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.

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.

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.

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.