Kinetics and thermodynamics of BI-BII interconversion altered by T:G mismatches in DNA.

T:G mismatches in DNA result in humans primarily from deamination of methylated CpG sites. They are repaired by redundant systems, such as thymine DNA glycosylase (TDG) and methyl-binding domain enzyme (MBD4), and maintenance of these sites has been implicated in epigenetic processes. The process by which these enzymes identify a canonical DNA base in the incorrect basepairing context remains a mystery. However, the conserved contacts of the repair enzymes with the DNA backbone suggests a role for protein-phosphate interaction in the recognition and repair processes. We have used 31P NMR to investigate the energetics of DNA backbone BI-BII interconversion, and for this work have focused on alterations to the activation barriers to interconversion and the effect of a mismatch compared with canonical DNA. We have found that alterations to the ΔG of interconversion for T:G basepairs are remarkably similar to U:G basepairs in the form of stepwise differences in ΔG of 1-2 kcal/mol greater than equivalent steps in unmodified DNA, suggesting a universality of this result for TDG substrates. Likewise, we see perturbations to the free energy (∼1 kcal/mol) and enthalpy (2-5 kcal/mol) of activation for the BI-BII interconversion localized to the phosphates flanking the mismatch. Overall our results strongly suggest that the perturbed backbone energetics in T:G basepairs play a significant role in the recognition process of DNA repair enzymes.

Dog introduction alters the home dust microbiota.

Research has largely reported that dog exposure is associated with reduced allergic disease risk. Responsible mechanism(s) are not understood. The goal was to investigate whether introducing a dog into the home changes the home dust microbiota. Families without dogs or cats planning to adopt a dog and those who were not were recruited. Dust samples were collected from the homes at recruitment and 12 months later. Microbiota composition and taxa (V4 region of the 16S rRNA gene) were compared between homes that did and did not adopt a dog. A total of 91 dust samples from 54 families (27 each, dog and no dog; 17 dog and 20 no dog homes with paired samples) were analyzed. A significant dog effect was seen across time in both unweighted UniFrac and Canberra metrics (both P = .008), indicating dog introduction may result in rapid establishment of rarer and phylogenetically related taxa. A significant dog-time interaction was seen in both weighted UniFrac (P < .001) and Bray-Curtis (P = .002) metrics, suggesting that while there may not initially be large relative abundance shifts following dog introduction, differences can be seen within a year. Therefore, dog introduction into the home has both immediate effects and effects that emerge over time.

Prenatal antimicrobial use and early-childhood body mass index.

BACKGROUND/OBJECTIVES: Growing evidence suggests that antibiotic use is associated with childhood body mass index (BMI), potentially via mechanisms mediated by gut microbiome alterations. Less is known on the potential role of prenatal antimicrobial use in offspring obesity risk. We examined whether prenatal antibiotic or antifungal use was associated with BMI at the age of 2 years in 527 birth cohort participants. METHODS/SUBJECTS: Antimicrobial use was obtained from the prenatal medical record. Height and weight were measured at the age of 2 years. Overweight/obesity was defined as a BMI ⩾85th percentile. RESULTS: A total of 303 (57.5%) women used antibiotics and 101 (19.2%) used antifungals during pregnancy. Prenatal antifungal use was not associated with child BMI at the age of 2 years. In the fully adjusted model, prenatal antibiotic use was associated with a 0.20±0.10 (P=0.046) higher mean BMI Z-score at the age of 2 years. Associations between prenatal antibiotic use and childhood BMI varied by trimester of exposure, with first or second-trimester exposure more strongly associated with larger BMI at the age of 2 years for both BMI Z-score (interaction P=0.032) and overweight/obesity (interaction P=0.098) after covariate adjustment. CONCLUSIONS: Prenatal antibiotic, but not antifungal, use is associated with larger BMI at the age of 2 years; associations were stronger for antibiotic exposures in earlier trimesters. Future studies examining whether these associations are due to alterations in the maternal and/or infant microbiome are necessary. Children who are overweight at the age of 2 years are at higher risk for being overweight as they age; prenatal antibiotic use is a potentially modifiable exposure that could reduce childhood obesity.

Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.

Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T-cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals. Thus L. johnsonii supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.

Subgroup differences in the associations between dog exposure during the first year of life and early life allergic outcomes.

BACKGROUND: 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. OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Maternal group B Streptococcus and the infant gut microbiota.

Early patterns of gut colonization may predispose children to adult disease. Exposures in utero and during delivery are associated with the infant gut microbiome. Although ~35% of women carry group B strep (GBS; Streptococcus agalactiae) during pregnancy, it is unknown if GBS presence influences the infant gut microbiome. As part of a population-based, general risk birth cohort, stool specimens were collected from infant's diapers at research visits conducted at ~1 and 6 months of age. Using the Illumina MiSeq (San Diego, CA) platform, the V4 region of the bacterial 16S rRNA gene was sequenced. Infant gut bacterial community compositional differences by maternal GBS status were evaluated using permutational multivariate analysis of variance. Individual operational taxonomic units (OTUs) were tested using a zero-inflated negative binomial model. Data on maternal GBS and infant gut microbiota from either 1 (n=112) or 6-month-old stool (n=150) specimens was available on 262 maternal-child pairs. Eighty women (30.5%) were GBS+, of who 58 (72.5%) were given intrapartum antibiotics. After adjusting for maternal race, prenatal antifungal use and intrapartum antibiotics, maternal GBS status was statistically significantly associated with gut bacterial composition in the 6 month visit specimen (Canberra R 2=0.008, P=0.008; Unweighted UniFrac R 2=0.010, P=0.011). Individual OTU tests revealed that infants of GBS+ mothers were significantly enriched for specific members of the Clostridiaceae, Ruminococcoceae, and Enterococcaceae in the 6 month specimens compared with infants of GBS- mothers. Whether these taxonomic differences in infant gut microbiota at 6 months lead to differential predisposition for adult disease requires additional study.

Evaluation of latent tuberculous infection and treatment completion for refugees in Philadelphia, PA, 2010-2012.

SETTING: Philadelphia, PA, USA. OBJECTIVES: To compare the evaluation and treatment of latent tuberculous infection (LTBI) in refugees seen at member clinics of the Philadelphia Refugee Health Collaborative (PRHC) vs. non-PRHC clinics. DESIGN: Refugees with Class B (non-communicable) tuberculosis (TB) admitted to the United States from 2010 to 2012 who were being treated at PRHC clinics were compared to those treated at non-PRHC clinics. Odds ratios (ORs) for attending a follow-up appointment, completing treatment, and time from arrival to the United States to the first TB screening test were calculated. RESULTS: Of the 2094 refugees who arrived in Philadelphia in 2010-2012, the Philadelphia Department of Public Health was notified of 149 who required additional evaluation for TB. Among these, 57 (38.3%) were confirmed to have LTBI, and none were diagnosed with active TB. All LTBI cases were recommended for anti-tuberculosis prophylaxis and 43 (75.4%) completed treatment. Refugees receiving care from PRHC clinics were more likely to be screened within 30 days of arrival (OR 4.70, 95%CI 2.12-10.44), attend a follow-up appointment (OR 4.53, 95%CI 1.36-16.27), and complete treatment (OR 9.44, 95%CI 2.39-37.3). CONCLUSION: Refugees who attended PRHC clinics were more likely to be evaluated promptly and to complete LTBI treatment. The PRHC clinics serve as a model for communities seeking to improve refugee health care.

Combined effects of prenatal medication use and delivery type are associated with eczema at age 2 years.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Are cats and dogs the major source of endotoxin in homes?

