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.].

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.

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.

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.

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.

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.

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.

Social isolation alters behavior, the gut-immune-brain axis, and neurochemical circuits in male and female prairie voles.

The absence of social support, or social isolation, can be stressful, leading to a suite of physical and psychological health issues. Growing evidence suggests that disruption of the gut-immune-brain axis plays a crucial role in the negative outcomes seen from social isolation stress. However, the mechanisms remain largely unknown. The socially monogamous prairie vole (Microtus ochrogaster) has been validated as a useful model for studying negative effects of social isolation on the brain and behaviors, yet how the gut microbiome and central immune system are altered in isolated prairie voles are still unknown. Here, we utilized this social rodent to examine how social isolation stress alters the gut-immune-brain axis and relevant behaviors. Adult male and female prairie voles (n = 48 per sex) experienced social isolation or were cohoused with a same-sex cagemate (control) for six weeks. Thereafter, their social and anxiety-like behaviors, neuronal circuit activation, neurochemical expression, and microgliosis in key brain regions, as well as gut microbiome alterations from the isolation treatment were examined. Social isolation increased anxiety-like behaviors and impaired social affiliation. Isolation also resulted in sex- and brain region-specific alterations in neuronal activation, neurochemical expression, and microgliosis. Further, social isolation resulted in alterations to the gut microbiome that were correlated with key brain and behavioral measures. Our data suggest that social isolation alters the gut-immune-brain axis in a sex-dependent manner and that gut microbes, central glial cells, and neurochemical systems may play a critical, integrative role in mediating negative outcomes from social isolation.

Role of Long Noncoding RNA Gas5 in Cocaine Action.

BACKGROUND: Long noncoding RNAs (lncRNAs) are a class of transcribed RNA molecules greater than 200 nucleotides in length. Although lncRNAs do not encode proteins, they play numerous functional roles in gene expression regulation. lncRNAs are notably abundant in brain; however, their neural functions remain largely unknown. METHODS: We examined the expression of the lncRNA Gas5 in nucleus accumbens (NAc), a key brain reward region, of adult male mice after cocaine administration. We then performed viral-mediated overexpression of Gas5 in NAc neurons to determine its role in addiction-related behaviors. We also carried out RNA sequencing to investigate Gas5-mediated transcriptomic changes. RESULTS: We demonstrated that repeated short-term or long-term cocaine administration decreased expression of Gas5 in NAc. Viral-mediated overexpression of Gas5 in NAc neurons decreased cocaine-induced conditioned place preference. Likewise, Gas5 overexpression led to decreased cocaine intake, decreased motivation, and compulsive-like behavior to acquire cocaine, and it facilitated extinction of cocaine-seeking behavior. Transcriptome profiling identified numerous Gas5-mediated gene expression changes that are enriched in relevant neural function categories. Interestingly, these Gas5-regulated gene expression changes significantly overlap with chronic cocaine-induced transcriptome alterations, suggesting that Gas5 may serve as an important regulator of transcriptional responses to cocaine. CONCLUSIONS: Altogether, our study demonstrates a novel lncRNA-based molecular mechanism of cocaine action.

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.

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.

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.

Mesohaline conditions represent the threshold for oxidative stress, cell death and toxin release in the cyanobacterium Microcystis aeruginosa.

