Nonbinary and Transgender Male Patient Preferences for Gender-Affirming Top Surgery.

BACKGROUND: This study aimed to identify patient preferences and outcomes of chest masculinization surgery in patients identifying as nonbinary versus transgender (trans-) males. METHODS: Patients who underwent chest masculinization (2003-2022) were included. Demographics, medical comorbidities, surgical approaches, complications, secondary procedures, and BODY-Q chest module survey responses were compared between cohorts. RESULTS: Three hundred two patients were included. Thirteen percent identified as nonbinary and 87% as trans-male. The most common surgical approach in both groups was double incision with free nipple-areola graft (63% vs 71%, P = 0.33). Nonbinary patients more frequently opted for double incision without free nipple areola graft compared to trans-male patients (18% vs 2.7%, P < 0.001). Other unique surgical requests of nonbinary patients included nipple areola preservation and small breast mound preservation (5.2%) and balance between losing bulk and achieving a more androgynous appearance (5.3%). The survey response rate was 31% (93/302). Both groups reported improved quality of life postoperatively (P = 0.16). Three nonbinary patients elected not to keep their nipple-areola complexes (P = 0.005). Trans-male patients were more likely to report having a male chest as very important for their gender identity (82% vs 95%, P = 0.043). Nonbinary patients were less likely to prefer small nipples (82% vs 95%, P = 0.033) and 18% stated that they preferred no nipples (vs 2.7% trans-male patients, P < 0.001). CONCLUSIONS: Nonbinary patients have distinct surgical preferences regarding nipple-areola complexes. Chest masculinization planning can differ for this group of patients compared to their trans-male counterparts.

miR-206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro.

miR-206, miR-1a-1, and miR-1a-2 are induced during differentiation of skeletal myoblasts and promote myogenesis in vitro. miR-206 is required for skeletal muscle regeneration in vivo. Although this miRNA family is hypothesized to play an essential role in differentiation, a triple knock-out (tKO) of the three genes has not been done to test this hypothesis. We report that tKO C2C12 myoblasts generated using CRISPR/Cas9 method differentiate despite the expected derepression of the miRNA targets. Surprisingly, their mitochondrial function is diminished. tKO mice demonstrate partial embryonic lethality, most likely due to the role of miR-1a in cardiac muscle differentiation. Two tKO mice survive and grow normally to adulthood with smaller myofiber diameter, diminished physical performance, and an increase in PAX7 positive satellite cells. Thus, unlike other miRNAs important in other differentiation pathways, the miR-206 family is not absolutely essential for myogenesis and is instead a modulator of optimal differentiation of skeletal myoblasts.

DNA replication in primary hepatocytes without the six-subunit ORC.

The six subunit ORC is essential for initiation of DNA replication in eukaryotes. Cancer cell-lines in culture can survive and replicate DNA replication after genetic inactivation of individual ORC subunits, ORC1, ORC2 or ORC5. In primary cells, ORC1 was dispensable in the mouse liver for endo-reduplication, but this could be explained by the ORC1 homolog, CDC6, substituting for ORC1 to restore functional ORC. Here, we have created mice with a conditional deletion of ORC2, which does not have a homolog. Although mouse embryo fibroblasts require ORC2 for proliferation, mouse hepatocytes synthesize DNA in cell culture and endo-reduplicate in vivo without ORC2. Mouse livers endo-reduplicate after simultaneous deletion of ORC1 and ORC2 both during normal development and after partial hepatectomy. Since endo-reduplication initiates DNA synthesis like normal S phase replication these results unequivocally indicate that primary cells, like cancer cell lines, can load MCM2-7 and initiate replication without ORC.

A taxonomy for cerebellar cavernous malformations: subtypes of cerebellar lesions.

