APOBEC3A is a prominent cytidine deaminase in breast cancer.

APOBEC cytidine deaminases are the second-most prominent source of mutagenesis in sequenced tumors. Previous studies have proposed that APOBEC3B (A3B) is the major source of mutagenesis in breast cancer (BRCA). We show that APOBEC3A (A3A) is the only APOBEC whose expression correlates with APOBEC-induced mutation load and that A3A expression is responsible for cytidine deamination in multiple BRCA cell lines. Comparative analysis of A3A and A3B expression by qRT-PCR, RSEM-normalized RNA-seq, and unambiguous RNA-seq validated the use of RNA-seq to measure APOBEC expression, which indicates that A3A is the primary correlate with APOBEC-mutation load in primary BRCA tumors. We also demonstrate that A3A has >100-fold more cytidine deamination activity than A3B in the presence of cellular RNA, likely explaining why higher levels of A3B expression contributes less to mutagenesis in BRCA. Our findings identify A3A as a major source of cytidine deaminase activity in breast cancer cells and possibly a prominent contributor to the APOBEC mutation signature.

Examining Women Veteran's Experiences, Perceptions, and Challenges With the Veterans Choice Program.

BACKGROUND: The Veterans Choice Program (VCP) was launched in 2014 to address the growing concerns about the timeliness and quality of Veterans Health Administration (VHA) care. Given that many sex-specific health services, such as mammography and maternity care, are not routinely provided in all VHA facilities, women Veterans may disproportionately rely on VCP care. Understanding the provision and coordination of VCP care is crucial in order to ensure that care is not fragmented across the 2 health care systems. OBJECTIVES: The main objective of this study was to understand women Veterans' experiences, perceptions, and challenges with VCP care. DESIGN: This study was a semistructured interview with 148 women at 13 VHA facilities nationwide. RESULTS: Four major themes emerged: (1) eligibility information for the VCP was limited and confusing; (2) women experienced difficulty scheduling VCP appointments; (3) VCP care results were not shared with women Veterans or their VHA providers in a timely manner; and (4) concerns with unpaid VCP bills were common. CONCLUSIONS: Our study highlights challenges women experienced with VCP care, and the need for improved care coordination. An ideal care coordination system would be the one in which all Veterans' non-Veteran Affairs care, including scheduling, follow-up, communication with community providers, coordination of services, and transition back to Veteran Affairs care is ensured.

Machine-learning analysis outperforms conventional statistical models and CT classification systems in predicting 6-month outcomes in pediatric patients sustaining traumatic brain injury.

OBJECTIVEModern surgical planning and prognostication requires the most accurate outcomes data to practice evidence-based medicine. For clinicians treating children following traumatic brain injury (TBI) these data are severely lacking. The first aim of this study was to assess published CT classification systems in the authors' pediatric cohort. A pediatric-specific machine-learning algorithm called an artificial neural network (ANN) was then created that robustly outperformed traditional CT classification systems in predicting TBI outcomes in children.METHODSThe clinical records of children under the age of 18 who suffered a TBI and underwent head CT within 24 hours after TBI (n = 565) were retrospectively reviewed.RESULTS"Favorable" outcome (alive with Glasgow Outcome Scale [GOS] score ≥ 4 at 6 months postinjury, n = 533) and "unfavorable" outcome (death at 6 months or GOS score ≤ 3 at 6 months postinjury, n = 32) were used as the primary outcomes. The area under the receiver operating characteristic (ROC) curve (AUC) was used to delineate the strength of each CT grading system in predicting survival (Helsinki, 0.814; Rotterdam, 0.838; and Marshall, 0.781). The AUC for CT score in predicting GOS score ≤ 3, a measure of overall functionality, was similarly predictive (Helsinki, 0.717; Rotterdam, 0.748; and Marshall, 0.663). An ANN was then constructed that was able to predict 6-month outcomes with profound accuracy (AUC = 0.9462 ± 0.0422).CONCLUSIONSThis study showed that machine-learning can be leveraged to more accurately predict TBI outcomes in children.

