A WEB-BASED CORE CURRICULUM TO MEET CERTIFICATION AND TRAINING NEEDS FOR MEDICAL RESIDENTS

To meet institutional requirements for resident education in a core curriculum, the UIC College of Medicine implemented an online educational program called the UIC Online Core Curriculum. The UIC residency is composed of 1,000 physicians in training in 60 programs at 18 training sites. Its size and distribution create substantial obstacles to classroom-based delivery. An online format offered a viable alternative to meet the college’s need to present uniform content, document participation, and confirm resident achievement while addressing the residents’ need for flexibility with the Internet’s anytime, anywhere availability. Development of an online core curriculum included a focus group of program directors, residents, medical directors, and other faculty who were asked to suggest course topics that met not only the "letter" of the requirement, but also the spirit of the general competencies. These discussions resulted in a list of 13 topics, or modules. In July 1999, a pilot study involving first year UIC residents demonstrated the feasibility of the program. The following year, all UIC residents began participating. In the past two years residents from other institutions have been added to the program, resulting in a current participant base of approximately 3,800 residents nationwide. An analysis of 2,544 anonymous end-of-module surveys demonstrates that most residents can effectively participate with minimal technical problems. Consistent with the "anytime-anywhere" approach to web-based instruction, residents complete the modules not only at home but also while at clinical and other university sites. Overall satisfaction as reported by residents is high, and the majority agrees that the material presented is useful. Based on findings to date, the online core curriculum is an efficient and cost-effective method of providing a required program to a large, distributed population of learners while maintaining a high level of participant satisfaction

Epidermal growth factor mediates spermatogonial proliferation in newt testis

The complex processes of spermatogenesis are regulated by various factors. The aim of the current study is to determine the effect of epidermal growth factor (EGF) on spermatogonial proliferation and clarify the mechanism causing the proliferation in newt testis. In the organ culture, EGF stimulated spermatogonial proliferation, but not their differentiation into spermatocytes. cDNA cloning identified 3 members of the EGF receptors, ErbB1, ErbB2, and ErbB4, in the testis. RT-PCR showed that all the receptors cloned were expressed in both Sertoli and germ cells at the spermatogonial stage. In the organ cultures with inhibitors for the EGF receptors, mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K), the EGF-induced spermatogonial proliferation was suppressed. Furthermore, when the organ culture was exposed to EGF, the expressions of stem cell factor (SCF), immunoglobulin-like domain containing neuregulin1 (Ig-NRG1), and ErbB4 mRNA were increased. These results suggested that, since the spermatogonia are sequestered within cysts by the blood-testis barrier consisted of Sertoli cells, EGF possibly mediates spermatogonial proliferation in an endocrine manner through the receptors including ErbB1, ErbB2, and ErbB4 expressed on Sertoli cells via activation of MAPK cascade or/and PI3K cascade by elevating the expressions of SCF, Ig-NRG1, and ErbB4

A de novo paradigm for male infertility

Funding Information: (DFG, CRU326) to C.F. and F.T. This project was also supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., by grants from the National Institutes of Health of the United States of America (R01HD078641 to D.F.C. and K.I.A., P50HD096723 to D.F.C.) and from the Biotechnology and Biological Sciences Research Council (BB/S008039/1) to D.J.E. Funding Information: We are grateful for the participation of all patients and their parents in this study. We thank Laurens van de Wiel (Radboudumc), Sebastian Judd-Mole (Monash University), Arron Scott and Bryan Hepworth (Newcastle University) for technical support, and Margot J Wyrwoll (University of Münster) for help with handling MERGE samples and data. This project was funded by The Netherlands Organization for Scientific Research (918-15-667) to J.A.V. as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. a grant from the Catherine van Tussenbroek Foundation to M.S.O. a grant from MERCK to R.S. a UUKi Rutherford Fund Fellowship awarded to B.J.H. and the German Research Foundation Clinical Research Unit “Male Germ Cells” Publisher Copyright: © 2022, The Author(s).De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10−5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10−4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.publishersversionpublishe

A de novo paradigm for male infertility

Genetics of Male Infertility Initiative (GEMINI) consortium: Donald F. Conrad, Liina Nagirnaja, Kenneth I. Aston, Douglas T. Carrell, James M. Hotaling, Timothy G. Jenkins, Rob McLachlan, Moira K. O’Bryan, Peter N. Schlegel, Michael L. Eisenberg, Jay I. Sandlow, Emily S. Jungheim, Kenan R. Omurtag, Alexandra M. Lopes, Susana Seixas, Filipa Carvalho, Susana Fernandes, Alberto Barros, João Gonçalves, Iris Caetano, Graça Pinto, Sónia Correia, Maris Laan, Margus Punab, Ewa Rajpert-De Meyts, Niels Jørgensen, Kristian Almstrup, Csilla G. Krausz & Keith A. Jarvi.De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10−5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10−4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.This project was funded by The Netherlands Organization for Scientific Research (918-15-667) to J.A.V. as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. a grant from the Catherine van Tussenbroek Foundation to M.S.O. a grant from MERCK to R.S. a UUKi Rutherford Fund Fellowship awarded to B.J.H. and the German Research Foundation Clinical Research Unit “Male Germ Cells” (DFG, CRU326) to C.F. and F.T. This project was also supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., by grants from the National Institutes of Health of the United States of America (R01HD078641 to D.F.C. and K.I.A., P50HD096723 to D.F.C.) and from the Biotechnology and Biological Sciences Research Council (BB/S008039/1) to D.J.E.info:eu-repo/semantics/publishedVersio