Chimeric CRISPR-CasX enzymes and guide RNAs for improved genome editing activity.

A compact protein with a size of <1,000 amino acids, the CRISPR-associated protein CasX is a fundamentally distinct RNA-guided nuclease when compared to Cas9 and Cas12a. Although it can induce RNA-guided genome editing in mammalian cells, the activity of CasX is less robust than that of the widely used S. pyogenes Cas9. Here, we show that structural features of two CasX homologs and their guide RNAs affect the R-loop complex assembly and DNA cleavage activity. Cryo-EM-based structural engineering of either the CasX protein or the guide RNA produced two new CasX genome editors (DpbCasX-R3-v2 and PlmCasX-R1-v2) with significantly improved DNA manipulation efficacy. These results advance both the mechanistic understanding of CasX and its application as a genome-editing tool.

Aesthetic outcome of intermediate closure versus intermediate closure followed by 2-octyl cyanoacrylate: A randomized evaluator-blinded split-wound comparative effectiveness trial.

BACKGROUND: Dermatologic surgeons are increasingly using surgical adhesives in their practice. Studies comparing sutured wounds to those that utilize a combination of suturing and skin adhesive have not been previously conducted. OBJECTIVE: To compare the cosmetic outcome and patient wound care satisfaction of an intermediate suture closure with an intermediate suture closure followed by the application of 2-octyl cyanoacrylate (2-OCA). METHODS: Fifty patients were enrolled in a randomized, evaluator-blinded, split-scar study. Following intermediate sutured closure of a surgical defect, one side of the wound was randomized to receive an additional application of 2-OCA. After 3 months, the scar was assessed using the POSAS tool and patients reported wound care preferences. RESULTS: As the primary outcome measure, the mean sum of observer POSAS was 12.80 for sutured closure alone versus 12.40 for sutured closures followed by 2-OCA (P = .49). LIMITATIONS: Single-center study of a relatively homogenous population. CONCLUSION: Although there were no significant differences in scar cosmesis, both patients and observers tended to prefer the side with an additional application of 2-OCA in most POSAS components, in overall opinion, and in patient wound care satisfaction. Dermatologic surgeons may add this to their practice without sacrificing scar outcomes or patient satisfaction.

Aesthetic outcome of running subcuticular suture versus running horizontal mattress suture in closure of linear wounds of the trunk and extremities: a randomized evaluator-blinded split-wound comparative effectiveness trial.

BACKGROUND: Both running horizontal mattress (HM) and running subcuticular (SQ) suturing techniques have been suggested to be superior to other running cuticular suturing techniques . These two techniques have not been directly compared. OBJECTIVE: To compare cosmetic outcomes between a running HM and a running SQ technique in a split scar model following linear closure of trunk and extremity defects. METHODS: Fifty patients were enrolled in a randomized, evaluator-blinded, split-scar study. One side of the surgical wound was randomized to receive one intervention (HM vs SQ) with the other side receiving the alternate intervention. The primary outcome was the POSAS score at a minimum of 3 months post-operatively. RESULTS: Observer POSAS sum of components was 19.49 and 17.76 for HM and SQ, respectively (p=0.14). The mean score for patient overall opinion was 4.71 for HM and 3.50 for the SQ technique (p=0.02). Overall opinion scores of evaluators were 3.87 and 3.29 for HM and SQ, respectively (p=0.03). LIMITATIONS: Single-center study of a relatively homogenous population. CONCLUSION: Although there was no significant difference in the sum of POSAS components between HM and SQ (p=0.14), both patients and evaluators had a superior overall opinion of the SQ-treated side (patient p=0.02, evaluator p=0.03).

Localized alopecic myxedema of the scalp.

Myxedema is a rare, cutaneous complication of autoimmune thyroid diseases that most often affects the anterior shins. Herein, we report a patient with a history of Graves disease and Hashimoto thyroiditis who presented with boggy, alopecic patches associated with scalp pruritus. Punch biopsies from these lesions showed increased interstitial mucin in the reticular dermis, consistent with localized myxedema. This report showcases a rare presentation of localized myxedema of the scalp, highlighting the diverse cutaneous manifestations of autoimmune thyroid diseases.