Translational effects and coding potential of an upstream open reading frame associated with DOPA Responsive Dystonia.

Upstream open reading frames (uORFs) have emerged as major post-transcriptional regulatory elements in eukaryotic species. In general, uORFs are initiated by a translation start codon within the 5' untranslated region of a gene (upstream ATG; uATG), and they are negatively correlated with translational efficiency. In addition to their translational regulatory role, some uORFs can code for biologically active short peptides. The importance of uATGs/uORFs is further underscored by human diseases associated with single nucleotide polymorphisms (SNPs), which disrupt existing uORFs or introduce novel uORFs. Although several functional proteins translated from naturally occurring uORFs have been described, the coding potential of uORFs created by SNPs has been ignored because of the a priori assumption that these proteins are short-lived with no likely impact on protein homeostasis. Thus, studies on SNP-created uORFs are limited to their translational effects, leaving unexplored the potential cellular consequences of a SNP/uORF-encoded protein. Here, we investigate functionality of a uATG/uORF introduced by a +142C>T SNP within the GCH1 gene and associated with a familial form of DOPA Responsive Dystonia. We report that the +142C>T SNP represses GCH1 translation, and introduces a short, frame shifted uORF that encodes a 73-amino acid peptide. This peptide is localized within the nucleus and compromises cell viability upon proteasome inhibition. Our work extends the list of uATG/uORF associated diseases and advances research on peptides translated from SNP-introduced uORFs, a neglected component of the proteome.

Drug Addiction and DNA Modifications.

Drug addiction is a complex disorder which can be influenced by both genetic and environmental factors. Research has shown that epigenetic modifications can translate environmental signals into changes in gene expression, suggesting that epigenetic changes may underlie the causes and possibly treatment of substance use disorders. This chapter will focus on epigenetic modifications to DNA, which include DNA methylation and several recently defined additional DNA epigenetic changes. We will discuss the functions of DNA modifications and methods for detecting them, followed by a description of the research investigating the function and consequences of drug-induced changes in DNA methylation patterns. Understanding these epigenetic changes may provide us translational tools for the diagnosis and treatment of addiction in the future.

Assessing the value of endoscopic ultrasound in predicting symptom severity and long-term clinical course in chronic pancreatitis.

BACKGROUND: To date, no studies have evaluated the correlation between number of endoscopic ultrasound (EUS) criteria met for chronic pancreatitis (CP) and symptom severity over the course of the disease. This study assessed the relationship between number of EUS-based diagnostic criteria for CP and CP severity over time. METHODS: A University of Louisville database was queried for patients undergoing EUS due to concern for chronic pancreatitis between 2005 and 2016. Patients were grouped based on EUS criteria met for CP and groups were compared along outcome and procedural variables. RESULTS: Of a total of 243 patients, 24, 129, and 90 patients met 1-3, 4-5, and ≥6 EUS diagnostic criteria, respectively. Median follow-up time was 33 months. Along all follow-up parameters, number of diagnostic criteria was positively correlated with an increased percentage of patients requiring operative intervention for chronic pancreatitis on univariate and multivariate analysis. CONCLUSIONS: In addition to the role of EUS criteria in establishing the diagnostic severity of patients with symptomatic chronic pancreatitis, the number of EUS-based criteria may help predict patients who will eventually require operative intervention and thus prompt referral to a pancreatobiliary surgeon earlier in the course of a patient's disease.

Rare Hematologic Malignancies and Pre-Leukemic Entities in Children and Adolescents Young Adults.

There are a variety of rare hematologic malignancies and germline predispositions syndromes that occur in children and adolescent young adults (AYAs). These entities are important to recognize, as an accurate diagnosis is essential for risk assessment, prognostication, and treatment. This descriptive review summarizes rare hematologic malignancies, myelodysplastic neoplasms, and germline predispositions syndromes that occur in children and AYAs. We discuss the unique biology, characteristic genomic aberrations, rare presentations, diagnostic challenges, novel treatments, and outcomes associated with these rare entities.

