The effects of neighborhood views containing multiple environmental features on road traffic noise perception at dwellings.

The importance of non-acoustical factors including the type of visual environment on human noise perception becomes increasingly recognized. In order to reveal the relationships between long-term noise annoyance and different types of neighborhood views, 2033 questionnaire responses were collected for studying the effect of perceptions of different combinations of views of sea, urban river, greenery, and/or noise barrier on the annoyance responses from residents living in high-rise apartments in Hong Kong. The collected responses were employed to formulate a multivariate model to predict the probability of invoking a high annoyance response from residents. Results showed that views of sea, urban river, or greenery could lower the probability, while views of noise barrier could increase the probability. Views of greenery had a stronger noise moderation capability than views of sea or urban river. The presence of an interaction effect between views of water and views of noise barrier exerted a negative influence on the noise annoyance moderation capability. The probability due to exposure to an environment containing views of noise barriers and urban rivers would be even higher than that due to exposure to an environment containing views of noise barriers alone.

Portable video media for presenting informed consent and wound care instructions for skin biopsies: a randomized controlled trial.

BACKGROUND: In fast-paced dermatology clinics, the process of obtaining informed consents for biopsies and providing postprocedure instructions may be incomplete and inconsistent. OBJECTIVES: To compare effectiveness of video-based education with that of verbal education for giving informed consent and providing postprocedure wound care instructions in patients undergoing skin biopsies. METHODS: In this randomized controlled trial, participants were randomized to receive either video education on portable video devices or conventional verbal instructions regarding skin biopsies. Participants completed a skin-biopsy knowledge assessment, patient satisfaction assessment and evaluation of educational medium. Main outcome measures were differences in the changes in the prestudy and poststudy knowledge assessment scores, patient satisfaction and evaluation of the educational medium. RESULTS: Eight-four patients undergoing skin biopsies at the University of California Davis dermatology clinic participated in the study. Participants in the control group had a nonstatistically significant increase in knowledge score (mean ± SD 1·12 ± 1·74), whereas those in the video group had a statistically significant increase in knowledge score (mean ± SD 1·55 ± 1·71). The difference in knowledge scores between the video and verbal groups was not statistically significant. Participants in both groups were highly satisfied with the biopsy education. On a 10-point scale, the mean ± SD usefulness and appeal of the videos were 9·01 ± 1·5 and 9·01 ± 1·66, respectively. CONCLUSIONS: Our study demonstrated a significant increase in knowledge score following video education, but not following oral education. Although between-group comparisons did not achieve statistical significance, portable video media for presenting informed consent and wound care instructions for skin biopsies appear to be more effective and result in higher satisfaction than traditional oral education.

Cyclooxygenase inhibitors modulate the p53/HDM2 pathway and enhance chemotherapy-induced apoptosis in neuroblastoma.

Cyclooxygenase-2 (COX-2) is upregulated in many tumors including neuroblastoma, and its overexpression has been implicated in resistance to p53-dependent apoptosis. Although p53 is rarely mutated in neuroblastoma, the p53 protein is rendered inactive via several mechanisms including sequestration in the cytoplasm. Here, we show that COX inhibitors inhibit the growth of neuroblastoma and when combined with low doses of chemotherapy, exert synergistic effects on neuroblastoma cells. Following COX inhibitor treatment, HDM2, which targets p53 for ubiquitin-mediated degradation, is downregulated, resulting in an attenuation of p53 ubiquitination and an increase in p53 half-life. The level of HDM2 phosphorylation at ser166, which influences both HDM2 and p53 subcellular distribution, is markedly diminished in response to COX inhibitors and is associated with increased p53 nuclear localization. Combining COX inhibitors with low-dose chemotherapy potentiates apoptosis and p53 stability, nuclear localization, and activity. p53 knockdown by siRNA resulted in the rescue of COX-inhibitor-treated cells, indicating that COX inhibitor-induced apoptosis is, at least in part, p53-dependent. Taken together, these results provide the first evidence that COX inhibitors enhance chemosensitivity in neuroblastoma via downregulating HDM2 and augmenting p53 stability and nuclear accumulation.

Risk factors for hospital readmission for COPD after implementation of the GOLD guidelines.

BACKGROUND: Few updated studies have investigated risk factors for readmission for chronic obstructive pulmonary disease (COPD) since the implementation of the latest treatment guidelines. OBJECTIVE: To evaluate a series of potential risk factors for readmission in patients with COPD and in a subgroup with very frequent readmissions after implementation of the Global Initiative for Chronic Obstructive Lung Disease guidelines. DESIGN: Two hundred and fifty patients admitted for acute exacerbation of COPD (AECOPD) were recruited over 1 year. The readmission frequency in the ensuing year following hospital discharge was recorded and analysed against potential risk factors collected during the index admission. RESULTS: In the ensuing year, 183 (73.2%) patients were readmitted at least once for AECOPD. Previous non-invasive ventilation for AECOPD (HR 1.56, 95%CI 1.08-2.26), COPD Assessment Test score (HR 1.03, 95%CI 1.00-1.05), 6-minute walk distance (HR 0.98 per 10 m increase, 95%CI 0.97-0.99) and number of admissions for AECOPD in the previous year (HR 1.11, 95%CI 1.06-1.16) were independently associated with time to first readmission. Subgroup analysis showed that anxiety (OR 3.97, 95%CI 1.49-10.57) was strongly associated with very frequent readmissions (⩾4 in 1 year). CONCLUSIONS: AECOPD is associated with high rates of readmission. Anxiety is a potential modifiable factor associated with very frequent readmissions.

Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease.

BACKGROUND: Transplanting autologous patient-derived enteric neuronal stem/progenitor cells (ENSCs) is an innovative approach to replacing missing enteric neurons in patients with Hirschsprung disease (HSCR). Using autologous cells eliminates immunologic and ethical concerns raised by other cell sources. However, whether postnatal aganglionic bowel is permissive for transplanted ENSCs and whether ENSCs from HSCR patients can be successfully isolated, cultured, and transplanted in vivo remains unknown. METHODS: ENSCs isolated from the ganglionic intestine of Ednrb(-/-) mice (HSCR-ENSCs) were characterized immunohistochemically and evaluated for their capacity to proliferate and differentiate in vitro. Fluorescently labeled ENSCs were co-cultured ex vivo with aganglionic Ednrb(-/-) colon. For in vivo transplantation, HSCR-ENSCs were labeled with lentivirus expressing green fluorescent protein (GFP) and implanted into aganglionic embryonic chick gut in ovo and postnatal aganglionic Ednrb(-/-) rectum in vivo. KEY RESULTS: HSCR-ENSCs maintain normal capacity self-renewal and neuronal differentiation. Moreover, the Ednrb(-/-) aganglionic environment is permissive to engraftment by wild-type ENSCs ex vivo and supports migratrion and neuroglial differentiation of these cells following transplantation in vivo. Lentiviral GFP-labeled HSCR-ENSCs populated embryonic chick hindgut and postnatal colon of Ednrb(-/-) HSCR, with cells populating the intermuscular layer and forming enteric neurons and glia. CONCLUSIONS & INFERENCES: ENSCs can be isolated and cultured from mice with HSCR, and transplanted into the aganglionic bowel of HSCR littermates to generate enteric neuronal networks. These results in an isogenic model establish the potential of using autologous-derived stem cells to treat HSCR and other intestinal neuropathies.

Evidence for joint genetic control of insulin sensitivity and systolic blood pressure in hispanic families with a hypertensive proband.

BACKGROUND: The clustering of hypertension, insulin resistance, and obesity remains unexplained. We tested for genetic and nongenetic influences on the association among these traits in Hispanic families with hypertension. METHODS AND RESULTS: Blood pressure and body mass index (BMI) were measured in 331 members of 73 Hispanic families in which an index case (proband) had hypertension. Insulin sensitivity (S(I)) was measured by euglycemic clamp in 287 probands and their spouses (parents' generation) or their adult offspring. Correlation analysis examined relationships among traits within and between generations. Path analysis estimated genetic and nongenetic contributions to variability in systolic blood pressure (SBP), S(I), and the correlation between them. In the offspring, there was a significant correlation between individuals for each trait, as well as significant correlations within and between individuals for all possible pairs of traits. Between generations, SBP, S(I), and BMI in parents correlated with the same traits in their offspring; BMI in parents correlated with S(I) and SBP in offspring; and S(I) in parents correlated with SBP in offspring. Path analysis estimated that among offspring, genetic effects unrelated to BMI accounted for 60.8% of the variation in SBP, 36.8% of the variation in S(I), and 31.5% of the correlation between SBP and S(I) after adjustment for age and sex. Heritable effects related to BMI accounted for an additional 14.0% of variation in SBP, 26.8% of variation in S(I), and 56.3% of variation in their correlation. CONCLUSIONS: Clustering of hypertension and insulin resistance in Hispanic Americans is accounted for in part by heritable factors both associated with and independent of BMI.

Coincident linkage of fasting plasma insulin and blood pressure to chromosome 7q in hypertensive hispanic families.

BACKGROUND: Insulin resistance (IR) and hyperinsulinemia are phenotypically associated with hypertension. We have previously provided evidence that blood pressure (BP) and IR cosegregate in Hispanic families, suggesting that this association has a genetic component. In the present study, we provide further support for the hypothesis of a genetic basis for the BP-IR relationship from a genetic linkage study. METHODS AND RESULTS: A 10-cM genome scan was conducted in 390 Hispanic family members of 77 hypertensive probands. Detailed measurements of BP, glucose, insulin levels, and insulin sensitivity (euglycemic clamp) were performed in adult offspring of probands. Multipoint variance component linkage analysis was used. A region on chromosome 7q seemed to influence both IR and BP. The greatest evidence for linkage was found for fasting insulin (lod score=3.36 at 128 cM), followed by systolic BP (lod score=2.06 at 120 cM). Fine mapping with greater marker density in this region increased the maximum lod score for fasting insulin to 3.94 at 125 cM (P=0.00002); lod score for systolic BP was 2.51 at 112 cM. Coincident mapping at this locus also included insulin sensitivity measured by the homeostasis assessment model (HOMA) and serum leptin concentrations. Insulin sensitivity by euglycemic clamp did not map to the same locus. CONCLUSIONS: Our results demonstrate that a major gene determining fasting insulin is located on chromosome 7q. Linkage of BP, HOMA, and leptin levels to the same region suggests this locus may broadly influence traits associated with IR and supports a genetic basis for phenotypic associations in IR syndrome.

Heritability of subclinical atherosclerosis in Latino families ascertained through a hypertensive parent.

Although clinical coronary heart disease and many cardiovascular risk factors are well known to aggregate within families, the heritability of carotid artery intima-media thickness (IMT) is less well documented. We report IMT heritability estimates in Mexican American, Salvadoran American, or Guatemalan American (all referred to as Latino) families ascertained through a hypertensive proband. IMT and cardiovascular risk factors (age, sex, blood pressure, body mass index, lipids, fasting glucose, and insulin sensitivity) were measured in 204 adult offspring of 69 hypertensive probands, along with 82 parents (54 probands and 28 spouses). In the offspring, variance component analysis revealed a heritability for IMT of 64% (P< 0.0001) after adjustment for significant cardiovascular risk factors. Genetic factors accounted for 50% of the total variation in IMT, whereas significant cardiovascular risk factors explained 22% (14% were due to age). For offspring and parents combined, adjusted IMT heritability was less, 34% (P=0.0005), with genetic factors accounting for 18% of the total IMT variation, whereas significant cardiovascular risk factors explained 46% (38% were due to age). We conclude that variation in common carotid artery IMT is heritable in Latino families with a hypertensive proband. Heritability is particularly evident in younger family members, suggesting that acquired factors contribute progressively to IMT variability with aging.

Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease.

BACKGROUND: Transplantation of enteric neural stem cells (ENSC) holds promise as a potential therapy for enteric neuropathies, including Hirschsprung disease. Delivery of transplantable cells via laparotomy has been described, but we propose a novel, minimally invasive endoscopic method of cell delivery. METHODS: Enteric neural stem cells for transplantation were cultured from dissociated gut of postnatal donor mice. Twelve recipient mice, including Ednrb(-/-) mice with distal colonic aganglionosis, underwent colonoscopic injection of ENSC under direct vision using a 30-gauge Hamilton needle passed through a rigid cystoureteroscope. Cell engraftment, survival, and neuroglial differentiation were studied 1-4 weeks after the procedure. KEY RESULTS: All recipient mice tolerated the procedure without complications and survived to sacrifice. Transplanted cells were found within the colonic wall in 9 of 12 recipient mice with differentiation into enteric neurons and glia. CONCLUSIONS & INFERENCES: Endoscopic injection of ENSC is a safe and reliable method for cell delivery, and can be used to deliver a large number of cells to a specific area of disease. This minimally invasive endoscopic approach may prove beneficial to future human applications of cell therapy for neurointestinal disease.

