Association Analysis of the FTO Gene with Obesity in Children of Caucasian and African Ancestry Reveals a Common Tagging SNP

Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI≥95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r2 = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08–1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91–1.21; P = 0.49) and of 1.31 (95% CI 1.050–1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact

Pregnancy Outcomes in Female Lung Transplant Recipients

Conclusions: Female lung recipients appear to face higher risks related to pregnancy when compared to other solid organ transplant recipients. Although successful pregnancies have been reported in female lung recipients, analyses of larger numbers of cases may help to identify pre-pregnancy factors predictive of adverse outcomes. Centers are encouraged to report all pregnancies in transplant recipients to the NTPR

Team-Taught Surface Anatomy for Health Professional Students

Purpose: The aim of the Student Team-Taught Surface Anatomy program was to provide a private and professional setting for first year medical students (MSIs) to learn surface anatomy. Methods: Second year medical student teaching assistants (MSII TAs) and MSIs reviewed the anatomy curriculum related to the thorax and abdomen, as well as six illustrations detailing surface landmarks and underlying anatomy essential for clinical appreciation of healthy and diseased states. MSII TAs worked with groups of 4-5 MSIs at a time to review the material on live models. An evaluation containing both Likert-scale and open-ended questions was created to solicit participant feedback. Results: 27 MSII TAs taught 76 workshops. 161 Jefferson MSIs participated (63%). Of these, 60% were female, and 40% were male; 96% reported workshops “enhanced their understanding of the material” and 94% would have attended additional workshops, had they been offered. All participants (100%) agreed that MSII TAs were respectful and professional. Conclusion: Peer-led education can be an effective tool for the instruction of basic elements of the medical school curriculum. Relevance to Interprofessional Education: This program was designed by a student with prior experience in theater and teaching, and illustrations were created by a student with a background in visual art. Furthermore, this curriculum could be expanded to engage students across and within other medical disciplines. Learning Objectives: 1. MSIIs will be re-acquainted to medical anatomy to a level where they can competently teach to MS1s the surface anatomy related to the thorax and abdomen, and MSIs will engage voluntarily in learning that takes place in a comfortable, private, and nurturing environment. 2. A template will be established upon which a more extensive surface anatomy curriculum can be built for future medical students, as well as for students across the other medical disciplines, such as PT, OT, and nursing. 3. The design process, teaching plan, methods, materials, and student feedback will be published for future use, with the intention of developing an interprofessional student-led surface anatomy program accessible to students across the health professions. Coordinating anatomy curricula across disciplines is a challenge that could be met by involving senior medical (MSIV), OT, PT, and nursing students

Low Prevalence of Hip and Knee Arthritis in Active Marathon Runners.

BACKGROUND: Existing evidence on whether marathon running contributes to hip and knee arthritis is inconclusive. Our aim was to describe hip and knee health in active marathon runners, including the prevalence of pain, arthritis, and arthroplasty, and associated risk factors. METHODS: A hip and knee health survey was distributed internationally to marathon runners. Active marathoners who completed ≥5 marathons and were currently running a minimum of 10 miles per week were included (n = 675). Questions assessed pain, personal and family history of arthritis, surgical history, running volume, personal record time, and current running status. Multivariable analyses identified risk factors for pain and arthritis. Arthritis prevalence in U.S. marathoners was compared with National Center for Health Statistics prevalence estimates for a matched group of the U.S. RESULTS: Marathoners (n = 675) with a mean age of 48 years (range, 18 to 79 years) ran a mean distance of 36 miles weekly (range, 10 to 150 miles weekly) over a mean time of 19 years (range, 3 to 60 years) and completed a mean of 76 marathons (range, 5 to 1,016 marathons). Hip or knee pain was reported by 47%, and arthritis was reported by 8.9% of marathoners. Arthritis prevalence was 8.8% for the subgroup of U.S. marathoners, significantly lower (p \u3c 0.001) than the prevalence in the matched U.S. population (17.9%) and in subgroups stratified by age, sex, body mass index (BMI), and physical activity level (p \u3c 0.001). Seven marathoners continued to run following hip or knee arthroplasty. Age and family and surgical history were independent risk factors for arthritis. There was no significant risk associated with running duration, intensity, mileage, or the number of marathons completed (p \u3e 0.05). CONCLUSIONS: Age, family history, and surgical history independently predicted an increased risk for hip and knee arthritis in active marathoners, although there was no correlation with running history. In our cohort, the arthritis rate of active marathoners was below that of the general U.S. POPULATION: Longitudinal follow-up is needed to determine the effects of marathon running on developing future hip and knee arthritis. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence

Selective control of synaptically-connected circuit elements by all-optical synapses

Understanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using bioluminescent light: Luciferase-generated light, originating from a presynaptic axon terminal, modulates an opsin in its postsynaptic target. Vesicular-localized luciferase is released into the synaptic cleft in response to presynaptic activity, creating a real-time Optical Synapse. Light production is under experimenter-control by introduction of the small molecule luciferin. Signal transmission across this optical synapse is temporally defined by the presence of both the luciferin and presynaptic activity. We validate synaptic Interluminescence by multi-electrode recording in cultured neurons and in mice in vivo. Interluminescence represents a powerful approach to achieve synapse-specific and activity-dependent circuit control in vivo

Pregnancy After Lung Transplant

The purpose of this study was to analyze pregnancy outcomes in female lung transplant recipients. Data were collected from the National Transplantation Pregnancy Registry via questionnaires, interviews, and hospital records. Twenty-one female lung recipients reported 30 pregnancies with 32 outcomes (1 triplet pregnancy). Outcomes included 18 live births, 5 therapeutic abortions, and 9 spontaneous abortions. No stillbirths or ectopic pregnancies were reported. Mean (SD) interval from transplant to conception was 3.6 (3.3) years (range, 0.1-11.3 years). Comorbid conditions during pregnancy included hypertension in 16, infections in 7, diabetes in 7, preeclampsia in 1, and rejection in 5 women. Ten of the 21 recipients received a transplant because of cystic fibrosis and accounted for 12 pregnancy outcomes (7 live births, 3 spontaneous abortions, and 2 therapeutic abortions). At last recipient contact, 13 had adequate function, 2 had reduced function, 5 recipients had died (2 with cystic fibrosis), and 1 recipient had a nonfunctioning transplant. Mean gestational age of the newborn was 33.9 (SD, 5.2) weeks, and 11 were born preterm (weeks). Mean birthweight was 2206 (SD, 936) g and 11 were low birthweight (g). Two neonatal deaths were associated with a triplet pregnancy; one fetus spontaneously aborted at 14 weeks and 2 died after preterm birth at 22 weeks. At last follow-up, all 16 surviving children were reported healthy and developing well. Successful pregnancy is possible after lung transplant, even among recipients with a diagnosis of cystic fibrosis