UNLABELLED: Previous studies have suggested that exposure to cats and dogs during early childhood reduces the risk of allergic disease, possibly by increasing home endotoxin exposure. This study asked the question of whether cats and dogs are the dominant influence on dust endotoxin concentrations in homes after considering other variables reportedly associated with endotoxin. The presence of cats or dogs in homes, household and home characteristics, and dust endotoxin concentrations from 5 locations were assessed in 966 urban and suburban homes. Whether considered together as pets or as cats and dogs separately, the presence of cats and dogs significantly contributed to living room and bedroom floor endotoxin concentrations, but not to bed endotoxin concentrations. However, the two variables consistently related to endotoxin in all home sites were the home occupant density (occupants/room) and cleanliness of the home. Our data suggest that reducing occupant density and improving home cleanliness would reduce home endotoxin concentrations more than removing pet cats or dogs from the home. PRACTICAL IMPLICATIONS: Many studies have shown that early childhood exposure to indoor cats or dogs is associated with a reduced risk of later allergic disease and asthma. An important question is whether alteration in allergic risk associated with cat and dog exposure results from increased endotoxin exposure or from some other associated exposure. Our findings show that cats and dogs are not the dominant source of endotoxin in homes; rather, the density of human occupation and poor cleaning contribute more consistently to higher home endotoxin concentrations especially in the beds.

Racial disparities in allergic outcomes in African Americans emerge as early as age 2 years.

BACKGROUND: Racial disparities in allergic disease outcomes have been reported with African Americans suffering disproportionately compared to White individuals. OBJECTIVE: To examine whether or not racial disparities are present as early as age 2 years in a racially diverse birth cohort in the Detroit metropolitan area. METHODS: All children who were participants in a birth cohort study in the Detroit metropolitan area were invited for a standardized physician exam with skin prick testing and parental interview at age 2 years. Physicians made inquiries regarding wheezing and allergy symptoms and inspected for and graded any atopic dermatitis (AD). Skin testing was performed for Alternaria, cat, cockroach, dog, Dermatophagoides farinae (Der F), Short Ragweed, Timothy grass, egg, milk and peanut. Specific IgE was measured for these same allergens and total IgE was determined. RESULTS: African American children (n = 466) were more likely than White children (n = 223) to have experienced any of the outcomes examined: at least 1 positive skin prick test from the panel of 10 allergens (21.7% vs. 11.0%, P = 0.001); at least one specific IgE ≥ 0.35 IU/mL (out of a panel of 10 allergens) (54.0% vs. 42.9%, P = 0.02); had AD (27.0% vs. 13.5%, Chi-square P < 0.001); and to ever have wheezed (44.9% vs. 36.0%, P = 0.03). African American children also tended to have higher total IgE (geometric means 23.4 IU/mL (95%CI 20.8, 27.6) vs. 16.7 IU/mL (95%CI 13.6, 20.6 IU/mL), Wilcoxon Rank Sum P = 0.004). With the exception of wheezing, the associations did not vary after adjusting for common social economic status variables (e.g. household income), environmental variables (endotoxin; dog, cat and cockroach allergen in house dust) or variables that differed between the racial groups (e.g. breastfeeding). After adjustment, the wheeze difference was ameliorated. CONCLUSIONS: With disparities emerging as early as age 2 years, investigations into sources of the disparities should include the prenatal period and early life.

Lifetime dog and cat exposure and dog- and cat-specific sensitization at age 18 years.

BACKGROUND: Prior research about whether keeping a dog or cat at home causes allergies to that pet has been limited to outcomes in early childhood. OBJECTIVE: Evaluate the association between lifetime dog and cat exposure and allergic sensitization to the specific animal at 18 years of age. METHODS: Participants enrolled in the Detroit Childhood Allergy Study birth cohort during 1987-1989 were contacted at the age 18 years. Sensitization to dog or cat was defined as animal-specific IgE ≥ 0.35 kU/L. Annual interview data from childhood and follow-up interviews at age 18 years were used to determine lifetime indoor dog and cat exposure (indoor was defined when the animal spent >50% of their time inside the house). Exposure was considered in various ways: first year, age groups and cumulative lifetime. Analyses were conducted separately for dogs and cats. RESULTS: Among males, those with an indoor dog during the first year of life had half the risk [relative risk (RR)=0.50, 95% confidence interval (CI) 0.27, 0.92] of being sensitized to dogs at age 18 compared with those who did not have an indoor dog in the first year. This was also true for males and females born via c-section (RR=0.33, 95% CI 0.07, 0.97). Overall, teens with an indoor cat in the first year of life had a decreased risk (RR=0.52, 95% CI 0.31, 0.90) of being sensitized to cats. Neither cumulative exposure nor exposure at any other particular age was associated with either outcome. CONCLUSIONS AND CLINICAL RELEVANCE: The first year of life is the critical period during childhood when indoor exposure to dogs or cats influences sensitization to these animals.

