Highly selective resolution of racemic 1-phenyl-1,2-ethanediol by a novel strain Kurthia gibsonii SC0312.

Chiral 1-phenyl-1,2-ethanediol (PED) performs vital effect for the preparation of pharmaceuticals, agrochemicals and cosmetics. In the study, a newly isolated strain Kurthia gibsoniiSC0312 with the ability to selectively oxidize racemic PED to achieve (S)-PED was evaluated in the aqueous reaction system. The strain showed excellent catalytic performances within the range of pH 5·5-8·5, temperature 25-45°C and the amount of cell 15 mg ml-1 to 30 mg ml-1 . Besides, 2-hydroxyacetophenone (HAP) as the oxidation product displayed a stronger inhibition to the catalytic activity of cell, only remaining <63% of catalytic activity after incubation at 40 mmol l-1 HAP for 6 h. For various metal ions, Cu2+ can obviously improve 1·7 times of the catalytic activity of cell at the concentration of 0·2 mmol l-1 . Acetone can stimulate the catalytic capacity of cell to improve the optical purity of (S)-PED at the PED concentration of 80 mmol l-1 , up to appropriately 94% from 85·4%; compared to the resting cell, growing cell exerted no positive effect in the yield and optical purity. Finally, a highly effective kinetic resolution system of racemic PED by the new strain was obtained, with the (S)-PED yield of 41% and optical purity of 94%. SIGNIFICANCE AND IMPACT OF THE STUDY: Biocatalyst is a vital component in the process of biotransformation. There are a growing number of studies of biocatalyst reporting the preparation of enantiomer of 1-phenyl-1,2-ethanediol. And the performance of this preparation reaction is also gradually improving. This study is the first to demonstrate that Kurthia gibsonii can efficiently and selectively oxidize racemic 1-phenyl-1,2-ethanediol, and we assess the effect of various factors on the catalytic performance of the strain. The work adds to a growing body of evidence for using biocatalytic method in the synthesis of chiral 1-phenyl-1,2-ethanediol and provides a probable approach to mine excellent properties of enzymes.

Efficient biocatalytic stereoselective reduction of methyl acetoacetate catalyzed by whole cells of engineered E. coli.

Asymmetric synthesis of chiral ß-hydroxy esters, the key building blocks for many functional materials, is currently of great interest. In this study, the biocatalytic anti-Prelog reduction of methyl acetoacetate (MAA) to methyl-(R)-3-hydroxybutyrate ((R)-HBME) was successfully carried out with high enantioselectivity using the whole cell of engineered E. coli, which harbored an AcCR (carbonyl reductase) gene from Acetobacter sp. CCTCC M209061 and a GDH (glucose dehydrogenase) gene from Bacillus subtilis 168 for the in situ regeneration of the coenzyme. Compared with the corresponding wild strain, the engineered E. coli cells were proved to be more effective for the bio-reduction of MAA, and afforded much higher productivity. Under the optimized conditions, the product e.e. was >99.9% and the maximum yield was 85.3% after a reaction time of 10 h, which were much higher than those reported previously. In addition, the production of (R)-HBME increased significantly by using a fed-batch strategy of tuning pH, with a space-time yield of approximately 265 g L-1 d-1, thus the issue in previous research of relatively low substrate concentrations appears to be solved. Besides, the established bio-catalytic system was proved to be feasible up to a 150 mL scale with a large-scale relatively high substrate concentration and selectivity. For further industrial application, these results open a way to use of whole cells of engineered E. coli for challenging higher substrate concentrations of ß-ketone esters enantioselective reduction reactions.

Patterns of allergic sensitization and atopic dermatitis from 1 to 3 years: Effects on allergic diseases.

