The hidden curriculum of peer teaching in developing a professional identity: Perspectives of medical students and junior doctors.

INTRODUCTION: Peer teaching has been utilised in the field of medical education to support learning of the curriculum in both pre-clinical and clinical contexts. The literature has shown that there is a hidden curriculum unique to peer teaching, but little is known about this from the peer learner perspective. This study explored the hidden curriculum of peer teaching and from the perspective of medical students and junior doctors. METHODS: Data was collected via one-on-one interviews with 10 participants including junior doctors and medical students (n = 10). The interviews were transcribed, and thematic analysis was used to interpret the data. RESULTS: Five themes were identified in relation to the hidden curriculum of peer teaching-specifically, learning how to be a professional; be a better learner; to care for self and others; to navigate career pathways; and to become a future teacher. CONCLUSION: Peer teaching is a powerful resource for professional identity development in medicine and can be better leveraged to deliver on this potential.

Can nutrition interventions tackle the global insulin affordability via improving diabetes management and reducing insulin demand?

Diabetes, a global health concern, requires insulin therapy. As insulin demand and prices rise dramatically, insulin affordability has increasingly become an issue facing patients with diabetes worldwide. To cut insulin costs, many patients ration their supply, which may have dire health consequences. This particularly affects lower-income populations, who are often forced to choose between purchasing their medications or paying for other necessities. Nutrition might be one solution for this. This commentary aims to provide comprehensive insight with historical context into intersectional components of diabetes in the global arena through analyses of insulin affordability, coupled with the critical role of nutrition intervention after searching the PubMed for relevant articles. More studies in personalized nutrition, supplementations, and dietary behaviors may develop evidence-based nutrition interventions to control diabetes. We argue that alongside price regulation, a greater focus to nutrition to address issues of food insecurity and food assistance programs may help to improve insulin affordability.

An evolutionarily acquired microRNA shapes development of mammalian cortical projections.

The corticospinal tract is unique to mammals and the corpus callosum is unique to placental mammals (eutherians). The emergence of these structures is thought to underpin the evolutionary acquisition of complex motor and cognitive skills. Corticospinal motor neurons (CSMN) and callosal projection neurons (CPN) are the archetypal projection neurons of the corticospinal tract and corpus callosum, respectively. Although a number of conserved transcriptional regulators of CSMN and CPN development have been identified in vertebrates, none are unique to mammals and most are coexpressed across multiple projection neuron subtypes. Here, we discover 17 CSMN-enriched microRNAs (miRNAs), 15 of which map to a single genomic cluster that is exclusive to eutherians. One of these, miR-409-3p, promotes CSMN subtype identity in part via repression of LMO4, a key transcriptional regulator of CPN development. In vivo, miR-409-3p is sufficient to convert deep-layer CPN into CSMN. This is a demonstration of an evolutionarily acquired miRNA in eutherians that refines cortical projection neuron subtype development. Our findings implicate miRNAs in the eutherians' increase in neuronal subtype and projection diversity, the anatomic underpinnings of their complex behavior.

A case report of septic shock and splenic abscess formation secondary to gastric band erosion: A rare complication of laparoscopic adjustable gastric banding.

INTRODUCTION: With the rising burden of obesity, bariatric surgery is becoming more common as a treatment option. Laparoscopic adjustable gastric banding (LAGB) is considered safe and effective and is a popular procedure in Australia. However there are recognised complications to be aware of such as band erosion which can lead to infection and abscess formation. PRESENTATION OF CASE: A 59-year-old caucasian female presented with fevers, rigors and feeling generally unwell. She was previously fit and well with her only past medical history being LAGB 14 years prior. Clinically the patient was in septic shock and required intensive care admission for inotropic support. On investigations the CRP was 227 and abdominal computed tomography (CT) revealed a splenic abscess. Follow up upper gastrointestinal endoscopy diagnosed an eroded gastric band in the stomach. The patient proceeded to laparoscopy, a gastrotomy was performed and the band was removed. The splenic abscess was concurrently drained and the patient treated with an extended course of intravenous and oral antibiotics. DISCUSSION: Band erosion is a rare but serious complications of LAGB surgery along with band slippage, pouch dilatation and abscess formation. Patients are often asymptomatic making early diagnosis difficult. Upper gastrointestinal endoscopy is used to locate the band and recommended treatment is band removal via laparoscopy or laparotomy. CONCLUSION: Band erosion should be suspected in patients with a history of LAGB presenting with nonspecific symptoms such as abdominal pain or fevers. This case also highlights the importance of appropriate patient follow up post operatively and counselling of operative risks and long-term complications.

Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1-3 family.