OBJECTIVE: An anatomical taxonomy has been established to guide surgical approach selection for resecting brainstem and deep and superficial cerebral cavernous malformations (CMs). The authors propose a novel taxonomy for cerebellar CMs, introduce 6 distinct neuroanatomical subtypes, and assess their clinical outcomes. METHODS: This bi-institutional, 2-surgeon cohort study included 143 cerebellar CMs that were microsurgically treated over a 25-year period. The proposed taxonomy classifies cerebellar CMs into 6 subtypes on the basis of anatomical location as identified on preoperative MR imaging. Neurological outcomes were assessed using the modified Rankin Scale (mRS), and outcomes were compared among the subtypes, with favorable outcomes defined as mRS scores ≤ 2. RESULTS: A total of 143 cerebellar CMs were resected in 140 patients. The mean (SD) age was 42.3 (15.2) years; 86 (60%) of the cerebellar CMs were in women, and 57 (40%) were in men. Cerebellar subtypes were suboccipital (17%, 25/143); tentorial (9%, 13/143); petrosal (43%, 62/143); vermian (13%, 18/143); tonsillar (2%, 3/143); and deep nuclear (15%, 22/143). Overall, 78 of 143 (55%) cerebellar CMs presenting to a cerebellar surface were resected without tissue transgression, and the remaining CMs (65/143, 45%) required translobular or transsulcal approaches. Complete resection was achieved in 134 of 143 cases (94%). Favorable outcomes were achieved in 91% (129/141) of cases with follow-up at a mean (SD) follow-up duration of 37.4 (53.8) months. Relative outcomes were unchanged or improved relative to the preoperative baseline in 93% (131/141) of cases with follow-up, without differences between subtypes. CONCLUSIONS: Most cerebellar CMs are convexity lesions that do not require deep dissection. However, transsulcal and fissural approaches are used for those beneath the cerebellar surface to minimize tissue transgression and preserve associated function. Complete resection without any new deficit is accomplished in most patients. The proposed taxonomy for cerebellar CMs (suboccipital, tentorial, petrosal, vermian, tonsillar, and deep nuclear) guides the selection of craniotomy and approach to enhance patient safety and optimize neurological outcomes.

Distinct MUNC lncRNA structural domains regulate transcription of different promyogenic factors.

Many lncRNAs have been discovered using transcriptomic data; however, it is unclear what fraction of lncRNAs is functional and what structural properties affect their phenotype. MUNC lncRNA (also known as DRReRNA) acts as an enhancer RNA for the Myod1 gene in cis and stimulates the expression of other promyogenic genes in trans by recruiting the cohesin complex. Here, experimental probing of the RNA structure revealed that MUNC contains multiple structural domains not detected by prediction algorithms in the absence of experimental information. We show that these specific and structurally distinct domains are required for induction of promyogenic genes, for binding genomic sites and gene expression regulation, and for binding the cohesin complex. Myod1 induction and cohesin interaction comprise only a subset of MUNC phenotype. Our study reveals unexpectedly complex, structure-driven functions for the MUNC lncRNA and emphasizes the importance of experimentally determined structures for understanding structure-function relationships in lncRNAs.

In vitro heparinization of canine whole blood with low molecular weight heparin (dalteparin) significantly and dose-dependently prolongs heparinase-modified tissue factor-activated thromboelastography parameters and prothrombinase-induced clotting time.

BACKGROUND: Low-molecular-weight heparin (LMWH) is being used increasingly in veterinary medicine for both treatment and prophylaxis of thromboembolic disease, but no predictable patient-side method exists to monitor its effect. OBJECTIVES: The aim of this study was to evaluate thromboelastography (TEG) and prothombinase-induced clotting time (PiCT) assays for detecting hemostatic alterations following in vitro heparinization of canine whole blood with dalteparin (Fragmin). METHODS: Citrated whole-blood samples were collected from 7 clinically healthy dogs. Dalteparin was added at concentrations of 0, 0.156, 0.625, 1.25, and 2.5 U/mL of whole blood. TEG was performed using heparinase cups with tissue factor (TF, 1:50,000) and kaolin as activators. Reaction time (R), clotting time (K), angle (alpha), and maximum amplitude (MA) were recorded. PiCT and anti-FXa activity were measured in plasma. RESULTS: With TF, increasing concentrations of dalteparin significantly prolonged R and K and significantly decreased alpha and MA. K, alpha, and MA ratios were significantly different from baseline at all dalteparin concentrations and R was significantly different from baseline at concentrations of 0.625, 1.25, and 2.5 U/mL. With kaolin, only R was significantly different from baseline at dalteparin concentrations of 0.625 and 2.5 U/mL. PiCT detected dalteparin concentrations < or = 0.625 U/mL, with a good linear correlation (r(2)=.96, P<.0001). CONCLUSION: These results suggest that TF-activated TEG and PiCT assays should be further evaluated as promising new methods for evaluating the effect of LMWH, using doses in the recommended clinical range and prospective clinical studies.