Requirement of Neuronal Ribosome Synthesis for Growth and Maintenance of the Dendritic Tree.

The nucleolus serves as a principal site of ribosome biogenesis but is also implicated in various non-ribosomal functions, including negative regulation of the pro-apoptotic transcription factor p53. Although disruption of the nucleolus may trigger the p53-dependent neuronal death, neurotoxic consequences of a selective impairment of ribosome production are unclear. Here, we report that in rat forebrain neuronal maturation is associated with a remarkable expansion of ribosomes despite postnatal down-regulation of ribosomal biogenesis. In cultured rat hippocampal neurons, inhibition of the latter process by knockdowns of ribosomal proteins S6, S14, or L4 reduced ribosome content without disrupting nucleolar integrity, cell survival, and signaling responses to the neurotrophin brain-derived neurotrophic factor. Moreover, reduced general protein synthesis and/or formation of RNA stress granules suggested diminished ribosome recruitment to at least some mRNAs. Such a translational insufficiency was accompanied by impairment of brain-derived neurotrophic factor-mediated dendritic growth. Finally, RNA stress granules and smaller dendritic trees were also observed when ribosomal proteins were depleted from neurons with established dendrites. Thus, a robust ribosomal apparatus is required to carry out protein synthesis that supports dendritic growth and maintenance. Consequently, deficits of ribosomal biogenesis may disturb neurodevelopment by reducing neuronal connectivity. Finally, as stress granule formation and dendritic loss occur early in neurodegenerative diseases, disrupted homeostasis of ribosomes may initiate and/or amplify neurodegeneration-associated disconnection of neuronal circuitries.

Association of Postoperative Sigmoid Sinus Occlusion and Cerebrospinal Fluid Leak in Translabyrinthine Surgery.

OBJECTIVE: To characterize the incidence of sigmoid sinus occlusion (SSO) following translabyrinthine (TL) surgery for posterior fossa tumor resection and determine the association with cerebrospinal fluid (CSF) leak. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. METHODS: Patients undergoing TL surgery for vestibular schwannoma from 2012 to 2020 were included. Demographic data, medical history, preoperative tumor length and volume, and postoperative complications including CSF leak were recorded. Neuroradiology review of postoperative magnetic resonance imaging was used to determine the presence or absence of flow through the sigmoid sinus. RESULTS: Of 205 patients undergoing TL, 21 (10.2%) experienced CSF leak postoperatively. Overall 56 (27%) demonstrated SSO on immediate postoperative magnetic resonance imaging. CSF leaks were more likely in those with SSO (19.6%) than those without SSO (6.7%; odds ratio, 3.54 [95% CI, 1.25-10.17]). Tumor volume and body mass index were not significantly associated with CSF leak. In total, 105 (51%) patients had some degree of sigmoid sinus thrombosis, but nonocclusive thrombosis was not associated with CSF leak. CONCLUSION: SSO after TL approaches is common and appears to be significantly associated with postoperative CSF leak development. Minimizing manipulation of the sigmoid sinus during TL surgery and compression after surgery may have a role in preventing CSF leak.

Women screened for breast cancer are dying from lung cancer: An opportunity to improve lung cancer screening in a mammography population.

OBJECTIVE: Lung cancer is the leading cancer killer in women, resulting in more deaths than breast, cervical and ovarian cancer combined. Screening for lung cancer has been shown to significantly reduce mortality, with some evidence that women may have a greater benefit. This study demonstrates that a population of women being screened for breast cancer may greatly benefit from screening for lung cancer. METHODS: Data from 18,040 women who were screened for breast cancer in 2015 at two imaging facilities that also performed lung screening were reviewed. A natural language-processing algorithm followed by a manual chart review identified women eligible for lung cancer screening by U.S. Preventive Services Task Force (USPSTF) criteria. A chart review of these eligible women was performed to determine subsequent enrollment in a lung screening program (2016-2019), current screening eligibility, cancer diagnoses and cancer-related outcomes. RESULTS: Natural language processing identified 685 women undergoing screening mammography who were also potentially eligible for lung screening based on age and smoking history. Manual chart review confirmed 251 were eligible under USPSTF criteria. By June 2019, 63 (25%) had enrolled in lung screening, of which three were diagnosed with screening-detected lung cancer resulting in zero deaths. Of 188 not screened, seven were diagnosed with lung cancer resulting in five deaths by study end. Four women received a diagnosis of breast cancer with no deaths. CONCLUSION: Women screened for breast cancer are dying from lung cancer. We must capitalize on reducing barriers to improve screening for lung cancer among high-risk women.

Unique Presentation of Hematuria in a Patient with Arterioureteral Fistula.

Active extravasation via an arterioureteral fistula (AUF) is a rare and life-threatening emergency that requires efficient algorithms to save a patient's life. Unfortunately, physicians may not be aware of its presence until the patient is in extremis. An AUF typically develops in a patient with multiple pelvic and aortoiliac vascular surgeries, prior radiation therapy for pelvic tumors, and chronic indwelling ureteral stents. We present a patient with a left internal iliac arterial-ureteral fistula and describe the evolution of management and treatment algorithms based on review of the literature.