Positive Outcomes of Optimizing Student–Preceptor Continuity in a Traditional Block Clerkship

Problem: Student–preceptor discontinuity during 3rd-year clerkships limits the quality and quantity of supervision, teaching, and feedback. Although longitudinal integrative clerkships increase continuity and are associated with improved student and preceptor experience, they require schoolwide curricular reform. Alternative innovations enhancing student–preceptor relationships within the constraints of a traditional block clerkship may demonstrate similar benefits. Intervention: We piloted a continuity-enhanced general pediatric ambulatory schedule during 2 consecutive clerkship blocks in 2013. Students in the continuity-enhanced model (n = 29) were assigned 1–3 primary clinic preceptors, whereas those in the traditional model (n = 30) worked with 5–8. Data were gathered from student assessments and anonymous student and preceptor surveys. We used t and Fisher's exact tests to compare the two groups and performed thematic analysis of free-text survey comments. Context: Our school utilizes a block clerkship model with approximately 30 students rotating through the pediatric clerkship every 8 weeks. During the 3-week ambulatory portion, students spend 8 half days in the general pediatric ambulatory clinic. At the conclusion of each clinic, attendings completed brief student evaluation cards. Traditionally, student and attending schedules were created independently, resulting in transient supervisory relationships and dissatisfaction with clinical engagement, feedback, and evaluation. Outcome: Seventy-three percent (43/59) of the students completed the survey. Ten general ambulatory attendings collectively completed 87.5% (35/40) of the monthly surveys. Continuity students received significantly more narrative evaluation comments (10.6 vs. 5.8, p <. 001) from general ambulatory clinic attendings and were more likely to have at least one general ambulatory clinic attending endorse being able to provide meaningful feedback and evaluation (n = 29, 100% vs. n = 20, 66.7%, p <. 001). Continuity students were also more likely to endorse being able to ask at least one of these attendings for a letter of recommendation (71.4% vs. 9.1%, p <. 001) and to have at least one general ambulatory clinic attending endorse being able to provide a meaningful letter of recommendation if asked (62.1% vs. 3.3%, p <. 001). Students (88.4%) and attendings (85.7%) preferred the continuity-enhanced schedule. The most frequent theme of both student and attending free-text survey remarks were relationships and assessment. Lessons Learned: Intentional scheduling of clerkship students to enhance preceptor continuity resulted in significant positive outcomes echoing the relationship-based educational benefits of longitudinal clerkships, particularly in regards to student assessment and feedback. Clerkship directors and other medical educators should consider implementing small changes within block clerkships to maximize student–preceptor continuity.     

Placental genomic risk scores and early neurodevelopmental outcomes

Tracing the early paths leading to developmental disorders is critical for prevention. In previous work, we detected an interaction between genomic risk scores for schizophrenia (GRSs) and early-life complications (ELCs), so that the liability of the disorder explained by genomic risk was higher in the presence of a history of ELCs, compared with its absence. This interaction was specifically driven by loci harboring genes highly expressed in placentae from normal and complicated pregnancies [G. Ursini et al., Nat. Med. 24, 792–801 (2018)]. Here, we analyze whether fractionated genomic risk scores for schizophrenia and other developmental disorders and traits, based on placental gene-expression loci (PlacGRSs), are linked with early neurodevelopmental outcomes in individuals with a history of ELCs. We found that schizophrenia’s PlacGRSs are negatively associated with neonatal brain volume in singletons and offspring of multiple pregnancies and, in singletons, with cognitive development at 1 y and, less strongly, at 2 y, when cognitive scores become more sensitive to other factors. These negative associations are stronger in males, found only with GRSs fractionated by placental gene expression, and not found in PlacGRSs for other developmental disorders and traits. The relationship of PlacGRSs with brain volume persists as an anlage of placenta biology in adults with schizophrenia, again selectively in males. Higher placental genomic risk for schizophrenia, in the presence of ELCs and particularly in males, alters early brain growth and function, defining a potentially reversible neurodevelopmental path of risk that may be unique to schizophrenia.

