Radiology's Engagement with Transgender Breast Imaging: Review of Radiology Practice Websites and Publications.

To assess engagement with transgender breast health among radiology investigators and providers, we analyzed: (1) trends in medical research regarding transgender breast health, and (2) breast imaging practices' websites, for inclusion of the word transgender and mention of services specifically for transgender patients. We viewed the analyses of both research articles and general websites as two real-world measures of engagement among the professional community, in contrast to surveys whose responses rely on the compliance of recipients. A PubMed search performed for the text words transgender breast cancer, Lesbian-Gay-Bisexual-Transgender (LGBT) breast cancer, and transgender breast imaging. Our search yielded 48 unique relevant publications from 2010-2019. While research publications regarding transgender breast health have been become more numerous since 2015, it is still a relatively small field of study. Websites were analyzed for mention of transgender breast health needs and were reviewed for gender-neutral language and design. Of the 20 breast imaging centers listed as top choices by a national consumer group in 2019, none of their websites included the term transgender. Likewise, of the 21 centers in New York City and in San Francisco listed using the Google search engine, none included the term transgender. Despite its growing importance, issues related to transgender breast imaging are not well addressed in the radiology literature or in the radiology community, even though more transgender patients are presenting to breast centers for imaging. Radiologists need to be aware of imaging recommendations for these patients and display sensitivity to specific patient concerns.

Predictors of outcomes in managing breast abscesses-A large retrospective single-center analysis.

We have retrospectively examined a wide range of clinical characteristics, sonographic features, microbiology, and antibiotic regimens in patients with breast abscesses to seek predictive features related to outcome. Because consensus for optimal treatment of breast abscesses has moved toward minimally invasive management using single or repeated needle aspiration (ASP) coupled with adjuvant antibiotics, we assessed whether any factors correlate with the need for repeat procedures by analyzing the number of ASPs and/or surgical incision and drainage (I&D) per abscess. We examined 127 abscesses in 114 patients from a single urban public hospital, and among clinical characteristics, we found that only smoking history (P = .021) and the presence of nipple rings (P = .005) were associated with greater likelihood of necessitating repeat for abscess resolution procedures. Neither diabetes, lactational status, and HIV nor ultrasound features imaging of an abscess including size >3 cm, multiloculation, rind thickness, or central vs peripheral location were correlated with the need for a repeat procedure. Likewise, no specific micro-organisms predicted a greater likelihood of requiring repeat procedures, and no specific initial antibiotic regimen (gram-positive and/or gram-negative or multiresistance coverage) impacted clinical outcomes. Our data indicate that no specific imaging abscess characteristics, type of micro-organism, or initial choice of antibiotics affect outcomes, and therefore, these features should not preclude attempts at conventional therapy by repeated aspiration and antibiotic treatment. While a smoking history and presence of a nipple ring may increase the risk of a prolonged course, the decision to change antibiotics or repeat aspiration should rely instead on clinical evaluation and judgment by experienced physicians.

Medical educators: How they define themselves - Results of an international web survey.

BACKGROUND: Little is known about medical educators' self-definition. AIMS: The aim of this study is to survey an international community of medical educators focusing on the medical educators' self-definition. METHODS: Within a comprehensive, web-based survey, an open question on the participants' views of how they would define a "medical educator" was sent to 2200 persons on the mailing list of the Association for Medical Education in Europe. The free text definitions were analysed using qualitative thematic analysis. RESULTS: Of the, 2200 medical educators invited to participate, 685 (31.1%) provided a definition of a "medical educator". The qualitative analysis of the free text definitions revealed that medical educators defined themselves in 13 roles, primarily as "Professional Expert", "Facilitator", "Information Provider", "Enthusiast", "Faculty Developer", "Mentor", "Undergraduate and Postgraduate Trainer", "Curriculum Developer", "Assessor and Assessment Creator", and "Researcher". CONCLUSIONS: Our survey revealed that medical educators predominantly define themselves as "Professional Experts" and identified 12 further self-defined roles of a medical educator, several of which not to have been reported previously. The results can be used to further the understanding of our professional identity.

