The Current State of Musculoskeletal Ultrasound Education in Physical Medicine and Rehabilitation Residency Programs.

BACKGROUND: Exposure to musculoskeletal ultrasound (MSUS) is now a mandatory component of physical medicine and rehabilitation (PM&R) residency training. However, reports on the extent of the implementation and efficacy of MSUS education are lacking in the literature. OBJECTIVE: To determine the extent to which PM&R residencies are implementing MSUS education. DESIGN: Cross-sectional. SETTING: Institutional. PARTICIPANTS: Thirty-six of the 78 United States PM&R residency programs accredited by the Accreditation Council for Graduate Medical Education. METHODS: All 78 programs were solicited with an online survey via the residency program director and coordinator in July 2014. The 25 questions on the survey were aimed at determining program MSUS educational characteristics and their effectiveness. MAIN OUTCOME MEASURES: Description of teaching methods used for MSUS, residency demographics, characteristics of MSUS faculty expertise, and faculty-perceived competency in MSUS examinations and procedures among residents. Data were analyzed using both descriptive statistics and tests for independence to identify correlations between program characteristics and resident MSUS competency. RESULTS: A response was received from 36 of the 78 residency programs (46.2%). Of the 36 residency programs that responded, 97.2% provide exposure to MSUS (a figure that drops to 44.9% when nonrespondents are included); 61% had mandatory MSUS training (28.2% when including nonrespondents); and 44.4% had a formal curriculum (20.5% when including nonrespondents). The most common MSUS educational tools used were lecture (88.9%), outpatient clinic (86.1%), and hands-on workshops (86.1%). Sixty-one percent of responding programs evaluate residents with formal assessment tools. Overall, faculty at 38.8% and 44.4% of programs believed that at least 50% of residents who graduate are competent in diagnostic and interventional MSUS, respectively. These rates were significantly associated with the use of formal assessment. CONCLUSION: MSUS education is growing in PM&R, but many programs still have not adopted a formal educational curriculum. Formal assessment to evaluate resident MSUS skills significantly improves faculty-perceived MSUS competency.

In vivo mutation analysis using the ΦX174 transgenic mouse and comparisons with other transgenes and endogenous genes.

The ΦX174 transgenic mouse was first developed as an in vivo Ames test, detecting base pair substitution (bps) at a single bp in a reversion assay. A forward mutational assay was also developed, which is a gain of function assay that also detects bps exclusively. Later work with both assays focused on establishing that a mutation was fixed in vivo using single-burst analysis: determining the number of mutant progeny virus from an electroporated cell by dividing the culture into aliquots before scoring mutants. We review results obtained from single-burst analysis, including testing the hypothesis that high mutant frequencies (MFs) of G:C to A:T mutation recovered by transgenic targets include significant numbers of unrepaired G:T mismatches. Comparison between the ΦX174 and lacI transgenes in mouse spleen indicates that the spontaneous bps mutation frequency per nucleotide (mf(n)) is not significantly lower for ΦX174 than for lacI; the response to ENU is also comparable. For the lacI transgene, the spontaneous bps mf(n) is highly age-dependent up to 12 weeks of age and the linear trend extrapolates at conception to a frequency close to the human bps mf(n) per generation of 1.7 × 10(-8). Unexpectedly, we found that the lacI somatic (spleen) bps mf(n) per cell division at early ages was estimated to be the same as for the human germ-line. The bps mf(n) in bone marrow for the gpt transgene is comparable to spleen for the lacI and ΦX174 transgenes. We conclude that the G:C to A:T transition is characteristic of spontaneous in vivo mutation and that the MFs measured in these transgenes at early ages reflect the expected accumulation of in vivo mutation typical of endogenous mammalian mutation rates. However, spontaneous and induced mf(n)s per nucleotide for the cII gene in spleen are 5-10 times higher than for these other transgenes.

Involvement of mast cells in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EE) is an emerging disorder with poorly understood pathogenesis. OBJECTIVE: Whereas prior studies have primarily focused on the role of eosinophils in disease diagnosis and pathogenesis, this study investigates the involvement of mast cells. METHODS: Total and degranulated mast cell counts were correlated to microarray and RT-PCR data to generate transcriptome expression profiles related to mast cell number and degranulation in patients with EE and healthy control subjects. RESULTS: Esophageal mastocytosis and mast cell degranulation were readily apparent in patients with EE compared with control subjects (P < .01), as assessed by staining for total mast cells and the presence of extracellular mast cell tryptase (P < .01). Microarray analysis revealed that mast cell levels correlated with the dysregulation of 0.8% (301 genes) of the genome, which was partially distinct from the genes that correlated with tissue eosinophilia. The expression of transcripts for the mast cell proteases carboxypeptidase A3 and tryptase, but not chymase, correlated with mast cell levels and distinguished patients with EE from control subjects. Suprabasilar mast cell counts (P < .01) and degranulation (P < .01) were proportional with KIT ligand mRNA expression. Treatment of patients with EE with swallowed fluticasone propionate normalized levels of mast cells and the mast cell-related transcriptome in responder patients. CONCLUSION: Herein we have identified local mastocytosis and mast cell degranulation in the esophagi of patients with EE; identified an esophageal mast cell-associated transcriptome that is significantly divergent from the eosinophil-associated transcriptome, with carboxypeptidase A3 mRNA levels serving as the best mast cell surrogate marker; and provided evidence for the involvement of KIT ligand in the pathogenesis of EE.

Frequency and spectrum of ENU-induced mutation in the Phi X174 transgene in mouse splenic lymphocytes and their significance to spontaneous transgenic rodent mutation frequencies.

A perceived disadvantage of transgenic rodent mutation assays is that spontaneous mutant frequencies are high compared to those of endogenous genes and may consequently reduce sensitivity to induced mutation. We have previously argued that unrepaired G:T mismatches from spontaneous deamination of 5-methylcytosine at CpG sites could be converted to apparent in vivo mutations in the bacterial recovery systems because of rapid, random, mismatch repair in Escherichia coli. In this study, we have measured mutation frequencies in spleen of male mice induced by N-ethyl-N-nitrosourea (ENU) using the PhiX174 transgene, which is not subject to mismatch repair in E.coli, using single-burst analysis, a unique method to identify in vivo mutation. In order to compare our results to those using the lacI and cII transgenes, we converted all mutant frequencies to base pair substitution (bps) mutation frequencies per nucleotide based on mutant spectra from this study and published literature. We found this frequency in control spleen to be similar for lacI (3.8 +/- 0.7 x 10(-8)) and PhiX174 (3.1 +/- 1.2 x 10(-8)) at 6 weeks of age. We found a strong age dependence for spontaneous lacI mutation that extrapolated to a value at conception (1.8 +/- 0.9 x 10(-8)) that was not significantly different from the human germ line bps mutation frequency per nucleotide of 1.7 +/- 0.2 x 10(-8). These two transgenes provided similar mutational responses to 40 mg/kg ENU, 7- to 9-fold. In contrast, the cII target gene in the same tissue produces both spontaneous and induced mutation frequencies approximately 10 times higher, for unknown reasons. We conclude that the spontaneous mutant frequencies measured by the lacI and PhiX174 transgenes in this moderately dividing tissue accurately measure in vivo mutation frequencies at early ages. For these two transgenes, seemingly high mutant frequencies may reflect the expected accumulation of somatic mutation with age.