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Introduction: The irregular shapes of white matter hyperintensities (WMHs) are associated with poor cognitive function, diabetes, or lacunes. However, the association between the WMH shape and dementia remains understudied. We investigated the association between the calculated shape index of WMH and the diagnosis of dementia and cognitive function. Methods: The inverse sphericity index (ISIWMH) and volume of WMHs (VOLWMH) were compared among 82 participants with normal cognition, 82 with Alzheimer’s dementia (AD), and 82 with subcortical vascular dementia (SVD). We examined the associations of ISIWMH and VOLWMH with the modified Hachinski Ischemic Score (mHIS), diagnosis of AD and SVD, and cognitive test scores, using linear, multinomial, or hierarchical linear regression models. Results: The mHIS was associated with both ISIWMH (β = 0.326, p < 0.001) and VOLWMH (β = 0.299, p < 0.001). Both ISIWMH and VOLWMH were associated with the SVD diagnosis (odds ratio [OR] = 2.685, p = 0.002, ISIWMH; OR = 2.597, p = 0.005, VOLWMH), but not with AD. The SVD diagnosis was better explained when the multinomial regression model included both ISIWMH and VOLWMH instead of VOLWMH alone (χ2 = 20.768, df = 2, p < 0.001). The Trail Making Test-D (TMT-D) scores of the SVD patients were associated with both ISIWMH (β = 0.308) and VOLWMH (β = 0.293). Conclusion: An irregular WMH shape may be associated with the high cerebrovascular component of cognitive impairment and the diagnosis and low cognitive flexibility of SVD, which may improve the prediction of SVD diagnosis when used in combination with WMH volume.

Background: Emotional disorders, including depression and anxiety, are more prevalent in individuals with asthma than in the general population and are associated with poor asthma outcomes. Identification of patients with increased levels of stress and anxiety may be helpful when treating asthma and during asthma counseling. Objective: To further characterize the relationship between asthma symptoms and perceived stress and trait anxiety in an adolescent population. Methods: Adolescents (N = 335) ages 14‐17 years were recruited to examine the effect of stress on health measures. They were included in the present analysis if they reported current asthma, defined as self-reported clinician-diagnosed asthma plus one or more episodes of asthma in the past year. Asthma symptoms were assessed on a 7-point scale by using a standardized questionnaire that targets nocturnal awakening due to asthma, symptoms on awakening, activity limitation, shortness of breath, time spent wheezing, and short-acting bronchodilator use. Stress was measured by using the Perceived Stress Scale (PSS), and trait anxiety was measured by using the State-Trait Anxiety Inventory. Linear regression was used to associate asthma symptoms with PSS and trait anxiety. Results: Thirty-eight adolescents (11.3%), with mean ± standard deviation age 16.7 ± 0.9 years, reported current asthma. Four of the six asthma symptom assessments had significant associations with PSS: symptoms on awakening (β = 4.82, p < 0.001), nocturnal awakening due to asthma (β = 4.47, p Conclusion: Asthma symptom severity is associated with increased perceived stress and trait anxiety. Adolescents with asthma may represent a population that is particularly vulnerable to perceived stress and anxiety, which highlights the importance of considering these factors in asthma counseling.

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

Background Previous analyses in the WHEALS birth cohort demonstrated that black children are more likely to experience allergic outcomes than white children by age 2 years. The results could not be explained by a host of variables. Objective Assess whether racial disparities persisted to age 10 years and determine whether any differences could be explained by a panel of variables related to early life exposures in WHEALS. Methods At age 10 years, WHEALS children (n = 481) completed skin prick testing, spirometry and methacholine challenge, and a physician examination for eczema and asthma. Allergen-specific immunoglobulin Es (sIgE) and total IgE were measured. Inverse probability weighting with logistic and linear regression models was used to assess associations between race (black or white) and the outcomes. Results Black children fared worse than white children with respect to each outcome. Black children were more likely to have eczema, asthma, sensitization (≥1 sIgE ≥ 0.35 IU/L) and at least 1 positive skin pick test; however, some variability was present in the magnitudes of association within subgroups defined by delivery mode, sex of the child, prenatal indoor dog exposure, and firstborn status. In some subgroups, black children were also more likely to have higher total IgE and worse pulmonary function test measures (PC 20 ≤ 25 mg/mL, % predicted forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1]/FVC, forced expiratory flow from 25% to 75% of vital capacity [FEF25-75]). Confounding did not explain these differences. Conclusion Racial differences persisted in this cohort through age 10 years. Future studies should include potentially important, but rarely studied factors such as segregation and structural racism, because these factors could explain the observed racial differences.