Investigating the safety and feasibility of osteopathic manipulative medicine in hospitalized children and adolescent young adults with cancer.

CONTEXT: Children and adolescents young adults (AYAs) undergoing treatment for oncologic diagnoses are frequently hospitalized and experience unwanted therapy-induced side effects that diminish quality of life. Osteopathic manipulative treatment (OMT) is a medical intervention that utilizes manual techniques to diagnose and treat body structures. Few studies have investigated the implementation of OMT in the pediatric oncology outpatient setting. To date, no studies have investigated the safety and feasibility of OMT in the pediatric oncology inpatient setting. OBJECTIVES: The objective of this study is to investigate the safety and feasibility of OMT in the pediatric oncology inpatient setting. METHODS: This is a prospective, single-institution pilot study evaluating children and AYAs aged ≥2 years to ≤30 years with a diagnosis of cancer hospitalized at Riley Hospital for Children (RH) from September 2022 to July 2023. Approval was obtained from the Indiana University Institutional Review Board (IRB). Patients were evaluated daily with a history and physical examination as part of routine inpatient management. Patients who reported chemotherapy side effects commonly encountered and managed in the inpatient setting, such as pain, headache, neuropathy, constipation, or nausea, were offered OMT. Patients provided written informed consent/assent prior to receiving OMT. OMT was provided by trained osteopathic medical students under the supervision of a board-certified osteopathic physician and included techniques commonly taught in first- and second-year osteopathic medical school curricula. Safety was assessed by a validated pain (FACES) scale immediately pre/post-OMT and by adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE) 24 h post-OMT. All data were summarized utilizing descriptive statistics. RESULTS: A total of 11 patients were screened for eligibility. All patients met the eligibility criteria and were enrolled in the study. The majority of patients were male (n=7, 63.6 %) with a median age of 18.2 years at time of enrollment (range, 10.2-29.8 years). Patients had a variety of hematologic malignancies including B-cell acute lymphoblastic leukemia (ALL) (n=5, 45.5 %), T-cell ALL (n=1, 9.1 %), acute myeloid leukemia (AML) (n=2, 18.2 %), non-Hodgkin's lymphoma (n=2, 18.2 %), and Hodgkin's lymphoma (n=1, 9.1 %). All patients were actively undergoing cancer-directed therapy at the time of enrollment. There were 40 unique reasons for OMT reported and treated across 37 encounters, including musculoskeletal pain (n=23, 57.5 %), edema (n=7, 17.5 %), headache (n=5, 12.5 %), peripheral neuropathy (n=2, 5.0 %), constipation (n=2, 5.0 %), and epigastric pain not otherwise specified (n=1, 2.5 %). Validated FACES pain scores were reported in 27 encounters. Of the 10 encounters for which FACES pain scores were not reported, 8 encounters addressed lower extremity edema, 1 encounter addressed peripheral neuropathy, and 1 encounter addressed constipation. The total time of OMT was documented for 33 of the 37 encounters and averaged 9.8 min (range, 3-20 min). CONCLUSIONS: Hospitalized children and AYAs with cancer received OMT safely with decreased pain in their reported somatic dysfunction(s). These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology inpatient setting and to a broader inpatient pediatric oncology population.

Correction to "Insights into the Effects of Violating Statistical Assumptions for Dimensionality Reduction for Chemical "-omics" Data with Multiple Explanatory Variables".

[This corrects the article DOI: 10.1021/acsomega.3c01613.].

A forensically validated genetic toolkit for the species and lineage identification of the highly trafficked shingleback lizard (Tiliqua rugosa).

