Responses to Wildfire and Prescribed Fire Smoke: A Survey of a Medically Vulnerable Adult Population in the Wildland-Urban Interface, Mariposa County, California.

California plans to substantially increase the use of prescribed fire to reduce risk of catastrophic wildfires. Although for a beneficial purpose, prescribed fire smoke may still pose a health concern, especially among sensitive populations. We sought to understand community health experience, adaptive capacity, and attitudes regarding wildland and prescribed fire smoke to inform public health guidance. We conducted a cross-sectional survey of medically vulnerable persons in a rural, high fire risk county (N = 106, 76% > 65 years) regarding wildfire and prescribed smoke health effects; health protective actions; information needs; and support for fire management policies. Qualitative comments were reviewed for context and emerging themes. More than half (58%) of participants reported health impacts from wildfire smoke; 26% experienced impacts from prescribed fire smoke. Participants expressed strong support for prescribed fire, although also concerns about safety and smoke. Respondents reported taking actions to reduce smoke exposure (average 5 actions taken per person), but many (47%) lacked confidence that they could successfully protect their health. Persons who were satisfied with the information received tended to be more confident in their ability to protect their health compared to those who were not satisfied (61% vs. 35%). More information was desired on many topics, including notifications about prescribed fire, health protection and exposure reduction. As California expands use of prescribed fire, the need for effective health protective communication regarding smoke is increasingly vital. We recommend seeking solutions that strengthen community resilience and address equity for vulnerable populations.

Neighborhood Characteristics and Adolescent Suicidal Behavior: Evidence from a Population-based Study.

Research on the relationship between neighborhood characteristics and adolescents' risk of nonfatal suicidal behavior is scarce. We used California survey data to examine associations between measures of objective neighborhood quality (levels of violent crime, property crime, and socioeconomic disadvantage) and subjective neighborhood quality (perceptions of neighborhood safety and social cohesion) and adolescents' self-reported suicidal ideation and suicide attempt. Objective measures of neighborhood quality were unrelated to adolescents' risk of suicidal behavior. However, adolescents who perceived their neighborhoods to be less safe and less cohesive were 20%-45% more likely than nonsuicidal peers to report suicidal ideation and attempt.

Rural/Urban Disparities in Adolescent Nonfatal Suicidal Ideation and Suicide Attempt: A Population-Based Study.

Adolescent suicide rates exhibit stark geographic disparities, with rates highest in rural areas. The causes of this disparity remain unclear. We investigated whether adolescent nonfatal suicidal ideation and attempt-leading risk factors for suicide-demonstrate the same rural/urban disparity. Using adolescent data from the 2011-2014 waves of the population-representative California Health Interview Survey (CHIS; N = 4,616), we estimated associations between residence in a rural area and suicidal ideation and suicide attempt, as well as access to psychological care. Survey-weighted logistic regression models controlled for individual- and family-level covariates. Results showed that rural adolescents were, compared to urban adolescents, substantially less likely to report recent suicidal ideation (OR = 0.25, 95% confidence interval [CI] = 0.10, 0.61) and suicide attempt (OR = 0.17, 95% CI = 0.05, 0.66). Suicidal youths in rural and urban areas were equally likely, however, to report receiving psychological care. In this study, rural adolescents in California reported lower rates of nonfatal suicidal behavior compared to urban peers. This pattern contrasts with rates of adolescent suicide fatality, which are higher in rural areas. Results suggest that reducing geographic disparities in youth suicide may require multifaceted public health approaches, in addition to better identification and treatment for high-risk adolescents.

Perceived and Objectively-Measured Neighborhood Violence and Adolescent Psychological Distress.

Prior research examining links between neighborhood violence and mental health has not been able to establish whether it is perceived levels of neighborhood violence, or actual levels of violent crime, that matter most for adolescents' psychological well-being. In this study, we ascertained both perceived neighborhood safety and objectively-measured neighborhood-level violent crime (using a novel geospatial index of police-reported crime incidents) for 4464 adolescent respondents from the California Health Interview Survey (CHIS 2011-2014). We used propensity score-matched regression models to examine associations between these measures and CHIS adolescents' symptoms of psychological distress. We found that adolescents who perceived their neighborhood to be unsafe were two times more likely than those who perceived their neighborhood to be safe to report serious psychological distress (OR = 2.4, 95 % CI = 1.20, 4.96). Adolescents who lived in areas objectively characterized by high levels of violent crime, however, were no more likely than their peers in safer areas to be distressed (OR = 1.41; 95 % CI = 0.60, 3.32). Our results suggest that, at the population level, adolescents' perceptions of neighborhood violence, rather than objective levels of neighborhood crime, are most salient for their mental health.