Binding of etiopurpurin and tin-coordinated etiopurpurin to human plasma proteins. Delivery in cremophore EL and dimethyl sulfoxide (paper II).

Purpurins are potent hydrophobic photosensitizers in vivo. Cremopfore EL is an important vehicle for the administration of hydrophobic drugs. Mode-delivery-effects on the binding of etiopurpurin (ET2) to human plasma (LDL, HDL, and high density proteins, HDP) is studied for delivery in CRMaq and in DMSO by ultracentrifugation. A similar study of SnET2 is available (Kongshaug et al., 1993) and has been extended. In the absence of plasma, only nonfluorescent ET2 entities (aggregates) were present, a portion of which moved unaffected by gravity (small aggregates), the remainder according to their densities (high density aggregates). Aggregated ET2 showed, at high salt density, similar positions and halfwidths in the gradient, and similar adsorption properties as the aggregates in plasma-containing samples. In CRMaq (1 mg CRM/ml) the adsorptive loss of the dye affected only marginally the binding of fluorescent monomeric ET2. In this mode (i) 20% of ET2 was bound as monomers, about 70% of which to CRM-modified LDL, most of the remainder to CRM-modified HDL; (ii) such HDL also marginally bound small aggregates; (iii) only monomeric ET2 was bound to CRM-modified LDL. In delivery in DMSO, aggregated ET2 (98% of ET2 in the gradient) converted, post centrifugally, into minor amounts of HDL-bound monomeric ET2; LDL-bound ET2 included monomers (about 50%) and small aggregates, mainly dimers. The percentage binding of SnET2 to HDP was independent of the concentrations of CRMaq and HDL. Plasma-bound small aggregates (such as dimers) and plasma-unbound high density aggregates (mean densities of 1.13-1.19 g/ml) were substantially present in the plasma-containing samples. There were mode-delivery-effects upon the yields and properties of aggregated ET2, and upon the yields of plasma-bound monomeric ET2. Monomeric ET2 showed a remarkably high percentage binding to LDL and was similarly distributed among the lipoproteins as is total cholesterol. There was little or no real mode-delivery-effect upon the distribution of monomeric ET2 among the plasma proteins. The affinity of CRM-modified LDL for SnET2 was similar to that of HDL plus HDP in native plasma.

Binding of etiopurpurin to human plasma proteins. Delivery in cremophor EL and dimethyl sulphoxide. III.

Binding of the photosensitizer etiopurpurin (ET2) to human plasma was assessed, using conditions that would yield a high percentage of ET2 in the form of LDL-bound monomers which may favor photosensitizer tumor localization. Two delivery systems, Cremophor EL (CRM) and dimethyl sulphoxide (DMSO), were used. The binding of ET2 to CRM-modified lipoproteins was compared to the binding of the dye to the native proteins using delivery in DMSO. Plasma-bound monomers and unbound high density aggregates were shown to coexist. The density and rate of formation of the dye aggregates were correlated. The aggregates formed by delivery in DMSO could be partially converted into plasma-bound monomeric ET2. There was no mode-delivery-effect upon the distribution of monomeric ET2 among the plasma proteins. 70% of monomeric ET2 was bound to LDL and most of the remainder to HDL. In delivery in DMSO the yield of LDL-bound dye monomers (up to 30% of added ET2) increased with decreasing concentration of ET2 in the delivery solution and with increasing time of incubation (< or = 48 hr). Long incubation also induced changes in the densities of LDL and HDL. The yields of LDL-bound monomers (up to 40%) increased with increasing concentration of CRM-bound ET2. High yields of LDL-bound monomers were obtained using both modes of delivery. Although the aggregates associated with the two modes of delivery had different properties. The change in lipoprotein composition might be involved in the conversion of aggregates into plasma-bound monomers.