Shingleback lizards (Tiliqua rugosa) are among the most trafficked native fauna from Australia in the illegal pet trade. There are four morphologically recognised subspecies of shinglebacks, all with differing overseas market values. Shinglebacks from different geographic locales are often trafficked and housed together, which may complicate identifying the State jurisdiction where the poaching event occurred. Additionally, shinglebacks can be housed and trafficked with other species within the same genus, which may complicate DNA analysis, especially in scenarios where indirect evidence (e.g. swabs, faeces) is taken for analysis. In this study, a forensic genetic toolkit was designed and validated to target shingleback DNA for species identification and geographic origin. To do this, field sampling across Australia was conducted to expand the phylogeographic sampling of shinglebacks across their species range and include populations suspected to be poaching hotspots. A commonly used universal reptile primer set (ND4/LEU) was then validated for use in forensic casework related to the genus Tiliqua. Two additional ND4 primer sets were designed and validated. The first primer set was designed and demonstrated to preferentially amplify an ∼510 bp region of the genus Tiliqua over other reptiles and builds on existing data to expand the available phylogeographic database. The second primer set was designed and demonstrated to solely amplify an ∼220 bp region of T. rugosa ND4 over any other reptile species. Through the validation process, all primers were demonstrated to amplify T. rugosa DNA from a variety of sample types (e.g. degraded, low quality and mixed). Two of the primer sets were able to distinguish the genetic lineage of T. rugosa from the phylogeographic database. This work provides the first forensically validated toolkit and phylogeographic genetic database for Squatmate lizards.

Insights into the Effects of Violating Statistical Assumptions for Dimensionality Reduction for Chemical "-omics" Data with Multiple Explanatory Variables.

Biological volatilome analysis is inherently complex due to the considerable number of compounds (i.e., dimensions) and differences in peak areas by orders of magnitude, between and within compounds found within datasets. Traditional volatilome analysis relies on dimensionality reduction techniques which aid in the selection of compounds that are considered relevant to respective research questions prior to further analysis. Currently, compounds of interest are identified using either supervised or unsupervised statistical methods which assume the data residuals are normally distributed and exhibit linearity. However, biological data often violate the statistical assumptions of these models related to normality and the presence of multiple explanatory variables which are innate to biological samples. In an attempt to address deviations from normality, volatilome data can be log transformed. However, whether the effects of each assessed variable are additive or multiplicative should be considered prior to transformation, as this will impact the effect of each variable on the data. If assumptions of normality and variable effects are not investigated prior to dimensionality reduction, ineffective or erroneous compound dimensionality reduction can impact downstream analyses. It is the aim of this manuscript to assess the impact of single and multivariable statistical models with and without the log transformation to volatilome dimensionality reduction prior to any supervised or unsupervised classification analysis. As a proof of concept, Shingleback lizard (Tiliqua rugosa) volatilomes were collected across their species distribution and from captivity and were assessed. Shingleback volatilomes are suspected to be influenced by multiple explanatory variables related to habitat (Bioregion), sex, parasite presence, total body volume, and captive status. This work determined that the exclusion of relevant multiple explanatory variables from analysis overestimates the effect of Bioregion and the identification of significant compounds. The log transformation increased the number of compounds that were identified as significant, as did analyses that assumed that residuals were normally distributed. Among the methods considered in this work, the most conservative form of dimensionality reduction was achieved through analyzing untransformed data using Monte Carlo tests with multiple explanatory variables.

The use of novel electronic nose technology to locate missing persons for criminal investigations.

The search for missing persons is a major challenge for investigations involving presumed deceased individuals. Currently, the most effective tool is the use of cadaver-detection dogs; however, they are limited by their cost, limited operation times, and lack of granular information reported to the handler. Thus, there is a need for discrete, real-time detection methods that provide searchers explicit information as to whether human-decomposition volatiles are present. A novel e-nose (NOS.E) developed in-house was investigated as a tool to detect a surface-deposited individual over time. The NOS.E was able to detect the victim throughout most stages of decomposition and was influenced by wind parameters. The sensor responses from different chemical classes were compared to chemical class abundance confirmed by two-dimensional gas chromatography - time-of-flight mass spectrometry. The NOS.E demonstrated its ability to detect surface-deposited individuals days and weeks since death, demonstrating its utility as a detection tool.

Surgical Diagnoses of Pancreatic Adenocarcinoma Not Found on Previous Endoscopic Ultrasound: A Case Series and Review of the Literature.