Dose-related effects of hyperoxia on the lung inflammatory response in septic rats.

We evaluated the effects of hyperoxia on pulmonary inflammatory changes in sepsis induced by cecal ligation and puncture (CLP) in rats. Seven groups were studied: sham-operated rats breathing air for 20 or 48 h; CLP breathing air for 20 or 48 h; and CLP + 100% oxygen for 20 h, or 70% oxygen for 48 h, or 100% oxygen intermittently (6 h/d) for 48 h. Video microscopy was used to monitor lung macromolecular leak, microvascular flow velocity, and shear rates, and lung morphometry was used for leukocyte infiltration and solid tissue area. Cell counts, tumor necrosis factor α, and nitrites were determined in peripheral blood and lung lavage fluid. Expression of adhesion molecules in blood leukocytes was evaluated by flow cytometry. Cecal ligation and puncture induced inflammation manifested in leukopenia, left shift, thrombocytopenia, increased expression of L selectin and CD11, increased serum and lavage fluid tumor necrosis factor α and leukocytes, and increased lung tissue area, macromolecular leak, and sequestration of leukocytes. Inhalation of 100% oxygen for 20 h increased nitrites (P < 0.01) and decreased leukocyte count in lavage fluid (P < 0.05) and attenuated lung macromolecular leak and changes in solid tissue area (P < 0.01). Inhalation of 70% oxygen (48 h) attenuated expression of adhesion molecules (P < 0.001) but failed to attenuate markers of lung inflammation. In contrast, intermittent 100% oxygen exerted favorable effects on markers of inflammation, attenuated leukocyte expression of L selectin and CD11 (P < 0.01), decreased pulmonary sequestration of leukocytes (P < 0.001), and ameliorated changes in macromolecular leak (P < 0.01) and lung solid tissue area (P < 0.05). Our data support the beneficial effects of safe subtoxic regimens of normobaric hyperoxia on the systemic and pulmonary inflammatory response following CLP.

MicroRNAs as a potential prognostic factor in gastric cancer.

AIM: To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer. METHODS: The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available. Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples, preserving the small RNA fraction. Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection. The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group, n = 14, 31%) and those who did not (good-prognosis group, n = 31, 69%). RESULTS: Three miRs, miR-451, miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P < 0.0002, 0.0027 and 0.0046 respectively). High expression of each miR was associated with poorer prognosis for both recurrence and survival. Using miR-451, the positive predictive value for non-recurrence was 100% (13/13). The expression of the differential miRs was verified by qRT-PCR, showing high correlation to the microarray data and similar separation into prognosis groups. CONCLUSION: This study identified three miRs, miR-451, miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer. Of these, miR-451 had the strongest prognostic impact.

Expertise, needs and challenges of medical educators: Results of an international web survey.

BACKGROUND: Little is known about how medical educators perceive their own expertise, needs and challenges in relation to medical education. AIM: To survey an international community of medical educators with a focus on: (1) their expertise, (2) their need for training and (3) perceived challenges. METHODS: A web-based survey comprising closed and open free-text questions was sent to 2200 persons on the mailing list of the Association for Medical Education in Europe. RESULTS: Of the 2200 medical educators invited to participate, 860 (39%) from 76 different countries took part in the survey. In general, their reported areas of expertise mainly comprised principles of teaching, communication skills training, stimulation of students in self-directed learning and student assessment. Respondents most often indicated a need for training with respect to development in medical-education-research methodology, computer-based training, curriculum evaluation and curriculum development. In the qualitative analysis of 1836 free-text responses concerning the main challenges faced, respondents referred to a lack of academic recognition, funding, faculty development, time for medical education issues and institutional support. CONCLUSIONS: The results of this survey indicate that medical educators face several challenges, with a particular need for more academic recognition, funding and academic qualifications in medical education.

