Divergent total syntheses of pyrroloiminoquinone alkaloids enabled by the development of a Larock/Buchwald-Hartwig annulation/cyclization.

Pyrroloiminoquinone alkaloids are a large class of natural products that display a wide range of biological activities. Synthetic approaches to these natural products typically rely on a common late-stage C10-oxygenated pyrroloiminoquinone intermediate, but these strategies often lead to lengthy synthetic sequences that are not amenable to divergent syntheses. We devised an alternative approach aimed at the early introduction of the C10 nitrogen, which we hypothesized would enable late-stage diversification.

Tertiary Amine Coupling by Oxidation for Selective Labeling of Dimethyl Lysine Post-Translational Modifications.

Lysine dimethylation (Kme) is a crucial post-translational modification (PTM) that regulates biological processes and is implicated in diseases. There is significant interest in globally identifying these methylation marks. Unfortunately, this remains challenging due to the lack of robust technologies for selectively labeling Kme.

Retzius-sparing vs. posterior urethral suspension: similar early-phase post-robotic radical prostatectomy continence outcomes.

Stress urinary incontinence (SUI) is a risk of robotic-assisted radical prostatectomy (RP) which can be a frustrating problem for both surgeons and patients. We aim to compare short-term continence outcomes between patients undergoing Retzius Sparing RP (RS-RP) and those undergoing standard RP with the inclusion of a PUS suture technique and suprapubic tube (PUS-RP). A retrospective review of 105 consecutive patients who underwent RP was performed, comparing patients who underwent RS-RP and PUS-RP.

Patient-Reported Outcomes for Robot-Assisted Laparoscopic Extravascular Renal Vein Stent Placements for Nutcracker Syndrome.

Nutcracker phenomenon is the compression of the left renal vein between the superior mesenteric artery (SMA) and the abdominal aorta. Nutcracker syndrome refers to the presence of nutcracker phenomenon with symptoms. Between 2016 and 2022, we performed 18 robot-assisted laparoscopic extravascular renal vein stent (RALERVS) placements.

Total Synthesis of Aleutianamine.

Aleutianamine is a recently isolated pyrroloiminoquinone natural product that displays potent and selective biological activity toward human pancreatic cancer cells with an IC of 25 nM against PANC-1, making it a potential candidate for therapeutic development. We report a synthetic approach to aleutianamine wherein the unique [3.3.

Histone H3 E50K mutation confers oncogenic activity and supports an EMT phenotype.

Sequencing of human patient tumors has identified recurrent missense mutations in genes encoding core histones. We report that mutations that convert histone H3 amino acid 50 from a glutamate to a lysine (H3E50K) support an oncogenic phenotype in human cells. Expression of H3E50K is sufficient to transform human cells as evidenced by a dramatic increase in cell migration and invasion, and a statistically significant increase in proliferation and clonogenicity.

Predictors of urinary outcomes following robotic-assisted laparoscopic prostatectomy.

Introduction: Incontinence and urgency are common after prostatectomy. The University of Virginia prostatectomy functional outcomes program (PFOP) was developed to comprehensively assess and optimise continence outcomes following robotic-assisted laparoscopic prostatectomy (RALP). Patients are prospectively evaluated by a Female Pelvic Medicine and Reconstructive Surgery specialist.

Chemical sensors for imaging total cellular aliphatic aldehydes in live cells.

Aliphatic aldehydes are reactive electrophilic carbonyls that cross-link with DNA and proteins leading to cellular toxicity and disease pathogenesis. This toxicity is due to the cooperative effect of multiple aldehydes a common mechanism. Therefore, live-cell imaging of total aliphatic aldehydes, small-to-long chain (C-C), is highly desired to decipher their physiological and pathological functions.

Comparison of In-person FPMRS-directed Pelvic Floor Therapy Program Versus Unsupervised Pelvic Floor Exercises Following Prostatectomy.

Objective: To compare comprehensive continence outcomes in patients receiving pelvic floor muscle training (PFMT) vs standard unsupervised home pelvic floor exercise therapy (UPFE).

Methods: As part of the UVA prostatectomy functional outcomes program, participating patients complete a 12-month PFMT program under FPMRS specialist supervision. We performed a retrospective review of prospectively collected longitudinal outcomes in patients receiving PFMT vs UPFE through 12-month follow-up.

Longitudinal urgency outcomes following robotic-assisted laparoscopic prostatectomy.

Purpose: Stress urinary incontinence (SUI) is a well-known adverse outcome following robotic-assisted laparoscopic prostatectomy (RALP). Although postoperative SUI has been extensively studied, little focus has been placed on understanding the natural history and impact of urgency symptoms following RALP. The UVA prostatectomy functional outcomes program (PFOP) was developed to comprehensively assess and optimize continence outcomes following RALP.

Obstetric and Perinatal Outcomes following Ovulation Induction and Unassisted Pregnancies in the Same Mother.

Objective: We aimed to assess whether ovulation induction treatments affect obstetric and neonatal outcomes.

Study Design: This was a historic cohort study of deliveries in a single university-affiliated medical center between November 2008 and January 2020. We included women who had one pregnancy following ovulation induction and one unassisted pregnancy.

Targeting MLL Methyltransferases Enhances the Antitumor Effects of PI3K Inhibition in Hormone Receptor-positive Breast Cancer.

Unlabelled: The high frequency of aberrant PI3K pathway activation in hormone receptor-positive (HR) breast cancer has led to the development, clinical testing, and approval of the p110α-selective PI3K inhibitor alpelisib. The limited clinical efficacy of alpelisib and other PI3K inhibitors is partially attributed to the functional antagonism between PI3K and estrogen receptor (ER) signaling, which is mitigated via combined PI3K inhibition and endocrine therapy. We and others have previously demonstrated chromatin-associated mechanisms by which PI3K supports cancer development and antagonizes ER signaling through the modulation of the H3K4 methylation axis, inhibition of KDM5A promoter H3K4 demethylation and KMT2D/MLL4-directed enhancer H3K4 methylation.

Complex Foley Catheter Placement After Radical Prostatectomy.

Objective: To describe a method for replacement of a dislodged critical urethral foley catheter following a robotic- assisted laparoscopic radical prostatectomy.

Background: Following robotic-assisted laparoscopic radical prostatectomy (RALP), a bladder drainage via catheter is necessary to allow for proper healing of the urethrovesical anastomosis. In most cases, this is done using a transurethral foley catheter.

The effect of SARS-CoV-2 mRNA vaccination on AMH concentrations in infertile women.

Research Question: Does SARS-CoV-2 mRNA vaccination affect the ovarian reserve of infertile women undergoing IVF?

Design: This was a prospective observational study at a single university-affiliated IVF unit that included infertile women aged 18-44 years who were undergoing IVF/intracytoplasmic sperm injection between November 2020 and September 2021, had received two doses of SARS-CoV-2 mRNA vaccination and had undergone measurement of baseline anti-Müllerian hormone (AMH) concentration within the 12 months preceding their recruitment. AMH concentrations before and after vaccination were evaluated and compared.

Results: Overall, 31 women were included in the study.

Can endocrine characteristics of early pregnancy following natural cycle cryopreserved embryo transfer predict live birth?

Research Question: Can serial measurements of serum oestradiol, progesterone and β-human chorionic gonadotrophin (HCG) concentrations, starting from the day of the first positive pregnancy test, predict live birth after natural cycle frozen-thawed embryo transfer (NC-FET)?

Design: This was a historical cohort study of women with a positive pregnancy test following NC-FET, between March 2009 and January 2020. Serum β-HCG, oestradiol and progesterone concentrations were measured on the day of the first pregnancy test and 48 and 96 h later. Pregnancies resulting in a live birth were compared with non-viable pregnancies.

Prediction, assessment, and management of suboptimal GnRH agonist trigger: a systematic review.

Purpose: This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa triggering, and available options for prevention and management of suboptimal response.

Methods: PubMed, Google Scholar, Medline, and the Cochrane Library were searched for keywords related to GnRHa triggering, and peer-reviewed articles from January 2000 to September 2021 included.

Results: Thirty-seven studies were included in the review.

Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine.

Proteome profiling by activated esters identified >9000 ligandable lysines but they are limited as covalent inhibitors due to poor hydrolytic stability. Here we report our efforts to design and discover a new series of tunable amine-reactive electrophiles (TAREs) for selective and robust labeling of lysine. The major challenges in developing selective probes for lysine are the high nucleophilicity of cysteines and poor hydrolytic stability.

Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement.

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up.

Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis.

Background: Spontaneous ovulation during a natural menstrual cycle is frequently used for timing frozen embryo transfer (FET). Nevertheless, it remains unclear whether or not women should receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET).

Objective And Rationale: The aim of this systematic review and meta-analysis was to study whether the administration of LPS improves the reproductive outcome following NC-FET.

Future fertility of patients with zero oocytes yield in their first IVF cycle attempt.

Purpose: We aim to estimate the future fertility of patient undergoing their first IVF cycle attempt with no oocyte retrieved, and to identify factors that might predict those who will conceive in subsequent IVF cycle attempt.

Methods: A cohort retrospective study of all consecutive women attending our IVF unit, for their first IVF cycle attempt, between January 2013 to December 2019, who reached the ovum pick-up (OPU) stage with zero oocyte retrieved. Patients' characteristics and infertility-treatment-related variables in the first IVF cycle attempt were compared between those who conceived in a subsequent cycle and those who did not.

Impact of environmental toxin exposure on male fertility potential.

Idiopathic infertility is the most common individual diagnosis in male infertility, representing nearly 44% of cases. Research studies dating over the last half-century consistently demonstrate a decline in male fertility that is incompletely explained by obesity, known genetic causes, or diet and lifestyle changes alone. Human exposures have changed dramatically over the same time course as this fertility decline.

A randomized controlled trial of vaginal progesterone for luteal phase support in modified natural cycle - frozen embryo transfer.

Objective: Our aim was to study whether luteal phase support (LPS) increases the live-birth rate (LBR) in women undergoing modified natural cycle (mNC) frozen-thawed embryo transfer (FET).

Methods: In a randomized controlled trial, conducted at a university-affiliated tertiary medical center, a total of 59 patients aged 18-45 years, underwent mNC-FET. FET was performed in mNC following ovulation triggering by hCG.