Long noncoding RNA mediates stroke-induced neurogenesis.

Neurogenesis contributes to poststroke recovery. Long noncoding RNAs (lncRNAs) participate in the regulation of stem cell self-renewal and differentiation. However, the role of lncRNAs in stroke-induced neurogenesis remains unknown. In this study, we found that H19 was the most highly upregulated lncRNA in neural stem cells (NSCs) of the subventricular zone (SVZ) of rats subjected to focal cerebral ischemia. Deletion of H19 suppressed cell proliferation, promoted cell death, and blocked NSC differentiation. RNA sequencing analysis revealed that genes deregulated by H19 knockdown were those that are involved in transcription, apoptosis, proliferation, cell cycle, and response to hypoxia. H19 knockdown significantly increased the transcription of cell cycle-related genes including p27, whereas overexpression of H19 substantially reduced expression of these genes through the interaction with chromatin remodeling proteins EZH2 and SUZ12. Moreover, H19 regulated neurogenesis-related miRNAs. Inactivation of H19 in NSCs of ischemic rats attenuated spontaneous functional recovery after stroke. Collectively, our data provide novel insights into the epigenetic regulation of lncRNAs in stroke-induced neurogenesis.

Analysis of Faculty Gender and Race in Scholarly Achievements in Academic Neurology.

Background: Intersection of gender and race and/or ethnicity in academic medicine is understudied; we aim to understand these factors in relation to scholarly achievements for neurology faculty. Methods: Faculty from 19 US neurology departments completed a survey (2021-2022) to report rank, leadership positions, publications, funded projects, awards, and speaker invitations. Regression analyses examined effects of gender, race, and their intersectionality on these achievements. Women, Black/Indigenous/People of Color (BIPOC), and BIPOC women were comparator groups. Results: Four hundred sixty-two faculty responded: 55% women, 43% men; 31% BIPOC, 63% White; 21% BIPOC women, 12% BIPOC men, 36% White women, 31% White men. Men and White faculty are more likely to be full professors than women and BIPOC faculty. The number of leadership positions, funded projects, awards, and speaker invitations are significantly greater in White compared to BIPOC faculty. Relative to BIPOC women, the number of leadership positions is significantly higher among BIPOC men, White women, and White men. Publication numbers for BIPOC men are lower, number of funded projects and speaker invitations for White women are higher, and number of awards among White men and White women is higher compared to BIPOC women. Discussion: Our study highlights that inequities in academic rank, award number, funded projects, speakership invitations, and leadership roles disproportionately impacted BIPOC women. More studies are needed to evaluate gender and race and/or ethnicity intersectionality effects on faculty achievements, reasons for inequities, recognition, and potential solutions.

Utilization of teledermatology services for dermatological diagnoses during the COVID-19 pandemic.

Little is known about trends in teledermatology adoption and use for managing dermatologic patients, especially changes in use influenced by the COVID-19 pandemic. In this retrospective cohort study, we analyzed encounter data from the Healthjump dataset (containing electronic health record data from throughout the USA) for visits from November 2019 to July 2021 with a primary dermatology-related diagnosis. There was a striking rise in teledermatology use with the onset of the pandemic in February 2020, peaking in April 2020 with 2178 teledermatology encounters (32.8% of all encounters). Subsequently, teledermatology use waned. Most teledermatology care was delivered via synchronous means with little use of asynchronous or telephone communication. When compared to those with neoplastic skin diseases, patients with inflammatory skin diseases were more likely to be seen via teledermatology (OR 3.30, 95% CI 3.12-3.49). Certain demographic groups were less likely to receive care via teledermatology, such as men (compared with females, OR 0.76, 95% CI 0.74-0.78) and patients 65 and older (compared with those below 65, OR 0.59, 95% CI 0.57-0.62). Our work shows increased adoption of teledermatology at the onset of the COVID-19 pandemic with decreasing use over time. Future efforts are needed to ensure continued and expanded use of a valuable care modality to reach vulnerable populations.

Cost effectiveness of melanoma in situ resection and repair by dermatology compared to non-dermatology specialties at a single institution.

