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The protein titin plays a key role in vertebrate muscle where it acts like a giant molecular spring. Despite its importance and conservation over vertebrate evolution, a lack of high quality annotations in non-model species makes comparative evolutionary studies of titin challenging. The PEVK region of titin—named for its high proportion of Pro-Glu-Val-Lys amino acids—is particularly difficult to annotate due to its abundance of alternatively spliced isoforms and short, highly repetitive exons. To understand PEVK evolution across mammals, we developed a bioinformatics tool, PEVK_Finder, to annotate PEVK exons from genomic sequences of titin and applied it to a diverse set of mammals. PEVK_Finder consistently outperforms standard annotation tools across a broad range of conditions and improves annotations of the PEVK region in non-model mammalian species. We find that the PEVK region can be divided into two subregions (PEVK-N, PEVK-C) with distinct patterns of evolutionary constraint and divergence. The bipartite nature of the PEVK region has implications for titin diversification. In the PEVK-N region, certain exons are conserved and may be essential, but natural selection also acts on particular codons. In the PEVK-C, exons are more homogenous and length variation of the PEVK region may provide the raw material for evolutionary adaptation in titin function. The PEVK-C region can be further divided into a highly repetitive region (PEVK-CA) and one that is more variable (PEVK-CB). Taken together, we find that the very complexity that makes titin a challenge for annotation tools may also promote evolutionary adaptation.

Centromeres are essential mediators of chromosomal segregation, but both centromeric DNA sequences and associated kinetochore proteins are paradoxically diverse across species. The selfish centromere model explains rapid evolution by both components via an arms-race scenario: centromeric DNA variants drive by distorting chromosomal transmission in female meiosis and attendant fitness costs select on interacting proteins to restore Mendelian inheritance. Although it is clear than centromeres can drive and that drive often carries costs, female meiotic drive has not been directly linked to selection on kinetochore proteins in any natural system. Here, we test the selfish model of centromere evolution in a yellow monkeyflower (Mimulus guttatus) population polymorphic for a costly driving centromere (D). We show that the D haplotype is structurally and genetically distinct and swept to a high stable frequency within the past 1500 years. We use quantitative genetic mapping to demonstrate that context-dependence in the strength of drive (from near-100% D transmission in interspecific hybrids to near-Mendelian in within-population crosses) primarily reflects variable vulnerability of the non-driving competitor chromosomes, but also map an unlinked modifier of drive coincident with kinetochore protein Centromere-specific Histone 3 A (CenH3A). Finally, CenH3A exhibits a recent (

Inferences about past processes of adaptation and speciation require a gene-scale and genome-wide understanding of the evolutionary history of diverging taxa. In this study, we use genome-wide capture of nuclear gene sequences, plus skimming of organellar sequences, to investigate the phylogenomics of monkeyflowers in Mimulus section Erythranthe (27 accessions from seven species). Taxa within Erythranthe, particularly the parapatric and putatively sister species M. lewisii (bee-pollinated) and M. cardinalis (hummingbird-pollinated), have been a model system for investigating the ecological genetics of speciation and adaptation for over five decades. Across >8000 nuclear loci, multiple methods resolve a predominant species tree in which M. cardinalis groups with other hummingbird-pollinated taxa (37% of gene trees), rather than being sister to M. lewisii (32% of gene trees). We independently corroborate a single evolution of hummingbird pollination syndrome in Erythranthe by demonstrating functional redundancy in genetic complementation tests of floral traits in hybrids; together, these analyses overturn a textbook case of pollination-syndrome convergence. Strong asymmetries in allele sharing (Patterson's D-statistic and related tests) indicate that gene tree discordance reflects ancient and recent introgression rather than incomplete lineage sorting. Consistent with abundant introgression blurring the history of divergence, low-recombination and adaptation-associated regions support the new species tree, while high-recombination regions generate phylogenetic evidence for sister status for M. lewisii and M. cardinalis. Population-level sampling of core taxa also revealed two instances of chloroplast capture, with Sierran M. lewisii and Southern Californian M. parishii each carrying organelle genomes nested within respective sympatric M. cardinalis clades. A recent organellar transfer from M. cardinalis, an outcrosser where selfish cytonuclear dynamics are more likely, may account for the unexpected cytoplasmic male sterility effects of selfer M. parishii organelles in hybrids with M. lewisii. Overall, our phylogenomic results reveal extensive reticulation throughout the evolutionary history of a classic monkeyflower radiation, suggesting that natural selection (re-)assembles and maintains species-diagnostic traits and barriers in the face of gene flow. Our findings further underline the challenges, even in reproductively isolated species, in distinguishing re-use of adaptive alleles from true convergence and emphasize the value of a phylogenomic framework for reconstructing the evolutionary genetics of adaptation and speciation.

