RESUMO
Host mitochondrial association (HMA) is a well-known phenomenon during Toxoplasma gondii infection of the host cell. The T. gondii locus mitochondrial association factor 1 (MAF1) is required for HMA and MAF1 encodes distinct paralogs of secreted dense granule effector proteins, some of which mediate the HMA phenotype (MAF1b paralogs drive HMA; MAF1a paralogs do not). To identify host proteins required for MAF1b-mediated HMA, we performed unbiased, label-free quantitative proteomics on host cells infected with type II parasites expressing MAF1b, MAF1a, and an HMA-incompetent MAF1b mutant. Across these samples, we identified â¼1,360 MAF1-interacting proteins, but only 13 that were significantly and uniquely enriched in MAF1b pull-downs. The gene products include multiple mitochondria-associated proteins, including those that traffic to the mitochondrial outer membrane. Based on follow-up endoribonuclease-prepared short interfering RNA (esiRNA) experiments targeting these candidate MAF1b-targeted host factors, we determined that the mitochondrial receptor protein TOM70 and mitochondria-specific chaperone HSPA9 were essential mediators of HMA. Additionally, the enrichment of TOM70 at the parasitophorous vacuole membrane interface suggests parasite-driven sequestration of TOM70 by the parasite. These results show that the interface between the T. gondii vacuole and the host mitochondria is characterized by interactions between a single parasite effector and multiple target host proteins, some of which are critical for the HMA phenotype itself. The elucidation of the functional members of this complex will permit us to explain the link between HMA and changes in the biology of the host cell.
Assuntos
Interações Hospedeiro-Parasita , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Toxoplasma/fisiologia , Toxoplasmose/metabolismo , Toxoplasmose/parasitologia , Proteínas de Transporte , Expressão Ectópica do Gene , Imunofluorescência , Interações Hospedeiro-Parasita/genética , Espectrometria de Massas , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Ligação Proteica , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Transporte Proteico , Interferência de RNA , RNA Interferente Pequeno/genética , Vacúolos/metabolismo , VirulênciaRESUMO
Purpose: This study aims to develop an accessible stepwise management algorithm for pediatric presentations of occipital condyle fractures (OCFs) based on a systematic review of the published literature regarding diagnostic evaluation, treatment, and outcomes. Methods: A systematic review of the literature was conducted on PubMed to locate English language studies reporting on the management of pediatric OCFs. Data extraction of clinical presentation, management strategies, imaging, and treatment outcome was performed. Results: A total of 15 studies reporting on 38 patients aged 18 years and younger presenting with OCFs were identified. Loss of consciousness (LOC), depressed level of consciousness, neck pain, decreased neck range of motion (ROM), and cranial nerve injury were the most common presenting symptoms. Diagnostic imaging included radiographs, computed tomography (CT) scans, magnetic resonance imaging (MRI), and functional radiographs to assess cervical stability. Treatment options varied and included soft collar, hard collar, and halo vest. All studies resulted in a complete healing of the OCF, with resolution of associated pain. Conclusion: The proposed treatment algorithm suggests a framework for the management of pediatric OCFs based on the available evidence (levels of evidence: 3, 4). This review of the literature indicated that a stepwise approach should be utilized in the management of isolated pediatric OCFs.
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This article explores the critical issue of underrepresentation in spine surgery, specifically addressing racial/ethnic diversity. The paper proposes actionable strategies to enhance diversity within spine surgery through early education and outreach, intentional mentorship and sponsorship, and addressing biases in recruitment and promotion processes. It emphasizes the importance of a supportive culture within spine surgery divisions and practices, advocating for a top-down approach to inclusivity, while underscoring the necessity of continuous evaluation and adaptation of diversity initiatives. By leveraging diverse perspectives, the field of spine surgery can better serve an increasingly heterogeneous population, ultimately improving patient care and healthcare outcomes.
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BACKGROUND AND OBJECTIVES: Health care providers' exposure to global surgical disparities is limited in current nursing and/or medical school curricula. For instance, global health is often associated with infectious diseases or maternal health without acknowledging the growing need for surgical care in low- and middle-income countries (LMICs). We propose an international virtual hackathon based on neurosurgical patient cases in under-resourced settings as an educational tool to bring awareness to global surgical disparities and develop relationships among trainees in different countries. METHODS: Participants were recruited through email listservs, a social media campaign, and prize offerings. A 3-day virtual hackathon event was administered, which included workshops, mentorship, keynote panels, and pitch presentations to judges. Participants were presented with real patient cases and directed to solve a barrier to their care. Surveys assessed participants' backgrounds and event experience. The hackathon was executed through Zoom at Harvard Innovation Lab in Boston, MA, on March 25 to 27, 2022. Participants included medical students, with additional participants from business, engineering, or current health care workers. RESULTS: Three hundred seven applications were submitted for 100 spots. Participants included medical students, physicians, nurses, engineers, entrepreneurs, and undergraduates representing 25 countries and 82 cities. Fifty-one participants previously met a neurosurgeon, while 39 previously met a global health expert, with no difference between LMIC and high-income countries' respondents. Teams spent an average of 2.75 hours working with mentors, and 88% of postevent respondents said the event was "very" or "extremely conducive" to networking. Projects fell into 4 categories: access, language barriers, education and training, and resources. The winning team, which was interdisciplinary and international, developed an application that analyzes patient anatomy while performing physical therapy to facilitate remote care and clinical decision-making. CONCLUSION: An international virtual hackathon can be an educational tool to increase innovative ideas to address surgical disparities in LMICs and establish early collaborative relationships with medical trainees from different countries.
Assuntos
Saúde Global , Neurocirurgia , Humanos , Neurocirurgia/educação , Países em Desenvolvimento , Procedimentos Neurocirúrgicos/educação , Neurocirurgiões/educaçãoRESUMO
Purpose: The purpose of this study is to develop an accessible step-wise management algorithm for the management of pediatric spinal osteoid osteomas (OOs) based on a systematic review of the published literature regarding the diagnostic evaluation, treatment, and outcomes following surgical resection. Methods: A systematic review of the literature was conducted on PubMed to locate English language studies reporting on the management of pediatric spinal OOs. Data extraction of clinical presentation, management strategies and imaging, and treatment outcomes were performed. Results: Ten studies reporting on 85 patients under the age of 18 years presenting with OOs were identified. Back pain was the most common presenting symptom, and scoliosis was described in 8 out of 10 studies, and radicular pain in 7 out of 10 studies. Diagnostic, intraoperative, and postoperative assessment included radiographs, computed tomography (CT) scans, magnetic resonance imaging (MRI), bone scans, and frozen section. Treatment options varied, including conservative management, open surgical resection with or without intraoperative imaging, and percutaneous image-guided treatment. All included studies described partial or complete resolution of pain in the immediate postoperative period. Conclusions: The proposed algorithm provides a suggested framework for management of pediatric spinal OOs based on the available evidence (levels of evidence: 3, 4). This review of the literature indicated that a step-wise approach should be utilized in the management of pediatric spinal OOs.