Fabrication of a multi-applicable removable intraoral denture system for rodent research.

The objective was to engineer an inexpensive intraoral removable denture system for rodents that can be utilised in numerous oral health research applications. At the forefront is biofilm research related to Candida-associated denture stomatitis. Previously described intraoral devices are primitive and inadequate. The denture system was engineered consisting of a fixed part that is anchored to the posterior palate by orthodontic wires and acrylic resin and a removable part fitted to the anterior palate that is retained by magnets embedded in the fixed part. Both parts are custom fitted to the rodent palate by impression making and cast fabrication. Rats fitted with the intraoral denture system maintained body weight and normal activity with the device maintaining integrity and durability for upwards of 8 weeks. The denture system was used successfully to establish a working model of denture stomatitis. This newly engineered inexpensive intraoral removable denture system for rodents can be utilised in numerous oral health research applications, including denture-associated infections, biofilms and a variety of biomaterial applications. The removable portion is advantageous for longitudinal analyses and charging/discharging of biomaterials.

Factors associated with nonresponse to a computer-tailored asthma management program for urban adolescents with asthma.

BACKGROUND: The ability to identify potentially resistant participants early in the course of an intervention could inform development of strategies for behavior change and improve program effectiveness. OBJECTIVE: The objective of this analysis was to identify factors related to nonresponse (i.e., lack of behavior change) to an asthma management intervention for urban teenagers. The intervention targeted several behaviors, including medication adherence, having a rescue inhaler nearby, and smoking. METHODS: A discriminate analysis was conducted using data from a randomized trial of the intervention. Included in this analysis are participants who reported a physician diagnosis of asthma, completed a baseline questionnaire, were randomized to the treatment group, completed >or=2 of 4 educational sessions, and completed >or=2 of 3 follow-up questionnaires. Ninety students met criteria for inclusion in this subgroup analysis. RESULTS: In logistic regression models for medication adherence, nonresponse was related to low baseline asthma self-regulation, odds ratio = 3.6 (95% confidence interval = 1.3-9.5). In models for having an inhaler nearby, nonresponse was related to low baseline self-regulation and to rebelliousness, OR = 4.7 (1.6-13.2) and 5.6 (1.7-18.0), respectively. Nonresponse to smoking messages was related to rebelliousness, low emotional support, and low religiosity, ORs = 7.6 (1.8-32.3), 9.5 (1.4-63.5), and 6.6 (1.5-29.8) respectively. CONCLUSIONS: Certain variables had the ability to discriminate the likelihood of response from that of nonresponse to an asthma program for urban, African American adolescents with asthma. These variables can be used to identify resistant subgroups early in the intervention, allowing the application of specialized strategies through tailoring. These types of analyses can inform behavioral interventions.

Inadequate vitamin D status in adolescents with substantial bone mineral density loss during the use of depot medroxyprogesterone acetate injectable contraceptive: a pilot study.

