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1.  Preimplantation Genetic Screening (PGS) with Comparative Genomic Hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages 
To determine benefits of cleavage-stage preimplantation genetic screening (PGS) by array comparative genomic hybridization (CGH).
A retrospective case–control study was performed at a tertiary care university-affiliated medical center. Implantation rate was looked at as a primary outcome. Secondary outcomes included clinical and ongoing pregnancy rates, as well as multiple pregnancy and miscarriage rates. Thirty five patients underwent 39 fresh cycles with PGS by aCGH and 311 similar patients underwent 394 invitro fertilization cycles.
The implantation rate in the CGH group doubled when compared to the control group (52.63 % vs. 19.15 %, p = <0.001), clinical pregnancy rate was higher (69.23 % vs. 43.91 %, p = 0.0002), ongoing pregnancy rate almost doubled (61.54 % vs. 32.49 %, p = <0.0001), multiple pregnancy rate decreased (8.33 % vs. 34.38 %, p = 0.0082) and miscarriage rate trended lower (11.11 % vs. 26.01 %, p = 0.13).
Cleavage stage PGS with CGH is a feasible and safe option for aneuploidy screening that shows excellent outcomes when used in fresh cycles. This is the first report of cleavage stage PGS by CGH showing improved ongoing pregnancy rates.
PMCID: PMC3824853  PMID: 23949213
Preimplantation genetic screening; Aneuploidy; Comparative genomic hybridization; Blastomere biopsy
Baked egg is tolerated by a majority of egg-allergic children.
To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets plays in the development of tolerance to regular egg.
Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance.
Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initial baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kUA/L) than those who subsequently tolerated baked egg (4.4 kUA/L; P=0.04) and regular egg (3.1 kUA/L, P=0.05). In subjects ingesting baked egg, EW-induced SPT wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG4 levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely to develop regular egg tolerance than subjects in the comparison group (P < 0.0001), and they developed tolerance earlier (median 50.0 versus 78.7 months; P<0.0001).
Initiation of a baked egg diet accelerates the development of regular egg tolerance compared to strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not.
PMCID: PMC3428057  PMID: 22846751
egg allergy; hen’s egg allergy; baked egg; heated egg; food allergy; egg tolerance; oral food challenge; egg allergy immunotherapy
3.  Prospective cohort study of the circadian rhythm pattern in allogeneic sibling donors undergoing standard granulocyte colony-stimulating factor mobilization 
Prior in vivo murine studies suggest circadian oscillations for hematopoietic stem cell release, which are maintained following administration of granulocyte colony-stimulating factor (G-CSF) or plerixafor. Furthermore, retrospective data analysis of healthy donors who underwent G-CSF-induced mobilization demonstrated significantly increased CD34+ cell yields when collected in the afternoon compared with the morning.
A prospective study was conducted to directly examine the number of peripheral blood CD34+ and CD34+CD38– progenitor/stem cells at baseline and then every 6 hours for 24 hours on days 4 to 5 of G-CSF (10 μg/kg/day in the morning) mobilization in 11 allogeneic donors. Data were analyzed using mixed-model analysis of repeated measures.
Whereas we observed a significant increase in CD34+ cell counts toward the evening, counts were then sustained on the morning of day 5. The correlation between CD34+CD38– cell counts and the less defined CD34+ populations was weak.
Our results suggest that the pharmacodynamic activity and timing of G-CSF may alter endogenous progenitor rhythms. Donor age, medical history, and medications may also impact circadian rhythm. Further studies should examine the circadian rhythm at the peak of G-CSF mobilization and should consider potential confounders such as the time of G-CSF administration and the age of the subjects.
PMCID: PMC3706980  PMID: 23514984
Antigens; CD34; Antigens; CD38; Circadian rhythm; Granulocyte-colony stimulating factor; Hematopoietic progenitor cells; Hematopoietic stem cell mobilization
4.  Dietary baked-milk accelerates resolution of cow's milk allergy in children 
The majority (∼75%) of cow's milk-allergic children tolerate extensively heated-(baked-) milk products. Long-term effects of inclusion of dietary baked-milk have not been reported.
We report on the outcomes of children who incorporated baked-milk products into their diets.
Children evaluated for tolerance to baked-milk (muffin) underwent sequential food challenges to baked-cheese (pizza) followed by unheated-milk. Immunologic parameters were measured at challenge visits. The comparison group were matched to active subjects (using age, sex, and baseline milk-specific IgE) to evaluate the natural history of tolerance development.