Circulating interleukin-10: association with higher mortality in systolic heart failure patients with elevated tumor necrosis factor-alpha.

BACKGROUND: Interleukin-10 is an anti-inflammatory cytokine and consequently is considered by many to have a protective role in heart failure, as opposed to the notorious tumor necrosis factor-alpha. OBJECTIVES: To test the hypothesis of the possible beneficial impact of IL-10 on mortality in systolic heart failure patients in relation to their circulating TNFalpha levels. METHODS: We measured circulating levels of IL-10 and TNFalpha in 67 ambulatory systolic heart failure patients (age 65 +/- 13 years). RESULTS: Mortality was or tended to be higher in patients with higher levels (above median level) of circulating TNFalpha (9/23, 39% vs. 6/44, 14%; P = 0.02) or IL-10 (10/34, 30% vs. 5/33, 15%; P = 0.10). However, mortality was highest in the subset of patients with elevation of both markers above median (7/16, 44% vs. 8/51, 16%; P = 0.019). Elevation of both markers was associated with more than a threefold hazard ratio for mortality (HR 3.67, 95% confidence interval 1.14-11.78). CONCLUSIONS: Elevated circulating IL-10 levels in systolic heart failure patients do not have a protective counterbalance effect on mortality. Moreover, patients with elevated IL-10 and TNFalpha had significantly higher mortality, suggesting that the possible interaction in the complex inflammatory and anti-inflammatory network may need further study.

Accurate molecular classification of renal tumors using microRNA expression.

Subtypes of renal tumors have different genetic backgrounds, prognoses, and responses to surgical and medical treatment, and their differential diagnosis is a frequent challenge for pathologists. New biomarkers can help improve the diagnosis and hence the management of renal cancer patients. We extracted RNA from 71 formalin-fixed paraffin-embedded (FFPE) renal tumor samples and measured expression of more than 900 microRNAs using custom microarrays. Clustering revealed similarity in microRNA expression between oncocytoma and chromophobe subtypes as well as between conventional (clear-cell) and papillary tumors. By basing a classification algorithm on this structure, we followed inherent biological correlations and could achieve accurate classification using few microRNAs markers. We defined a two-step decision-tree classifier that uses expression levels of six microRNAs: the first step uses expression levels of hsa-miR-210 and hsa-miR-221 to distinguish between the two pairs of subtypes; the second step uses either hsa-miR-200c with hsa-miR-139-5p to identify oncocytoma from chromophobe, or hsa-miR-31 with hsa-miR-126 to identify conventional from papillary tumors. The classifier was tested on an independent set of FFPE tumor samples from 54 additional patients, and identified correctly 93% of the cases. Validation on qRT-PCR platform demonstrated high correlation with microarray results and accurate classification. MicroRNA expression profiling is a very effective molecular bioassay for classification of renal tumors and can offer a quantitative standardized complement to current methods of tumor classification.

Discovery of microRNAs and other small RNAs in solid tumors.

MicroRNAs (miRNAs) are ∼22-nt long, non-coding RNAs that regulate gene silencing. It is known that many human miRNAs are deregulated in numerous types of tumors. Here we report the sequencing of small RNAs (17-25 nt) from 23 breast, bladder, colon and lung tumor samples using high throughput sequencing. We identified 49 novel miRNA and miR-sized small RNAs. We further validated the expression of 10 novel small RNAs in 31 different types of blood, normal and tumor tissue samples using two independent platforms, namely microarray and RT-PCR. Some of the novel sequences show a large difference in expression between tumor and tumor-adjacent tissues, between different tumor stages, or between different tumor types. We also report the identification of novel small RNA classes in human: highly expressed small RNA derived from Y-RNA and endogenous siRNA. Finally, we identified dozens of new miRNA sequence variants that demonstrate the existence of miRNA-related SNP or post-transcriptional modifications. Our work extends the current knowledge of the tumor small RNA transcriptome and provides novel candidates for molecular biomarkers and drug targets.