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression critical for organismal viability. Changes in miRNA activity are common in cancer, but how these changes relate to subsequent alterations in transcription and the process of tumorigenesis is not well understood. Here, we report a deep transcriptional, oncogenic network regulated by miRNAs. We present analysis of the gene expression and phenotypic changes associated with global miRNA restoration in miRNA-deficient fibroblasts. This analysis uncovers a miRNA-repressed network containing oncofetal genes Imp1, Imp2, and Imp3 (Imp1-3) that is up-regulated primarily transcriptionally >100-fold upon Dicer loss and is resistant to resilencing by complete restoration of miRNA activity. This Dicer-resistant epigenetic switch confers tumorigenicity to these cells. Let-7 targets Imp1-3 are required for this tumorigenicity and feed back to reinforce and sustain expression of the oncogenic network. Together, these Dicer-resistant genes constitute an mRNA expression signature that is present in numerous human cancers and is associated with poor survival.

Polymorphisms at the microRNA binding-site of the stem cell marker gene CD133 modify susceptibility to and survival of gastric cancer.

CD133 is one of the most common stem cell markers, and functional single nucleotide polymorphisms (SNPs) of CD133 may modulate its gene functions and thus cancer risk and patient survival. We hypothesized that potentially functional CD133 SNPs are associated with gastric cancer (GC) risk and survival. To test this hypothesis, we conducted a case-control study of 371 GC patients and 313 cancer-free controls frequency-matched by age, sex, and ethnicity. We genotyped four selected, potentially functional CD133 SNPs (rs2240688A>C, rs7686732C>G, rs10022537T>A, and rs3130C>T) and used logistic regression analysis for associations of these SNPs with GC risk and Cox hazards regression analysis for survival. We found that compared with the miRNA binding site rs2240688 AA genotype, AC + CC genotypes were associated with significantly increased GC risk (adjusted OR = 1.52, 95% CI = 1.09-2.13); for another miRNA binding site rs3130C>T SNP, the TT genotype was associated with significantly reduced GC risk (adjusted OR = 0.68, 95% CI = 0.48-0.97), compared with CC + CT genotypes. In all patients, the risk rs3130 TT variant genotype was significantly associated with overall survival (OS) (adjusted P(trend) = 0.016 and 0.007 under additive and recessive models, respectively). These findings suggest that these two CD133 miRNA binding site variants, rs2240688 and rs3130, may be potential biomarkers for genetic susceptibility to GC and possible predictors for survival in GC patients but require further validation by larger studies.

Clinically silent clonal cytogenetic abnormalities arising in patients treated for lymphoid neoplasms.

Newly emerged clonal cytogenetic abnormalities (CCA) in patients with prior cytotoxic therapy are highly concerning for therapy-related myeloid neoplasms (t-MN). In some patients, however, CCA appeared to be clinically "silent". In this study, we describe 25 patients who developed CCA after they received cytotoxic therapies for lymphoid neoplasms but never developed t-MN. These clinically "silent" CCA were always present as single abnormalities, often detected in a small subset of cells, and tended to disappear over time. We conclude that the occurrence of CCA is not always associated with t-MN. Clinical correlation is essential to guide a proper management of these patients.

B acute lymphoblastic leukemia with t(14;19)(q32;p13.1) involving IGH/EPOR: a clinically aggressive subset of disease.

B acute lymphoblastic leukemia (B-ALL) with t(14;19)(q32;p13.1), in which IGH and EPOR are juxtaposed, has been reported rarely. We describe the clinicopathological features of six patients, three men and three women, with a median age of 39 years. Initial and follow-up bone marrow samples were examined from each patient. The clinical, morphologic, and immunophenotypic results were compared with data obtained from conventional cytogenetic analysis and by using home-brew fluorescence in situ hybridization (FISH) probes for IGH at 14q32 and EPOR at 19p13.1. The bone marrow specimens were hypercellular (median 90%; range 80-100%), with a median blast count of 90% (range 60-93%). Immunophenotypic analysis performed by flow cytometry demonstrated a stable, precursor B-cell immunophenotype. The t(14;19)(q32;p13.1) was present in all cases with morphologic evidence of disease. The translocation was stable and appeared morphologically subtle on conventional karyotypic analysis. Detection was facilitated using FISH, which confirmed IGH/EPOR rearrangement in all cases. All patients received aggressive multiagent chemotherapy as part of a variety of regimens. Four of six patients achieved an initial complete remission, but all relapsed. At last follow-up, five of six patients had died of disease (median survival, 12 months after diagnosis). We conclude that B-ALL associated with t(14;19)(q32;p13.1) is a distinctive form of disease that is associated with younger patient age and an aggressive clinical course.

The miR-184 binding-site rs8126 T>C polymorphism in TNFAIP2 is associated with risk of gastric cancer.