BACKGROUND Immunoglobulin E - mediated food allergy (IgE-FA) has emerged as a global public health concern. Immune dysregulation is an underlying mechanism for IgE-FA, caused by "dysbiosis" of the early intestinal microbiota. We investigated the association between infant gut bacterial composition and food-related atopy at age 3-5 years using a well-characterized birth cohort. METHODS The study definition of IgE-FA to egg, milk, or peanut was based on physician panel retrospective review of clinical and questionnaire data collected from birth through age 3-5 years. Using 16S rRNA sequencing, we profiled the bacterial gut microbiota present in stool specimens collected at 1 and 6 months of age. RESULTS Of 447 infants with data for analysis, 44 (9.8%) met physician panel review criteria for IgE-FA to ≥1 of the three allergens. Among children classified as IgE-FA at 3-5 years, infant stool samples showed significantly less diversity of the gut microbiota compared to the samples of children classified as no IgE-FA at age 3-5 years, especially for milk and peanut (all covariate adjusted p's for alpha metrics

Background In infants, distinct nasopharyngeal bacterial microbiotas differentially associate with the incidence and severity of acute respiratory tract infection and childhood asthma development. Objective We hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes. Methods Nasal secretion samples (n = 3122) collected after randomization during the fall season from children with asthma (6-17 years, n = 413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling. Statistical analyses with exacerbation as the primary outcome and rhinovirus infection and respiratory illnesses as secondary outcomes were performed. Using A549 epithelial cells, we assessed nasal isolates of Moraxella, Staphylococcus, and Corynebacterium species for their capacity to induce epithelial damage and inflammatory responses. Results Six nasal airway microbiota assemblages, each dominated by Moraxella, Staphylococcus, Corynebacterium, Streptococcus, Alloiococcus, or Haemophilus species, were observed. Moraxella and Staphylococcus species–dominated microbiotas were most frequently detected and exhibited temporal stability. Nasal microbiotas dominated by Moraxella species were associated with increased exacerbation risk and eosinophil activation. Staphylococcus or Corynebacterium species–dominated microbiotas were associated with reduced respiratory illness and exacerbation events, whereas Streptococcus species–dominated assemblages increased the risk of rhinovirus infection. Nasal microbiota composition remained relatively stable despite viral infection or exacerbation; only a few taxa belonging to the dominant genera exhibited relative abundance fluctuations during these events. In vitro, Moraxella catarrhalis induced significantly greater epithelial damage and inflammatory cytokine expression (IL-33 and IL-8) compared with other dominant nasal bacterial isolates tested. Conclusion Distinct nasal airway microbiotas of children with asthma relate to the likelihood of exacerbation, rhinovirus infection, and respiratory illnesses during the fall season.

The number of breast reconstructions following mastectomy has increased significantly during the last decades, but women are experiencing a number of conflicts with breast reconstruction decisions. The aim of this study was to develop a decision tree model of breast reconstruction and to examine its predictability. Mixed method design using ethnographic decision tree modeling was used. In the qualitative stage, data were collected using individual and focus group interviews and analyzed to construct a decision tree model. In the quantitative stage, the questionnaire was developed questions based on the criteria identified in the qualitative stage. A total of 61 women with breast cancer participated in 2017. Five major criteria: recovery of body image, impact on recurrence, recommendations from others, financial resources, and confirmation by physicians. The model also included nine predictive pathways. It turns out that the model predicted 90% of decisions concerning whether or not to have breast reconstruction. The findings indicate that the five criteria play a key role in decision-making about whether or not to have breast reconstruction. Thus, more comprehensive issues, including these five criteria, need to be integrated into an intervention for women with breast cancer to make their best decision on breast reconstruction.

Rationale: Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. Objectives: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. Methods: Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection. Measurements and Main Results: In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (P

Childhood sensitization patterns have been previously found to be related to variable risk of early life allergic disease in several birth cohorts.To determine whether these risks persist into later childhood.In the birth cohort of the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, previous latent class analysis based on sensitization to 10 allergens found the following 4 early life sensitization patterns at age 2 years: "highly sensitized," "milk/egg dominated," "peanut and inhalant(s)," and "low to no sensitization." At an age 10 study-specific visit, children were evaluated by an allergist for current asthma and atopic dermatitis through a physical examination and interviews with the child and parent or guardian. Total and specific immunoglobulin E (IgE), spirometry, and methacholine challenge were also completed.Compared with children sensitized to none or 1 allergen, children sensitized to 4 or more food and inhalant allergens at age 2 had the highest risk of current asthma (relative risk [RR], 4.42; 95% confidence interval [CI], 2.58-7.59; P.001) and bronchial hyperresponsiveness (RR, 1.77; 95% CI, 1.29-2.42; P.001). In addition, they had the highest levels of total IgE (geometric mean, 800 IU/mL; 95% CI, 416-1536) among the 4 groups. Risk of current atopic dermatitis did not depend on pattern of sensitization but remained increased for children with any sensitization (RR, 2.23; 95% CI, 1.40-3.55; P.001). No differences in spirometry (forced expiratory volume in 1 second, forced expiratory flow between 25% and 75%, and forced expiratory volume in 1 second/forced vital capacity) were identified.The previously reported importance of a specific pattern of sensitization in early life (sensitization to ≥4 inhalant and food allergens) continues to be associated with an increased risk of asthma, bronchial hyperresponsiveness, and high total IgE at age 10 years.

