective: The C-type natriuretic peptide (CNP) signaling pathway is a major contributor to postnatal skeletal growth in humans. This study was undertaken to investigate whether CNP signaling could prevent growth delay and cartilage damage in an animal model of inflammatory arthritis. Methods: We generated transgenic mice that overexpress CNP (B6.SJL-Col2a1-NPPC) in chondrocytes. We introduced the CNP transgene into mice with experimental systemic inflammatory arthritis (K/BxN T cell receptor [TCR]) and determined the effect of CNP overexpression in chondrocytes on the severity of arthritis, cartilage damage, and linear growth. We also examined primary chondrocyte cultures for changes in gene and protein expression resulting from CNP overexpression. Results: K/BxN TCR mice exhibited linear growth delay (P < 0.01) compared to controls, and this growth delay was correlated with the severity of arthritis. Diminished chondrocyte proliferation and matrix production was also seen in K/BxN TCR mice. Compared to non–CNP-transgenic mice, K/BxN TCR mice with overexpressed CNP had milder arthritis, no growth delay, and less cartilage damage. Primary chondrocytes from mice overexpressing CNP were less sensitive to inflammatory cytokines than wild-type mouse chondrocytes. Conclusion: CNP overexpression in chondrocytes can prevent endochondral growth delay and protect against cartilage damage in a mouse model of inflammatory arthritis. Pharmacologic or biologic modulation of the CNP signaling pathway may prevent growth retardation and protect cartilage in patients with inflammatory joint diseases, such as juvenile idiopathic arthritis

Erratum to: How Can Psychological Science Inform Research About Genetic Counseling for Clinical Genomic Sequencing?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147141/1/jgc40372.pd

How Can Psychological Science Inform Research About Genetic Counseling for Clinical Genomic Sequencing?

Next generation genomic sequencing technologies (including whole genome or whole exome sequencing) are being increasingly applied to clinical care. Yet, the breadth and complexity of sequencing information raise questions about how best to communicate and return sequencing information to patients and families in ways that facilitate comprehension and optimal health decisions. Obtaining answers to such questions will require multidisciplinary research. In this paper, we focus on how psychological science research can address questions related to clinical genomic sequencing by explaining emotional, cognitive, and behavioral processes in response to different types of genomic sequencing information (e.g., diagnostic results and incidental findings). We highlight examples of psychological science that can be applied to genetic counseling research to inform the following questions: (1) What factors influence patients’ and providers’ informational needs for developing an accurate understanding of what genomic sequencing results do and do not mean?; (2) How and by whom should genomic sequencing results be communicated to patients and their family members?; and (3) How do patients and their families respond to uncertainties related to genomic information?Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147034/1/jgc40193.pd

Multi-Factor Impact Analysis of Agricultural Production in Bangladesh with Climate Change

Diverse vulnerabilities of Bangladesh's agricultural sector in 16 sub-regions are assessed using experiments designed to investigate climate impact factors in isolation and in combination. Climate information from a suite of global climate models (GCMs) is used to drive models assessing the agricultural impact of changes in temperature, precipitation, carbon dioxide concentrations, river floods, and sea level rise for the 2040-2069 period in comparison to a historical baseline. Using the multi-factor impacts analysis framework developed in Yu et al. (2010), this study provides new sub-regional vulnerability analyses and quantifies key uncertainties in climate and production. Rice (aman, boro, and aus seasons) and wheat production are simulated in each sub-region using the biophysical Crop Environment REsource Synthesis (CERES) models. These simulations are then combined with the MIKE BASIN hydrologic model for river floods in the Ganges-Brahmaputra-Meghna (GBM) Basins, and the MIKE21Two-Dimensional Estuary Model to determine coastal inundation under conditions of higher mean sea level. The impacts of each factor depend on GCM configurations, emissions pathways, sub-regions, and particular seasons and crops. Temperature increases generally reduce production across all scenarios. Precipitation changes can have either a positive or a negative impact, with a high degree of uncertainty across GCMs. Carbon dioxide impacts on crop production are positive and depend on the emissions pathway. Increasing river flood areas reduce production in affected sub-regions. Precipitation uncertainties from different GCMs and emissions scenarios are reduced when integrated across the large GBM Basins' hydrology. Agriculture in Southern Bangladesh is severely affected by sea level rise even when cyclonic surges are not fully considered, with impacts increasing under the higher emissions scenario

Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA

Background: Vericiguat reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HF) in patients with worsening HF and reduced left ventricular ejection fraction (LVEF).Objectives: The authors assessed the association of LVEF with biomarker levels, risk of outcome, and whether the effect of vericiguat was homogeneous across LVEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction) trial.Methods: Patients were grouped by LVEF tertiles (≤24%, 25%-33%, and &gt;33%). Patient characteristics, clinical outcomes, and efficacy and safety of vericiguat were examined by tertile. Prespecified biomarkers including N-terminal pro–B-type natriuretic peptide, cardiac troponin T, growth differentiation factor 15, interleukin 6, high-sensitivity C-reactive protein, and cystatin C were examined.Results: The mean LVEF was 29% ± 8% (range: 5%-45%). A pattern of higher N-terminal pro–B-type natriuretic peptide, high-sensitivity C-reactive protein, and interleukin 6 was evident in patients in the lowest LVEF tertile vs the other tertiles. Patients with lower LVEF experienced higher rates of the composite outcome (41.7%, 36.3%, and 33.4% for LVEF ≤24, 25-33, and &gt;33; P &lt; 0.001). There was no significant treatment effect heterogeneity of vericiguat across LVEF groups (adjusted HR from lowest to highest tertiles: 0.79 [95% CI: 0.68-0.94]; 0.95 [95% CI: 0.82-1.11]; 0.94 [95% CI: 0.79-1.11]; P for interaction = 0.222), although the HR was numerically lower in the lowest tertile. There was also no heterogeneity of effect for CVD and HF hospitalization individually (P interaction for CVD = 0.964; HF hospitalization = 0.438). Discontinuation of treatment because of adverse events, symptomatic hypotension, or syncope was consistent across the range of LVEF.Conclusions: Patients with lower LVEF had a distinctive biomarker profile and a higher risk for adverse clinical outcomes vs those with a higher LVEF. There was no significant interaction for the benefit of vericiguat across LVEF tertiles, although the largest signal for benefit in both the primary outcome and HF hospitalizations was noted in tertile 1 (LVEF ≤24%).</p

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

Urban Areas in Coastal Zones

[First Paragraph] Coastal cities have been subjected to extreme weather events since the onset of urbanization. Climatic change, in particular sea level rise, coupled with rapid urban development are amplifying the challenge of managing risks to coastal cities. Moreover, urban expansion and changes and intensification in land use further pressure sensitive coastal environments through pollution and habitat loss