Racial Disparities in Surgical Treatment of Obstructive Sleep Apnea.

Objective: Determine risk factors for failure to receive surgical treatment among patients with obstructive sleep apnea. Study Design: Population-based observational longitudinal cohort study. Setting: Population-based database. Methods: Multivariate analysis of 500,792 individuals with obstructive sleep apnea from Optum's deidentified Clinformatics Data Mart database (2004-2018). Results: Black race, increased age, diabetes, atrial fibrillation, obesity, and congestive heart failure were independently associated with a decreased rate of surgery for obstructive sleep apnea. Asian race, hypertension, arrhythmias other than atrial fibrillation, pulmonary disease, and liver disease were independently associated with an increased rate of surgery for obstructive sleep apnea. Conclusion: Racial disparities in health outcomes related to health care access and in economic resources have an enormous impact on public health and social equity. We found differences in rates of surgery for obstructive sleep apnea based on race. These data are consistent with others demonstrating disparities in medical treatment of sleep apnea with positive pressure and underline a need for a change in awareness and treatment in these populations.

Accessioning and automation compatible anterior nares swab design.

The COVID-19 pandemic has resulted in an unparalleled need for viral testing capacity across the world and is a critical requirement for successful re-opening of economies. The logistical barriers to near-universal testing are considerable. We have designed an injection molded polypropylene anterior nares swab, the Rhinostic, with a screw cap integrated into the swab handle that is compatible with fully automated sample accessioning and processing. The ability to collect and release both human and viral material is comparable to that of several commonly used swabs on the market. SARS-CoV-2 is stable on dry Rhinostic swabs for at least 3 days, even at 42 °C, and elution can be achieved with small volumes. To test the performance of the Rhinostic in patients, 119 samples were collected with Rhinostic and the positive and negative determinations were 100 % concordant with samples collected using Clinical Laboratory Improvement Amendments (CLIA) use approved nasal swabs at a clinical lab. The Rhinostic swab and barcoded tube set can be produced, sterilized, and packaged cost effectively and is designed to be adopted by clinical laboratories using automation to increase throughput and dramatically reduce the cost of a standard SARS-CoV-2 detection pipeline.

Translucent Customized Cranial Implants Made of Clear Polymethylmethacrylate: An Early Outcome Analysis of 55 Consecutive Cranioplasty Cases.

BACKGROUND: Large skull reconstruction, with the use of customized cranial implants, restores cerebral protection, physiologic homeostasis, and one's preoperative appearance. Cranial implants may be composed of either bone or a myriad of alloplastic biomaterials. Recently, patient-specific cranial implants have been fabricated using clear polymethylmethacrylate (PMMA), a visually transparent and sonolucent variant of standard opaque PMMA. Given the new enhanced diagnostic and therapeutic applications of clear PMMA, we present here a study evaluating all outcomes and complications in a consecutive patient series. METHODS: A single-surgeon, retrospective, 3-year study was conducted on all consecutive patients undergoing large cranioplasty with clear PMMA implants (2016-2019). Patients who received clear PMMA implants with embedded neurotechnologies were excluded due to confounding variables. All outcomes were analyzed in detail and compared with previous studies utilizing similar alloplastic implant materials. RESULTS: Fifty-five patients underwent cranioplasty with customized clear PMMA implants. Twenty-one (38%) were performed using a single-stage cranioplasty method (ie, craniectomy and cranioplasty performed during the same operation utilizing a prefabricated, oversized design and labor-intense, manual modification), whereas the remaining 34 (62%) underwent a standard, 2-stage reconstruction (craniectomy with a delayed surgery for cranioplasty and minimal-to-no implant modification necessary). The mean cranial defect size was 101.8 cm. The mean follow-up time was 9 months (range, 1.5-39). Major complications requiring additional surgery occurred in 7 patients (13%) consisting of 2 (4%) cerebrospinal fluid leaks, 2 (4%) epidural hematomas, and 3 (4%) infections. In addition, 3 patients developed self-limiting or nonoperative complications including 2 (4%) with new onset seizures and 1 (2%) with delayed scalp healing. CONCLUSIONS: This is the first reported consecutive case series of cranioplasty reconstruction using customized clear PMMA implants, demonstrating excellent results with regard to ease of use, safety, and complication rates well below published rates when compared with other alloplastic materials. Clear PMMA also provides additional benefits, such as visual transparency and sonolucency, which is material specific and unavailable with autologous bone. Although these early results are promising, further studies with multicenter investigations are well justified to evaluate long-term outcomes.

B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity.

The antibody gene mutator activation-induced cytidine deaminase (AID) promiscuously damages oncogenes, leading to chromosomal translocations and tumorigenesis. Why nonimmunoglobulin loci are susceptible to AID activity is unknown. Here, we study AID-mediated lesions in the context of nuclear architecture and the B cell regulome. We show that AID targets are not randomly distributed across the genome but are predominantly grouped within super-enhancers and regulatory clusters. Unexpectedly, in these domains, AID deaminates active promoters and eRNA(+) enhancers interconnected in some instances over megabases of linear chromatin. Using genome editing, we demonstrate that 3D-linked targets cooperate to recruit AID-mediated breaks. Furthermore, a comparison of hypermutation in mouse B cells, AID-induced kataegis in human lymphomas, and translocations in MEFs reveals that AID damages different genes in different cell types. Yet, in all cases, the targets are predominantly associated with topological complex, highly transcribed super-enhancers, demonstrating that these compartments are key mediators of AID recruitment.

Loss of nuclear PTEN in HCV-infected human hepatocytes.

BACKGROUND: Hepatitis C virus (HCV) infection is a major risk factor for chronic hepatitis and hepatocellular carcinoma (HCC); however, the mechanism of HCV-mediated hepatocarcinogenesis is not well understood. Insufficiency of PTEN tumor suppressor is associated with more aggressive cancers, including HCC. We asked whether viral non-coding RNA could initiate oncogenesis in HCV infected human hepatocytes. The results presented herein suggest that loss of nuclear PTEN in HCV-infected human hepatocytes results from depletion of Transportin-2, which is a direct target of viral non-coding RNA, vmr11. METHODS: The intracellular distribution of PTEN in HCV-infected cells was monitored by immunostaining and Western blots of nuclear and cytoplasmic proteins. Effects of PTEN depletion were examined by comparing expression arrays of uninfected cells with either HCV-infected or vmr11-transfected cells. Target genes suggested by array analyses were validated by Western blot. The influence of nuclear PTEN deficiency on virus production was determined by quantitative analysis of HCV genomic RNA in culture media of infected hepatocytes. RESULTS: Import of PTEN to the nucleus relies on the interaction of Transportin-2 and PTEN proteins; we show that depletion of Transportin-2 by HCV infection or by the introduction of vmr11 in uninfected cells results in reduced nuclear PTEN. In turn, nuclear PTEN insufficiency correlates with increased virus production and the induction of γ-H2AX, a marker of DNA double-strand breaks and genomic instability. CONCLUSION: An HCV-derived small non-coding RNA inhibits Transportin-2 and PTEN translocation to the nucleus, suggesting a direct viral role in hepatic oncogenesis.