Longitudinal Continuity Learning Experiences and Primary Care Career Interest: Outcomes from an Innovative Medical School Curriculum.

BACKGROUND: Medical students in the USA have negative perceptions of primary care careers, which are exacerbated by the hidden curriculum and medical school culture. Longitudinal integrated clerkships (LICs) have shown promise in ameliorating this situation by promoting student/preceptor continuity relationships and helping students maintain empathy. AIM: The aim of this study is to describe the Student Continuity of Practice Experience (SCOPE) program and demonstrate program outcomes using evaluation data from residency match results, course evaluations, and student grades. SETTING: University of Texas Medical Branch, an academic health center in Galveston, Texas. PARTICIPANTS: Undergraduate medical students. PROGRAM DESCRIPTION: Learners participate in a longitudinal curriculum designed to enhance their skills as primary care physicians. They regularly attend continuity clinic, establishing a panel of patients by their third year. Students receive frequent feedback from a faculty mentor on assignments and clinical performance. PROGRAM EVALUATION: SCOPE students have high primary care residency match rates and experience patient continuity rates comparable to an intern. Their interest in primary care increases between years one and three, a departure from typical medical student trends. DISCUSSION: SCOPE appears to promote and maintain primary care career interest in participants and has transferability to other institutions.

Skill Session on Writing Patient Assessments for Pediatric Clerkship Students.

Introduction: Formulating written patient assessments requires the student to synthesize subjective and objective information and use clinical reasoning to reach a diagnosis. Medical students lack this skill, and clinical experience is not enough to acquire it. This session provides a structured process for learning how to formulate a patient assessment. Methods: Third-year medical students participated in a large-group interactive skill session at the beginning of their pediatrics clerkship. Instructors following a scripted model walked students through practice examples to ultimately formulate a complete written patient assessment. The session covered data synthesis, use of appropriate medical terminology, and differential diagnosis development. Students used an audience response system to practice these skills. Results: Over 1 academic year, 250 medical students participated in six sessions, with an average of 40-50 attendees per session. Over 90% of students completed pre- and postsession written patient assessments. These assessments were evaluated using portions of the Pediatric History and Physical Exam Evaluation grading rubric. The session had a positive effect on patient assessment formulation skills, with a significant increase in scores after the session. Discussion: The session improved students' skill in generating more complete written patient assessments. Almost all students found the session valuable regardless of prior clinical experience. Nearly 50% of students felt inadequately prepared to formulate a written patient assessment prior to the session, revealing a skills gap for learners and a curricular teaching gap. This skill session provided a structured method and active learning format for teaching this essential clinical skill.

Soliciting feedback on the wards: a peer-to-peer workshop.

BACKGROUND: For medical students, soliciting feedback is a critical but difficult skill that merits proper training. This skill may be taught effectively by peers who have experienced challenges with feedback on the wards. METHODS: Two medical students developed and taught a workshop on feedback skills. The workshop was presented to 248 third-year students. The workshop trained students in soliciting, receiving and responding to feedback through interactive discussions of case scenarios. Students were given pre- and post-surveys to assess changes in their confidence in and attitudes towards the feedback process. RESULTS: There were statistically significant increases in students' likeliness to solicit feedback and confidence in their ability to solicit feedback. Students' view on the importance of feedback did not change. The most commonly cited barriers to feedback were time constraints, fear of negative feedback, emotions and skills when asking for feedback, and student-mentor relationship. The content the students valued the most was management of internal triggers to negative feedback. Students noted that the peer-to-peer format, case scenarios, and interactive questions were strengths of the workshop. DISCUSSION: Although medical students recognise the importance of feedback, they often lack the confidence and skills to obtain quality feedback. A peer-to-peer workshop on soliciting, receiving, and responding to feedback can be an effective method to improve students' confidence and skills in this area. More research needs to be done to conclude if this workshop increases the instances of students soliciting high-quality feedback on the wards and improves clinical performance.

A mutation in bovine keratin 5 causing epidermolysis bullosa simplex, transmitted by a mosaic sire.

A mechanobullous skin disorder was identified in the progeny of a 3-y-old Friesian-Jersey crossbred bull. The condition presented as loss of skin and mucosa from contact areas and inflammation. Examination of skin samples under light microscopy revealed separation of the epidermis from the dermis. Electron microscopic analysis refined the site of cleavage to above the basement membrane involving lysis of basal keratinocytes. These observations were consistent with the simplex form of epidermolysis bullosa (EB) in humans. Candidate genes based on human gene mutations were assessed, resulting in keratin 5 being identified as the most likely candidate gene. The sequence of bovine keratin 5 was established and sequencing led to identification of a G to A substitution in all affected animals. This mutation leads to an amino acid change of glutamic acid to lysine in the final E (478) of the KLLEGE motif of the protein. The sire carried a de novo mutation and was mosaic, explaining his asymptomatic status and the less than expected frequency of affected offspring. Remarkably, the same mutation has been previously described in EB simplex in humans.

