RATIONALE AND OBJECTIVES: Previous cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aimed to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma. MATERIALS AND METHODS: Phenotypic characterization and quantitative multidetector-row computed tomography (MDCT) of the chest were performed at baseline and ∼2.6 years later in 38 participants with asthma (severe n = 24 and mild-to-moderate n = 14) and nine normal controls from the Severe Asthma Research Program. RESULTS: Subjects with severe asthma had a significant decline in postbronchodilator forced expiratory volume in 1 second percent (FEV1%) predicted over time (P < .001). Airway wall thickness measured by MDCT was increased at multiple airway generations in severe asthma compared to mild-to-moderate asthma (wall area percent [WA%]: P < .05) and normals (P < .05) at baseline and year 2. Over time, there was an increase in WA% and wall thickness percent (WT%) in all subjects (P = .030 and .009, respectively) with no change in emphysema-like lung or air trapping. Baseline prebronchodilator FEV1% inversely correlated with WA% and WT% (both P < .05). In a multivariable regression model, baseline WA%, race, and health care utilization were predictors of subsequent airway remodeling. CONCLUSIONS: Severe asthma subjects have a greater decline in lung function over time than normal subjects or those with mild-to-moderate asthma. MDCT provides a noninvasive measure of airway wall thickness that may predict subsequent airway remodeling.

The U.S. Tox21 program has screened a library of approximately 10,000 (10K) environmental chemicals and drugs in three independent runs for estrogen receptor alpha (ERα) agonist and antagonist activity using two types of ER reporter gene cell lines, one with an endogenous full length ERα (ER-luc; BG1 cell line) and the other with a transfected partial receptor consisting of the ligand binding domain (ER-bla; ERα β-lactamase cell line), in a quantitative high-throughput screening (qHTS) format. The ability of the two assays to correctly identify ERα agonists and antagonists was evaluated using a set of 39 reference compounds with known ERα activity. Although both assays demonstrated adequate (i.e. >80%) predictivity, the ER-luc assay was more sensitive and the ER-bla assay more specific. The qHTS assay results were compared with results from previously published ERα binding assay data and showed >80% consistency. Actives identified from both the ER-bla and ER-luc assays were analyzed for structure-activity relationships (SARs) revealing known and potentially novel ERα active structure classes. The results demonstrate the feasibility of qHTS to identify environmental chemicals with the potential to interact with the ERα signaling pathway and the two different assay formats improve the confidence in correctly identifying these chemicals.

GNE myopathy is an autosomal recessive muscle disease caused by biallelic mutations in GNE, a gene encoding for a single protein with key enzymatic activities, UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase, in sialic acid biosynthetic pathway. The diagnosis should be considered primarily in patients presenting with distal weakness (foot drop) in early adulthood (other onset symptoms are possible too). The disease slowly progresses to involve other lower and upper extremities' muscles, with marked sparing of the quadriceps. Characteristic findings on biopsies of affected muscles include 'rimmed' (autophagic) vacuoles, aggregation of various proteins and fibre size variation. The diagnosis is confirmed by sequencing of the GNE gene. Note that we use a new mutation nomenclature based on the longest transcript (GenBank: NM_001128227), which encodes a 31-amino acid longer protein than the originally described one (GenBank: NM_005476), which has been used previously in most papers. Based upon the pathophysiology of the disease, recent clinical trials as well as early gene therapy trials have evaluated the use of sialic acid or N-acetylmannosamine (a precursor of sialic acid) in patients with GNE myopathy. Now that therapies are under investigation, it is critical that a timely and accurate diagnosis is made in patients with GNE myopathy.