BACKGROUND: TNFAIP2 is a crucial gene involved in apoptosis. Single nucleotide polymorphisms (SNPs) in its miRNA binding sites could modulate functions of the miRNA-target genes and thus risk of cancers. In this study, we investigated associations between potentially functional SNPs in the miRNA binding sites of the 3'UTR of TNFAIP2 and gastric cancer risk in a US population. METHODS: We conducted a case-control study of 301 gastric cancer patients and 313 cancer-free controls frequency-matched by age, sex and ethnicity. We genotyped four selected TNFAIP2 SNPs (rs8126 T>C, rs710100 G>A, rs1052912 G>A and rs1052823 G>T) and used the logistic regression analysis to assess associations of these SNPs with cancer risk. RESULTS: The rs8126 CC genotype was associated with a significantly elevated risk of gastric cancer (adjusted OR = 2.00, 95% CI = 1.09-3.64 and P = 0.024), compared with the combined rs8126 TT+TC genotypes, particularly in current drinkers. However, none of other TNFAIP2 SNPs was associated with risk of gastric cancer. CONCLUSIONS: Our data suggested that the TNFAIP2 miRNA binding site rs8126 T>C SNP may be a marker for susceptibility to gastric cancer, and this finding requires further validation by larger studies.

Proliferation and tumorigenesis of a murine sarcoma cell line in the absence of DICER1.

MicroRNAs are a class of short ~22 nucleotide RNAs predicted to regulate nearly half of all protein coding genes, including many involved in basal cellular processes and organismal development. Although a global reduction in miRNAs is commonly observed in various human tumors, complete loss has not been documented, suggesting an essential function for miRNAs in tumorigenesis. Here we present the finding that transformed or immortalized Dicer1 null somatic cells can be isolated readily in vitro, maintain the characteristics of DICER1-expressing controls and remain stably proliferative. Furthermore, Dicer1 null cells from a sarcoma cell line, though depleted of miRNAs, are competent for tumor formation. Hence, miRNA levels in cancer may be maintained in vivo by a complex stabilizing selection in the intratumoral environment.

In vivo structure-function analysis of human Dicer reveals directional processing of precursor miRNAs.

Dicer is an RNase III family endoribonuclease and haploinsufficient tumor suppressor that processes mature miRNAs from the 5' (5p) or 3' (3p) arm of hairpin precursors. In murine Dicer knockout fibroblasts, we expressed human Dicer with point mutations in the RNase III, helicase, and PAZ domains and characterized miRNA expression by Northern blot and massively parallel sequencing of small RNAs. We report that inactivation of the RNase IIIA domain results in complete loss of 3p-derived mature miRNAs, but only partial reduction in 5p-derived mature miRNAs. Conversely, inactivation of the RNase IIIB domain by mutation of D1709, a residue mutated in a subset of nonepithelial ovarian cancers, results in complete loss of 5p-derived mature miRNAs, including the tumor-suppressive let-7 family, but only partial reduction in 3p-derived mature miRNAs. Mutation of the PAZ domain results in global reduction of miRNA processing, while mutation of the Walker A motif in the helicase domain of Dicer does not alter miRNA processing. These results provide insight into the biochemical activity of human Dicer in vivo and, furthermore, suggest that mutation of the clinically relevant residue D1709 within the RNase IIIB results in a uniquely miRNA-haploinsufficient state in which the let-7 family of tumor suppressor miRNAs is lost while a complement of 3p-derived miRNAs remains expressed.

Efficacy of synthetic peptides RP-1 and AA-RP-1 against Leishmania species in vitro and in vivo.

Host defense peptides are naturally occurring molecules that play essential roles in innate immunity to infection. Based on prior structure-function knowledge, we tested two synthetic peptides (RP-1 and AA-RP-1) modeled on the conserved, microbicidal α-helical domain of mammalian CXCL4 platelet kinocidins. These peptides were evaluated for efficacy against Leishmania species, the causative agents of the group of diseases known as leishmaniasis. In vitro antileishmanial activity was assessed against three distinct Leishmania strains by measuring proliferation, metabolic activity and parasite viability after exposure to various concentrations of peptides. We demonstrate that micromolar concentrations of RP-1 and AA-RP-1 caused dose-dependent growth inhibition of Leishmania promastigotes. This antileishmanial activity correlated with rapid membrane disruption, as well as with a loss of mitochondrial transmembrane potential. In addition, RP-1 and AA-RP-1 demonstrated distinct and significant in vivo antileishmanial activities in a mouse model of experimental visceral leishmaniasis after intravenous administration. These results establish efficacy of RP-1 lineage synthetic peptides against Leishmania species in vitro and after intravenous administration in vivo and provide further validation of proof of concept for the development of these and related systemic anti-infective peptides targeting pathogens that are resistant to conventional antibiotics.