Background There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age. Objectives To examine ...the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children. Methods Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area. Results In multivariate analyses, early exposure to high levels of dust mite allergen (≥10 μg/g) was associated with increased risks of asthma at age 7 years (odds ratio OR, 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% CI, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages 1 and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43). Conclusion Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze. Clinical implications Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children.
Purpose
Obesity is an epidemic which increases risk of many surgical procedures. Previous studies in spine and hip arthroplasty have shown that fat thickness measured on preoperative imaging may be ...as or more reliable in assessment of risk of post-operative infection and/or wound complications than body mass index (BMI). We hypothesized that, similarly, increased local fat thickness at the surgical site is a predictor of wound complication in acetabulum fracture surgery.
Methods
Patients who underwent open reduction and internal fixation (ORIF) of an acetabulum fracture through a Kocher-Langenbeck (K-L) approach at a single institution from 2013 to 2020 were identified. Pre-operative CT scans were used to measure fat thickness from the skin to the greater trochanter in line with the surgical approach. Post-operative infections and wound complications were recorded and associated with fat thickness and BMI.
Results
238 patients met inclusion criteria. 12 patients had either infection or a wound complication (5.0%). There was no significant association with BMI or preoperative fat thickness on post-operative infection or wound complication (
p
-value 0.73 and 0.86).
Conclusions
There is no statistically significant association of post-operative infection or wound complications in patients with increased soft tissue thickness or increased BMI. ORIF of acetabulum fractures through a K-L approach can be performed safely in patients with large subcutaneous fat thickness and high BMI with low risk of infection or wound complications.
The association between home dampness and lower respiratory symptoms in children has been well documented. Whether fungal exposures contribute to this association is uncertain. In a prospective birth ...cohort of 499 children of parents with asthma/allergies, we examined in-home fungal concentrations as predictors of lower respiratory illnesses (LRI) (croup, pneumonia, bronchitis, and bronchiolitis) in the first year. In multivariate analyses, we found a significant increased relative risk (RR) between LRI and high levels (more than the 90th percentile) of airborne Penicillium (RR = 1.73, 95% confidence interval CI, 1.23, 2.43), dust-borne Cladosporium (RR = 1.52; CI, 1.02, 2.25), Zygomycetes (RR = 1.96; CI, 1.35, 2.83), and Alternaria (RR = 1.51; CI, 1.00, 2.28), after controlling for sex, presence of water damage or visible mold/mildew, born in winter, breastfeeding, and being exposed to other children through siblings. In a multivariate analysis, the RR of LRI was elevated in households with any fungal level at more than the 90th percentile (RR = 1.86; CI, 1.21, 2.88). Exposure to high fungal levels increased the risk of LRI in infancy, even for infants with nonwheezing LRI. Actual mechanisms remain unknown, but fungi and their components (glucans, mycotoxins, and proteins) may increase the risk of LRI by acting as irritants or through increasing susceptibility to infection.