White matter hyperintensities (WMH) and cerebral microbleeds (CMBs) are known to be associated with small vessel diseases (SVD) and neuroinflammation. The purpose was to investigate the relationship between CMBs and WMH in patients with systemic lupus erythematosus (SLE). Thirty-one SLE patients with WMH and 27 SLE patients with normal brain MRI were compared. The presence, location, and grading of CMBs were assessed using susceptibility-weighted images. WMH volume was quantitatively measured. Clinical characteristics and serologic markers were compared. We also performed two separate subgroup analyses after (1) dividing WMH into inflammatory lesion vs. SVD subgroups and (2) dividing WMH into those with vs. without CMB subgroups. The WMH group showed more frequent CMBs than the normal MR group (p

Dissolved oxygen (DO) can be influenced by both physical and biogeochemical conditions of the ocean and is hence an important index for predicting changes in ocean environments. However, the relationship between biogeochemical activities and the DO concentration has not been quantified clearly in the Japan Sea (JS). In this study, we developed a coupled physical-biogeochemical model and clarified the contributions of biological processes to the DO content in the upper JS. We conducted two numerical experiments: with and without the biogeochemical compartments. Taking the biogeochemical factors into account gave better estimations for the spring-to-autumn seasonal migration of the subsurface DO maximum. In the euphotic zone, high photosynthetic production increases the DO concentration from spring to autumn. The strongest positive effect of biological processes on DO concentrations appears in summer at a depth of 30 m and is more than 0.5 ml l−1. As summer progresses to autumn, the vertical pattern of DO concentration in the Tsushima Warm Current (TWC) region shows minima at depths between 50 and 100 m, which is caused by the intrusion of low DO water from the East China Sea. The strongest negative effect on DO concentrations mainly due to the decomposition of detritus occurs in the TWC region below 150 m depth because the water is poorly ventilated by the relatively weak winter convection.

Living with a person with dementia considerably affects the lives of both the primary caregiver and the entire family. This study aimed to synthesize the findings of qualitative studies that explored dementia caregivers’ experiences, to further understand the impact of dementia caregiving on family dynamics. Thirty-seven qualitative studies were analyzed and synthesized according to the meta-synthesis methods suggested by Sandelowski and Barroso. Four themes were identified to describe the impact of dementia caregiving on the family: cracked foundation of the family caused by dementia, voluntary or involuntary setup of a marked boundary of care, family as supportive foreground versus reluctant or interfering background, and re-established relationships within and outside the family. The findings illuminate that dementia caregiving has a destructive impact on the entire family, and therefore, it is imperative to develop interventions and infrastructures for both the caregiver and the entire family of individuals with dementia.

Serum IL-6 was associated with asthma exacerbation risk but not with symptoms or lung function in urban children; further studies to evaluate the role of IL-6 in the life course of asthma are needed.

The effect of dog exposure on the risk of children developing allergic disease remains controversial. Many analyses have not considered that associations may vary within population subgroups.To examine whether associations between living with a dog in the first year of life and allergic outcomes vary within subgroups selected a priori (race, gender and delivery mode).Black (n = 496) and White (n = 196) children enrolled in the WHEALS birth cohort study had a clinical examination at age 2 years to assess eczema and allergen-specific IgE (sIgE) and perform skin prick testing (SPT). Whether the child lived with an indoor dog in the first year of life was assessed through interview, as was doctor diagnosis of asthma at ages 3-6 years.Living with a dog was associated with decreased odds of having ≥ 1 positive SPT (OR = 0.56, 95% CI: 0.34, 0.91) and having eczema (OR = 0.34, 95% CI: 0.20, 0.60). The association with SPT was stronger in those children born via caesarean section (c-section) vs. vaginally (OR = 0.29, 95% CI: 0.12, 0.74 vs. OR = 0.76, 95% CI: 0.43, 1.37, respectively, interaction P = 0.087) and in those who were firstborn vs. not (OR = 0.27, 95% CI: 0.11, 0.67 vs. OR = 0.82, 95% CI: 0.45, 1.47, respectively, interaction P = 0.044). The association with eczema was stronger in children born vaginally compared with those born via caesarean section (OR = 0.17, 95% CI: 0.06, 0.43 vs. OR = 0.65, 95% CI: 0.31, 1.35, respectively, interaction P = 0.025) and was stronger in Black vs. White children (OR = 0.30, 95% CI: 0.15, 0.61 vs. OR = 0.78, 95% CI: 0.29, 2.11, respectively, interaction P = 0.12). Dog keeping was not significantly inversely associated with having ≥ 1 elevated sIgE and only approached statistical significance with asthma.Results likely vary between studies due to variability of specific exposure-outcome associations in subgroups defined by other factors as well as the relative distributions of those subgroups. Important allergic disorder associations will be missed without subgroup analyses.