As aquatic ecosystems become increasingly affected by hydrologic alterations, drought and sea level rise a need exists to better understand the biological effects of elevated salinity on toxigenic cyanobacteria such as Microcystis aeruginosa. This study investigated the impacts of oligohaline/low mesohaline conditions and exposure time on selected physiological and biochemical responses in M. aeruginosa including cell viability, oxidative stress, antioxidant responses, in addition to microcystin synthesis and release into the surrounding environment. M. aeruginosa was able to grow in most test salinity treatments (1.4-10 ppt), as supported by cell abundance data and chlorophyll-a (chl-a) concentrations. Physiological data showed that after certain salinity thresholds (∼7ppt) were surpassed, salt stress had cascading effects, such as increased ROS production and lipid peroxidation, potentiating the decline in cellular viability. Furthermore, elevated salinity induced oxidative stress which was concomitant with a decrease in cell abundance, chl-a concentration and photochemical efficiency in the 7-10 ppt treatments. M. aeruginosa did not synthesize microcystins (MCs) in response to increased saline conditions, and mcy-D expression was not correlated with either salinity treatment or extracellular MC concentrations, indicating that salinity stress could inhibit toxin production and that released toxins were likely synthesized prior to exposure. Additionally, extracellular MC concentrations were not correlated with decreased cellular integrity, as evidenced by SYTOX analyses, suggesting that toxins may be released through mechanisms other than cellular lysis. Results from this study support that M. aeruginosa can survive with limited negative impacts to cellular structure and function up to a certain threshold between 7-10 ppt. However, after these thresholds are surpassed, there is radical decline in cell health and viability leading to toxin release. This work underscores the importance of understanding the balance between ROS production and antioxidant capacities when assessing the fate of M. aeruginosa under mesohaline conditions.

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.

Correlation of Biliary Colic in the Absence of Cholelithiasis with Pancreaticobiliary Obstruction.

A small fraction of patients undergoing cholecystectomy for biliary colic are subsequently diagnosed with an obstructive pancreatic head mass. We review our experience with such patients to provide insight into improving evaluation before cholecystectomy. Retrospective chart review of patients undergoing cholecystectomy from 2004 to 2015 identified six patients who underwent laparoscopic cholecystectomy for biliary colic before being diagnosed with a pancreatic head neoplasm within six months after cholecystectomy. Charts were analyzed for presenting symptoms, evaluation before and after cholecystectomy, and operative findings. Patients ranged from 50 to 72 years of age and included five males and one female. None had evidence of cholelithiasis or acute cholecystitis on initial evaluation. Median time from cholecystectomy to diagnosis of pancreatic head mass was two months (range 1-5 months). Two patients eventually underwent pancreaticoduodenectomy. Patients with symptoms of biliary colic in the absence of evidence of cholecystitis or choledochal abnormality should undergo intraoperative cholangiogram at the time of cholecystectomy as well as close clinical follow-up to ensure resolution of symptoms. Abnormalities of either should prompt radiographic evaluation focused on identification of a pancreatic mass causing extrinsic compression of the bile duct.

Detection of cyanotoxins (microcystins/nodularins) in livers from estuarine and coastal bottlenose dolphins (Tursiops truncatus) from Northeast Florida.

Microcystins/Nodularins (MCs/NODs) are potent hepatotoxic cyanotoxins produced by harmful algal blooms (HABs) that occur frequently in the upper basin of the St. Johns River (SJR), Jacksonville, FL, USA. Areas downstream of bloom locations provide critical habitat for an estuarine population of bottlenose dolphins (Tursiops truncatus). Since 2010, approximately 30 of these dolphins have stranded and died within this impaired watershed; the cause of death was inconclusive for a majority of these individuals. For the current study, environmental exposure to MCs/NODs was investigated as a potential cause of dolphin mortality. Stranded dolphins from 2013 to 2017 were categorized into estuarine (n = 17) and coastal (n = 10) populations. Because estuarine dolphins inhabit areas with frequent or recurring cyanoblooms, they were considered as a comparatively high-risk group for cyanotoxin exposure in relation to coastal animals. All available liver samples from estuarine dolphins were tested regardless of stranding date, and samples from coastal individuals that stranded outside of the known cyanotoxin bloom season were assessed as controls. The MMPB (2-methyl-3-methoxy-4-phenylbutiric acid) technique was used to determine total (bound and free) concentrations of MCs/NODS in liver tissues. Free MCs/NODs extractions were conducted and analyzed using ELISA and LC-MS/MS on MMPB-positive samples to compare test results. MMPB testing resulted in low-level total MCs/NODs detection in some specimens. The Adda ELISA produced high test values that were not supported by concurrent LC-MS/MS analyses, indicative of false positives. Our results indicate that both estuarine and coastal dolphins are exposed to MCs/NODs, with potential toxic and immune health impacts.

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.