Reading disability and enhanced dynamic spatial reasoning: A review of the literature.

Previous research on reading disabilities (RD) has primarily focused on the cause and expression of the disability. The vast majority of this research has focused on the disorder itself, although it has been proposed that RD embodies other qualities not necessarily related to language or reading deficits. In fact, strengths in nonverbal processing and visual-spatial talents have been proposed to exist in persons with RD. However, the limited empirical data on this matter have yielded inconsistent results. The purpose of this review was to examine this literature, focusing on research concerning dynamic and complex spatial processing or reasoning in people with dyslexia. Our review suggests that there is little evidence in support of a spatial advantage in people with dyslexia, and, in fact, the data show that RD samples most often perform worse or equal to non-RD samples. An exception to this general conclusion may be performance on holistic visualization of complex figures, where RD samples have consistently demonstrated faster response times even though accuracy rates often do not exceed that of controls. The possibility of a unique spatial processing neurology that develops through right-left hemisphere interactions in persons with RD is discussed based on preliminary fMRI data.

A cell-based Dkk1 binding assay reveals roles for extracellular domains of LRP5 in Dkk1 interaction and highlights differences between wild-type and the high bone mass mutant LRP5(G171V).

Dkk1 is a secreted antagonist of the LRP5-mediated Wnt signaling pathway that plays a pivotal role in bone biology. Because there are no well-documented LRP5-based assays of Dkk1 binding, we developed a cell-based assay of Dkk1/LRP5 binding using radioactive (125)I-Dkk1. In contrast to LRP6, transfection of LRP5 alone into 293A cells resulted in a low level of specific binding that was unsuitable for routine assay. However, co-transfection of LRP5 with the chaperone protein MesD (which itself does not bind Dkk1) or Kremen-2 (a known Dkk1 receptor), or both, resulted in a marked enhancement of specific binding that was sufficient for evaluation of Dkk1 antagonists. LRP5 fragments comprising the third and fourth beta-propellers plus the ligand binding domain, or the first beta-propeller, each inhibited Dkk1 binding, with mean IC(50)s of 10 and 196 nM, respectively. The extracellular domain of Kremen-2 ("soluble Kremen") was a weaker antagonist (mean IC(50) 806 nM). We also found that cells transfected with a high bone mass mutation LRP5(G171V) had a subtly reduced level of Dkk1 binding, compared to wild type LRP5-transfected cells, and no enhancement of binding by MesD. We conclude that (1) LRP5-transfected cells do not offer a suitable cell-based Dkk1 binding assay, unless co-transfected with either MesD, Kremen-2, or both; (2) soluble fragments of LRP5 containing either the third and fourth beta-propellers plus the ligand binding domain, or the first beta-propeller, antagonize Dkk1 binding; and (3) a high bone mass mutant LRP5(G171V), has subtly reduced Dkk1 binding, and, in contrast to LRP5, no enhancement of binding with MesD.

Structure-based mutation analysis shows the importance of LRP5 beta-propeller 1 in modulating Dkk1-mediated inhibition of Wnt signaling.

A single point mutation (G to T) in the low-density lipoprotein receptor related protein 5 (LRP5) gene results in a glycine to valine amino acid change (G171V) and is responsible for an autosomal dominant high bone mass trait (HBM) in two independent kindreds. LRP5 acts as a co-receptor to Wnts with Frizzled family members and transduces Wnt-canonical signals which can be antagonized by LRP5 ligand, Dickkopf 1 (Dkk1). In the presence of Wnt1, LRP5 or the HBM variant (LRP5-G171V) induces beta-catenin nuclear translocation and activates T cell factor (TCF)-luciferase reporter activity. HBM variant suppresses Dkk1 function and this results in reduced inhibition of TCF activity as compared to that with LRP5. Structural analysis of LRP5 revealed that the HBM mutation lies in the 4th blade of the first beta-propeller domain. To elucidate the functional significance and consequence of the LRP5-G171V mutation in vitro, we took a structure-based approach to design 15 specific LRP5 point mutations. These included (a) substitutions at the G171 in blade 4, (b) mutations in blades 2-6 of beta-propeller 1, and (c) mutations in beta-propellers 2, 3 and 4. Here we show that substitutions of glycine at 171 to K, F, I and Q also resulted in HBM-like activity in the presence of Wnt1 and Dkk1. This indicates the importance of the G171 site rather than the effect of specific amino acid modification to LRP5 receptor function. Interestingly, G171 equivalent residue mutations in other blades of beta-propeller 1 (A65V, S127V, L200V, A214V and M282V) resulted in LRP5-G171V-like block of Dkk1 function. However G171V type mutations in other beta-propellers of LRP5 did not result in resistance to Dkk1 function. These results indicate the importance of LRP5 beta-propeller 1 for Dkk1 function and Wnt signaling. These data and additional comparative structural analysis of the LRP5 family member LDLR suggest a potential functional role of the first beta-propeller domain through intramolecular interaction with other domains of LRP5 wherein Dkk1 can bind. Such studies may also lead to a better understanding of the mechanisms underlying the reduced function of Dkk1-like inhibitory ligands of LRP5 with HBM-like mutations and its relationship to increased bone density phenotypes.