Early comparative genomics studies originally uncovered a nonintuitive pattern; genes involved in reproduction appeared to evolve more rapidly than other classes of genes. Currently, the emerging consensus is that genes encoding reproductive proteins evolve under variable selective pressures, producing more heterogeneous divergence patterns than previously appreciated. Here, we investigate a facet of that heterogeneity and explore the factors that drive male reproductive tissue-based heterogeneity in evolutionary rates. In Japanese quail (Coturnix japonica), genes with enriched expression in the testes evolve much more rapidly than those enriched in the foam gland (FG), a novel gland that secretes an airy foam that males transfer to females during mating. We compared molecular evolutionary patterns among (1) genes with induced expression in breeding vs. wintering conditions for both tissues and (2) genes that encode foam proteins (FPs) vs. those with varying degrees of expression specificity in the FG. We report two major findings. First, genes upregulated in breeding condition testes evolve exceptionally rapidly, while those induced in breeding condition FGs evolve slowly. These differences hold even after correcting for hormonally-dependent gene expression and chromosomal location. Second, genes encoding FPs are extremely conserved in terms of gene identity and sequence. Together, these finding suggest that genes involved in the reproductive function of each tissue drive the marked rate of heterogeneity.

De novo assembled transcriptomes, in combination with RNA-Seq, are powerful tools to explore gene sequence and expression level in organisms without reference genomes. Investigators must first choose which high throughput sequencing platforms will provide data most suitable for their experimental goals. In this study, we explore the utility of 454 and Illumina sequences for de novo transcriptome assembly and downstream RNA-Seq applications in a reproductive gland from a non-model bird species, the Japanese quail (Coturnix japonica). Four transcriptomes composed of either pure 454 or Illumina reads or mixtures of read types were assembled and evaluated for the same cost. Illumina assemblies performed best for de novo transcriptome characterization in terms of contig length, transcriptome coverage, and complete assembly of gene transcripts. Improvements over the Hybrid assembly were marginal, with the exception that the addition of 454 data significantly increased the number of genes annotated. The Illumina assembly provided the best reference to align an independent set of RNA-Seq data as ∼84% of reads mapped to single genes in the transcriptome. Contigs constructed solely from 454 data may impose problems for RNA-Seq as our 454 transcriptome revealed a high number of indels and many ambiguously mapped reads. Correcting the 454 transcriptome with Illumina reads was an effective strategy to deal with indel and frameshift errors inherent to the 454 transcriptome, but at the cost of transcriptome coverage. In the absence of a reference genome, we find that Illumina reads alone produced a high quality transcriptome appropriate for RNA-Seq gene expression analyses.

Copy number variation (CNV) is a major part of the genetic diversity segregating within populations, but remains poorly understood relative to single nucleotide variation. Here, we report on a tRNA ligase gene (Migut.N02091; RLG1a) exhibiting unprecedented, and fitness‐relevant, CNV within an annual population of the yellow monkeyflower Mimulus guttatus. RLG1a variation was associated with multiple traits in pooled population sequencing (PoolSeq) scans of phenotypic and phenological cohorts. Resequencing of inbred lines revealed intermediate‐frequency three‐copy variants of RLG1a (trip+; 5/35 = 14%), and trip+ lines exhibited elevated RLG1a expression under multiple conditions. trip+ carriers, in addition to being over‐represented in late‐flowering and large‐flowered PoolSeq populations, flowered later under stressful conditions in a greenhouse experiment (p < 0.05). In wild population samples, we discovered an additional rare RLG1a variant (high+) that carries 250–300 copies of RLG1a totalling ~5.7 Mb (20–40% of a chromosome). In the progeny of a high+ carrier, Mendelian segregation of diagnostic alleles and qPCR‐based copy counts indicate that high+ is a single tandem array unlinked to the single‐copy RLG1a locus. In the wild, high+ carriers had highest fitness in two particularly dry and/or hot years (2015 and 2017; both p < 0.01), while single‐copy individuals were twice as fecund as either CNV type in a lush year (2016: p < 0.005). Our results demonstrate fluctuating selection on CNVs affecting phenological traits in a wild population, suggest that plant tRNA ligases mediate stress‐responsive life‐history traits, and introduce a novel system for investigating the molecular mechanisms of gene amplification. [ABSTRACT FROM AUTHOR]