Preferential translation of Hsp83 in Leishmania requires a thermosensitive polypyrimidine-rich element in the 3' UTR and involves scanning of the 5' UTR.

Heat shock proteins (HSPs) provide a useful system for studying developmental patterns in the digenetic Leishmania parasites, since their expression is induced in the mammalian life form. Translation regulation plays a key role in control of protein coding genes in trypanosomatids, and is directed exclusively by elements in the 3' untranslated region (UTR). Using sequential deletions of the Leishmania Hsp83 3' UTR (888 nucleotides [nt]), we mapped a region of 150 nt that was required, but not sufficient for preferential translation of a reporter gene at mammalian-like temperatures, suggesting that changes in RNA structure could be involved. An advanced bioinformatics package for prediction of RNA folding (UNAfold) marked the regulatory region on a highly probable structural arm that includes a polypyrimidine tract (PPT). Mutagenesis of this PPT abrogated completely preferential translation of the fused reporter gene. Furthermore, temperature elevation caused the regulatory region to melt more extensively than the same region that lacked the PPT. We propose that at elevated temperatures the regulatory element in the 3' UTR is more accessible to mediators that promote its interaction with the basal translation components at the 5' end during mRNA circularization. Translation initiation of Hsp83 at all temperatures appears to proceed via scanning of the 5' UTR, since a hairpin structure abolishes expression of a fused reporter gene.

Does COLIA1 SP1-binding site polymorphism predispose women to pelvic organ prolapse?

INTRODUCTION AND HYPOTHESIS: COLIA1 polymorphism is associated with increased risk for stress urinary incontinence. We hypothesize that a similar association exists with pelvic organ prolapse (POP). METHODS: Patients with advanced prolapse and healthy controls were evaluated by interview, validated questionnaires, and pelvic examination. DNA was extracted from peripheral blood, and polymerase chain reaction was performed to determine the presence or absence of the polymorphism. Power calculation indicated the need for 36 patients in each arm. RESULTS: The prevalence of the polymorphic heterozygous genotype (GT) in the study and control groups was 33.3% and 19.4%, respectively, leading to an odds ratio of 1.75. This difference, however, did not reach statistical significance (p = 0.27). CONCLUSIONS: The COLIA1 polymorphism was not significantly associated with increased risk for POP.

Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients.

BACKGROUND: Ovarian cancer, the leading cause of gynecologic cancer deaths, is usually diagnosed in advanced stages. Prognosis relates to stage at diagnosis and sensitivity to platinum based chemotherapy. We aimed to assess the expression of microRNAs in ovarian tumors and identify microRNA expression patterns that are associated with outcome, response to chemotherapy and survival. METHODS: Patients, who were surgically treated for ovarian cancer between January 2000 and December 2004 were identified. Patient charts were reviewed for clinicopathologic information, follow-up and survival. Total RNA was extracted from tumor samples and microRNA expression levels were measured by microarrays. Expression levels were compared between groups of samples and statistically analyzed. RESULTS: Fifty-seven patients were identified to fit study criteria. Of them, 19 patients had stage I disease at diagnosis, and 38 patients, stage III. All patients received platinum based chemotherapy as first line treatment. 18 microRNAs were differentially expressed (p<0.05) between stage I and stage III disease. Seven microRNAs were found to be significantly differentially expressed in tumors from platinum-sensitive vs. platinum-resistant patients (p<0.05). Five microRNAs were associated with significant differences (p<0.05) in survival or recurrence-free survival. High expression of hsa-mir-27a identified a sub-group of patients with very poor prognosis. CONCLUSIONS: We have found an array of tumor specific markers that are associated with response to platinum based first line chemotherapy. Expression of some of these miRNAs also correlated closely with prognosis. This approach can potentially be used to tailor chemotherapy and further management to specific patient needs.

