Double strand breaks (DSBs) as indicators of genomic instability in PATRR-mediated translocations.

Genomic instability contributes to a variety of potentially damaging conditions, including DNA-based rearrangements. Breakage in the form of double strand breaks (DSBs) increases the likelihood of DNA damage, mutations and translocations. Certain human DNA regions are known to be involved in recurrent translocations, such as the palindrome-mediated rearrangements that have been identified at the breakpoints of several recurrent constitutional translocations: t(11;22)(q23;q11), t(17;22)(q11;q11) and t(8;22) (q24;q11). These breakpoints occur at the center of palindromic AT-rich repeats (PATRRs), which suggests that the structure of the DNA may play a contributory role, potentially through the formation of secondary cruciform structures. The current study analyzed the DSB propensity of these PATRR regions in both lymphoblastoid (mitotic) and spermatogenic cells (meiotic). Initial results found an increased association of sister chromatid exchanges (SCEs) at PATRR regions in experiments that used SCEs to assay DSBs, combining SCE staining with fluorescence in situ hybridization (FISH). Additional experiments used chromatin immunoprecipitation (ChIP) with antibodies for either markers of DSBs or proteins involved in DSB repair along with quantitative polymerase chain reaction to quantify the frequency of DSBs occurring at PATRR regions. The results indicate an increased rate of DSBs at PATRR regions. Additional ChIP experiments with the cruciform binding 2D3 antibody indicate an increased rate of cruciform structures at PATRR regions in both mitotic and meiotic samples. Overall, these experiments demonstrate an elevated rate of DSBs at PATRR regions, an indication that the structure of PATRR containing DNA may lead to increased breakage in multiple cellular environments.

Scapholunate Ligament: Comparing the Native Strength of the Ligament to an All-suture Anchor Construct.

Our aim was to compare the tensile strength of the native scapholunate ligament (SLL) with that of an all-suture anchor construct in a cadaveric model. The scaphoid and lunate were isolated, preserving all segments of the SLL. Using a servohydraulic testing machine, we increased the load until peak load-to-failure of the native SLL was reached in nine specimens (mean ± standard deviation, 273 ± 132 N). Using the same specimens, two JuggerKnot 1.4-mm suture anchors (Zimmer Biomet) were placed into the lunate and tensioned through transosseous tunnels in the scaphoid. Sutures were tied over the radial nonarticular aspect of the scaphoid. Load-to-failure testing was repeated. The mean peak load-to-failure for the all-suture anchor constructs was 172 ± 59 N versus 231 ± 117 N for the native group (p = 0.157). This represents approximately 75% of the native ligament strength. (Journal of Surgical Orthopaedic Advances 29(3):169-172, 2020).

Prevention of Postoperative Constipation in Urogynecology Patients: A Systematic Review.

IMPORTANCE: Constipation is common after pelvic surgery, and studies suggest that surgeons underestimate the negative impact of constipation on patients. Patients undergoing pelvic reconstructive surgery are a unique population requiring special consideration in the prevention and management of constipation. OBJECTIVE: This study aimed to systematically review the literature to identify evidence for prevention of postoperative constipation with medications or fiber in patients undergoing reconstructive pelvic surgery. STUDY DESIGN: A structured literature search was performed of five databases (MEDLINE, Embase, Scopus, Web of Science, the Cochrane Library) from inception to June 2022 for studies of postoperative laxative or fiber use in adult patients undergoing benign pelvic reconstructive surgery. Studies of preoperative bowel preparation and nonsurgical patients were excluded. Data on postoperative constipation were extracted for a qualitative analysis of the literature. Grading of Recommendations Assessment, Development, and Evaluation methodology was applied to assess the quality of evidence. RESULTS: We identified 86 references after deduplication. Only 4 studies with a total of 344 patients were eligible for inclusion in the review. The included studies were all randomized controlled trials assessing time to first bowel movement with the earliest published in 2010. Laxative use decreased constipation more than placebo. Multiple-agent laxative use appeared to decrease bothersome constipation more than single-agent docusate. Preoperative fiber did not decrease constipation. By Grading of Recommendations Assessment, Development, and Evaluation criteria, all four studies provide moderate-quality evidence. CONCLUSIONS: Few studies have investigated laxative regimens in patients after urogynecologic surgery. The available literature is moderate quality and suggests benefit of multiple-agent treatment over docusate only or no treatment.