Introduction: Worldwide, ERAS ® Society guidelines have ushered in a new era of perioperative care. The purpose of this systematic review is to compare published core elements and pharmacotherapy recommendations embedded within ERAS ® Society abdominal and thoracic surgery (ATS) guidelines. Determining whether a consensus exists for pharmacological core items would make future guideline preparation for similar surgeries more standardized and could improve patient care by reducing unnecessary protocol variations., Methods: From the ERAS ® Society website as of May 2023, 16 current ERAS ® published ATS guidelines were included in the analysis to determine consensus and differing statements regarding each ERAS ® perioperative and pharmacotherapy-related item. The aims were to (a) determine whether a consensus for each item could be derived, (b) identify gaps in ERAS ® protocol development, and (c) propose potential research directions for addressing the identified gaps in the literature., Results: Core items with consensus included: preoperative smoking and alcohol cessation; avoiding bowel reparation and fasting; multimodal preanesthetic, perioperative analgesia, and postoperative nausea and vomiting regimens; low molecular weight heparins for in-hospital and at-home venous thromboembolism prophylaxis; antibiotic prophylaxis; skin preparation; goal-directed perioperative fluid management with balanced crystalloids; perioperative nutrition care; ileus prevention with peripherally-acting mu receptor antagonists; and glucose control., Conclusion: While consensus was found for aspects of 21 current ERAS ® guideline core items related to pharmacotherapy choice, details related to doses, regimen, timing of administration as well as unique aspects pertaining to specific surgeries remain to be researched and harmonized to promote guideline consistency and further optimize patient outcomes., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: The application of enhanced recovery after surgery principles decreases postoperative complications (POCs), length of stay (LOS), and readmissions. Pharmacoprophylaxis decreases morbidity, but the effect of specific regimens on clinical outcomes is unclear., Methods and Materials: Records of 476 randomly selected adult patients who underwent elective colorectal surgeries (ECRS) at 10 US hospitals were abstracted. Primary outcomes were surgical site infection (SSI), venous thromboembolism (VTE), postoperative nausea and vomiting (PONV), pain, and ileus rates. Secondary outcomes included LOS and 7- and 30-day readmission rates., Results: POC rates were SSI (3.4%), VTE (1.5%), PONV (47.9%), pain (58.1%), and ileus (16.1%). Cefazolin 2 g/metronidazole 500 mg and ertapenem 1 g were associated with the shortest LOS; cefotetan 2 g and cefoxitin 2 g with the longest LOS. No SSI occurred with ertapenem and cefotetan. More Caucasians than Blacks received oral antibiotics before intravenous antibiotics without impact. Enoxaparin 40 mg subcutaneously daily was the most common inpatient and discharge VTE prophylaxis. All in-hospital VTEs occurred with unfractionated heparin. Most received rescue rather than around-the-clock antiemetics. Scopolamine patches, spinal opioids, and IV lidocaine continuous infusion were associated with lower PONV. Transversus abdominis plane block with long-acting local anesthetics, celecoxib, non-anesthetic ketamine bolus, ketorolac IV, lidocaine IV, and pregabalin were associated with lower in-hospital pain severity rates. Gabapentinoids and alvimopan were associated with lower ileus rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches were associated with shorter LOS., Conclusions: Significant differences in pharmacotherapy regimens that may improve primary and secondary outcomes in ECRS were identified. In adult ECRS, cefotetan or ertapenem may be better regimens for preventing in-hospital SSI, while ertapenem or C/M may lead to shorter LOS. The value of OA to prevent SSI was not demonstrated. Inpatient enoxaparin, compared to UFH, may reduce VTE rates with a similar LOS. A minority of patients had a documented PONV risk assessment, and a majority used as-needed rather than around-the-clock strategies. Preoperative scopolamine patches continued postoperatively may lower PONV and PDNV severity and shorter LOS. Alvimopan may reduce ileus and shorten LOS. Anesthesia that includes TAP block, ketorolac IV, and pregabalin use may lead to reduced pain rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches may shorten LOS. Given the challenges of pain management and the incidence of PONV/PDNV found in this study, additional studies should be conducted to determine optimal opioid-free anesthesia and the benefit of newer antiemetics on patient outcomes. Moreover, future research should identify latent pharmacotherapy variables that impact patient outcomes, correlate pertinent laboratory results, and examine the impact of order or care sets used for ECRS at study hospitals.