The effect of glucose administration on the uptake of photofrin II in a human tumor xenograft.

Athymic BALB/c nude mice, bearing a human melanoma LOX, were given the photosensitizing drug Photofrin II (10 mg/kg body wt.) intraperitoneally. The mice were also given one of the following chemicals intraperitoneally: glucose, galactose and glucose plus nordihydroguaiaretic acid (NDGA) which is an inhibitor of glycolysis. Multiple injections of glucose (3 g/kg body wt. given at -1, 0, +1 and +3 h relative to the injection of 10 mg/kg of Photofrin II at time 0) resulted in a significant increase in the uptake of Photofrin II in the tumor 4 h after a Photofrin II injection, while the uptake of Photofrin II in the other tissues remained unchanged. Administration of galactose had no significant effect on the uptake of Photofrin II in the tissues studied (tumor, muscle, skin and liver). NDGA seemed to abolish the effect of glucose injection.

Segregation analysis of drinking problem in elderly men and their first-degree relatives from the Western Collaborative Group Study.

PURPOSE: The purpose of this study is to determine the mode of inheritance of alcohol-related drinking problems. METHODS: Family history was collected by interview from 493 elderly male participants (probands) in a follow-up cardiovascular exam of healthy white men living in the San Francisco Bay Area and Los Angeles. Segregation analysis was used to test for the presence of a major gene effect underlying the liability to develop an alcohol-related drinking problem. RESULTS: The results showed that the liability to drinking problem is due, in part, to a single major gene with no residual effects from shared familial influences. CONCLUSIONS: These results suggest that at least one major gene is involved in the genetic predisposition to develop drinking problem in late adulthood.

Segregation analysis of asthma: recessive major gene component for asthma in relation to history of atopic diseases.

Although asthma has a significant heritable component, the mode of inheritance remains controversial because of the complexity of the disease and the influence of environmental factors. Segregation analysis for asthma are performed with and without a history of atopic diseases (dermatitis and rhinitis) after adjusting for environmental factors. To investigate whether asthma may be inherited through a major gene with two alleles, the REGD program of the Statistical Analysis for Genetic Epidemiology (SAGE) package was conducted in 1,990 individuals from 227 families with at least one asthmatic child in a cross-sectional study of respiratory diseases in Southern Taiwan. Other covariates adjusted for included age, sex, current smoking, and environmental tobacco smoking. The hypothesis of Mendelian model and no parent-offspring transmission was rejected. However, when the variables of atopic disease and environmental factors were included in the model as covariates, the models for a two-allele gene with a recessive or codominant inheritance could not be rejected, and Akaike's Information Criterion was smaller (1,377. 13) for the recessive model than all of the other models tested, assuming a major gene with a population frequency of 0.56 +/- 0.04. However, Mendelian model without family effect was rejected. In conclusion, a history of asthma in parents is a strong risk factor for asthma in offspring. Under the assumptions of the applied segregation, at least one major gene exists that could be a gene involved also in allergy. However, the data suggest that a single locus gene explains a portion of asthma that is related to the history of atopic diseases. In addition, a polygenic/multifactorial (genetic and environmental factors) influence with a recessive component inheritance may be involved in the pathogenesis of asthma.

A genetic analysis of smoking behavior in family members of older adult males.

AIMS: To conduct a genetic study of smoking behavior in 493 three-generation families. DESIGN: Complex segregation analysis and maximum likelihood statistics were used to describe the familial clustering of ever-smoking under several transmission models. SETTING: The Western Collaborative Group Study, an ageing and health study currently in its 39th year of follow-up. PARTICIPANTS: Probands were male participants who were of mean age 71.6 years at the time of the family history interview in 1986-88. MEASUREMENTS: Data were collected via an interview that focused on the family smoking history of participants. Smoking histories of all first-degree relatives were obtained from probands. FINDINGS: Evidence for genetic transmission was indicated by rejection of both the environmental and sporadic models in favor of a Mendelian genetic model with residual familial effects from spouses and both parents. CONCLUSIONS: The best-fitting model was that of a dominant major gene with low estimated frequency and residual familial correlations. This is the first study to date to model the familial transmission of ever-smoking in three-generation families.