STUDY OBJECTIVE: To examine vitamin D and parathormone (PTH) levels in adolescents who experienced substantial bone mineral density (BMD) loss during depot medroxyprogesterone acetate (DMPA) use. DESIGN: A non-randomized, multi-center study, during which DMPA was administered every 12 weeks and evaluation of lumbar spine and hip BMD by dual-energy X-ray absorptiometry (DXA) was conducted every 6 months. A blood sample for vitamin D and PTH measurements was obtained from adolescents who experienced >5% BMD loss. Vitamin D deficiency was defined as 25-hydroxyvitamin D (25OHD) level of <20 ng/mL, insufficiency as 25OHD level of 20-30 ng/mL, and sufficiency as 25OHD level of >30 ng/mL. RESULTS: Evaluation of vitamin D and PTH was carried out in 15 participants who experienced BMD loss of > or = 5% during DMPA use. At initiation of DMPA, participants had mean (+SE) age 17+1 years, gynecologic age 61+4 months, and body mass index 24+1.5 kg/m2. Racial/ethnic distribution was: Caucasian--7 girls, Hispanic--4 girls, African-American--3 girls, and other--1 girl. Six participants had BMD loss of >5% after 2 DMPA injections, five after 3 injections, one after 5 injections, one after 8 injections, one after 10 injections, and one after 13 injections. Only one girl (7%) had sufficient vitamin D. The other participants had vitamin D insufficiency (50%) or deficiency (43%). Participants' mean (+SE) PTH was 22+4 pg/mL (reference range 7-53 pg/mL), and mean (+SE) 1,25-dihydroxyvitamin D was 56+5 pg/mL (reference range 22-67 pg/mL). CONCLUSIONS: Inadequate vitamin D status was evident among the majority of female adolescents who experienced a substantial BMD loss while using DMPA.

Energy density of foods, but not beverages, is positively associated with body mass index in adult women.

BACKGROUND/OBJECTIVES: Energy density (kJ/g) may have a strong influence on energy balance. Although beverages are a considerable source of energy in the United States diet, rarely have studies among free-living populations investigated the energy density of foods (EDF) and the energy density of beverages (EDB) simultaneously. We examined the independent simultaneous associations of EDF and EDB on energy intake and body mass index (BMI) in adult women. SUBJECTS/METHODS: This cross-sectional design focused on 348 elementary school employees randomly selected at baseline of a worksite wellness trial in southeastern Louisiana. Two 24-h recalls were collected, and measured heights and weights were converted into BMI (kg/m(2)). RESULTS: Those in the highest EDF tertile consumed more energy and had higher BMIs than those in the lowest tertile (P<0.05). Employees in the highest EDB tertile consumed more energy than those in the lowest, yet there was no difference in BMIs between the two groups. Multivariate regression, with controls for demographic and health variables, confirmed the positive association between EDF and BMI; a 1 kJ/g increase in EDF was associated with a 0.39 kg/m(2) increase in BMI (P=0.038). Models that did not control for EDB gave estimates of EDF that were 8-10% lower. CONCLUSIONS: These findings suggest that EDF and EDB have important, yet distinct, functions in energy intake and BMI. Future studies should evaluate both types of energy density as independent predictors as our results suggest that EDB can confound the association of EDF with BMI.

Gender differences in the association of overweight and asthma morbidity among urban adolescents with asthma.

Asthma and obesity disproportionately affect US African-American youth. Among youth with asthma, obesity has been associated with poor control. The impact of gender on this association is unclear. We examined these relationships in a sample of urban, African-American adolescents with asthma. Questionnaires were used to identify high school students with asthma, and to examine the association of body mass index (BMI) to asthma morbidity, by gender. Of 5967 students completing questionnaires, 599 (10%) met criteria for asthma and 507 had data sufficient for inclusion in further analyses (46% male, mean age = 15.1 yr). Univariately, BMI > 85th percentile was significantly related only to reported emergency department visits (ED) and school days missed for any reason, Odds Ratio (95%Confidence Interval) = 1.7(1.1-2.7), p = 0.01 and 1.8(1.1-3.0), p = 0.01, respectively. A significant gender-BMI interaction (p < 0.05) was observed in multivariate models for ED visits, hospitalizations and school days missed for asthma. In gender-specific models, adjusted Risk Ratios for BMI > 85th and ED visits, hospitalizations, and school days missed because of asthma were 1.7(0.9-3.2), 6.6(3.1-14.6) and 3.6(1.8-7.2) in males. These associations were not observed in females. Gender modifies the association between BMI and asthma-related morbidity among adolescents with asthma. Results have implications for clinical management as well as future research.