Understanding the deviations from normal trajectories of brain development may be crucial for predicting illness and for prevention. Epidemiological studies have consistently identified early antecedents, including complications during pregnancy (1–4) and delays in developmental milestones (5–8). The incidence of many developmental disorders tends to be higher in males (9), and risk is typically highly heritable (10). While rare and moderately penetrant genetic variations account for a minority of cases, genome-wide association studies (GWASs) show that most risk is attributable to common variants across the genome (11, 12). Genomic risk scores (GRSs) from GWASs allow a much greater prediction of liability of the disorder than single common variant genotypes, but GRSs per se are not useful in predicting individual risk (13).We previously identified an environmental context in early life in which genomic risk for schizophrenia may enhance disease susceptibility (14). We found that the liability of schizophrenia explained by genomic risk (that is, schizophrenia GRS, also referred to as polygenic risk score; PRS) was more than five times higher in individuals with a history of obstetrical complications (here, early-life complications; ELCs; i.e., during pregnancy, at labor/delivery, and early in neonatal life) compared with its absence (14). Such interaction was exclusive of the GRSs constructed from the loci with the most significant associations with schizophrenia (GRS1: GWAS P < 5 × 10⁻⁸; GRS2: GWAS P < 1 × 10⁻⁶). Genes in the GRS1 and GRS2 loci were more highly expressed in placental tissue compared with genes in GWAS loci not interacting with ELCs (GRS3 to 10); they were up-regulated in placentae from complicated pregnancies and strongly correlated within placenta with expression of immune response genes (14), consistent with previous evidence linking placenta, inflammation, and brain development (15, 16).To investigate the role of placenta biology in the interaction between schizophrenia GRSs and ELCs, we derived sets of GRSs based on single-nucleotide polymorphisms (SNPs) marking schizophrenia-GWAS loci containing genes highly expressed in placenta and differentially expressed in placentae from complicated compared with normal pregnancies (PlacGRSs; placental genomic risk scores) and also from the remaining GWAS loci (NonPlacGRSs; nonplacental genomic risk scores). We found that only PlacGRSs interacted with ELCs on schizophrenia-case control status, while NonPlacGRSs did not, implicating genes involved in placenta stress as driving the interaction between genomic risk and ELCs. These interactions were specifically related to placental gene expression, in that they were not detected when calculating GRSs based on SNPs marking loci highly expressed or epigenetically regulated in other tissues, including various adult and fetal tissues/embryonic cells, and fetal brain. Finally, we detected a much stronger enrichment of expression of the schizophrenia-risk genes in placentae from male compared with female offspring, suggesting a role of placenta in the higher incidence of schizophrenia in males (14).We here investigate whether placental genomic risk for schizophrenia as well as several other developmental disorders and traits is linked with early neurodevelopmental outcomes in individuals with a history of ELCs associated with placenta pathophysiology. Abundant evidence shows that ELCs have implications for early developmental trajectories, including brain size, intellectual development, and neuromotor function as well as for schizophrenia later in life (3, 5, 17–19). Based on these prior observations and our earlier findings (14), we hypothesized that schizophrenia PlacGRSs, in contrast to NonPlacGRSs, have a negative effect on early developmental outcomes, especially in males. Further consistent with our earlier findings, we hypothesized that this negative relationship is characteristic of the PlacGRSs constructed from the placental schizophrenia-GWAS loci with the strongest association with the disorder (PlacGRS1: GWAS P < 5 × 10⁻⁸; PlacGRS2: GWAS P < 1 × 10⁻⁶). We studied the relationship of PlacGRSs and NonPlacGRSs with brain volume in a unique sample of neonates who underwent MRI scanning shortly after birth, and analyzed the relationship with neurocognitive development at 1 and 2 y of age in the same subjects. Finally, we analyzed the relationship of PlacGRSs and NonPlacGRSs with brain volume in a sample of adult controls and patients with schizophrenia.     