Molecular dissection of a quantitative trait locus: a phenylalanine-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated with a major effect on milk yield and composition.

We herein report on our efforts to improve the mapping resolution of a QTL with major effect on milk yield and composition that was previously mapped to bovine chromosome 20. By using a denser chromosome 20 marker map and by exploiting linkage disequilibrium using two distinct approaches, we provide strong evidence that a chromosome segment including the gene coding for the growth hormone receptor accounts for at least part of the chromosome 20 QTL effect. By sequencing individuals with known QTL genotype, we identify an F to Y substitution in the transmembrane domain of the growth hormone receptor gene that is associated with a strong effect on milk yield and composition in the general population.

Phenotypic population screen identifies a new mutation in bovine DGAT1 responsible for unsaturated milk fat.

Selective breeding has strongly reduced the genetic diversity in livestock species, and contemporary breeding practices exclude potentially beneficial rare genetic variation from the future gene pool. Here we test whether important traits arising by new mutations can be identified and rescued in highly selected populations. We screened milks from 2.5 million cows to identify an exceptional individual which produced milk with reduced saturated fat content, and improved unsaturated and omega-3 fatty acid concentrations. The milk traits were transmitted dominantly to her offspring, and genetic mapping and genome sequencing revealed a new mutation in a previously unknown splice enhancer of the DGAT1 gene. Homozygous carriers show features of human diarrheal disorders, and may be useful for the development of therapeutic strategies. Our study demonstrates that high-throughput phenotypic screening can uncover rich genetic diversity even in inbred populations, and introduces a novel strategy to develop novel milks with improved nutritional properties.

Use of the Pediatric Symptom Checklist in a low-income, Mexican American population.

OBJECTIVE: To evaluate the usefulness of the Pediatric Symptom Checklist (PSC) in identifying behavioral problems in low-income, Mexican American children. DESIGN: A cross-sectional study design was used to examine the PSC as a screening test, with the Child Behavior Checklist (CBCL) as the criterion standard. SETTING: The study was conducted at a health center in a diverse low-income community. Patients Eligible patients were children and adolescents, 4 to 16 years of age, who were seen for nonemergent, well-child care. Of 253 eligible children during a 9-month study period, 210 agreed to participate in the study. There was a 100% completion rate of the questionnaires. The average age of the children was 7.5 years, and 45% were female. Ninety-five percent of patients were of Hispanic descent (Mexican American); 86% of families spoke only Spanish. Socioeconomic status was low (more than three fourths of families earned <$20 000 annually). RESULTS: The CBCL Total scale determined that 27 (13%) of the children had clinical levels of behavioral problems. With a cutoff score of 24, the PSC screened 2 (1%) of the 210 children as positive for behavioral problems. Using the CBCL as the criterion standard, the PSC sensitivity was 7.4%, and the specificity was 100%. Receiver operator characteristic analysis determined that a PSC cutoff score of 12 most correctly classified children with and without behavioral problems (sensitivity, 0.74; specificity, 0.94). CONCLUSIONS: When using the PSC, a new cutoff score of 12 for clinical significance should be considered if screening low-income, Mexican American children for behavioral problems. Additional study is indicated to determine the causes of the PSC's apparently lower sensitivity in Mexican American populations.

Estimation of the compaction of the denatured state by a protein variant involved in a reverse hydrophobic effect.

Fluorescence resonance energy transfer methods have been used to evaluate changes in the dimension of the denatured state for position 73 variants of iso-1-cytochrome c that show a reverse hydrophobic effect [Herrmann et al. (1995)]. The experiments take advantage of the Trp 59/heme donor-acceptor pair in cytochrome c. Two large aliphatic variants, Ile 73 and Leu 73, were compared directly to the wild-type protein (lysine 73). The Leu 73 was an outlier in the original work and serves as an internal control. The data show that the volume of the denatured state is contracted by a small but significant degree, 4-6%, for the Ile 73 variant whereas the Leu 73, which does not conform to the reverse hydrophobic effect, shows no significant compaction. Given that position 73 is beyond Trp 59 in the sequence, the denatured state compaction appears to be a global effect.

Patterns of agreement between parent and child ratings of emotional and behavioral problems in an outpatient clinical setting: when children endorse more problems.

This study examined clinically relevant patterns of agreement between parent and child ratings of child behavior problems and factors associated with these patterns. Subjects were 274 children, ages 11 to 18 years, and their parents. Overall agreement between parent-child ratings was modest. Twenty-five percent of parent-child pairs agreed children's behavior problems were clinically elevated ("both" group), 29% agreed problems were nonclinical ("neither" group), in 39% of pairs only parents reported clinically elevated problems ("parent only" group) and in 8% of pairs only children rated clinically elevated problems ("child only" group). Maternal stress and child age, but not child gender, were associated with parent-child agreement patterns. Children with depressive/mood disorders were more likely to be in the "child only" group than in any other group. This study discusses the importance of paying attention to child reports of elevated behavior problems, particularly when parents report that child behavior problems are not clinically elevated.