Prior research has linked either basal cortisol levels or stress-induced cortisol responses to adiposity; however, it remains to be determined whether these distinct cortisol measures exert joint or independent effects. Further, it is unclear how they interact with individual and environmental characteristics to predict adiposity. The present study aims to address whether morning cortisol levels and cortisol responses to a psychosocial stressor independently and/or interactively influence body mass index (BMI) in 218 adolescents (117 female) participating in a longitudinal community study, and whether associations are moderated by sex and exposure to early maternal depression. Reports of maternal depressive symptoms were obtained in infancy and preschool. Salivary cortisol measures included a longitudinal morning cortisol measure comprising sampling points across ages 11, 13, 15, and 18 and measures of stress-induced cortisol responses assessed via the Trier Social Stress Test (TSST) at age 18. Lower morning cortisol and higher TSST cortisol reactivity independently predicted higher age 18 BMI. Morning cortisol also interacted with sex and exposure to early maternal depression to predict BMI. Specifically, girls exposed to lower levels of early maternal depression displayed a strong negative morning cortisol-BMI association, and girls exposed to higher levels of maternal depression demonstrated a weaker negative association. Among boys, those exposed to lower levels of maternal depression displayed no association, while those exposed to higher levels of maternal depression displayed a negative morning cortisol-BMI association. Results point to the independent, additive effects of morning and reactive cortisol in the prediction of BMI and suggest that exposure to early maternal depression may exert sexually dimorphic effects on normative cortisol-BMI associations.

Mental clouding is an almost universal complaint among patients with postural tachycardia syndrome (POTS) but remains poorly understood. Thus, we have determined whether POTS patients exhibit deficits during neuropsychological testing relative to healthy subjects. A comprehensive battery of validated neuropsychological tests was administered to 28 female POTS patients and 24 healthy subjects in a semi-recumbent position. Healthy subjects were matched to POTS patients on age and gender. Selective attention, a primary outcome measure, and cognitive processing speed were reduced in POTS patients compared with healthy subjects (Ruff 2&7 Speed t-score: 40±9 compared with 49±8; P=0.009; Symbol Digit Modalities Test t-score: 45±12 compared with 51±8; P=0.011). Measures of executive function were also lower in POTS patients (Trails B t-score: 46±8 compared with 52±8; P=0.007; Stroop Word Color t-score: 45±10 compared with 56±8; P=0.001), suggesting difficulties in tracking and mental flexibility. Measures of sustained attention, psychomotor speed, memory function or verbal fluency were not significantly different between groups. The present study provides evidence for deficits in selective attention and cognitive processing in patients with POTS, in the seated position when orthostatic stress is minimized. In contrast, other measures of cognitive function, including memory assessments, were not impaired in these patients, suggesting selectivity in these deficits. These findings provide new insight into the profile of cognitive dysfunction in POTS and provide the basis for further studies to identify clinical strategies to better manage the mental clouding associated with this condition.

Vasovagal syncope (VVS) is a common disorder of the autonomic nervous system. While recurrent syncope can cause very impaired quality of life, the spells are not generally life-threatening. Both non-pharmacological and pharmacological approaches can be used to treat patients. Conservative management with education, exercise and physical maneuvers, and aggressive volume repletion is adequate for controlling symptoms in most patients. Unfortunately, a minority of patients will continue to have recurrent syncope despite conservative therapy, and they may require medications. These could include vasopressor agents, beta-blockers, or neurohormonal agents. Some patients may require more aggressive device based therapy with pacemakers or radiofrequency ablation, which are emerging therapies for VVS. This paper will review non-procedure based treatments for VVS.

OBJECTIVE: To describe children's consumption of sugar-sweetened beverages (SSBs) and 100% fruit juice (FJ), and identify factors that may reduce excessive consumption. DESIGN: A total of 830 parents of young children completed a 36-item questionnaire at the pediatricians' office. RESULTS: Children consumed soda (62.2%), other SSBs (61.6%), and FJ (88.2%): 26.9% exceeded the American Academy of Pediatrics' recommended daily FJ intake. 157 (18.9%) children consumed excessive calories (>200 kcal/d) from beverages (median = 292.2 kcal/d, range 203.8-2177.0 kcal/d). Risk factors for excessive calorie consumption from beverages were exceeding recommendations for FJ (odds ratio [OR] = 119.7, 95% confidence interval [CI] = 52.2-274.7), being 7 to 12 years old (OR = 4.3, 95%CI = 1.9-9.9), and having Medicaid insurance (OR = 2.6, 95%CI = 1.1-6.0). Parents would likely reduce beverage consumption if recommended by the physician (65.6%). CONCLUSIONS: About 1 in 5 children consumes excessive calories from soda, other SSBs and FJ, with FJ the major contributor.