BACKGROUND: While allergic sensitization and atopic dermatitis (AD) are known to increase the risk for allergic diseases, the impact of different temporal and clinical patterns of sensitization and AD is less well defined. OBJECTIVE: We investigated patterns of sensitization and AD from early infancy to age 3, and the differential risk of developing allergic diseases within each pattern in a general cohort. METHODS: Children (n = 2629) from the Canadian Healthy Infant Longitudinal Development (CHILD) Study underwent skin prick tests and were assessed clinically for AD at ages 1 and 3 years. We applied an unsupervised latent class analysis (LCA) to the following 5 factors at these ages: AD, food sensitization, inhalant sensitization, poly-sensitization to foods and poly-sensitization to inhalants. The risks for developing asthma, allergic rhinitis and food allergy at 3 years were evaluated for each identified group. RESULTS: Five distinct classes were revealed by LCA: healthy (81.8%), atopic dermatitis (7.6%), inhalant sensitization (3.5%), transient sensitization (4.1%) and persistent sensitization (3.2%). Using healthy children as the baseline, children in the "atopic dermatitis" group had the next lowest risk for all allergic outcomes at 3 years; those in the "inhalant sensitization" group had the highest risk for allergic rhinitis; children in the "transient sensitization" group were at an increased risk for food allergy; while children in the "persistent sensitization" group had the highest risk for all allergic diseases. CONCLUSION AND CLINICAL RELEVANCE: There is substantial heterogeneity among allergen-sensitized children. Researchers and clinicians need to be aware of the non-specificity associated with labelling children simply as "atopic" and "non-atopic" without considering the timing of their atopic history, type of sensitization and AD status. Children with AD who were poly-sensitized to foods at an early age appear to be at greatest risk of developing other allergic diseases.

The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma.

The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study recruited 3624 pregnant women, most partners and 3542 eligible offspring. We hypothesise that early life physical and psychosocial environments, immunological, physiological, nutritional, hormonal and metabolic influences interact with genetics influencing allergic diseases, including asthma. Environmental and biological sampling, innate and adaptive immune responses, gene expression, DNA methylation, gut microbiome and nutrition studies complement repeated environmental and clinical assessments to age 5. This rich data set, linking prenatal and postnatal environments, diverse biological samples and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases.

Estimating survival probabilities by exposure levels: utilizing vital statistics and complex survey data with mortality follow-up.

We present a two-step approach for estimating hazard rates and, consequently, survival probabilities, by levels of general categorical exposure. The resulting estimator utilizes three sources of data: vital statistics data and census data are used at the first step to estimate the overall hazard rate for a given combination of gender and age group, and cohort data constructed from a nationally representative complex survey with linked mortality records, are used at the second step to divide the overall hazard rate by exposure levels. We present an explicit expression for the resulting estimator and consider two methods for variance estimation that account for complex multistage sample design: (1) the leaving-one-out jackknife method, and (2) the Taylor linearization method, which provides an analytic formula for the variance estimator. The methods are illustrated with smoking and all-cause mortality data from the US National Health Interview Survey Linked Mortality Files, and the proposed estimator is compared with a previously studied crude hazard rate estimator that uses survey data only. The advantages of a two-step approach and possible extensions of the proposed estimator are discussed.

Emergency department presentations for self-harm among Ontario youth.

OBJECTIVES: Self-harm is an important public health issue among youth, including as a major risk factor for suicide (a leading cause of death in this age group). This study used population-based emergency department data to describe clinical and demographic characteristics of emergency department presentations for self-harm among youth (12-17 year-olds) in the province of Ontario, Canada. METHODS: Administrative data capturing every emergency department visit in Ontario between April 1, 2002 and March 31, 2009 were used to identify and describe self-harm presentations. RESULTS: Over the 7-year period between 2002/03 and 2008/09, there were 16,835 self-harm presentations by 12,907 youth. Two thirds of self-harm presentations were self-poisonings (almost always with medicinal agents), followed by self-cutting, which accounted for about one quarter. Incidence rates were higher in girls than boys, increased with age, were inversely related to neighbourhood income and were highest in rural areas. Self-harm accounted for about 1 in 100 emergency department presentations by youth, but also a disproportionate number of presentations triaged as high acuity or admitted to hospital (about 1 in 20). CONCLUSION: Self-harm is an important public health issue, requiring a comprehensive approach to prevention. Ontario has useful data with which to study emergency department presentations for self-harm, and the similarities between self-harm presentations among Ontario youth and those reported from the United States and Europe suggest generalizability of results between populations. Further research is needed to address the reasons for the geographic differences in frequency of self-harm.

Estrogen and aging affect the synaptic distribution of estrogen receptor ß-immunoreactivity in the CA1 region of female rat hippocampus.