INTRODUCTION: Pancreatic cancer is a leading cause of death in North America and Western Europe with rising rates in the developing world. Endoscopic ultrasound (EUS) with FNA (fine needle aspiration) is a critical component in the evaluation and diagnosis of pancreatic lesions with a high sensitivity and specificity. In this paper, we report patients at our center who eventually developed pancreatic cancer despite an early negative EUS, and identifying factors that may result in a missed diagnosis. METHODS: The University of Louisville database was queried for patients who had a Whipple procedure for presumed benign disease and had a pre-operative EUS between 2008 and 2018. Patients who had pancreatic adenocarcinoma on final pathology were identified. Demographic, clinical, EUS, operative, and pathologic details were reviewed for each case in efforts to identify factors associated with failure to diagnose a pancreatic malignancy on EUS. RESULTS: Five patients who had pancreatic adenocarcinoma on final pathology were reviewed in detail and their cases are presented in the paper. Four of the patients had dilation of the common bile duct, three had chronic pancreatitis. Two of them had previous surgery on the pancreas or bile ducts. CONCLUSIONS: All of the patients presented in the paper had variables that made their EUS evaluation challenging. A high index of suspicion must be maintained in patients that do not improve after appropriate treatment of their strictures or pancreatic lesions. In the future, new techniques, such as fine needle biopsy and biomarker assays, may improve diagnosis accuracy.

Limosilactobacillus reuteri administration alters the gut-brain-behavior axis in a sex-dependent manner in socially monogamous prairie voles.

Research on the role of gut microbiota in behavior has grown dramatically. The probiotic L. reuteri can alter social and stress-related behaviors - yet, the underlying mechanisms remain largely unknown. Although traditional laboratory rodents provide a foundation for examining the role of L. reuteri on the gut-brain axis, they do not naturally display a wide variety of social behaviors. Using the highly-social, monogamous prairie vole (Microtus ochrogaster), we examined the effects of L. reuteri administration on behaviors, neurochemical marker expression, and gut-microbiome composition. Females, but not males, treated with live L. reuteri displayed lower levels of social affiliation compared to those treated with heat-killed L. reuteri. Overall, females displayed a lower level of anxiety-like behaviors than males. Live L. reuteri-treated females had lower expression of corticotrophin releasing factor (CRF) and CRF type-2-receptor in the nucleus accumbens, and lower vasopressin 1a-receptor in the paraventricular nucleus of the hypothalamus (PVN), but increased CRF in the PVN. There were both baseline sex differences and sex-by-treatment differences in gut microbiome composition. Live L. reuteri increased the abundance of several taxa, including Enterobacteriaceae, Lachnospiraceae NK4A136, and Treponema. Interestingly, heat-killed L. reuteri increased abundance of the beneficial taxa Bifidobacteriaceae and Blautia. There were significant correlations between changes in microbiota, brain neurochemical markers, and behaviors. Our data indicate that L. reuteri impacts gut microbiota, gut-brain axis and behaviors in a sex-specific manner in socially-monogamous prairie voles. This demonstrates the utility of the prairie vole model for further examining causal impacts of microbiome on brain and behavior.

Regulation of BDNF expression by cocaine.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. It is expressed throughout the nervous system. A unique feature of the BDNF gene is the existence of multiple mRNA transcripts, all of which are translated into BDNF protein, suggesting a multilevel regulation of expression. In particular, the BDNF exon IV promoter region is a preferential target for epigenetic alterations, as it contains binding sites for CREB and MeCP2, two transcriptional regulators known to mediate epigenetic changes. Exposure to drugs of abuse is known to modulate epigenetic regulation of BDNF gene expression. This review will discuss how exposure to cocaine, one of the most addictive drugs known to mankind, can produce alterations in BDNF gene expression, especially in the mesolimbic dopaminergic system, which lead to alterations in the reward-mediated behaviors involved in addiction.

CyPPA, a positive modulator of small-conductance Ca(2+)-activated K(+) channels, inhibits phasic uterine contractions and delays preterm birth in mice.