Background: Survival benefits of post-operative systemic and radiation therapy in high-risk stage I endometrial cancer are uncertain., Objective: To compare recurrence patterns and survival outcomes of post-surgical treatment in patients with high-risk stage I endometrial cancer and to determine whether adjuvant therapy significantly improves outcomes., Methods: High-risk stage I endometrial cancer was defined as either stage IB grade 3 endometrioid histology or myoinvasive non-endometrioid histology. Consecutive patients diagnosed between January 2000 and December 2010 in eight cancer centers were included. Patients, disease, and treatment characteristics were summarized by descriptive statistics. Overall survival, disease-specific survival, and relapse-free survival were examined using Cox's proportional hazards regression and log-rank test. Survival curves were estimated using the Kaplan-Meier method., Results: Of 2317 patients with stage I endometrial cancer, 414 patients had high-risk disease. Use of chemotherapy did not improve overall survival (relative risk (RR) 0.70, 95% CI 0.46 to 1.14, p=0.13) or disease-specific survival (RR 1.06, 95% CI 0.61 to 1.85, p=0.84). Significant improvement in recurrence-free survival was observed in patients who received chemotherapy (RR 0.61, 95% CI 0.39 to 0.95, p=0.03). Use of radiation therapy did not improve overall survival, recurrence-free survival, or disease-specific survival. Patients who received four cycles or fewer of chemotherapy versus five to six cycles had similar overall survival, disease-specific survival, and recurrence-free survival., Conclusions: Post-operative chemotherapy or radiation in stage I high-risk endometrial cancer is not associated with improved cancer-specific or overall survival. More than four cycles of chemotherapy did not improve survival compared with four cycles or fewer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pharmacotherapy prophylaxis embedded in Enhanced Recovery After Surgery (ERAS®) protocols is largely unknown because data related to agent choice, dosing, timing, and duration of treatment currently are not collected in the ERAS Interactive Audit System (EIAS®). This exploratory retrospective randomized cohort study characterized pharmacologic regimens pertaining to prophylaxis of surgical site infections (SSI), venous thromboembolism (VTE), and post-operative nausea and vomiting (PONV)., Materials and Methods: The records of 250 randomly-selected adult patients that underwent elective colorectal (CR) and gynecologic/oncology procedures (GO) at an ERAS® site in North America were abstracted using REDCap. In addition to descriptive statistics, bivariate associations between categorical variables were compared., Results: Rates of SSI, VTE, & PONV were 3.3%, 1.1%, and 53.6%, respectively. Mean length of stay (LOS) for CR was 6.9 days and for GO, 3.5 days (p < 0.001). The most common antibiotic prophylaxis was one-time combination cefazolin 2 g and metronidazole 500 mg between 16 and 30 min preoperatively after chlorhexidine skin preparation. The most frequent VTE prophylaxis was tinzaparin 4500 units SC daily continued for at least 7 days after hospital discharge in oncology patients. PONV was related to longer LOS in both groups. Total morphine milligram equivalents (MME) was positively related to PONV and LOS in both CR & GO groups., Conclusion: Guideline-consistent pharmacologic prophylaxis for SSI and VTE for both CR and GO patients was associated with low complication, LOS, and readmission rates. LOS in both groups was highly influenced by total MME, incidence of PONV and multi-modal anesthesia., Competing Interests: No conflicts to disclose., (© 2021 The Authors.)

Introduction: Venous thromboembolism remains a significant complication following major gynecologic surgery. Evidence is lacking on whether it is beneficial to give pharmacologic thromboprophylaxis pre-operatively. The aim of this meta-analysis was to assess the role of pre-operative pharmacologic thromboprophylaxis in preventing post-operative venous thromboembolism., Methods: PubMed, EMBASE, and the Cochrane Central Register of Clinical Trials were searched to find randomized controlled, cohort, and case-control trials comparing pre-operative pharmacologic thromboprophylaxis to no prophylaxis, mechanical prophylaxis, or only post-operative pharmacologic thromboprophylaxis for open and minimally invasive major gynecologic surgery (benign and malignant conditions). Two authors independently assessed abstracts, full-text articles, and methodological quality. Data were extracted and pooled using ORs for random effects meta-analysis. Heterogeneity was explored using forest plots, Q-statistic, and I 2 statistics. Planned subgroup analysis of use of sequential compression devices, equivalent versus non-equivalent post-operative prophylaxis, cancer diagnosis, and methodological quality were performed., Results: Some 503 unique studies were found, and 16 studies (28 806 patients) were included in the systematic review. Twelve studies (14 273 patients) were included in the meta-analysis. The OR for incidence of post-operative venous thromboembolism was 0.59 (95% CI 0.39, 0.89), favoring pre-operative pharmacologic thromboembolism prophylaxis compared with no pre-operative pharmacologic prophylaxis (Q=13.80, I 2 =20.30). In studies where post-operative care was equivalent between groups, the OR for venous thromboembolism was 0.56 (95% CI 0.22, 1.40). Pre-operative pharmacologic prophylaxis demonstrated greatest benefit when utilized with both intra-operative and post-operative sequential compression devices (OR 0.43, 95% CI 0.30, 0.64) compared with when no sequential compression devices were utilized (OR 1.27, 95% CI 0.63, 2.56). When looking at only studies determined to be of high quality, the results no longer reached significance (OR 0.73, 95% CI 0.36, 1.46)., Conclusions: Pre-operative pharmacologic thromboprophylaxis decreases the odds of venous thromboembolism in the peri-operative period for major gynecologic oncology surgery by approximately 40%. It remains unclear whether this benefit is present in benign and minor procedures. Adequately powered studies are needed., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