Estradiol (E) mediates increased synaptogenesis in the hippocampal CA1 stratum radiatum (sr) and enhances memory in young and some aged female rats, depending on dose and age. Young female rats express more estrogen receptor α (ERα) immunolabeling in CA1sr spine synapse complexes than aged rats and ERα regulation is E sensitive in young but not aged rats. The current study examined whether estrogen receptor ß (ERß) expression in spine synapse complexes may be altered by age or E treatment. Young (3-4 months) and aged (22-23 months) female rats were ovariectomized 7 days prior to implantation of silastic capsules containing either vehicle (cholesterol) or E (10% in cholesterol) for 2 days. ERß immunoreactivity (ir) in CA1sr was quantitatively analyzed using post-embedding electron microscopy. ERß-ir was more prominent post-synaptically than pre-synaptically and both age and E treatment affected its synaptic distribution. While age decreased the spine synaptic complex localization of ERß-ir (i.e., within 60 nm of the pre- and post-synaptic membranes), E treatment increased synaptic ERß in both young and aged rats. In addition, the E treatment, but not age, increased dendritic shaft labeling. This data demonstrates that like ERα the levels of ERß-ir decrease in CA1 axospinous synapses with age, however, unlike ERα the levels of ERß-ir increase in these synapses in both young and aged rats in response to E. This suggests that synaptic ERß may be a more responsive target to E, particularly in aged females.

Effects of estrogen and aging on the synaptic distribution of phosphorylated Akt-immunoreactivity in the CA1 region of the female rat hippocampus.

The estrogen 17ß-estradiol (E) increases the axospinous synaptic density and plasticity in the hippocampal CA1 region of young female rats but fails to do so in aged female rats. This E stimulus on synaptic plasticity is associated with the phosphorylation-dependent activation of Akt kinase. Our previous findings demonstrated that increased estrogen levels subsequently increase phosphorylated Akt (pAkt)-immunoreactivity (-IR) within the dendritic shafts and spines of pyramidal neurons in young female rats. Therefore, because Akt can promote cell survival and growth, we tested the hypothesis that the less plastic synapses of aged female rats would contain less E-stimulated pAkt-IR. Here, young (3-4 months) and aged (22-23 months) female rats were ovariectomized 7 days prior to a 48-h administration of either vehicle or E. The pAkt-IR synaptic distribution was then analyzed using post-embedding electron microscopy. In both young and aged rats, pAkt-IR was found in dendritic spines and terminals, and pAkt-IR was particularly abundant at the post-synaptic density. Quantitative analyses revealed that the percentage of pAkt-labeled synapses was significantly greater in young rats compared to aged rats. Nonetheless, E treatment significantly increased pAkt-IR in pre- and post-synaptic profiles of both young and aged rats, although the stimulus in young rats was notably more widespread. These data support the evidence that hormone-activated signaling associated with cell growth and survival is diminished in the aged brain. However, the observation that E can still increase pAkt-IR in aged synapses presents this signaling component as a candidate target for hormone replacement therapies.

Repeat self-harm: application of hurdle models.

Among those who present to the emergency department for self-harm, many will repeat. Self-harm repetition is an outcome of interest in both observational and intervention studies. However, few such studies analyse the number of repeat self-harm presentations. Here, hurdle models are introduced as a potentially useful statistical method for these analyses. Emergency department data from the Province of Ontario, Canada, are used to illustrate an example of implementing hurdle models and interpreting their results.

Cats and dogs and the risk of atopy in childhood and adulthood.

BACKGROUND: Exposure to cats and dogs during childhood has been linked to a lower risk of developing allergies. It remains unclear whether this is due to selective avoidance of pets by families with a history of allergies. The effects of pet ownership in adulthood are unknown. OBJECTIVES: We sought to assess the association between cat and dog ownership in childhood and early adulthood and the development of atopy in a population-based birth cohort of 1037 subjects. METHODS: Ownership of cats or dogs between birth and age 9 years and between the ages of 18 and 32 years was reported. Skin prick tests to common allergens were performed at 13 and 32 years. RESULTS: There was no evidence that families with a history of atopy avoided owning pets. There were significant cat-by-dog interactions for the development of atopy in both childhood and adulthood. Children who had owned both a cat and a dog were less likely to be atopic at age 13 years. Living with only one of these animals was not protective against atopy. Among those who were not atopic by age 13 years, having both a cat and a dog in adulthood was associated with a lower risk of new atopy by age 32 years. This association was only significant among those with a parental history of atopy. These effects were independent of a range of potential confounding factors. CONCLUSIONS: There is a synergistic interaction between cat and dog exposure that is associated with a lower risk of developing atopy in childhood and young adulthood.