Organized uterine contractions, including those necessary for parturition, are dependent on calcium entry through voltage-gated calcium channels in myometrial smooth muscle cells. Recent evidence suggests that small-conductance Ca(2+)-activated potassium channels (K(Ca)2), specifically isoforms K(Ca)2.2 and 2.3, may control these contractions through negative feedback regulation of Ca(2+) entry. We tested whether selective pharmacologic activation of K(Ca)2.2/2.3 channels might depress uterine contractions, providing a new strategy for preterm labor intervention. Western blot analysis and immunofluorescence microscopy revealed expression of both K(Ca)2.2 and K(Ca)2.3 in the myometrium of nonpregnant (NP) and pregnant (gestation day 10 and 16; D10 and D16, respectively) mice. Spontaneous phasic contractions of isolated NP, D10, and D16 uterine strips were all suppressed by the K(Ca)2.2/2.3-selective activator CyPPA in a concentration-dependent manner. This effect was antagonized by the selective K(Ca)2 inhibitor apamin. Whereas CyPPA sensitivity was reduced in D10 and D16 versus NP strips (pIC(50) 5.33 ± 0.09, 4.64 ± 0.03, 4.72 ± 0.10, respectively), all contractions were abolished between 30 and 60 µM. Blunted contractions were associated with CyPPA depression of spontaneous Ca(2+) events in myometrial smooth muscle bundles. Augmentation of uterine contractions with oxytocin or prostaglandin F(2α) did not reduce CyPPA sensitivity or efficacy. Finally, in an RU486-induced preterm labor model, CyPPA significantly delayed time to delivery by 3.4 h and caused a 2.5-fold increase in pup retention. These data indicate that pharmacologic stimulation of myometrial K(Ca)2.2/2.3 channels effectively suppresses Ca(2+)-mediated uterine contractions and delays preterm birth in mice, supporting the potential utility of this approach in tocolytic therapies.

Single-stranded DNA binding proteins influence APOBEC3A substrate preference.

The cytidine deaminase, APOBEC3A (A3A), is a prominent source of mutations in multiple cancer types. These APOBEC-signature mutations are non-uniformly distributed across cancer genomes, associating with single-stranded (ss) DNA formed during DNA replication and hairpin-forming sequences. The biochemical and cellular factors that influence these specificities are unclear. We measured A3A's cytidine deaminase activity in vitro on substrates that model potential sources of ssDNA in the cell and found that A3A is more active on hairpins containing 4 nt ssDNA loops compared to hairpins with larger loops, bubble structures, replication fork mimics, ssDNA gaps, or linear DNA. Despite pre-bent ssDNAs being expected to fit better in the A3A active site, we determined A3A favors a 4 nt hairpin substrate only 2- to fivefold over linear ssDNA substrates. Addition of whole cell lysates or purified RPA to cytidine deaminase assays more severely reduced A3A activity on linear ssDNA (45 nt) compared to hairpin substrates. These results indicate that the large enrichment of A3A-driven mutations in hairpin-forming sequences in tumor genomes is likely driven in part by other proteins that preferentially bind longer ssDNA regions, which limit A3A's access. Furthermore, A3A activity is reduced at ssDNA associated with a stalled T7 RNA polymerase, suggesting that potential protein occlusion by RNA polymerase also limits A3A activity. These results help explain the small transcriptional strand bias for APOBEC mutation signatures in cancer genomes and the general targeting of hairpin-forming sequences in the lagging strand template during DNA replication.

Long-term Follow-up of Patients Undergoing Endoscopic Intervention for Abdominal Pain with Minimal Biliary Ductal Dilation, Stone Disease, or Malignancy.

BACKGROUND: Safety and efficacy of endoscopic methods in management of biliary colic after cholecystectomy in patients with minimal biliary ductal dilation and no evidence of biliary stones or malignancy have not been clearly demonstrated. This study aimed to assess the efficacy of endoscopic management of such patients. METHODS: The University of Louisville database was queried for patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for colicky abdominal pain between 1996 and 2016 who had a common bile duct (CBD) diameter of ≤12 mm. All patients had undergone prior cholecystectomy and were free of malignancy. Demographic, serologic, procedural, and outcome variables were assessed. RESULTS: A total of 35 patients underwent a total of 99 ERCPs. Median CBD diameter was 10 (range 4-12) mm. A total of 31 patients (89%) underwent sphincterotomy, 28 (80%) underwent stent placement, and 5 (14%) underwent balloon dilation. The median number of ERCPs performed was 2 (range 1-10). Three of the 35 patients (9%) developed post-ERCP pancreatitis at some point during their treatment. At last follow-up since initial ERCP (median 16 months, range 2.4-184 months), 12 (34%) patients endorsed abdominal pain and 11 (31%) reported experiencing nausea. CONCLUSION: For select patients with abdominal pain in the setting of minimal CBD dilation and no evidence of stone disease or malignancy, ERCP can safely and effectively be used to manage symptoms. While patients may require multiple interventions, they can derive long-term relief from these procedures.

Women Veterans' Experiences with Perceived Gender Bias in U.S. Department of Veterans Affairs Specialty Care.

BACKGROUND: In the past decade, the U.S. Department of Veterans Affairs (VA) has responded to a dramatic increase in women veterans seeking care by expanding Women's Health training to more than 5,000 women's health primary care providers and changing the culture of the VA to be more inclusive of women veterans. These initiatives have resulted in increased patient satisfaction and quality of care, but have focused mostly on primary care settings. Less is known about women's experiences in specialty care within VA. This qualitative study sought to examine women veterans' experiences with VA specialty care providers, with a focus on cardiovascular, musculoskeletal, and mental health care settings. METHODS: Semistructured interviews were conducted with 80 women veterans who served during the Iraq and Afghanistan conflicts at four VA facilities nationwide. Interviews focused on understanding women veterans' experiences with VA specialty care providers, including their perceptions of gender bias. RESULTS: Four major themes emerged from interviews, including that 1) women did not feel that VA specialty care providers listened to them or took their symptoms seriously, 2) women were told their health conditions or symptoms were attributable to hormonal fluctuations, 3) women noted differences in care based on whether the VA specialty provider was male or female, and 4) women provided recommendations for how gender-sensitive specialty care might be improved. CONCLUSIONS: This study is the first to highlight the perceived gender bias experienced by women veterans in VA specialty care. Women felt that their symptoms were disregarded or diminished by their specialty care providers. Although women veterans report positive experiences within women's health clinics and the primary care setting, their negative experiences in VA specialty care suggest that some providers may harbor unintentional or unconscious gender biases.

Safety, Efficacy, and Technical Details of Endoscopic Retrograde Cholangiopancreatography After Irreversible Electroporation for Locally Advanced Pancreatic Cancer.

BACKGROUND: Patients undergoing irreversible electroporation (IRE) for locally advanced pancreatic cancer (LAPC) may experience biliary obstruction owing to inflammation generated by tumor ablation. This study assessed the safety, efficacy, and technical details of endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression after IRE. METHODS: A single-institution database of patients undergoing IRE for LAPC between 2012 and 2017 was queried for patients requiring post-IRE ERCP. Patients were evaluated along demographic, laboratory, procedural, and outcome measures. RESULTS: Of 113 patients with LAPC who underwent IRE, 6 (5.3%) required subsequent ERCP for biliary obstruction. A total of 12 ERCPs were performed. Two patients (33%) had duodenal bulb narrowing requiring dilation, and one patient (17%) had a pancreatic head cyst complicating guidewire passage. Biliary cannulation was achieved in all patients in a median time of 30 min. Four patients (67%) underwent sphincterotomy, and 5 (83%) underwent stent placement. Post-procedurally, all showed liver test improvement. None developed pancreatitis. Four patients underwent a 2nd ERCP. All were successful and included stent placement. CONCLUSIONS: For patients with biliary obstruction after IRE, ERCP with sphincterotomy and stent placement can safely relieve this obstruction. Duodenal dilation and careful guidewire manipulation may be required to maximize technical success in these patients.