Prolactin and its receptor are expressed in murine hair follicle epithelium, show hair cycle-dependent expression, and induce catagen.

Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp and report that both PRL and PRLR are stringently restricted to the hair follicle epithelium and are strongly hair cycle-dependent. In addition we show that PRL exerts functional effects on anagen hair follicles in murine skin organ culture by down-regulation of proliferation in follicular keratinocytes. In telogen follicles, PRL-like immunoreactivity was detected in outer root sheath (ORS) keratinocytes. During early anagen (III to IV), the developing inner root sheath (IRS) and the surrounding ORS were positive for PRL. In later anagen stages, PRL could be detected in the proximal IRS and the inner layer of the ORS. The regressing (catagen) follicle showed a strong expression of PRL in the proximal ORS. In early anagen, PRLR immunoreactivity occurred in the distal part of the ORS around the developing IRS, and subsequently to a restricted area of the more distal ORS during later anagen stages and during early catagen. The dermal papilla (DP) stayed negative for both PRL and PRLR throughout the cycle. Telogen follicles showed only a very weak PRLR staining of ORS keratinocytes. The long-form PRLR transcript was shown by real-time polymerase chain reaction to be transiently down-regulated during early anagen, whereas PRL transcripts were up-regulated during mid anagen. Addition of PRL (400 ng/ml) to anagen hair follicles in murine skin organ culture for 72 hours induced premature catagen development in vitro along with a decline in the number of proliferating hair bulb keratinocytes. These data support the intriguing concept that PRL is generated locally in the hair follicle epithelium and acts directly in an autocrine or paracrine manner to modulate the hair cycle.

A mass spectrometry method for measuring 15N incorporation into pheophytin.

The 15N content of pheophytin, the magnesium-free derivative of chlorophyll, can be measured with great accuracy and precision using positive-ion atmospheric pressure ionization electrospray mass spectroscopy following a simple solvent extraction of small amounts of plant tissue. The molecular weight of pheophytin prepared from Chlamydomonas reinhardtii grown in different ratios of 14N/15N showed linear regression with the isotopic input, with a precision of 0.5-1%. Using an isotope dilution strategy, we have shown that nitrogen fixation can contribute substantial 14N to pheophytin isolated from Medicago truncatula plants grown in symbiosis with Sinorhizobium meliloti. The assay is sensitive, precise, rapid, simple, and robust. These features suggest that it could become an important tool for measuring the contribution of symbiotic and associative nitrogen fixation to plant metabolism.

Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition.

We recently mapped a quantitative trait locus (QTL) with a major effect on milk composition--particularly fat content--to the centromeric end of bovine chromosome 14. We subsequently exploited linkage disequilibrium to refine the map position of this QTL to a 3-cM chromosome interval bounded by microsatellite markers BULGE13 and BULGE09. We herein report the positional candidate cloning of this QTL, involving (1) the construction of a BAC contig spanning the corresponding marker interval, (2) the demonstration that a very strong candidate gene, acylCoA:diacylglycerol acyltransferase (DGAT1), maps to that contig, and (3) the identification of a nonconservative K232A substitution in the DGAT1 gene with a major effect on milk fat content and other milk characteristics.

AAV2 vector harboring a liver-restricted promoter facilitates sustained expression of therapeutic levels of alpha-galactosidase A and the induction of immune tolerance in Fabry mice.

The successful application of gene therapy for the treatment of genetic diseases such as Fabry is reliant on the development of vectors that are safe and that facilitate sustained expression of therapeutic levels of the transgene product. Here, we report that intravenous administration of a recombinant AAV2 vector encoding human alpha-galactosidase A under the transcriptional control of a liver-restricted enhancer/promoter (AAV2/DC190-alphagal) generated significantly higher levels of expression in BALB/c and Fabry mice than could be realized using the ubiquitous CMV promoter (AAV2/CMVHI-alphagal). Moreover, AAV2/DC190-alphagal-mediated hepatic expression of alpha-galactosidase A was sustained for 12 months in BALB/c mice and was associated with a significantly reduced immune response to the expressed enzyme. Subsequent challenge of the AAV2/DC190-alphagal-treated animals with recombinant human alpha-galactosidase A at 6 months failed to elicit the production of anti-alpha-galactosidase A antibodies, suggesting the induction of immune tolerance in these animals. The levels of expression attained with AAV2/DC190-alphagal in the Fabry mice were sufficient to reduce the abnormal accumulation of globotriaosylceramide in the liver, spleen, and heart to basal levels and in the kidney by approximately 40% at 8 weeks. Together, these results demonstrate that AAV2-mediated gene transfer that limits the expression of alpha-galactosidase A to the liver may be a viable strategy for treating Fabry disease.