Temporal and spatial variation of heat-related illness using 911 medical dispatch data.

BACKGROUND: The adverse effect of hot weather on health in urban communities is of increasing public health concern, particularly given trends in climate change. OBJECTIVES: To demonstrate the potential public health applications of monitoring 911 medical dispatch data for heat-related illness (HRI), using historical data for the summer periods (June 1-August 31) during 2002-2005 in Toronto, Ontario, Canada. METHODS: The temporal distribution of the medical dispatch calls was described in relation to a current early warning system and emergency department data from the National Ambulatory Care Reporting System (NACRS). Geospatial methods were used to map the percentage of heat-related calls in each Toronto neighborhood over the study period. RESULTS: The temporal pattern of 911 calls for HRI was similar, and sometimes peaked earlier, than current heat health warning systems (HHWS). The pattern of calls was similar to NACRS HRI visits, with the exception of 2005 where 911 calls peaked earlier. Areas of the city with a relatively higher burden of HRI included low income inner-city neighborhoods, areas with high rates of street-involved individuals, and areas along the waterfront which include summer outdoor recreational activities. CONCLUSIONS: Identifying the temporal trends and geospatial patterns of these important environmental health events has the potential to direct targeted public health interventions to mitigate associated morbidity and mortality.

Development of a surveillance case definition for heat-related illness using 911 medical dispatch data.

OBJECTIVES: The adverse effects of hot weather on public health are of increasing concern. A surveillance system using 911 medical dispatch data for the detection of heat-related illness (HRI) could provide new information on the impact of excessive heat on the population. This paper describes how we identified medical dispatch call codes, called "determinants", that could represent HRI events. METHODS: Approximately 500 medical dispatch determinants were reviewed in focus groups composed of Emergency Medical Services (EMS) paramedics, dispatchers, physicians, and public health epidemiologists. Each group was asked to select those determinants that might adequately represent HRI. Selections were then assessed empirically using correlations with daily mean temperature over the study period (June 1-August 31,2005). RESULTS: The focus groups identified 12 determinant groupings and ranked them according to specificity for HRI. Of these, "Heat/cold exposure" was deemed the most specific. The call determinant groupings with the clearest positive associations with daily mean temperature empirically were "Heat/cold exposure" (Spearman's correlation coefficient (SCC) 0.71, p < 0.0001) and "Unknown problem (man down)" (SCC 0.21, p = 0.04). Within each grouping, the determinant "Unknown status (3rd party caller)" showed significant associations, SCC = 0.34 (p = 0.001) and SCC = 0.22 (p = 0.03) respectively. CONCLUSIONS: Clinically-informed expertise and empirical evidence both contributed to identification of a group of 911 medical dispatch call determinants that plausibly represent HRI events. Once evaluated prospectively, these may be used in public health surveillance to better understand environmental health impacts on human populations and inform targeted public health interventions.

Personal factors influencing agreement between expert and self-reported assessments of an occupational exposure.

This study aimed to identify personal factors associated with expert and respondent agreement on past occupational exposure. Epidemiologic data was collected from 1995 to 1998 in a community-based, case-control study of prostate cancer. Using longest jobs and excluding agreement on "never" exposure, self-reported and expert estimates of ever/ never exposure, by skin or ingestion, to polycyclic aromatic hydrocarbons were compared. Agreement between respondents and the expert was 53.9 percent (N=1,038), with overreporting being more common than underreporting relative to the expert (31.8 percent versus 14.4 percent). In multiple logistic regression models, white-collar occupational status was significantly associated with overreporting (odds ratio [OR] = 0.142; 95 percent confidence interval [CI]: 0.095-0.211; blue-collar versus white-collar), while age was associated with underreporting (OR=1.077; 95 percent CI: 1.043-1.112; one-year increase). Neither job satisfaction nor risk perception appeared to confound other associations. In future studies, overreporting by white-collar workers might be avoided by providing clearer definitions of exposure, whereas elderly respondents may require aids to enhance exposure recall.

