The ACGME recently released its recommendation for updates to the program requirements for pediatrics. These updates proposed changes to allocation of resident clinical time and a greater emphasis on ...individualization. The potential impact of these changes on the training of physician-scientists is discussed.
Discussion of the proposed changes was held within the members of the National Pediatrician-Scientist Collaborative Workgroup, a group that represents scientists, trainees, program directors, chairs, and physician-scientist educators at nearly 30 residency programs from across the US with a focus on understanding and developing optimal approaches to physician-scientist training. Consideration was given to the both the personal and institutional impact of the proposal for physician-scientist development.
Both threats and opportunities were identified. Key opportunities include the enhanced individualized training time that could be used to explore research. Threats include re-allocation of clinical training time that may strain institutions financially, expand clinical service requirements for other early career stage individuals, and alter exposure to a broad range of pediatric specialists and sub-specialists that impact career development.
The NPSCW encourages consideration of the impact of changing program requirements on physician-scientist development to include ongoing discussion amongst mentors, programs, and trainees to understand and mitigate impact of new program requirements on the development of pediatrician-scientists.
To investigate the relationship between pacing strategy and performance during uphill and downhill running-specifically, what distribution of energy corresponds to faster race finish times between ...and among participants.
Eighteen years of race data from a 10.2-mile running race with an uphill first half and a downhill second half were analyzed to identify relationships between pacing and performance. A pacing coefficient (PC), equal to a participant's ascent time divided by finishing time (FT), was used to define each participant's pacing strategy. The American College of Sports Medicine metabolic running equation was used to estimate energy expenditure during the ascent, descent, and total race. Statistical analyses compared participants' PC to their FT and finishing place within their age and gender category. Additionally, FT and finishing place were compared between groups of participants who exhibited similar pacing strategies.
PCs were positively associated with faster FTs (r2 = .120, P < .001) and better finishing positions (r2 = .104, P < .001). PCs above .600 were associated with the fastest average FTs and best average finishing position within age and gender categories (all P ≤ .047).
Participants performed the best when energy expenditure increased no more than 10.4% during the uphill portion compared to their overall average. It is not possible to state that overly aggressive uphill efforts resulted in premature fatigue and thus slower decent times and worse race performance. However, participants should still avoid overly aggressive uphill pacing, as performance was associated with larger PCs.
Precise spatiotemporal expression of the
-
-
cascade in the lateral plate mesoderm establishes the left-right axis, which provides vital cues for correct organ formation and function. Mutations of ...one cascade constituent
and, separately, the Forkhead transcription factor
independently cause a multi-system disorder known as Axenfeld-Rieger syndrome (ARS). Since cardiac involvement is an established ARS phenotype and because disrupted left-right patterning can cause congenital heart defects, we investigated in zebrafish whether
contributes to organ laterality or situs. We demonstrate that CRISPR/Cas9-generated
and
mutants exhibit abnormal cardiac looping and that the prevalence of cardiac situs defects is increased in
;
homozygotes. Similarly, double homozygotes exhibit isomerism of the liver and pancreas, which are key features of abnormal gut situs. Placement of the asymmetric visceral organs relative to the midline was also perturbed by mRNA overexpression of
and
. In addition, an analysis of the left-right patterning components, identified in the lateral plate mesoderm of
mutants, reduced or abolished the expression of the
antagonist
. Together, these data reveal a novel contribution from
to left-right patterning, demonstrating that this role is sensitive to
gene dosage, and provide a plausible mechanism for the incidence of congenital heart defects in Axenfeld-Rieger syndrome patients.
Ocular mal-development results in heterogeneous and frequently visually disabling phenotypes that include coloboma and microphthalmia. Due to the contribution of bone morphogenetic proteins to such ...processes, the function of the paralogue Growth Differentiation Factor 3 was investigated. Multiple mis-sense variants were identified in patients with ocular and/or skeletal (Klippel–Feil) anomalies including one individual with heterozygous alterations in GDF3 and GDF6. These variants were characterized, individually and in combination, through integrated biochemical and zebrafish model organism analyses, demonstrating appreciable effects with western blot analyses, luciferase based reporter assays and antisense morpholino inhibition. Notably, inhibition of the zebrafish co-orthologue of GDF3 accurately recapitulates patient phenotypes. By demonstrating the pleiotropic effects of GDF3 mutation, these results extend the contribution of perturbed BMP signaling to human disease and potentially implicate multi-allelic inheritance of BMP variants in developmental disorders.