Tin etiopurpurin dichloride-sensitized lipid photooxidation of erythrocyte membranes.

Tin(IV) etiopurpurin dichloride (SnET2 x 2Cl) is a photosensitizer which has been shown to be an effective photodynamic agent for the treatment of transplantable animal tumors in vivo. The purpose of this study was to understand the effect of SnET2 x 2Cl on membrane lipid peroxidation. When erythrocyte membranes were exposed to visible light in the presence of SnET2 x 2Cl, lipid peroxidation was observed. An accumulation of lipid hydroperoxides and an increase in lipid fluorescence were also observed. Thin layer chromatography of lipid extracts from photooxidized membrane revealed photoperoxide products derived from phospholipid. Investigations into the mechanism(s) of lipid peroxidation by SnET2 x 2Cl and light-sensitized membranes were also performed. Results indicate that singlet oxygen (1O2) plays a major role in lipid peroxidation.

DNA damage induced by hypocrellin-A photosensitization.

Hypocrellin-A (HC-A) isolated from Hypocrellia bambusae Sacc., is a new and effective photosensitizer. Illumination of sarcoma 180 cells with visible light in the presence of HC-A leads to a decrease in cell viability and 3H-TdR incorporation, causes DNA strand breakage, and results in the selective destruction of guanine moieties in DNA. HC-A photosensitization causes an increase in the theta 260/theta 280 ratio in the circular dichroism spectra of DNA in vitro. Of the four usual 2'-deoxynucleotides illuminated in the presence of HC-A only 2'-deoxyguanylic acid was destroyed.

Effects of Five Naturally Occurring Sugars on the Longevity, Oogenesis, and Nutrient Accumulation Pattern in Adult Females of the Synovigenic Parasitoid Neochrysocharis formosa (Hymenoptera: Eulophidae).

Neochrysocharis formosa (Westwood) (Hymenoptera: Eulophidae), one of the dominant natural enemies of agromyzid leafminers, is a synovigenic parasitoid. We compared the longevity, oogenesis, and nutrient levels of female wasps provided with 10% solutions of five naturally occurring sugars. All five sugars significantly increased the longevity of female wasps, which was 6.5-9.3-fold higher than that of parasitoids provided with water only. We found no significant difference in longevity of female wasps fed on glucose versus fructose or trehalose versus melezitose, but longevity of wasps fed on glucose or fructose was significantly longer than those fed on trehalose or melezitose. Also, we examined the oosorption capability of wasps fed on the five sugars. Some mature eggs were present in the ovaries of newly emerged females, but these were fully reabsorbed within 72 h when wasps were starved. Once wasps were fed with any of the sugars, the number of mature eggs increased at first and then decreased due to oosorption. The longevity and oogenesis dynamics of female wasps fed on five sugars were related with their function of hydrolysis and digestion. As female wasps have no lipogenesis capability, by acquiring exogenous sugars for oogenesis, they can either maintain or exceed the original level of capital nutrients held on adult emergence because none of the wasps' glycogen need be metabolized to burn as sugar.

Evaluation of testing capabilities for the determination of melamine in milk through an interlaboratory proficiency test programme during the melamine crisis.

An interlaboratory proficiency testing programme for melamine in milk was organized for field laboratories in Hong Kong, China, during the melamine crisis in late September 2008. One blank test sample and three homogenous samples prepared by gravimetric spiking of melamine at the concentration range of zero to 4.5 mg kg(-1) were given to participants in this programme. A total of 13 participants returned the results to the organizer and they used either liquid chromatography-tandem mass spectrometry (LC-MS/MS) or gas chromatography-mass spectrometry (GC-MS) for their determinations. The performance of the participants was assessed by determining z-scores, calculated from the bias from the assigned reference values and Horwitz standard deviation. The median values of pooled data were found to be in good agreement with the reference values and the majority of the participants demonstrated their capabilities in the quantitative measurement of melamine in milk samples. However, four participants gave false-positive results for the blank test sample, probably due to cross-contamination from other samples, and they were requested to investigate the actual causes. In summary, eight participants (or 62%) demonstrated their competence for all the four test samples.