INTRODUCTION: The burn wound exudate represents the burn tissue microenvironment. Extracting information from the exudate relating to cellular components, signaling mediators and protein content can provide much needed data relating to the local tissue damage, depth of the wound and probable systemic complications. This review examines the scientific data extracted from burn wound exudates over the years and proposes new investigations that will provide useful information from this underutilized resource. METHOD: A literature review was conducted using the electronic database PubMed to search for literature pertaining to burn wound or blister fluid analysis. Key words included burn exudate, blister fluid, wound exudate, cytokine burn fluid, subeschar fluid, cytokine burns, serum cytokines. 32 relevant articles were examined and 29 selected as relevant to the review. 3 papers were discarded due to questionable methodology or conclusions. The reports were assessed for their affect on management decisions and diagnostics. Furthermore, traditional blood level analysis of these mediators was made to compare the accuracy of blood versus exudate in burn wound management. Extrapolations are made for new possibilities of burn wound exudate analysis. RESULTS: Studies pertaining to burn wound exudate, subeschar fluid and blister fluid analyses may have contributed to burn wound management decisions particularly related to escharectomies and early burn wound excision. In addition, information from these studies has the potential to impact on areas such as healing, scarring, burn wound conversion and burn wound depth analysis. CONCLUSION: Burn wound exudate analysis has proven useful in burn wound management decisions. It appears to offer a far more accurate reflection of the burn wound pathophysiology than the traditional blood/serum investigations undertaken in the past. New approaches to diagnostics and treatment efficacy assessment are possible utilizing data from this fluid. Burn wound exudate is a useful, currently under-utilized resource that is likely to take a more prominent role in burn wound management.

Many viral structural proteins and their truncated domains share a common feature of homotypic interaction forming dimers, trimers, and/or oligomers with various valences. We reported previously a simple strategy for construction of linear and network polymers through the dimerization feature of viral proteins for vaccine development. In this study, technologies were developed to produce more sophisticated polyvalent complexes through both the dimerization and oligomerization natures of viral antigens. As proof of concept, branched-linear and agglomerate polymers were made via fusions of the dimeric glutathione-s-transferase (GST) with either a tetrameric hepatitis E virus (HEV) protruding protein or a 24-meric norovirus (NoV) protruding protein. Furthermore, a monomeric antigen, either the M2e epitope of influenza A virus or the VP8* antigen of rotavirus, was inserted and displayed by the polymer platform. All resulting polymers were easily produced in Escherichia coli at high yields. Immunization of mice showed that the polymer vaccines induced significantly higher specific humoral and T cell responses than those induced by the dimeric antigens. Additional evidence in supporting use of polymer vaccines included the significantly higher neutralization activity and protective immunity of the polymer vaccines against the corresponding viruses than those of the dimer vaccines. Thus, our technology for production of polymers containing different viral antigens offers a strategy for vaccine development against infectious pathogens and their associated diseases.

BACKGROUND: Planners have relied on the urban development boundary (UDB)/urban growth boundary (UGB) and central business district (CBD) to encourage contiguous urban development and conserve infrastructure. However, no studies have specifically examined the relationship between proximity to the UDB/UGB and CBD and walking behavior. PURPOSE: To examine the relationship between UDB and CBD distance and walking in a sample of recent Cuban immigrants, who report little choice in where they live after arrival to the U.S. METHODS: Data were collected in 2008-2010 from 391 healthy, recent Cuban immigrants recruited and assessed within 90 days of arrival to the U.S. who resided throughout Miami-Dade County FL. Analyses in 2012-2013 examined the relationship between UDB and CBD distances for each participant's residential address and purposive walking, controlling for key sociodemographics. Follow-up analyses examined whether Walk Score(®), a built-environment walkability metric based on distance to amenities such as stores and parks, mediated the relationship between purposive walking and each of UDB and CBD distance. RESULTS: Each one-mile increase in distance from the UDB corresponded to an 11% increase in the number of minutes of purposive walking, whereas each one-mile increase from the CBD corresponded to a 5% decrease in the amount of purposive walking. Moreover, Walk Score mediated the relationship between walking and each of UDB and CBD distance. CONCLUSIONS: Given the lack of walking and walkable destinations observed in proximity to the UDB/UGB boundary, a sprawl repair approach could be implemented, which strategically introduces mixed-use zoning to encourage walking throughout the boundary's zone.