Abstract
The ability of a heifer to calve earlier in a breeding season has implications on the economic success of heifers in a production system. Heifers that calve earlier in a calving season have ...increased calf performance, improved subsequent fertility, and a longer productive life in the herd. Production systems typically breed heifers during fixed breeding dates, with heifers of variable ages in the same contemporary group. The objective of this study was to determine if heifer yearling weight (YW) or age differences going into a fixed breeding period influenced the additive genetic variance of age at first calving (AFC) explained in a multi-breed population. Heifer fertility data were obtained from International Genetic Solutions. Females with exposure and calf production records were used to identify individuals calving between 630 and 810 days of age. Females with embryo transfer, multiple birth progeny, and an age differential (DIFF) greater than 100 days were excluded. Age differential was defined as the difference in days between an individual’s birth date and the earliest birth date of an animal in a defined contemporary group. Contemporary group was defined as; breeder, herd, year born, birth and yearling group. After data filtering, there were 149,350 calving records. A 3-generation pedigree file was used containing 365,637 animals, with 37,420 unique sires and 219,533 unique dams. Two bivariate multi-trait animal models for AFC and YW with random additive genetic and residual effects and fixed effects of contemporary group, breed proportion, and % retained hybrid vigor were used. The first model consisted of the aforementioned effects while the second model included DIFF as an additional fixed effect. Analyses were performed using ASReml 3.0. When DIFF was not included as a fixed effect, the additive, residual and phenotypic variances for AFC were 126.1, 456.8, and 582.9 d2, respectively, and the genetic correlation between AFC and YW was 0.36 ± 0.02. When DIFF was included as a fixed effect, the additive, residual, and phenotypic variances for AFC were 10.0, 326.0, and 336.0 d2, respectively. The genetic correlation between AFC and YW was 0.19 ± 0.04. In the absence of DIFF, the heritability estimates for AFC and YW were 0.22 ± 0.01 and 0.44 ± 0.01, respectively but were 0.03 ± 0.003 and 0.44 ± 0.01 respectively, when DIFF was included. Age differential was a significant effect on AFC at –0.86 (P < 0.0001). The low additive variance of AFC when accounting for DIFF suggests that the influence of a female's age going into a fixed breeding date explains much of the variation in AFC. The low heritability estimate for AFC and genetic correlation with YW suggests that selection for improved AFC will be difficult using this method and that producers should instead focus on improved management practices to ensure females calve earlier in a calving season.
Recent efforts to develop an enterotoxigenic
(ETEC) vaccine have focused on the antigenically conserved tip adhesins of colonization factors. We showed previously that intranasal immunization with ...dsc
CfaE, a soluble variant of the in
donor strand-complemented tip adhesin of a colonization factor of the class 5 family (CFA/I) fimbria, is highly immunogenic and protects against oral challenge with CFA/I-positive (CFA/I
) ETEC strain H10407 in the
nonhuman primate. We also reported a cholera toxin (CT)-like chimera (called dsc
CfaE-CTA2/CTB) in which the CTA1 domain of CT was replaced by dsc
CfaE that was strongly immunogenic when administered intranasally or orogastrically in mice. Here, we evaluate the immunogenicity and protective efficacy (PE) of a refined and more stable chimera comprised of a pentameric B subunit of ETEC heat-labile toxin (LTB) in lieu of the CTB pentamer and a donor strand truncation (dsc
) of CfaE. The refined chimera, dsc
CfaE-sCTA2/LTB, was highly immunogenic in mice when administered intranasally or intradermally, eliciting serum and fecal antibody responses against CfaE and LTB, as well as strong hemagglutination inhibition titers, a surrogate for neutralization of intestinal adhesion mediated by CfaE. Moreover, the chimera was safe and highly immunogenic when administered intradermally to guinea pigs. In
, intradermal (i.d.) immunization with chimera plus single-mutant heat-labile toxin LT(R192G) elicited strong serum anti-CfaE and anti-LTB antibody responses and conferred significant reduction of diarrhea compared to phosphate-buffered saline (PBS) controls (PE = 84.1%;
0.02). These data support the further evaluation of dsc
CfaE-sCTA2/LTB as an ETEC vaccine in humans.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder accounting for 60–80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. ...Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted toward the aggregation of the tau protein as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed. Diagnosis of AD has shifted from measuring late stage senile plaques to early stage biomarkers, amyloid-β and tau monomers and oligomeric assemblies. Synthetic peptides and some derivative structures are being explored for use as theranostic tools as they possess the capacity both to bind the biomarkers and to inhibit their pathological self-assembly. Several studies have demonstrated that O-linked glycoside addition can significantly alter amyloid aggregation kinetics. Furthermore, natural O-glycosylation of amyloid-forming proteins, including amyloid precursor protein (APP), tau, and α-synuclein, promotes alternative nonamyloidogenic processing pathways. As such, glycopeptides and related peptidomimetics are being investigated within the AD field. Here we review advancements made in the last 5 years, as well as the arrival of sugar-based derivatives.