The infant gut microbiota has become a focus of multiple epidemiologic and cohort studies. This microbiome is derived from the mother (via the vaginal canal, maternal skin contact, breastfeeding, and possibly in utero microbial transfer) and is likely influenced by multiple external factors. It is now believed by some experts that colonization and formation of the newborn and alterations of gut microbiota in children are dependent on earlier alterations of the microbiota of mothers during or perhaps even before pregnancy. This review will focus on specific factors (pet keeping, breastfeeding, antibiotic use, and mode of delivery) that influence the infant gut microbiome and atopy. This is a review of recent literature describing how pet keeping, breastfeeding, antibiotic use, and mode of delivery influences and changes the infant gut microbiome and atopy. General trends in gut microbiota differences have emerged in different birth cohorts when each external factor is analyzed, but consistency between studies is difficult to replicate. The aforementioned factors do not seem to confer an overwhelming risk for development of atopy alone. This review provides a comprehensive review of early life environmental factors and their influence on the infant gut microbiome and atopy.

Environment and diet are two major factors affecting the human gut microbiome. In this study, we used a pig model to determine the impact of these two factors during lactation on the gut microbiome, immune system, and growth performance. We assigned 80 4-day-old pigs from 20 sows to two rearing strategies at lactation: conventional rearing on sow’s milk (SR) or isolated rearing on milk replacer supplemented with solid feed starting on day 10 (IR). At weaning (day 21), SR and IR piglets were co-mingled (10 pens of 4 piglets/pen) and fed the same corn-soybean meal-dried distiller grain with solubles- and antibiotic-free diets for eight feeding phase regimes. Fecal samples were collected on day 21, 62, and 78 for next-generation sequencing of the V4 hypervariable region of the bacterial 16S rRNA gene. Results indicate that IR significantly increased swine microbial diversity and changed the microbiome structure at day 21. Such changes diminished after the two piglet groups were co-mingled and fed the same diet. Post-weaning growth performance also improved in IR piglets. Toward the end of the nursery period (NP), IR piglets had greater average daily gain (0.49 vs. 0.41 kg/d; P < 0.01) and average daily feed intake (0.61 vs. 0.59 kg/d; P < 0.01) but lower feed efficiency (0.64 vs. 0.68; P = 0.05). Consequently, IR piglets were heavier by 2.9 kg (P < 0.01) at the end of NP, and by 4.1 kg (P = 0.08) at market age compared to SR piglets. Interestingly, pigs from the two groups had similar lean tissue percentage. Random forest analysis showed that members of Leuconostoc and Lactococcus best differentiated the IR and SR piglets at weaning (day 21), were negatively correlated with levels of Foxp3 regulatory T cell populations on day 20, and positively correlated with post-weaning growth performance. Our results suggest that rearing strategies may be managed so as to accelerate early-life establishment of the swine gut microbiome to enhance growth performance in piglets.

Purpose of review Children living in US inner cities experience disparate burdens of asthma, especially in severity, impairment, exacerbations, and morbidity. Investigations seeking to better understand the factors and mechanisms underlying asthma prevalence, severity, and exacerbation in children living in these communities can lead to interventions that can narrow asthma disparities and potentially benefit all children with asthma. This update will focus on recent (i.e. late 2016-2017) advances in the understanding of asthma in US inner city children. Recent findings Studies published in the past year expand understanding of asthma prevalence, severity, exacerbation, and the outcomes of guidelines-based management of these at-risk children, including: asthma phenotypes in US inner city children that are severe and difficult-to-control; key environmental determinants and mechanisms underlying asthma severity and exacerbations (e.g. allergy-mediated exacerbation susceptibility to rhinovirus); the importance of schools as a place for provocative exposures (e.g. mouse allergen, nitrogen dioxide) as well as a place where asthma care and outcomes can be improved; and the development and validation of clinically useful indices for gauging asthma severity and predicting exacerbations. Summary These recent studies provide a trove of actionable findings that can improve asthma care and outcomes for these at-risk children.

5,3'-Dihydroxy-6,7,4'-trimethoxyflavanone (DHTMF) is one of the constituents of Vitex rotundifolia, a medicinal herb that is used for the treatment of various disorders in China and Korea. In this study we evaluated the antitumor and antiangiogeneic activities of DHTMF. DHTMF significantly suppressed growth and induced apoptosis in lung carcinoma cells in a dose-dependent manner, as indicated by a decrease in Bcl-2 levels and increases in Bax and cleaved caspase-3 levels. In addition, DHTMF treatment significantly reduced the phosphorylation of Akt and mammalian target of rapamycin (mTOR), accompanied by reductions in the protein level of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF), which are key angiogenic molecules in H522 lung cancer cells. Furthermore DHTMF inhibited VEGF-induced angiogenesis, as indicated by reduced expression of CD34, tube formation and migration in human umbilical vein endothelial cells (HUVECs), as well as reduced neovascularization in an in vivo mouse Matrigel plug assay. DHTMF also inhibited phosphorylation of Akt, mTOR, and p70S6K in HUVECs and lung cancer cells. Taken together, our finding indicated that DHTMF inhibits Akt/mTOR signaling and reduces the expression of HIF-1 α and VEGF in tumor cells, which in turns inhibits endothelial cell-mediated angiogenesis. These results suggest that DHTMF inhibits angiogenesis as well as induces apoptosis via the Akt/mTOR pathway and might elicit pharmacological effects that are useful for treatment of lung cancer.

Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.To test whether omalizumab treatment to reduce IgE would shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma.In the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6-17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression.RVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P 0.001). Exacerbations were significantly associated with detection of rhinovirus C (OR, 2.85; P 0.001) and rhinovirus A (OR, 2.92; P 0.001), as well as, to a lesser extent, rhinovirus B (OR, 1.98; P = 0.019). Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, -0.77 to -0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49-0.84).In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).

Angiogenesis, the process of new vessel formation from the pre-existing blood vasculature, is critical for continuous tumor growth and is considered to be a validated antitumor target. The results of our previous study demonstrate the anti-angiogenic potential of an extract of Gleditsia sinensis thorns, which has been traditionally used in Korean medicine to remedy diverse diseases, including tumors. In the present study, we attempted to identify the active anti-angiogenic constituents of the ethanol extract of G. sinensis thorns (EEGS). By virtue of in vitro activity-guided fractionation using human umbilical vein endothelial cells (HUVEC) primary endothelial cells, chromatographic separation, and NMR spectral analyses, we isolated and identified the potent active constituent, cytochalasin H, a biologically active secondary metabolite of fungi. This unexpected active constituent may have originated from the endophytic fungi, Chaetomium globosum, which naturally populate G. sinensis, the identity of which was determined by analysis of fungal community. Cytochalasin H isolated from the EEGS showed in vitro anti-angiogenic activities such as suppressed cell growth and mobility in HUVEC, and inhibited the pro-angiogenic protein-induced formation of new blood vessels in vivo. The anti-angiogenic effect of cytochalasin H was in part due to reduced expression of pro-angiogenic factor, such as endothelin-1. This is the first report regarding the isolation and identification of cytochalasin H, as an active anti-angiogenic constituent of G. sinensis thorns.

Background Environmental allergens may induce the generation of allergen-specific IgE (sIgE) and IgG4 (sIgG4). Some studies report an association of sIgG4 to protection against allergic symptoms after exposure to the relevant allergen. Objective We examined the relationship of dog and cat sIgE and sIgG4 levels to self-reported allergic symptoms on pet contact. Methods Participants 18 years of age in the Detroit Childhood Allergy Study cohort were asked whether they experienced symptoms on exposure to cats and dogs. Serum was assayed for cat and dog sIgE and sIgG4. Geometric means, ratios of cat and dog sIgE, sIgG4, and ratios of sIgG4/sIgE were compared between symptomatic and asymptomatic teens with the use of Wilcoxon rank sum tests. Ratios of sIgG4/sIgE, adjusted for presence of sIgE (≥0.35 kU/mL), were analyzed with logistic regression. Results Data on 500 participants were analyzed. Compared with asymptomatic teens, teens symptomatic with cat exposure had higher cat sIgE, sIgG4, and lower ratio of sIgG4/sIgE. Teens symptomatic after dog exposure had higher dog sIgE levels and lower sIgG4/sIgE, but similar levels of sIgG4 compared with asymptomatic participants. Increasing cat and dog sIgG4/sIgE ratios were associated with a lower likelihood of reporting allergic symptoms (cat: adjusted odds ratio, 0.8; 95% CI, 0.6-0.9; dog: adjusted odds ratio, 0.8; 95% CI, 0.7-1.0). Conclusion sIgG4 levels to cat and dog allergens correlate with lower rates of pet-induced allergic symptoms when interpreted in the context of concomitant sIgE. However, sIgG4 appears to have little utility as an isolated marker to indicate that pet exposure will be well tolerated.

A new sinapoyl glycoside, 1,3-di-O-sinapoyl-β-D-glucopyranose (1) along with 13 known compounds, including, sinapoyl glycosides (2 and 3), cardenolide glycoside (4), flavonoids (5-10), lignan (11), phenolic acids (12 and 13), and phytosterol (14), were isolated from the seeds of Descurainia sophia by chromatographic separation methods. The structures of 1-14 were determined by the interpretation of spectroscopic data as well as by comparison of that data with previously reported values. Compounds 2, 3, 5, 6, and 11 were identified in and isolated from this plant for the first time in this study. All isolates were evaluated for in vitro cytotoxic activities against seven human cancer cell lines and for in vitro anti-inflammatory potential using LPS-stimulated RAW264.7 murine macrophages. Compound 4 showed potent cytotoxicity (IC50 values ranging from 0.034 to 0.596 μM) against all human cancer cell lines tested and was identified as the main active cytotoxic constituent of this plant. Compound 8 (ED50 = 5.45 μM) and 11 (ED50 = 10.02 μM) exerted dose-dependent inhibitory effects on NO production in LPS-stimulated RAW264.7 cells.

This paper presents a portion of a state highway agency pooled fund research project to develop performance criteria for concrete that will be resistant to penetration of chlorides, cycles of freezing and thawing, and sulfate attack. This paper presents the portion of the study pertaining to penetration of chlorides. To simulate standard and service conditions, specimens were subjected to either immersion or to a cyclic wetting and drying exposure in chloride solution. Measured apparent chloride diffusion coefficients, determined in accordance with American Society for Testing and Materials (ASTM) C1556, were correlated with results of rapid index test methods that provide an indication of the transport characteristics of concrete. Rapid index test methods included were rapid chloride permeability, rapid migration, conductivity, absorption, and initial and secondary sorptivity. A set of rapid index test methods and specification criteria that can reliably classify mixtures based on their resistance to chloride ion penetration are proposed.

The joint impact of pregnancy, environmental, and sociocultural exposures on early life gut microbiome is not yet well-characterized, especially in racially and socioeconomically diverse populations. Gut microbiota of 298 children from a Detroit-based birth cohort were profiled using 16S rRNA sequencing: 130 neonates (median age = 1.2 months) and 168 infants (median age = 6.6 months). Multiple factors were associated with neonatal gut microbiome composition in both single- and multi-factor models, with independent contributions of maternal race-ethnicity, breastfeeding, mode of delivery, marital status, exposure to environmental tobacco smoke, and indoor pets. These findings were consistent in the infants, and networks demonstrating the shared impact of factors on gut microbial composition also showed notable topological similarity between neonates and infants. Further, latent groups defined by these factors explained additional variation, highlighting the importance of combinatorial effects. Our findings also have implications for studies investigating the impact of the early life gut microbiota on disease.

A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials.This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy.The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab.A higher saEPI was associated with an exacerbation in both the GBT alone (P.001; area under the curve, 0.76) and the GBT + omalizumab group (P .01; area under the curve, 0.65). In the GBT group, younger age at recruitment, higher total IgE, higher blood eosinophil percentage and number, and higher treatment step were associated with those who had an exacerbation compared with those who did not. In the GBT + omalizumab group, younger age at recruitment, increased eosinophil number, recent exacerbation, and higher treatment step were also associated with those who had an exacerbation. The saEPI was associated with a high negative predictive value in both groups.An exacerbation in children treated with GBT with or without omalizumab was associated with a higher saEPI along with higher markers of allergic inflammation, treatment step, and a recent exacerbation. Those that exacerbated on omalizumab had similar features with the exception of some markers of allergic sensitization, indicating a need to develop better markers to predict poor response to omalizumab therapy and alternative treatment strategies for children with these risk factors. The saEPI was able to reliably predict those children unlikely to have an asthma exacerbation in both groups.

Background: Multiple population-based and high-risk cohort studies use parental questionnaire responses to define allergic rhinitis (AR) in children. Individual questionnaire items have not been validated by comparison with physician-diagnosed AR (PDAR). Objective: To identify routine clinical questions that best agree with a physician diagnosis of AR and can be used for early case identification. Methods: Children participating in a longitudinal birth cohort study were evaluated at ages 1 through 4 and at age 7 (n 531) using questionnaires, physical examinations, and skin prick tests (SPT) with 15 aeroaller- gens (AG). Parents answered 3 stem questions pertaining to their child, including presence of nasal symptoms absent a cold/flu (ISAAC-validated question), presence of hayfever, and ocular itch. Substem questions were answered with details regarding seasonality, nasal triggers, and ocular seasonality. A global assessment of allergic diseases, including AR, was performed by a specialty-trained clinician. Percent agreement, sensitivity, specificity, and positive predictive values were assessed for individual stem and substem questions. Results: Positive response to having hayfever and presence of ocular symptoms had the highest specificity (84% and 69%, respectively) and the highest percent agreement (74% and 68%) with PDAR. Identification of triggers for nasal and ocular symptoms had the highest sensitivity (89%). Positive predictive values ranged from 31 to 39%. Combining 2 responses with highest agreement increased specificity for PDAR to 91%. Conclusion: Responses to hayfever and ocular symptoms had better specificity and percent agreement with PDAR than the ISAAC-validated questionnaire item. Combining 2 rhinitis questions sharply increases speci- ficity and may improve diagnostic accuracy of clinical questions.

BACKGROUND: Rhinitis and asthma are linked, but substantial knowledge gaps in this relationship exist. OBJECTIVE: To determine the prevalence of rhinitis and its phenotypes in children and adolescents with asthma, assess symptom severity and medication requirements for rhinitis control, and investigate associations between rhinitis and asthma. METHODS: 749 children with asthma participating in the Asthma Phenotypes in the Inner-City study received baseline evaluations and were managed for 1 year with algorithm-based treatments for rhinitis and asthma. Rhinitis was diagnosed by questionnaire focusing on individual symptoms, and pre-defined phenotypes were determined by combining symptom patterns with skin testing and serum specific IgE. RESULTS: Analyses were done on 619 children with asthma who completed at least 4 of 6 visits. Rhinitis was present in 93.5%, and phenotypes identified at baseline were confirmed during the observation/management year. Perennial allergic rhinitis with seasonal exacerbations (PARSE) was most common (34.2%) and severe. Nonallergic rhinitis was least common (11.3%) and least severe. The majority of children remained symptomatic despite the use of nasal corticosteroids ± oral antihistamines. Rhinitis was worse in difficult-to-control vs. easy-to-control asthma and its seasonal patterns partially corresponded to those of difficult-to-control asthma. CONCLUSION: Rhinitis is almost ubiquitous in urban children with asthma, and its activity tracks that of lower airway disease. PARSE is the most severe phenotype and most likely to be associated with difficult-to-control asthma. This study offers strong support to the concept that rhinitis and asthma represent the manifestations of one disease in two parts of the airways. CAPSULE SUMMARY: Almost all children and adolescents with asthma have rhinitis of various, stable phenotypes based on sensitization and seasonal pattern. Conventional medications control rhinitis symptoms only in a minority. Difficult-to- control asthma is associated with worse rhinitis.

Exclusive breastfeeding during the first month of life and vaginal delivery may mitigate the transmission of atopy from mother to child. These results could have implications for potential targeted prevention strategies in high-risk offspring of atopic mothers.

Introduction Microbial-related exposures in early life stimulate immune development and may protect against allergic disease manifestations later in life. Parental pacifier sucking in early life may offer protection through the transfer of beneficial oral microbes from parent to offspring. Methods Using maternal-child pairs from the Microbes, Allergy, Asthma and Pets cohort(N=141), we investigated whether pacifier cleaning methods reported at 6-months of age were associated with differences in serum total IgE over the first 18 months of life(cord, 6-months, and 18-months). Linear mixed effect models were used to model log-transformed total IgE trajectories. Results Of 128 mothers completing an interview at 6 months, 74(58%) reported current child pacifier use. Of these 74, 30(41%) reported pacifier cleaning by sterilization, 53(72%) reported handwashing the pacifier, and 9(12%) reported parental pacifier sucking. Pacifier sterilization or handwashing were not associated with serum total IgE trajectory. A significant time interaction was detected for pacifier sucking(p=0.079), indicating that the trajectory shape differed between children of pacifier-sucking versus non-pacifier sucking parents. Specifically, parental pacifier sucking appeared to suppress serum IgE levels beginning around 10 months(p=0.048), and continued to diverge through 18 months(p=0.014). Conclusions These results show an association between parental pacifier sucking and lower early-life total IgE production. Further research is needed to assess whether these differences are due to the transfer of parental oral microbes, and if allergic disease risk later in life is sustained. These findings support a previous Swedish study reporting a protective effect of parental pacifier sucking on the risk of allergic diseases in children. Difference in total IgE trajectory by parental sucking of pacifiers - among children who used pacifiers at 6-months of age.

AMG 386 is an investigational first-in-class peptide-Fc fusion protein (peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 (Ang1) and Ang2 with their receptor, Tie2. Although the therapeutic value of blocking Ang2 has been shown in several models of tumorigenesis and angiogenesis, the potential benefit of Ang1 antagonism is less clear. To investigate the consequences of Ang1 neutralization, we have developed potent and selective peptibodies that inhibit the interaction between Ang1 and its receptor, Tie2. Although selective Ang1 antagonism has no independent effect in models of angiogenesis-associated diseases (cancer and diabetic retinopathy), it induces ovarian atrophy in normal juvenile rats and inhibits ovarian follicular angiogenesis in a hormone-induced ovulation model. Surprisingly, the activity of Ang1 inhibitors seems to be unmasked in some disease models when combined with Ang2 inhibitors, even in the context of concurrent vascular endothelial growth factor inhibition. Dual inhibition of Ang1 and Ang2 using AMG 386 or a combination of Ang1- and Ang2-selective peptibodies cooperatively suppresses tumor xenograft growth and ovarian follicular angiogenesis; however, Ang1 inhibition fails to augment the suppressive effect of Ang2 inhibition on tumor endothelial cell proliferation, corneal angiogenesis, and oxygen-induced retinal angiogenesis. In no case was Ang1 inhibition shown to (a) confer superior activity to Ang2 inhibition or dual Ang1/2 inhibition or (b) antagonize the efficacy of Ang2 inhibition. These results imply that Ang1 plays a context-dependent role in promoting postnatal angiogenesis and that dual Ang1/2 inhibition is superior to selective Ang2 inhibition for suppression of angiogenesis in some postnatal settings. Mol Cancer Ther; 9(10); 2641–51. ©2010 AACR.

Whole plants of Vitex rotundifolia were extracted for 2 days with methylene chloride () followed by extraction of the residue for an additional 2 days. The same procedure was also applied using methanol (MeOH). The two crude extracts were combined and partitioned between and . The organic layer was further partitioned between n-hexane and 85% aq. MeOH, and the aqueous layer was also further fractionated with n-BuOH and , successively. From the 85% aq. MeOH fraction, one compound was isolated through the repeated HPLC. According to the results of physicochemical data including NMR and MS, the chemical structure of the compound was determined as artemetin (1). The antiproliferative effects of the crude extracts, fractions, and compound against HT1080, AGS, MCF-7 and HT-29 human cancer cells were compared with the control by using MTT assay. In the comparative analysis, the 85% aq. MeOH fraction exhibited the strongest antiproliferative effects on human cancer cell lines in a dose-dependent manner (p