Ca2+ influx through T- and L-type Ca2+ channels have different effects on myocyte contractility and induce unique cardiac phenotypes

T-type Ca(2+) channels (TTCCs) are expressed in the developing heart, are not present in the adult ventricle, and are reexpressed in cardiac diseases involving cardiac dysfunction and premature, arrhythmogenic death. The goal of this study was to determine the functional role of increased Ca(2+) influx through reexpressed TTCCs in the adult heart. A mouse line with cardiac-specific, conditional expression of the alpha1G-TTCC was used to increase Ca(2+) influx through TTCCs. alpha1G hearts had mild increases in contractility but no cardiac histopathology or premature death. This contrasts with the pathological phenotype of a previously studied mouse with increased Ca(2+) influx through the L-type Ca(2+) channel (LTCC) secondary to overexpression of its beta2a subunit. Although alpha1G and beta2a myocytes had similar increases in Ca(2+) influx, alpha1G myocytes had smaller increases in contraction magnitude, and, unlike beta2a myocytes, there were no increases in sarcoplasmic reticulum Ca(2+) loading. Ca(2+) influx through TTCCs also did not induce normal sarcoplasmic reticulum Ca(2+) release. alpha1G myocytes had changes in LTCC, SERCA2a, and phospholamban abundance, which appear to be adaptations that help maintain Ca(2+) homeostasis. Immunostaining suggested that the majority of alpha1G-TTCCs were on the surface membrane. Osmotic shock, which selectively eliminates T-tubules, induced a greater reduction in L- versus TTCC currents. These studies suggest that T- and LTCCs are in different portions of the sarcolemma (surface membrane versus T-tubules) and that Ca(2+) influx through these channels induce different effects on myocyte contractility and lead to distinct cardiac phenotypes.     

Arterial calcifications and osteoprotegerin in chronic hemodialysis patients: impact on 6-year survival

International Urology and Nephrology - The association between end-stage renal disease and cardiovascular mortality may be influenced through vascular alterations, in particular atherosclerosis and...     

Evidence of the immunomodulatory role of dual PI3K/mTOR inhibitors in transplantation: an experimental study in mice

The PI3K/mTOR signaling cascade is fundamental in T‐cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T‐cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T‐cell activities. Substantial adverse effects in long‐term clinical usage of rapamycin suggest the use of alternative treatments in restraining effector T‐cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative. Here we show that dual PI3K/mTOR PI‐103 and PKI‐587 inhibitors interfered IL‐2‐dependent responses in T‐cells. However, in contrast to the inhibitory effects in non‐Treg T‐cell proliferation and effector functions, dual inhibitors increased the differentiation, preferential expansion, and suppressor activity of iTregs. Rapamycin, PI‐103, and PKI‐587 targeted different signaling events and induced different metabolic patterns in primary T‐cells. Similar to rapamycin, in vivo administration of PI‐103 and PKI‐587 controlled effectively the immunological response against allogeneic skin graft. These results characterize specific regulatory mechanisms of dual PI3K/mTOR inhibitors in T‐cells and support their potential as a novel therapeutic option in transplantation.     

Pneumoconiose au noir de fumée

Résumé Les auteurs ont constanté chez 29 sujets sur 143 (20.3%) exposés au noir de fumée, des lésions de pneumoconiose du type p et q. La durée moyenne d'exposition a été de 19.1 ans. La pneumoconiose au noir de fumée est fréquement associée à l'emphysème généralisé ou circonscrit et à des troubles de la perfusion pulmonaire décelable par la scintigraphie. Les séquelles pleuro-pulmonaires tuberculeuses ont eu une fréquence de 27.2%, les lésions tuberculeuses actives étant absenteq. Du point de vue histopathologique on a signalé, dans un cas autopsié, un emphysème diffus et une réaction collagéneuse réduite mais systématique. Du côte immunologique, on a constanté une augmentation des valeurs d'IgA et la baisse des valeurs d'IgM, statistiquement significatives.     

A profile of registered nurses in rural and remote Canada.

Research on nursing practice issues in rural and remote areas of Canada is very limited. This report describes the method and initial results of a comprehensive survey of registered nurses (RNs) practising outside the commuting zones of large urban centres, designed to determine: who practises nursing in rural and remote Canada; the nature and scope of their nursing practice; and their satisfaction with their work, community, and practice supports. Using a mailed questionnaire with persistent follow-up, the data-collection frame included a stratified random sample of rural RNs and the full population of RNs who worked in the northern territories and outpost ("remote") settings. The analyses focus on regional comparisons of demographics and primary work settings and on provincial comparisons of satisfaction levels related to work and community. The survey is part of a larger multi-method project intended to inform policy on rural nursing practice in Canada.