Melanoma-in-situ (MIS) is treated with surgical resection by many specialties. Dermatologists perform these procedures in outpatient settings while others often employ operating rooms and general anesthesia. We hypothesized that MIS managed by dermatology was less costly than that managed by other specialties. All cases of MIS treated at our institution over a 3-year period were evaluated retrospectively for demographic and clinical characteristics and categorized by treating specialty. Estimated cost information was determined using records of charges billed. The mean total cost for MIS treated with wide local excision (WLE) by dermatologists was $1089 (CI = $941-1237) versus all other specialties at $5172 (CI = $2419-7925) (p < 0.001). MIS treated with Mohs micrographic surgery and repaired by dermatology (mean = $2325, CI = $2241-2409) was also less expensive than MIS treated by other specialties with WLE (p < 0.001). The results suggest MIS is significantly less costly to patients and the health care system when treatment is performed by dermatologists compared to other surgical specialties. This is likely due to dermatologists performing the procedures in less expensive outpatient settings.

Cerebral endothelial cell derived small extracellular vesicles improve cognitive function in aged diabetic rats.

Small extracellular vesicles (sEVs) mediate cell-cell communication by transferring their cargo biological materials into recipient cells. Diabetes mellitus (DM) induces cerebral vascular dysfunction and neurogenesis impairment, which are associated with cognitive decline and an increased risk of developing dementia. Whether the sEVs are involved in DM-induced cerebral vascular disease, is unknown. Therefore, we studied sEVs derived from cerebral endothelial cells (CEC-sEVs) of aged DM rats (DM-CEC-sEVs) and found that DM-CEC-sEVs robustly inhibited neural stem cell (NSC) generation of new neuroblasts and damaged cerebral endothelial function. Treatment of aged DM-rats with CEC-sEVs derived from adult healthy normal rats (N-CEC-sEVs) ameliorated cognitive deficits and improved cerebral vascular function and enhanced neurogenesis. Intravenously administered N-CEC-sEVs crossed the blood brain barrier and were internalized by neural stem cells in the neurogenic region, which were associated with augmentation of miR-1 and -146a and reduction of myeloid differentiation primary response gene 88 and thrombospondin 1 proteins. In addition, uptake of N-CEC-sEVs by the recipient cells was mediated by clathrin and caveolin dependent endocytosis signaling pathways. The present study provides ex vivo and in vivo evidence that DM-CEC-sEVs induce cerebral vascular dysfunction and neurogenesis impairment and that N-CEC-sEVs have a therapeutic effect on improvement of cognitive function by ameliorating dysfunction of cerebral vessels and increasing neurogenesis in aged DM rats, respectively.

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy.

OBJECTIVES: CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin-methatrexate/ifusamide, etoposide, cytarabine) chemotherapy is commonly used to treat Burkitt lymphoma and in the HIV-negative population. Rituximab is often added with suggested survival benefits. Concerns over increased toxicity in an already immunocompromized population have prevented its routine addition in people living with HIV (PLWH). This study evaluated the effect on treatment-related toxicity and efficacy of adding rituximab to CODOX-M/IVAC chemotherapy in PLWH. DESIGN: Retrospective review of 91 PLWH (74 men) with Burkitt lymphoma treated in five London centers between 2003 and 2013. All patients received combination antiretroviral therapy. RESULTS: Forty-nine patients received CODOX-M/IVAC and 42 rituximab (R)-CODOX-M/R-IVAC. The addition of rituximab did not confer any significant increase in grade 3/4 toxicities including infections, mucositis, diarrhea, renal impairment, and tumor lysis syndrome. There was no significant difference in toxic deaths between groups (P = 0.14). The 2-year overall survival (OS) was greater for patients receiving rituximab {2-year OS 72% [95% confidence interval (CI) 0.22-0.92, hazard ratio 0.46] vs. 55% [95% CI 1.1-4.5, hazard ratio 2.2]; log-rank P = 0.04}. Similarly, the 2-year progression-free survival (PFS) was greater in the rituximab cohort [2-year PFS 81% (95% CI 0.21-0.99, hazard ratio 0.46) vs. 55% (95% CI 1.0-4.8, hazard ratio 2.2); log-rank P = 0.04]. CONCLUSION: Our multicenter analysis is the largest to date in this population and showed that the addition of rituximab to CODOX-M/IVAC chemotherapy confers no increase in toxicity and results in significantly improved OS and PFS in PLWH with Burkitt lymphoma who receive concomitant combination antiretroviral therapy.