Over a median of 37 months (range 8-75 months), 88 children underwent challenges at varying intervals (range 6-54 months). Among 65 subjects initially tolerant to baked-milk, 39 (60%) now tolerate unheated-milk, 18 (28%) tolerate baked-milk/baked-cheese and 8 (12%) chose to avoid milk strictly. Among the baked-milk-reactive subgroup (n=23), 2 (9%) tolerate unheated-milk, 3 (13%) tolerate baked-milk/baked-cheese, while the majority (78%) avoid milk strictly. Subjects who were initially tolerant to baked-milk were 28 times more likely to become unheated-milk-tolerant compared to baked-milk-reactive subjects (P<.001). Subjects who incorporated dietary baked-milk were 16 times more likely than the comparison group to become unheated-milk-tolerant (P<.001). Median casein IgG4 levels in the baked-milk-tolerant group increased significantly (P<.001); median milk IgE values did not change significantly.
Tolerance of baked-milk is a marker of transient IgE-mediated cow's milk allergy whereas reactivity to baked-milk portends a more persistent phenotype. The addition of baked-milk to the diet of children tolerating such foods appears to accelerate development of unheated-milk tolerance compared to strict avoidance.
Clinical implications
Addition of dietary baked-milk is safe, convenient, and well-accepted by patients. Prescribing baked-milk products to milk-allergic children represents an important shift in the treatment paradigm for milk allergy.
Capsule summary
The majority of cow's milk-allergic children tolerate extensively baked-milk products, which is a marker of transient IgE-mediated cow's milk allergy. Dietary baked-milk appears to accelerate development of unheated-milk tolerance compared to strict avoidance.
PMCID: PMC3151608  PMID: 21601913
cow's milk allergy; milk allergy; tolerance; extensively heated; baked; immunotherapy; immunomodulation
5.  Gender and respiratory findings in workers occupationally exposed to organic aerosols: A meta analysis of 12 cross-sectional studies 
Gender related differences in respiratory disease have been documented. The aim of this study was to investigate gender related differences in respiratory findings by occupation. We analyzed data from 12 of our previously published studies.
Three thousand and eleven (3011) workers employed in "organic dust" industries (1379 female and 1632 male) were studied. A control group of 806 workers not exposed to any kind of dust were also investigated (male = 419, female = 387). Acute and chronic respiratory symptoms and lung function were measured. The weighted average method and the Mantel-Haentszel method were used to calculate the odds ratios of symptoms. Hedge's unbiased estimations were used to measure lung function differences between men and women.
There were high prevalences of acute and chronic respiratory symptoms in all the "dusty" studied groups compared to controls. Significantly less chronic cough, chronic phlegm as well as chronic bronchitis were found among women than among men after the adjustments for smoking, age and duration of employment. Upper respiratory tract symptoms by contrast were more frequent in women than in men in these groups. Significant gender related lung function differences occurred in the textile industry but not in the food processing industry or among farmers.
The results of this study suggest that in industries processing organic compounds there are gender differences in respiratory symptoms and lung function in exposed workers. Whether these findings represent true physiologic gender differences, gender specific workplace exposures or other undefined gender variables not defined in this study cannot be determined. These data do not suggest that special limitations for women are warranted for respiratory health reasons in these industries, but the issue of upper respiratory irritation and disease warrants further study.
PMCID: PMC2633315  PMID: 19138417
6.  The Ambulatory Pediatric Association Fellowship in Pediatric Environmental Health: A 5-Year Assessment 
Environmental Health Perspectives  2007;115(10):1383-1387.
Evidence is mounting that environmental exposures contribute to causation of disease in children. Yet few pediatricians are trained to diagnose, treat, or prevent disease of environmental origin.
To develop a cadre of future leaders in pediatric environmental health (PEH), the Ambulatory Pediatric Association (APA) launched a new 3-year fellowship in 2001—the world’s first formal training program in PEH. Sites were established at Boston Children’s Hospital, Mount Sinai School of Medicine, George Washington University, University of Cincinnati, and University of Washington. Fellows are trained in epidemiology, biostatistics, toxicology, risk assessment, and preventive medicine. They gain clinical experience in environmental pediatrics and mentored training in clinical research, policy development, and evidence-based advocacy. Thirteen fellows have graduated. Two sites have secured follow-on federal funding to enable them to continue PEH training.
To assess objectively the program’s success in preparing fellows for leadership careers in PEH, we conducted a mailed survey in 2006 with follow-up in 2007.
Fifteen (88%) of 17 fellows and graduates participated; program directors provided information on the remaining two. Nine graduates are pursuing full-time academic careers, and two have leadership positions in governmental and environmental organizations. Ten have published one or more first-authored papers. Seven graduates are principal investigators on federal or foundation grants. The strongest predictors of academic success are remaining affiliated with the fellowship training site and devoting < 20% of fellowship time to clinical practice.
The APA fellowship program is proving successful in preparing pediatricians for leadership careers in PEH.
PMCID: PMC2022661  PMID: 17938724
community pediatrics; environmental medicine; environmental pediatrics; fellowship training; medical education

Results 1-6 (6)