Association of nutritional markers with physical and mental health status in prevalent hemodialysis patients from the HEMO study.

OBJECTIVE: To determine associations of potentially modifiable nutritional factors with physical and mental health status after adjusting for sociodemographic and comorbid conditions. DESIGN: Cross-sectional multivariable analysis. SETTING: Fifteen dialysis centers across the United States participating in the Reduction of Morbidity and Mortality Among Hemodialysis Patients (HEMO) study. PATIENTS: Enrollment of 1,545 prevalent hemodialysis subjects in the HEMO study. INDEPENDENT (PREDICTOR) VARIABLES: The following nutritional markers were assessed in this analysis: serum albumin, energy intake, protein catabolic rate, serum creatinine, midarm muscle circumference, calf circumference, and smoking status. Smoking status, although not a nutritional factor per se, was also included because it is a modifiable lifestyle factor. MAIN OUTCOME MEASURES: Physical and mental health status were assessed using the medical staff-assessed Karnofsky Index and the patient self-assessed Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: After adjusting for sociodemographic factors and comorbid conditions, serum albumin, serum creatinine, and calf circumference were independently associated with Karnofsky Index scores. Similarly, serum creatinine and calf circumference were also independently associated with the Physical Component Summary (PCS) score of the SF-36. Of the nutritional variables selected, no variables were significantly associated with the Mental Component Summary (MCS) score of the SF-36. CONCLUSIONS: Markers of poor nutrition were associated with decreased physical functioning scores, independent of case mix. Measures that improve nutrition may therefore have wide-reaching effects to improve not only morbidity and mortality but also health-related quality of life for patients with end-stage renal disease.

Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness.

Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.

Mapping of the mouse hyh gene to a YAC/BAC contig on proximal Chromosome 7.

Mice that are homozygous for the autosomal recessive hydrocephaly with hop gait (hyh) mutation on Chromosome (Chr) 7 have congenital hydrocephalus characterized by an interhemispheric cyst arising from the third ventricle and agenesis of the corpus callosum. Analysis of more than 500 backcross and intercross progeny maps the hyh locus to proximal Chr 7, approximately 13 cM centromeric to its originally reported map position. Analysis of recombinants at several MIT microsatellite markers localized the hyh locus between D7Mit75 and D7Mit56. Development of several new SSLP markers allowed us to refine the hyh candidate interval to a region defined by the cone-rod homeobox ( Crx) gene proximally and D7Mit56 distally. A contig of yeast artificial chromosome (YAC) clones and bacterial artificial chromosome (BAC) clones spanning this entire region has been developed, and a number of potential candidate genes for hyh within this interval have been identified. Gene content is conserved between this region of mouse Chr 7 and human Chr 19q13.3. Physical mapping of the regions around D7Mit75 and D7Mit56 has also determined the order of a number of MIT markers that remain unresolved on the Mouse Genome Database (MGD) map. Our physical map and transcript map may be useful for positional cloning of genes in this unusually gene-rich region of the genome.

A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.

Osteoporosis is a complex disease that affects >10 million people in the United States and results in 1.5 million fractures annually. In addition, the high prevalence of osteopenia (low bone mass) in the general population places a large number of people at risk for developing the disease. In an effort to identify genetic factors influencing bone density, we characterized a family that includes individuals who possess exceptionally dense bones but are otherwise phenotypically normal. This high-bone-mass trait (HBM) was originally localized by linkage analysis to chromosome 11q12-13. We refined the interval by extending the pedigree and genotyping additional markers. A systematic search for mutations that segregated with the HBM phenotype uncovered an amino acid change, in a predicted beta-propeller module of the low-density lipoprotein receptor-related protein 5 (LRP5), that results in the HBM phenotype. During analysis of >1,000 individuals, this mutation was observed only in affected individuals from the HBM kindred. By use of in situ hybridization to rat tibia, expression of LRP5 was detected in areas of bone involved in remodeling. Our findings suggest that the HBM mutation confers a unique osteogenic activity in bone remodeling, and this understanding may facilitate the development of novel therapies for the treatment of osteoporosis.