Mycobacterium tuberculosis, the cause of human tuberculosis, and Mycobacterium marinum, a non-tubercular pathogen with a broad host range, require the ESX-1 secretion system for virulence. The ESX-1 system secretes proteins which cause phagosomal lysis within the macrophage via an unknown mechanism. As reported in R.E. Bosserman et al (Proc Natl Acad Sci U S A doi:10.1073/pnas.1710167114), we recently discovered that the ESX-1 system regulates gene expression in M. marinum This finding has been confirmed in M. tuberculosis in reports by C. Sala et al (PLoS Pathog 14 (12):e1007491. doi: 10.1371/journal.ppat.1007491) and A.M. Abdallah et al (PLoS One 14:e0211003, 2019, https://doi.org/10.1371/journal.pone.0211003). We further demonstrated that a feedback control mechanism connects protein secretion to WhiB6-dependent expression of the esx-1 genes via an unknown mechanism. Here, we connect protein secretion and gene expression by showing for the first time that specific ESX-1 substrates have dual functions inside and outside the mycobacterial cell. We demonstrate that the EspE and EspF substrates negatively control esx-1 gene expression in the M. marinum cytoplasm through the conserved WhiB6 transcription factor. We found that EspE and EspF are required for virulence and promote lytic activity independently of the major EsxA and EsxB substrates. We show that the dual functions of EspE and EspF are conserved in the orthologous proteins from M. tuberculosis. Our findings support a role for EspE and EspF in virulence that is independent of the EsxA and EsxB substrates, and demonstrate that ESX-1 substrates have a conserved role in regulating gene expression.

Medical errors can involve multiple team members. Few curricula are being developed to provide instruction on disclosing medical errors that include simulation training with interprofessional team disclosure. To explore more objective evidence for the value of an educational activity on team disclosure of errors, faculty developed and assessed the effectiveness of a multimodal educational activity for learning team‐based disclosure of a medical error. This study employed a methodological triangulation research design. Participants (N = 458) included students enrolled in academic programs at three separate institutions. The activity allowed students to practice team communication while: (1) discussing a medical error within the team; (2) planning for the disclosure of the error; and (3) conducting the disclosure. Faculty assessed individual student's change in knowledge and, using a rubric, rated the performance of the student teams during a simulation with a standardized family member (SFM). Students had a high level of preexisting knowledge and demonstrated the greatest knowledge gains in questions regarding the approach to disclosure (P < .001) and timing of an apology (P < .001). Both SFMs and individual students rated the team error disclosure behavior highly (rho = 0.54; P < .001). Most participants (more than 80%) felt the activity was worth their time and that they were more comfortable with disclosing a medical error as a result of having completed the activity. This activity for interprofessional simulation of team‐based disclosure of a medical error was effective for teaching students about and how to perform this type of important disclosure.

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Auditory neuropathy is a type of hearing loss. This is a case study that describes an 18 months old child presenting with hearing loss reported by his parents. The parents reported that although he exhibited signs of hearing loss, they were told by multiple experts that tests confirmed that he was not deaf. The child sometimes acted as if he was deaf and sometimes did not, which lead to confusion about additional diagnoses that might be included in the diagnosis. An early diagnosis of auditory neuropathy is time sensitive as early development of learning and language is more beneficial for the child. Listening to parents and understanding the subtleties that segregate the diagnosis of auditory neuropathy from auditory processing disorder, autism or other similar presentations is important in the diagnosis and treatment of auditory neuropathy in children.

Public interest in the analgesic potential of cannabinoids has grown, but there is no consensus regarding orthopedic applications. Available evidence was identified for cannabinoid use in arthritis, neuropathic pain, fibromyalgia, multiple sclerosis, and postoperative pain. Extracted information included the risks of preoperative use, associations with opioid dependence, and surgical complications. There is limited evidence for therapeutic benefit of cannabinoids in rheumatoid arthritis and fibromyalgia. Cannabinoids are not indicated for postoperative pain. Preoperative unregulated use has been linked with postoperative opioid dependence. Cannabinoids may be considered a second- or third-line treatment for analgesia for some orthopedic pathologies. [ Orthopedics . 2022;45(4):e183–e189.]