•Three patients with cytology positive pericardial effusions from high grade serous carcinoma.•Patients' conditions amenable to treatment with chemotherapy after effusion symptom improvement.•Patient with pericardial effusion from high grade serous ovarian cancer post a poly ADP ribose polymerase inhibitor., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Objective: This study sought to estimate the association of adverse perinatal outcomes with pregnancies complicated by fetal echogenic bowel., Methods: Data for pregnancies complicated with echogenic bowel identified in the second trimester were derived from the tertiary referral IWK Health Centre (Halifax, NS) Viewpoint Ultrasound Database augmented by medical chart review. The study was undertaken between 2003 and 2014. Rates of positive cytomegalovirus and toxoplasmosis infection were determined using maternal serology and amniocentesis results. Rates of intrauterine growth restriction, abnormal karyotype, cystic fibrosis, antenatal bleeding, and bowel abnormalities were also determined. Neonatal information included newborn urine culture results and postnatal genetic testing. Univariate analyses compared rates of infection with isolated echogenic bowel and echogenic bowel with other ultrasound findings, with statistical significance set at P <0.05., Results: There were 422 pregnancies identified prenatally with echogenic bowel (82% had isolated echogenic bowel). Of these, 92 (22%) had at least one of the foregoing associated abnormalities. Three percent of women had serologic test results positive for cytomegalovirus or toxoplasmosis, with <1% documented newborn infections. Cystic fibrosis and other genetic diagnoses were observed in 8%, intrauterine growth restriction in 14%, antenatal bleeding in 19%, and bowel abnormalities in 3% of the cases of echogenic bowel. Pregnancies with isolated echogenic bowel had an 80% reduction in risk for these significant outcomes, in contrast to a four- to 11-fold increased risk of specific outcomes when additional ultrasound findings were present., Conclusion: An overall rate of adverse conditions of 22% with prenatally detected echogenic bowel serves to inform women and health care providers and emphasizes the importance of careful screening fetal ultrasound studies and timely referral for comprehensive assessment with findings of echogenic bowel for evaluation for associated findings., (Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)

Context: Effective handover within the health care setting is vital to patient safety. Despite published literature discussing strategies to improve handover, the extent to which educational interventions have been used and how such interventions relate to the published theoretical models of handover remain unclear. These issues were investigated through a systematic review of the literature., Methods: Any studies involving educational interventions to improve handover amongst undergraduate or postgraduate doctors or nurses were considered. A standardised search of online databases was carried out independently by both authors and consensus reached on the inclusion of studies. Data extraction and quality assessment were also completed independently, after which a content analysis of interventions was conducted and key themes extracted., Results: Ten studies met the inclusion criteria. Nine studies reported outcomes demonstrating improved attitudes or knowledge and skills, and one demonstrated transfer of skills to the workplace. Amongst the included studies, the strength of conclusions was variable. Poor reporting of interventions impeded replication. Analysis of available content revealed themes in three major areas: teamwork and leadership; professional responsibility with regard to error prevention, and information management systems. Methods used included exercises based on simulation and role-play, and group discussions or lectures focused on errors and patient safety., Conclusions: There is a paucity of research describing educational interventions to improve handover and assessing their effectiveness. The quality of published studies is generally poor. Some evidence exists to demonstrate that skills can be transferred to the workplace, but none was found to demonstrate that interventions improve patient safety., (© Blackwell Publishing Ltd 2011.)