General Versus Regional Anesthesia in Sacrospinous Ligament Fixation for Pelvic Organ Prolapse: Assessment of a National Database.

IMPORTANCE: Sacrospinous ligament fixation is a prolapse repair surgical procedure that can be performed under general or regional anesthesia. Little is known about the impact of anesthesia on postoperative outcomes. OBJECTIVES: The primary objective of this study was to compare 30-day complication rates for patients undergoing sacrospinous ligament fixation by anesthesia type. Secondary objectives were to assess factors associated with type of anesthesia selected. STUDY DESIGN: This was a retrospective cohort analysis of the American College of Surgeons National Surgical Quality Improvement Program for the years of 2015 to 2020. Cases were selected based on procedural codes for sacrospinous ligament fixation and diagnostic codes for prolapse. Complications, readmissions, and reoperations were compared between general versus regional anesthesia cohorts. RESULTS: A total of 2,984 cases were included with 2,742 (91.9%) performed under general and 242 (8.1%) performed under regional anesthesia. The regional anesthesia cohort was older (69.2 vs 65.4 years old; P < 0.001) with no differences in medical history variables. Fewer patients in the regional anesthesia cohort were Hispanic (0.4% in regional vs 10.8% in general cohorts, P < 0.001). More superficial surgical site infections (2.5% vs 0.8%, P = 0.026) and cardiac complications (0.8% vs 0.1%, P = 0.035) were noted in the regional anesthesia cohort. However, multivariable regression analysis showed that anesthesia type was not associated with increased rates of minor or major complications. CONCLUSIONS: Mode of anesthesia was not a significant predictor of minor or major complications. Racial and ethnic differences in mode of anesthesia warrant further investigation to reduce racial disparities.

Universal screening for SARS-CoV-2 infection among pregnant women at Elmhurst Hospital Center, Queens, New York.

BACKGROUND: Universal screening for SARS-CoV-2 infection on Labor and Delivery (L&D) units is a critical strategy to manage patient and health worker safety, especially in a vulnerable high-prevalence community. We describe the results of a SARS-CoV-2 universal screening program at the L&D Unit at Elmhurst Hospital in Queens, NY, a 545-bed public hospital serving a diverse, largely immigrant and low-income patient population and an epicenter of the global pandemic. METHODS AND FINDINGS: We conducted a retrospective cross-sectional study. All pregnant women admitted to the L&D Unit of Elmhurst Hospital from March 29, 2020 to April 22, 2020 were included for analysis. The primary outcomes of the study were: (1) SARS-CoV-2 positivity among universally screened pregnant women, stratified by demographic characteristics, maternal comorbidities, and delivery outcomes; and (2) Symptomatic or asymptomatic presentation at the time of testing among SARS-CoV-2 positive women. A total of 126 obstetric patients were screened for SARS-CoV-2 between March 29 and April 22. Of these, 37% were positive. Of the women who tested positive, 72% were asymptomatic at the time of testing. Patients who tested positive for SARS-CoV-2 were more likely to be of Hispanic ethnicity (unadjusted difference 24.4 percentage points, CI 7.9, 41.0) and report their primary language as Spanish (unadjusted difference 32.9 percentage points, CI 15.8, 49.9) than patients who tested negative. CONCLUSIONS: In this retrospective cross-sectional study of data from a universal SARS-Cov-2 screening program implemented in the L&D unit of a safety-net hospital in Queens, New York, we found over one-third of pregnant women testing positive, the majority of those asymptomatic. The rationale for universal screening at the L&D Unit at Elmhurst Hospital was to ensure safety of patients and staff during an acute surge in SARS-Cov-2 infections through appropriate identification and isolation of pregnant women with positive test results. Women were roomed by their SARS-CoV-2 status given increasing space limitations. In addition, postpartum counseling was tailored to infection status. We quickly established discharge counseling and follow-up protocols tailored to their specific social needs. The experience at Elmhurst Hospital is instructive for other L&D units serving vulnerable populations and for pandemic preparedness.

Chromatin accessibility dynamics across C. elegans development and ageing.

An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here, we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one Caenorhabditis elegans stage. Based on nuclear transcription profiles, we define 15,714 protein-coding promoters and 19,231 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, more than 1000 promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements changes during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing.