RESUMO
Muscle function is dependent on innervation by the correct motor nerves. Motor nerves are composed of motor axons which extend through peripheral tissues as a compact bundle, then diverge to create terminal nerve branches to specific muscle targets. As motor nerves approach their targets, they undergo a transition where the fasciculated nerve halts further growth then after a pause, the nerve later initiates branching to muscles. This transition point is potentially an intermediate target or guidepost to present specific cellular and molecular signals for navigation. Here we describe the navigation of the oculomotor nerve and its association with developing muscles in mouse embryos. We found that the oculomotor nerve initially grew to the eye three days prior to the appearance of any extraocular muscles. The oculomotor axons spread to form a plexus within a mass of cells, which included precursors of extraocular muscles and other orbital tissues and expressed the transcription factor Pitx2. The nerve growth paused in the plexus for more than two days, persisting during primary extraocular myogenesis, with a subsequent phase in which the nerve branched out to specific muscles. To test the functional significance of the nerve contact with Pitx2+ cells in the plexus, we used two strategies to genetically ablate Pitx2+ cells or muscle precursors early in nerve development. The first strategy used Myf5-Cre-mediated expression of diphtheria toxin A to ablate muscle precursors, leading to loss of extraocular muscles. The oculomotor axons navigated to the eye to form the main nerve, but subsequently largely failed to initiate terminal branches. The second strategy studied Pitx2 homozygous mutants, which have early apoptosis of Pitx2-expressing precursor cells, including precursors for extraocular muscles and other orbital tissues. Oculomotor nerve fibers also grew to the eye, but failed to stop to form the plexus, instead grew long ectopic projections. These results show that neither Pitx2 function nor Myf5-expressing cells are required for oculomotor nerve navigation to the eye. However, Pitx2 function is required for oculomotor axons to pause growth in the plexus, while Myf5-expressing cells are required for terminal branch initiation.
Assuntos
Músculos Oculomotores/inervação , Nervo Oculomotor/embriologia , Animais , Axônios/metabolismo , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Desenvolvimento Muscular , Fator Regulador Miogênico 5/metabolismo , Músculos Oculomotores/crescimento & desenvolvimento , Músculos Oculomotores/metabolismo , Nervo Oculomotor/metabolismo , Gravidez , Fatores de Transcrição/metabolismo , Proteína Homeobox PITX2RESUMO
Northern Nevada's most utilized emergency department (ED) could represent a locale of missed opportunity for human immunodeficiency virus (HIV) detection, as the ED serves as a source of primary care for many patients at risk for HIV infection. The authors conducted a retrospective chart review, through the electronic health record, evaluating new diagnoses of HIV between 2012 and 2017 within a single hospital system. An opportunity for prior detection of HIV in the hospital's adult ED, within the past 5 years, was recorded as a missed testing opportunity (MTO). Out of 46 new HIV diagnoses at this hospital for a 5-year period, 19 patients with at least one MTO were identified. Eight of these patients with an MTO were diagnosed with acquired immunodeficiency syndrome (AIDS) concomitant with detection of their HIV status. Encouraging earlier HIV detection in the ED could reduce transmission, mortality, and health care expenditures.
Assuntos
Infecções por HIV , Soropositividade para HIV , Adulto , Diagnóstico Precoce , Serviço Hospitalar de Emergência , Infecções por HIV/diagnóstico , Humanos , Programas de Rastreamento , Estudos RetrospectivosRESUMO
Health education is an important topic in high school given its lasting effect on learners. Medical students are in a unique position to deliver this curriculum as they can provide information from a relatable standpoint. Ten medical students created a health education program, The Healthier Nevada Project (HNVP), designed for high school students using four modules focused on adolescent public health concerns: substance use and addiction, exercise, personal relationships, and stress and mental health. The curriculum was administered to over 700 health class students at three schools in Reno, Nevada, U.S.A., from August 2019-March 2020. This cross-sectional study measured whether the modules increased students' comfort level, familiarity, and likelihood of discussing each topic with a healthcare provider. The method of evaluation was pre- and post-Likert scale surveys with 7-10 questions regarding students' understanding of each topic, knowledge of related resources, and likelihood of future discussions with healthcare providers. Linear regression analysis showed significant increases in mean scores (in all cases p < 0.0001) for all four modules after the training. The modules were adjusted for the cluster effect of School and showed no significant two-way interaction between pre- and post-survey, although overall differences between schools were present. These findings indicate that HNVP significantly increased students' knowledge, comfort, and likelihood of discussing each topic with a healthcare professional following module administration. Future efforts will aim to evaluate the long-term impact of HNVP on student behavior and evaluate if presenter type influences program success among adolescents.