Access to and utilization of care for HIV-positive Asians (A) and Pacific Islanders (PI) have been largely unaddressed despite the rising influx of immigrants from Asia and the Pacific to the United States and the growing HIV prevalence in these regions. This paper describes the cultural attitudes, behaviors, and perceptions that affect access to and utilization of care among Asian undocumented noncitizens living with HIV/AIDS (UNWHA) in New York City. Sixteen semistructured interviews with HIV-positive UNWHAs revealed that their access to care was influenced by community misperceptions of HIV transmission, discriminatory attitudes towards persons living with HIV, competing immigration related stressors, and difficulty navigating service systems. These findings underscore the importance of integrating HIV treatment with primary prevention and awareness of immigration-related stressors to ensure timely access to screening services and care among Asian UNWHAs.

PURPOSE This study aimed to synthesize the caring experiences of Korean family members of patients with dementia through a qualitative meta-synthesis method. METHODS By searching through nine Korean and English databases, we compared 37 qualitative studies on caring experiences of family members of patients with dementia. The selected studies were synthesized through meta-synthesis, proposed by Sandelowski and Barroso (2007). RESULTS The meta-synthesis elicited four themes: tough life due to care for patients, changes in relationships, adaptation to caregiver's roles, and new perspectives of life through personal growth. Caregivers were shocked when a sudden diagnosis of dementia was made prior to any preparation on their part. They were tied to their patients all the time and their mind and body got exhausted. Their relationship with patients began to change and they looked at them differently. They experienced conflicts with the other non-caring family members and were alienated from them. They were also socially isolated. However, by building their own care strategies and utilizing social resources, they gradually adapted to their caregiver roles. Finally, they experienced personal growth and acquired a new perspective toward life by accepting their roles and finding meaning in their lives. Shifting the caregiver's centricity from themselves to the patient was the process of becoming human beings who actively constructed their realities while giving meaning to their painful lives and interacting with the environment. CONCLUSION The results of the study can be useful for nurses in understanding the experiences of caregivers of the patients with dementia and in providing them with practical interventions.

Separately, prenatal antibiotics and Caesarian delivery have been found to be associated with increased risk of allergic diseases. It is not clear whether these factors may modify the effect of each other.To assess whether the associations between delivery types and eczema, sensitization and total IgE at age 2 years were modified by maternal use of prenatal medications.Prenatal charts of women enrolled in the WHEALS birth cohort were reviewed for delivery mode and medications prescribed and administered throughout their entire pregnancy, including systemic antibiotics and vaginally applied antifungal medications. The associations between the delivery mode and select medications and, eczema, sensitization (≥ 1 of 10 allergen-specific IgE ≥ 0.35 IU/mL) and total IgE at age 2 years were assessed.There was a lower risk of eczema among vaginally vs. c-section born children (relative risk adjusted for race = aRR = 0.77, 95% CI 0.56, 1.05). Although not statistically significantly different, this association was stronger among the subset of children born vaginally to a mother who did not use systemic antibiotics or vaginal antifungal medications (aRR = 0.69, 95% CI 0.44, 1.08) compared to those born vaginally to mothers who used systemic antibiotics or vaginal antifungals (aRR = 0.81, 95% CI 0.57, 1.14). A protective association between vaginal birth and sensitization (aRR = 0.86, 95% CI 0.72, 1.03) was similar for those children born vaginally to a mother who did not (aRR = 0.87, 95% CI 0.69, 1.10) and who did (RR = 0.85, 95% CI 0.70, 1.04) use systemic antibiotics or vaginal antifungal medications. There were no associations with total IgE.Children born vaginally had lower risk of eczema and sensitization compared with those born via c-section; however, the protective association with eczema may be slightly weakened when mothers took systemic antibiotics or vaginally applied medications during pregnancy.

and emesis. In the present study, we investigated the antiobesity effects and antioxidant activity of KE-06. Methods: 3T3-L1 preadipocytes were differentiated into adipocytes with or without KE-06. After differentiation, we measured Oil Red O staining, glycerol-3-phosphate dehydrogenase (GPDH) activity and leptin production in 3T3-L1 adipocytes. In addition, we analyzed its effect on scavenging activities of 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (A BTS) and 2,2’-diphenyl-1-picrylhydrazyl (DPPH) radicals in in vitro systems. Its effect on low-density lipoprotein (LD L) oxidation was assessed by measuring production of malondialdehyde (MDA). Results: KE-06 significantly inhibited lipid accumulation and triglyceride production, and mediated GPDH, a major enzyme in the process of adipogenesis. Consistent with this, KE-06 stimulation significantly decreased the amount of leptin in 3T3-L1 adipose cells. Furthermore, KE-06 enhanced the scavenging activities on ABTS and DPPH radicals. The generation of MDA during LDL oxidation was significantly reduced by KE-06 treatment. Conclusion:Overall, our findings suggest thatKE-06has the potential for anti-adipogenic activity and antioxidant properties. Contact: Sae-Rom Yoo, k2aori@kiom.re.kr