Vigabatrin, lamotrigine, topiramate and serum carnitine levels.

Clinical studies indicate a decrease in free and total carnitine in children treated with old-generation antiepileptic drugs (especially valproate). Here, we studied the effect of new-generation antiepileptic drugs on serum carnitine levels. Serum carnitine levels were measured in 91 children: 24 treated with vigabatrin, 28 treated with lamotrigine, and 21 treated with topiramate. These drugs were given as monotherapy (54 children) or polytherapy (19 children). Eighteen additional children treated with valproate served as control subjects. Reduced mean serum carnitine level was evident only in children treated with valproate, with mean free and total carnitine level of 26.9 +/- 8.6 micromol/L and 29.1 +/- 10.4 micromol/L, respectively. In contrast, the mean serum carnitine levels of children treated with vigabatrin, lamotrigine, or topiramate were similar and normal. In these children, the free carnitine levels were 38.5 +/- 7.8 micromol/L, 37.2 +/- 7.7 microg/mL, and 40.4 +/- 8.7 micromol/L, respectively, and total carnitine levels were 43.5 +/- 8.8 micromol/L, 44.4 +/- 9.2 micromol/L, and 45.5 +/- 9.8 micromol/L (+/-S.D.), respectively. Only 4 children (treated with valproate) exhibited considerably lower serum carnitine levels. None of these children had significant clinical adverse effects attributable to carnitine deficiency. In conclusion, these new-generation antiepileptic drugs probably do not cause carnitine deficiency. In contrast, valproate may induce carnitine deficiency, but most cases are asymptomatic.

Carrier frequency of autosomal-recessive disorders in the Ashkenazi Jewish population: should the rationale for mutation choice for screening be reevaluated?

BACKGROUND: Ashkenazi Jewish (AJ) population is at increased risk for several recessive inherited diseases. Therefore, carrier testing of AJ members is important in order to identify couples at risk of having offspring with an autosomal recessive disorder. METHODS: In the present study, a database containing the results of 28 410 genotyping assays was screened. Ten thousand seventy eight nonselected healthy members of the AJ population were tested for carrier status for the following diseases; Gaucher disease (GD), cystic fibrosis (CF), Familial dysautonomia (FD), Alpha 1 antitrypsin (A1AT), Mucolipidosis type 4 (ML4), Fanconi anemia type C (FAC), Canavan disease (CD), Neimann-Pick type 4 (NP) and Bloom syndrome (BLM). RESULTS: The results demonstrated that 635 members were carriers of one mutation and 30 members were found to be carriers of two mutations in the different genes related to the development of the above mentioned diseases. GD was found to have the highest carrier frequency (1:17) followed by CF (1:23), FD (1:29), A1AT (1:65), ML4 (1:67) and FAC (1:77). The carrier frequency of CD, NP and BLM was 1:82, 1:103 and 1:157, respectively. CONCLUSIONS: The frequency of the disease-causing mutations screened routinely among the AJ population indicated that there are rare mutations with very low frequencies. The screening policy of the disease-causing mutations should be reevaluated and mutations with a high frequency should be screened, while rare mutations with a lower frequency may be tested in partners of carriers.

Breast problems presenting in the emergency room.

A variety of breast complaints may present in the emergency setting. Therefore, the radiologist in the emergency department must be familiar with the pathology encountered and the associated imaging findings. While mammography is the most commonly and frequently used modality for breast imaging, in the emergency setting, ultrasound may be more readily available and better tolerated by the patient. This pictorial essay describes the spectrum of breast complaints encountered in the acute setting and the associated mammographic and sonographic findings.

Paternal isodisomy of chromosome 7 with cystic fibrosis and overgrowth.

