Primary Cutaneous Adenoid Cystic Carcinoma of the Back: A Case Report.

Adenoid cystic carcinoma (ACC) is a rare type of carcinoma that arises from the salivary glands. When ACC is present on the skin with no other primary site of malignancy in the body, it is termed primary cutaneous adenoid cystic carcinoma (PCACC). The only way to differentiate between ACC and other benign cutaneous masses is through the use of histopathology and immunohistochemistry. This case report describes a 67-year-old Asian female with a history of an epidermal inclusion cyst. She was seen in consultation with general surgery for the removal of a mass on her lower back. The initial excision's pathology revealed an ACC with perineural invasion. However, there were positive margins, as the mass was originally thought to be benign. Consequently, she underwent a second procedure for the total excision of the mass, resulting in subsequent negative margins. The patient was referred to radiation oncology; however, she ultimately opted to defer postoperative adjuvant radiation therapy, with the understanding that she would undergo biannual screening examinations.

Impaired dynamic X-chromosome inactivation maintenance in T cells is a feature of spontaneous murine SLE that is exacerbated in female-biased models.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a highly female-biased systemic autoimmune disease, but the molecular basis for this female bias remains incompletely elucidated. B and T lymphocytes from patients with SLE and female-biased mouse models of SLE exhibit features of epigenetic dysregulation on the X chromosome which may contribute to this strong female bias. We therefore examined the fidelity of dynamic X-chromosome inactivation maintenance (dXCIm) in the pathogenesis of two murine models of spontaneous lupus-NZM2328 and MRL/lpr-with disparate levels of female-bias to determine whether impaired dXCIm contributes to the female bias of disease. METHODS: CD23+ B cells and CD3+ T cells were purified from age-matched C57BL/6 (B6), MRL/lpr, and NZM2328 male and female mice, activated in vitro, and processed for Xist RNA fluorescence in situ hybridization, H3K27me3 immunofluorescence imaging, qPCR, and RNA sequencing analyses. RESULTS: The dynamic relocalization of Xist RNA and the canonical heterochromatin mark, H3K27me3, to the inactive X chromosome was preserved in CD23+ B cells, but impaired in activated CD3+ T cells from the MRL/lpr model (p < 0.01 vs. B6), and even more impaired in the heavily female-biased NZM2328 model (p < 0.001 vs. B6; p < 0.05 vs. MRL/lpr). RNAseq of activated T cells from NZM2328 mice revealed the female-biased upregulation of 32 X-linked genes distributed broadly across the X chromosome, many of which have roles in immune function. Many genes encoding Xist RNA-interacting proteins were also differentially expressed and predominantly downregulated, which may account for the observed mislocalization of Xist RNA to the inactive X chromosome. CONCLUSIONS: Although evident in T cells from both the MRL/lpr and NZM2328 models of spontaneous SLE, impaired dXCIm is more severe in the heavily female-biased NZM2328 model. The aberrant X-linked gene dosage in female NZM2328 mice may contribute towards the development of female-biased immune responses in SLE-prone hosts. These findings provide important insights into the epigenetic mechanisms contributing to female-biased autoimmunity.

Long-Term Safety, Efficacy, Indications, and Criteria of Arteriovenous Fistula Ligation Following Kidney Transplant: A Patient-Driven Approach.

OBJECTIVES: In patients with end-stage renal disease, arteriovenous fistulas are the standard of care to ensure long-term vascular access. Recent studies suggest some long-term posttransplant cardiac benefits and quality of life improvements in kidney transplant recipients due to arteriovenous fistula ligation. However, there are no guidelines regarding arteriovenous fistula management after transplant. Our study objective was to evaluate the long-term safety of arteriovenous fistula ligation and the frequency of returning to hemodialysis after ligation. MATERIALS AND METHODS: Retrospective chart review from February 2014 to December 2020 identified 578 adult patients who underwent successful kidney transplant at our center. Of these patients, 47 underwent subsequent arteriovenous fistula ligation. Both medically driven and patient-driven cases were assessed and approved by a transplant nephrology team with regard to allograft function and ligation suitability. RESULTS: Our results showed that, of the 47 renal transplant patients, 70.2% chose to undergo arteriovenous fistula ligation due to aneurysmal formation, 44.7% due to pain, and 14.9% due to high-output heart failure. In total, 68.1% of arteriovenous fistula ligations performed were primarily patient driven. There was an average follow-up of 2.9 years after ligation, with 1 unrelated reoperation and no returns to dialysis for all patients who underwent arteriovenous fistula ligation. CONCLUSIONS: In our study, the long-term risks of surgical complications and allograft impairment after ligation were negligible. As a result of our current findings and known positive cardiovascular benefit, patient-driven arteriovenous fistula ligation after kidney transplant should be routinely considered in patients with stable allograft function.

Loss of epigenetic modifications on the inactive X chromosome and sex-biased gene expression profiles in B cells from NZB/W F1 mice with lupus-like disease.

The mechanisms underlying the female-bias in autoimmunity are poorly understood. The contribution of genetic and epigenetic factors from the inactive X chromosome (Xi) are beginning to emerge as critical mediators of autoimmunity in females. Here, we ask how epigenetic features of the Xi change during disease development in B cells from the NZB/W F1 spontaneous mouse model of lupus, which is female-biased. We find that Xist RNA becomes increasingly mislocalized from the Xi with disease onset. While NZB/W F1 naïve B cells have H3K27me3 foci on the Xi, which are missing from healthy C57BL/6 and BALB/c mice, these foci are progressively lost in stimulated B cells during disease. Using single-molecule RNA FISH, we show that the X-linked gene Tlr7 is biallelically expressed in ~20% of NZB/W F1 B cells, and that the amount of biallelic expression does not change with disease. We also present sex-specific gene expression profiles for diseased NZB/W F1 B cells, and find female-specific upregulation of 20 genes, including the autoimmunity-related genes Cxcl13, Msr1, Igj, and Prdm1. Together, these studies provide important insight into the loss of epigenetic modifications from the Xi and changes with gene expression in a mouse model of female-biased SLE.

(Poly)cationic λ3-Iodane Mediated Oxidative Ring Expansion of Secondary Alcohols.

Herein, we report a simplified approach to the synthesis of medium-ring ethers through the electrophilic activation of secondary alcohols with (poly)cationic λ3-iodanes (N-HVI). Excellent levels of selectivity are achieved for C-O bond migration over established α-elimination pathways, enabled by the unique reactivity of a novel 2-OMe-pyridine-ligated N-HVI. The resulting HFIP-acetals are readily derivatized with a range of nucleophiles, providing a versatile functional handle for subsequent manipulations. The utility of this methodology for late-stage natural product derivatization was also demonstrated, providing a new tool for diversity-oriented synthesis and complexity-to-diversity (CTD) efforts. Preliminary mechanistic investigations reveal a strong effect of alcohol conformation on reactive pathway, thus providing a predictive power in the application of this approach to complex molecule synthesis.

Diversity of Epigenetic Features of the Inactive X-Chromosome in NK Cells, Dendritic Cells, and Macrophages.

In females, the long non-coding RNA Xist drives X-chromosome Inactivation (XCI) to equalize X-linked gene dosage between sexes. Unlike other somatic cells, dynamic regulation of Xist RNA and heterochromatin marks on the inactive X (Xi) in female lymphocytes results in biallelic expression of some X-linked genes, including Tlr7, Cxcr3, and Cd40l, implicated in sex-biased autoimmune diseases. We now find that while Xist RNA is dispersed across the nucleus in NK cells and dendritic cells (DCs) and partially co-localizes with H3K27me3 in bone marrow-derived macrophages, it is virtually absent in plasmacytoid DCs (p-DCs). Moreover, H3K27me3 foci are present in only 10-20% of cells and we observed biallelic expression of Tlr7 in p-DCs from wildtype mice and NZB/W F1 mice. Unlike in humans, mouse p-DCs do not exhibit sex differences with interferon alpha production, and interferon signature gene expression in p-DCs is similar between males and females. Despite the absence of Xist RNA from the Xi, female p-DCs maintain dosage compensation of six immunity-related X-linked genes. Thus, immune cells use diverse mechanisms to maintain XCI which could contribute to sex-linked autoimmune diseases.