Abstract
The objective of this study was to determine genetic parameter estimates for age at first calving (AFC) in Red Angus and Simmental heifers. The ability for a heifer to calve earlier has ...implications on calf performance and the heifer's successive re-breeding. Heifer pregnancy data were obtained from International Genetic Solutions, where females with exposure records were included in the population. Females with a subsequent record of calving between 630 and 810 days of age were included in the analysis. Females with embryo transfer or multiple birth progeny were excluded. Records from single-animal and contemporary groups with no variation were eliminated and after data filtering, there were 149,379 Simmental with a mean Simmental breed proportion of 0.58 ± 0.25, and 83,191 Red Angus records with a mean Red Angus breed proportion of 0.80 ± 0.13. A 3-generation pedigree file containing 291,530 Simmental animals with 25,585 unique sires and 161,921 unique dams, and a 3-generation pedigree file containing 174,914 Red Angus animals with 19,733 unique sires and 99,464 unique dams were used for the separate analysis. The mean AFC in Simmental and Red Angus was 724.8 ± 28.64 d, and 724.2 ± 29.93 d, respectively. Data for each breed were modeled separately using a single trait animal model with random additive genetic and residual effects, and the fixed effect of contemporary group using ASReml 3.0. Contemporary group was defined as breeder, herd, year born, birth group and yearling group. The additive, residual, and phenotypic variances for Simmental were 120.08, 520.37, and 640.45 d2, respectively. For Red Angus, 85.67, 543.56, and 629.24 d2 were the additive, residual, and phenotypic variances, respectively. The heritability estimates of AFC for Simmental and Red Angus were 0.19 ± 0.0059 and 0.14 ± 0.0076, respectively. These results demonstrate AFC in days is lowly to moderately heritable. Lower residual and higher additive variance in Simmental compared to Red Angus may suggest the Simmental population has larger variation for underlying fertility influences such as age at puberty. The mean breeding values for AFC in Simmental was 6.1 ± 8.0, with a minimum of -24.4 and maximum of 54.7. Whereas Red Angus breeding values for AFC resulted in a mean of 4.0 ± 5.6 and a minimum and maximum of -16.1, and 37.3, respectively. The comparable heritability estimates, low standard error, and range in breeding values suggest selection for improved AFC can be attained. It is worth further exploring the impact of breed effects and heterosis influences on age at first calving. While this study does not account for heifers that did not calve in their first year, tandem selection for heifer fertility and age at calving should be heavily emphasized due to the economic importance of both traits.
There is sparse literature on the development of malignancy in remnant gastric stomach after bariatric Roux-en-Y gastric bypass surgery. We report a case of overt upper gastrointestinal bleeding from ...malignant adenocarcinoma in the remnant stomach presenting several years after bariatric Roux-En-Y gastric bypass surgery. The mass in the remnant stomach was surgically resected, and the patient was subsequently diagnosed with Lynch syndrome on genetic analysis.
We describe a process to produce aqueous precursor solutions of the flat -Al 13 hydroxo cluster (Al13(μ3-OH)6(μ2-OH)18(H2O)24(NO3)15) via stoichiometric dissolution of bulk Al(OH)3(s) in HNO3(aq). ...We highlight its facility by demonstrating high yields and large-scale synthesis. X-ray diffraction confirms formation of a single-phase product, and Raman spectra show characteristic O-Al-O vibrational modes, both techniques confirming the identity of the flat -Al 13 cluster in the bulk. 27Al NMR spectroscopy and dynamic light scattering also confirm the presence of the cluster in aqueous solution. We show the as-prepared solution produces smooth and continuous thin films via spin-coating. In capacitors, the films exhibit low leakage currents (near 10 nA/cm2) and dielectric constants expected for amorphous Al2O3. Because the precursor preparation requires no postsynthesis purification, it is readily scalable to large volumes.
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