We have diagnosed a boy with cystic fibrosis (CF) due to paternal UPD presenting with overweight and developmental delay, not typical features to CF patients. Two previously reported patients with paternal UPD(7) did not present overgrowth. The discrepancy between the phenotype of this boy and the other two patients raises the question of imprinted genes or homozygotization of a disease-causing gene in paternal UPD7.

Setting school-level outcome standards.

BACKGROUND: To establish international standards for medical schools, an appropriate panel of experts must decide on performance standards. A pilot test of such standards was set in the context of a multidimensional (multiple-choice question examination, objective structured clinical examination, faculty observation) examination at 8 leading schools in China. METHODS: A group of 16 medical education leaders from a broad array of countries met over a 3-day period. These individuals considered competency domains, examination items, and the percentage of students who could fall below a cut-off score if the school was still to be considered as meeting competencies. This 2-step process started with a discussion of the borderline school and the relative difficulty of a borderline school in achieving acceptable standards in a given competency domain. Committee members then estimated the percentage of students falling below the standard that is tolerable at a borderline school and were allowed to revise their ratings after viewing pilot data. RESULTS: Tolerable failure rates ranged from 10% to 26% across competency domains and examination types. As with other standard-setting exercises, standard deviations from initial to final estimates of the tolerable failure rates fell, but the cut-off scores did not change significantly. Final, but not initial cut-off scores were correlated with student failure rates (r = 0.59, P = 0.03). DISCUSSION: This paper describes a method to set school-level outcome standards at an international level based on prior established standard-setting methods. Further refinement of this process and validation using other examinations in other countries will be needed to achieve accurate international standards.

Effects of basic clinical skills training on objective structured clinical examination performance.

OBJECTIVES: The aim of curriculum reform in medical education is to improve students' clinical and communication skills. However, there are contradicting results regarding the effectiveness of such reforms. METHODS: A study of internal medicine students was carried out using a static group design. The experimental group consisted of 77 students participating in 7 sessions of communication training, 7 sessions of skills-laboratory training and 7 sessions of bedside-teaching, each lasting 1.5 hours. The control group of 66 students from the traditional curriculum participated in equally as many sessions but was offered only bedside teaching. Students' cognitive and practical skills performance was assessed using Multiple Choice Question (MCQ) testing and an objective structured clinical examination (OSCE), delivered by examiners blind to group membership. RESULTS: The experimental group performed significantly better on the OSCE than did the control group (P < 0.01), whereas the groups did not differ on the MCQ test (P < 0.15). This indicates that specific training in communication and basic clinical skills enabled students to perform better in an OSCE, whereas its effects on knowledge did not differ from those of the traditional curriculum. CONCLUSION: Curriculum reform promoting communication and basic clinical skills are effective and lead to an improved performance in history taking and physical examination skills.

Ensuring global standards for medical graduates: a pilot study of international standard-setting.

Increasing physician and patient mobility has led to a move toward internationalization of standards for physician competence. The Institute for International Medical Education proposed a set of outcome-based standards for student performance, which were then measured using three assessment tools in eight leading schools in China: a 150-item multiple-choice examination, a 15-station OSCE and a 16-item faculty observation form. The purpose of this study was to empanel a group of experts to determine whether international student-level performance standards could be set. The IIME convened an international panel of experts in student education with specialty and geographic diversity. The group was split into two, with each sub-group establishing standards independently. After a discussion of the borderline student, the sub-groups established minimally acceptable cut-off scores for performance on the multiple-choice examination (Angoff and Hofstee methods), the OSCE station and global rating performance (modified Angoff method and holistic criterion reference), and faculty observation domains (holistic criterion reference). Panelists within each group set very similar standards for performance. In addition, the two independent parallel panels generated nearly identical performance standards. Cut-off scores changed little before and after being shown pilot data but standard deviations diminished. International experts agreed on a minimum set of competences for medical student performance. In addition, they were able to set consistent performance standards with multiple examination types. This provides an initial basis against which to compare physician performance internationally.