Multilocus sequence typing (MLST), an accurate and phylogenetically robust characterization method for population studies of Campylobacter, was applied to Campylobacter jejuni isolates (n = 297) from ...the fecal samples of cattle from five dairy farms in Cheshire, United Kingdom, collected throughout 2003. The population dynamics of the C. jejuni strains, as identified by the occurrence of sequence types and clonal complexes, demonstrated variations within and between cattle populations over time. Three clonal lineages have emerged to predominate among the cattle isolates, namely, the ST-61 complex (24.2%), ST-21 complex (23.6%), and ST-42 complex (20.5%). This provided further evidence that the ST-61 clonal complex may present a cattle-adapted C. jejuni genotype. In addition, the ST-42 clonal complex may also represent an important cattle-associated genotype. Strong geographical associations for these genotypes were also found among the farms. This is the first longitudinal study and the largest study to date for C. jejuni involving cattle populations using MLST for accurate strain characterization. This study shows the important associations between cattle and C. jejuni clonal complexes ST-61, ST-21, and ST-42, and it suggests that cattle and/or dairy products are likely to be a source of the human Campylobacter gastroenteritis caused by such genotypes. The reported findings have significant implications for the design of effective intervention strategies for disease control and prevention.
Colobomata represent visually impairing ocular closure defects that are associated with a diverse range of developmental anomalies. Characterization of a chromosome 8q21.2-q22.1 segmental deletion in ...a patient with chorioretinal coloboma revealed elements of nonallelic homologous recombination and nonhomologous end joining. This genomic architecture extends the range of chromosomal rearrangements associated with human disease and indicates that a broader spectrum of human chromosomal rearrangements may use coupled homologous and nonhomologous mechanisms. We also demonstrate that the segmental deletion encompasses
GDF6, encoding a member of the bone-morphogenetic protein family, and that inhibition of gdf6a in a model organism accurately recapitulates the proband’s phenotype. The spectrum of disorders generated by morpholino inhibition and the more severe defects (microphthalmia and anophthalmia) observed at higher doses illustrate the key role of
GDF6 in ocular development. These results underscore the value of integrated clinical and molecular investigation of patients with chromosomal anomalies.
Objectives
To determine whether the addition of ultrasound to traditional physical examination instruction improves junior medical students' abilities to locate the femoral pulse.
Methods
Initially, ...150 second‐year medical students were taught the femoral pulse examination using traditional bedside teaching on standardized patients and online didactic videos. Students were then randomized into 2 groups: group 1 received ultrasound training first and then completed the standardized examination; and group 2 performed the standardized examination first and then received ultrasound training. On the standardized patients, the femoral artery was marked with invisible ink before the sessions using ultrasound. Compared to these markers, students were then evaluated on the accuracy of femoral artery pulse palpation and the estimated location of the femoral vein. All students completed a self‐assessment survey after the ultrasound sessions.
Results
Ultrasound training improved the students' ability to palpate the femoral pulse (P= .02). However, ultrasound did not facilitate correct estimation of the femoral vein's anatomic location (P = .09). Confidence levels in localizing the femoral artery and vein were equal between groups at baseline, and both increased after the ultrasound sessions.
Conclusions
The addition of ultrasound teaching to traditional physical examination instruction enhanced medical student competency and confidence with the femoral vascular examination. However, understanding of anatomy may require emphasis on precourse didactic material, but further study is required.
High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment ...guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing.
We retrospectively reviewed the records at a single tertiary-care children's hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis, and complications from treatment.
Of the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (IQR 3-7.5). Myositis control was achieved in a median of 7.1 months (IQR 0.9-63.4). Cutaneous disease control was achieved in a median of 16.7 months (IQR 4.3-89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (IQR 0.5-1.74). The median duration of steroid treatment was 9.1 months, (IQR 4.7-17.4), while the median duration of any pharmacotherapy was 29.2 months (IQR 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%).
Current accepted treatment paradigms for Juvenile Dermatomyositis include oral glucocorticoids beginning at 2 mg/kg/day and reduced over a prolonged time period. However, our results suggest that treatment using reduced doses and duration with early use of steroid-sparing agents is comparably effective in achieving favorable outcomes in Juvenile Dermatomyositis.
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