Prenatal exposure to household pets influences fetal immunoglobulin E production.

BACKGROUND: Early life pet exposure may protect against allergic sensitization during childhood. Few studies have evaluated the effect of prenatal pet exposure on potential neonatal markers of allergic risk. OBJECTIVE: The aim of this study was to investigate whether maternal exposure to pets affects cord blood IgE levels in a population-based, general risk, ethnically mixed birth cohort. METHODS: Pet keeping during pregnancy was ascertained from women residing in a defined area of Wayne County Michigan and recruited from five staff model obstetric clinics. Maternal venous blood was analysed for total and allergen-specific IgE along with cord blood total IgE from 1049 infants. RESULTS: Compared with infants from households with no cats or dogs kept indoors during pregnancy, infants whose homes had either cats or dogs had significantly reduced mean cord IgE levels [0.34 IU/mL (95% CI 0.30-0.38) vs. 0.24 IU/mL (0.20-0.27), P=0.025]. Similar effects were apparent in cat-only households [0.21 IU/mL (0.16-0.27), P=0.020] and dog-only households [0.24 IU/mL (0.19-0.29), P=0.045]. There was no effect on results when excluding mothers who reported avoiding pets due to allergy-related concerns. CONCLUSION: Mothers with either cats or dogs in their home during pregnancy deliver children with lower cord blood IgE levels compared with mothers who do not live with these pets, supporting the hypothesis that pet exposure influences immune development in a manner that is protective for atopy and is operant even before birth.

Process evaluation results from a school- and community-linked intervention: the Trial of Activity for Adolescent Girls (TAAG).

Process evaluation is a component of intervention research that evaluates whether interventions are delivered and received as intended. Here, we describe the process evaluation results for the Trial of Activity for Adolescent Girls (TAAG) intervention. The intervention consisted of four synergistic components designed to provide supportive school- and community-linked environments to prevent the decline in physical activity in adolescent girls. Process evaluation results indicate that the intervention components were delivered from intervention staff to teachers with high fidelity (84-97%) to the protocol and with lower fidelity (range: 18-93%) from teachers to students. Physical activity programs for girls, a unique feature of the TAAG intervention, increased from a mean of 10 programs per school to a mean of 16 and 15 in years 1 and 2, respectively, in intervention schools, with no change in control schools. These findings suggest that a multicomponent school- and community-based physical activity intervention can be delivered with fidelity and result in a middle school environment that supports physical activity for girls.

Laparoscopic coloanal anastomosis for low rectal cancer.

OBJECTIVES: Low anterior resection with hand-sutured coloanal anastomosis for low rectal cancer is technically feasible, and it does not compromise oncologic results. We describe herein the effectiveness of the operation in treating low rectal cancer by a laparoscopic approach followed by intraanal canal dissection. METHODS: From February 1999 to October 1999, we used a laparoscopic procedure to divide the inferior mesenteric vessels and to dissect downward into the pelvic cavity as low as possible. A purse-string suture 1-cm distal to the lower margin of the tumor was secured and transection of the rectum was performed circumferentially via the anal canal near the dentate line. The specimen was removed by the pull-through method and coloanal anastomosis was completed with hand suture. A protective loop ileostomy was fashioned. RESULTS: We operated on 8 patients (4 males) with low tumor localization (average 4-cm above the dentate line). The age ranged from 45 to 83 years, with a median age of 64. The average operation time was 210 minutes (150 to 360 minutes), and the average blood loss was 250 cc (minimal to 750 cc). No operative mortalities occurred, but 2 patients had minor anastomotic slough complications. The average hospital stay was 13 days (7 to 26 days). The postoperative pathologic stage was T2N0M0 in 4 patients, T3N0M0 in 2 patients, T2N1M0 in 1 patient, and T3N2M0 in 1 patient. No local recurrence or distant metastasis occurred during the median 14 months (12 to 20 months) of follow-up. CONCLUSION: Laparoscopic coloanal anastomosis combined with intraanal canal dissection is safe and technically feasible. The oncologic results seem not to be compromised, but need further evaluation.