Asthma hospitalization patterns in young children relating to admission age, infection presence, sex, and race.

BACKGROUND: Although childhood hospitalizations for asthma are common, there are few detailed temporal and demographic descriptions of these hospitalizations. OBJECTIVE: To relate temporal patterns of asthma hospitalization in young children to admission age, sex, comorbid infection, and race. METHODS: Retrospective analysis of 151,391 New York State hospitalizations with a principal diagnosis of asthma between January 1, 1990, and December 31, 2004, in children younger than 5 years. Admission patterns across time were related to admission age, sex, race, and comorbid diagnoses of common infections. RESULTS: Although the overall hospitalization rate decreased, it was still 63.8 per 10,000 in 2004. Higher hospitalization rates were consistently observed in children younger than 3 years, African Americans, and boys. Fall increases and summer declines in overall monthly hospitalization rates and monthly median ages exemplified the seasonality observed in the study population. However, admissions with concomitant common infections peaked in the winter, not fall months. Sex did not affect the observed seasonality. Compared with white patients, African Americans not only manifested more than 3-fold higher hospitalization rates but also more repeated hospitalizations. CONCLUSIONS: The concurrent cyclical increases in median age and monthly admissions suggest that seasonal factors affecting older children may relate to fall increases in asthma admissions. These fall peaks are not accounted for by recognizable concomitant common respiratory tract infections. Understanding the basis for these seasonal variations may lead to prevention strategies that could decrease asthma admissions. Asthma hospitalizations in young children continued to be highly prevalent in New York State, especially in African American patients.

Effect of the SARS outbreak on visits to a community hospital emergency department.

OBJECTIVES: To examine the effect of severe acute respiratory syndrome (SARS) on visits to a community hospital emergency department (ED) during the early stage of the Toronto outbreak in 2003 and for the same period in 2004. We focused on visits for respiratory illness (SARS-like symptoms) and different age groups. METHODS: This study is a retrospective review of ED discharge diagnoses obtained from a computerized database, examining the 4-week period starting March 28 for the years 2001-2004. We obtained the discharge diagnosis, age and visit date for each ED patient during the relevant time intervals, then compared visit data from 2003 and 2004 with a baseline derived from the average number of visits during 2001 and 2002. We constructed groupings based on age and respiratory-illness symptoms. RESULTS: During the SARS outbreak in 2003, ED visits declined by 21% (95% confidence interval [CI], 18%-24%) over the 4-week study period. The greatest reduction was for combined infant and toddler visits (69%; 95% CI, 58%-79%); these did not recover the following year. However, during the SARS outbreak there was a large increase in the number of visits for respiratory illnesses in adults (61%; 95% CI, 46%-75%) and in teenagers (132%; 95% CI, 82%-182%). CONCLUSIONS: During the SARS outbreak, total ED visits fell. The relative decline was most notable for infants and toddlers. By contrast, there was an increase in respiratory illness-related visits for adults and teenagers. In 2004, the year following the SARS outbreak, visit patterns shifted toward baseline levels, but ED visits by infants and toddlers remained depressed.

Body mass index and the risk of asthma in adults.

Asthma and obesity are both chronic conditions and their prevalences have risen in affluent societies. A positive association between asthma and being overweight or obese has been reported in children and women, but associations in men are less clearly described. The objective of this study was to explore the association between body mass index (BMI) and asthma in men and women of diverse ethnic and socioeconomic background living in New York State, USA. In this study, we analyzed cross-sectional data on 5524 subjects aged 18 years and older who were interviewed by telephone in the 1996 and 1997 New York State Behavioral Risk Factor Surveillance System. Asthma (doctor-diagnosed), and weight and height were self-reported. BMI (kg/m2) was used as a measure of adiposity. Weighted logistic regression analysis, with stratification by gender and age, was used to examine the relationship between asthma prevalence and BMI, adjusting for race/ethnicity, education, health insurance, time since last physical examination, physical activity and smoking status. The results showed that the prevalence of asthma was 4.6% (CI: 3.6-5.5%) among men and 8.1% (CI: 7.1-9.1%) among women. In women, the prevalence of asthma was significantly increased in those with a BMI 25 kg/m2 or higher (BMI 25-27.5: OR = 1.76, 95% CI: 1.06-2.94; BMI 27.5-29.9: OR = 2.45, 95% CI: 1.41-4.25; BMI > or = 30: OR = 2.67, 95% CI: 1.66-4.29) when compared to the reference category (BMI: 22-24.9 kg/m2). In men, the prevalence of asthma was increased in the lowest weight category, BMI < 22 kg/m2 (OR = 3.05, 95% CI: 1.37-6.78) and in the highest category, BMI > or = 30 kg/m2 (OR = 2.92, 95% CI: 1.39-6.14). This U-shaped association persisted when restricting the analysis to men who had never smoked and was more pronounced for those between 18 and 49 years of age. In conclusion, this cross-sectional study showed that men and women differ significantly in the association between BMI and asthma prevalence only with respect to the lowest weight category. While women had a monotonic association, men showed a U-shaped relationship, indicating that both extremes of weight are associated with a higher prevalence of asthma.

Treatment of "swing point stenoses" in hemodialysis arteriovenous fistulae.

AIM: This is a retrospective study of percutaneous transluminal balloon angioplasty (PTA) efficacy for treatment of surgical vein mobilization site ("swing point") stenoses in hemodialysis arteriovenous fistulae (AVF) that fail to mature or are poorly functioning. METHOD: Between February 1, 1999, and February 28, 2001, 65 non-maturing or poorly functioning AVF were studied in 63 consecutive hemodialysis patients (30 male, 33 female, aged 26-92 years). All AVF underwent contrast angiography to study the inflow artery, AVF, outflow and central veins. PTA of stenotic sites was performed to initiate or restore AVF function. RESULTS: Seventy-eight venous and 2 arterial stenoses were found and treated with PTA in the 65 AVF. All PTA were technically successful. A total of 55 stenoses were identified in the vein at the site of surgical mobilization ("swing point"). Additionally, 19 cephalic and 4 central venous stenoses were found. During the study, 13 AVF underwent repeat PTA at the "swing point". Of the 65 AVF treated, 50 were being successfully used as an access site, 4 AVF were lost during follow-up (34-688 days; mean: 258 days) and 8 patients died within the study period. The duration of functional patency of the treated AVF was 39-660 days (mean: 280 days). CONCLUSION: Non-maturing or poorly functioning AVF frequently have stenoses in the outflow vein at the original site of surgical vein mobilization. These "swing point stenoses" are amenable to PTA, which is a safe and effective treatment for prolonging AVF patency and function.

Hepatic arterial complications in liver transplant recipients treated with pretransplantation chemoembolization for hepatocellular carcinoma.

PURPOSE: To compare the prevalence of hepatic arterial complications in patients who underwent hepatic arterial chemoembolization for hepatocellular carcinomas before orthotopic liver transplantation with the prevalence of hepatic arterial complications in the total population of liver transplant recipients. MATERIALS AND METHODS: Forty-seven patients underwent selective hepatic arterial chemoinfusion with mitomycin C, doxorubicin hydrochloride, and cisplatin combined with embolization. The prevalence rates for hepatic arterial complications, including pseudoaneurysm, stenosis, anastomotic disruption, and thrombosis, were tabulated and compared with results in 1,154 patients who underwent orthotopic liver transplantation but not chemoembolization. RESULTS: Of the 47 patients who had undergone preoperative hepatic arterial chemotherapy, 13% developed hepatic arterial complications within a mean of 7 days after transplantation; an 8% prevalence of hepatic arterial thrombosis was observed. Of the 1,154 patients who underwent orthotopic liver transplantation but not chemotherapy, 6% developed hepatic arterial complications; a 5% prevalence of hepatic arterial thrombosis was observed. There was no statistically significant difference in the prevalence rates for thrombosis and complications between the patients who underwent chemoembolization before orthotopic liver transplantation and those who did not. The mean interval between chemotherapy and orthotopic liver transplantation was 111 days (range, 3-428 days). CONCLUSION: Patients who undergo hepatic arterial chemotherapy are not at an increased risk of developing hepatic arterial thrombosis or other hepatic arterial complications after orthotopic liver transplantation.