Diagnostic and surgical treatment for traumatic bile peritonitis in dogs and cats.

OBJECTIVE: To describe short-term outcomes of dogs and cats undergoing surgery for traumatic bile peritonitis. ANIMALS: 13 dogs and 4 cats. METHODS: Multi-institutional, retrospective study. Medical records from 6 institutions were reviewed for cases of traumatic bile peritonitis between 2006 and 2022. Clinical presentation, additional injuries, surgical treatment, and outcome were recorded. RESULTS: Trauma occurred a median of 2 (range, 1 to 22) and 4 (range, 1 to 22) days prior to presentation in dogs and cats, respectively. Total bilirubin was increased in 11 of 13 dogs and 2 of 4 cats. Rupture occurred at the common bile duct (CBD) in 10 dogs and 1 cat, gallbladder in 3 dogs, cystic duct in 2 cats, and hepatic duct in 1 dog and 1 cat. The most common surgeries were cholecystoduodenostomy and CBD repair in dogs and cholecystectomy in cats. Eleven of 13 dogs and all cats survived to hospital discharge (88.2% overall survival). Median follow-up in surviving dogs and cats was 35 days (range, 14 to 401) and 30 days (range, 14 to 90), respectively. One dog that underwent cholecystectomy experienced recurrent bile peritonitis 20 days postoperatively. Short-term survival following surgical treatment of traumatic bile peritonitis was excellent and recurrence appears uncommon. The most frequent site of rupture was the CBD in dogs and the cystic duct in cats. CLINICAL RELEVANCE: Measurement of peritoneal bilirubin should be considered in dogs and cats with peritoneal effusion following trauma. Surgeons should be prepared to identify and address ruptures in locations other than the gallbladder.

Occupation-specific, high-intensity cardiac rehabilitation for return to work of a young police officer after myocardial infarction from traumatic coronary artery dissection.

Following a traumatic coronary artery dissection and subsequent myocardial infarction from a nonpenetrating strike to the chest by an airborne metal pipe, a 33-year-old male police officer completed 12 weeks of high-intensity, symptom-limited cardiac rehabilitation in order to return to active duty. Physiological and perceptual responses to exercise were used to progress the patient through high-intensity activities that challenged the musculoskeletal and cardiorespiratory systems while simulating real work activities. In addition to substantial improvements in functional capacity (8.6 to 10.3 METS) and left ventricular ejection fraction (20% to 45%), the patient was able to fully return to work as an active-duty police officer.

Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study.

PURPOSE: Determine whether specific CTNNB1 or APC mutations in patients with desmoid tumor were associated with differences in clinical responses to systemic treatments. EXPERIMENTAL DESIGN: We established a multi-institutional dataset of previously treated patients with desmoid tumor across four U.S. sarcoma centers, including demographic and clinicopathologic characteristics, treatment regimens, and clinical and radiographic responses. CTNNB1 or APC mutation status was determined from prior pathology records, or archival tissue was requested and analyzed by Sanger sequencing and/or next-generation sequencing. Evaluable patients with mutation results were analyzed to determine clinical progression-free survival (cPFS), RECIST 1.1 PFS (rPFS), time to next treatment (TTNT), and overall survival (OS). Kaplan-Meier analysis and Cox proportional hazards regression were performed to identify differences in cPFS, rPFS, TTNT, and OS by mutation subtype, desmoid tumor location, and treatment regimen. RESULTS: A total of 259 evaluable patients were analyzed for at least one of the survival outcomes, with 177 patients having mutation data. First- and second-line cPFS, rPFS, and TTNT were not significantly affected by mutation subtype; however, APC-mutant desmoid tumors demonstrated nonstatistically significant inferior outcomes. Extremity/trunk desmoid tumor location and treatment with doxorubicin-based, methotrexate/vinca alkaloids and sorafenib regimens were associated with better clinical outcomes compared with surgery or "other" therapies, including estrogen-receptor blockade and imatinib. OS was significantly worse with APC or CTNNB1 negative/other mutations. CONCLUSIONS: Mutation subtype did not affect responses to specific systemic therapies. APC mutations and nonextremity desmoid tumor locations remain prognostic for worse outcomes, and earlier initiation of systemic therapy for these higher-risk desmoid tumors should be prospectively evaluated. See related commentary by Greene and Van Tine, p. 3911.

Multiplexed transcriptional repression identifies a network of bactericidal interactions between mycobacterial respiratory complexes.

Mycobacterium tuberculosis remains a leading cause of infectious disease morbidity and mortality for which new drug combination therapies are needed. Combinations of respiratory inhibitors can have synergistic or synthetic lethal interactions with sterilizing activity, suggesting that regimens with multiple bioenergetic inhibitors could shorten treatment times. However, realizing this potential requires an understanding of which combinations of respiratory complexes, when inhibited, have the strongest consequences on bacterial growth and viability. Here we have used multiplex CRISPR interference (CRISPRi) and Mycobacterium smegmatis as a physiological and molecular model for mycobacterial respiration to identify interactions between respiratory complexes. In this study, we identified synthetic lethal and synergistic interactions between respiratory complexes and demonstrated how the engineering of CRISPRi-guide sequences can be used to further explore networks of interacting gene pairs. These results provide fundamental insights into the functions of and interactions between bioenergetic complexes and the utility of CRISPRi in designing drug combinations.

Impact of symptom-guided, progressive cardiac rehabilitation after left ventricular assist device implantation.

A 29-year-old woman with a left ventricular assist device (LVAD) completed a progressive, symptom-limited cardiac rehabilitation program consisting of boxing, weight-lifting, and aerobic exercise, where she improved her exercise capacity by 2.7 metabolic equivalents (P < 0.001) and demonstrated significant myocardial recovery, allowing for successful LVAD explant 9 months after implantation.

The effects of a novel inhibitor of tumor necrosis factor (TNF) alpha on prepulse inhibition and microglial activation in two distinct rodent models of schizophrenia.

Increased neuroinflammation has been shown in individuals diagnosed with schizophrenia (SCHZ). This study evaluated a novel immune modulator (PD2024) that targets the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) to alleviate sensorimotor gating deficits and microglial activation employing two different rodent models of SCHZ. In Experiment 1, rats were neonatally treated with saline or the dopamine D2-like agonist quinpirole (NQ; 1 mg/kg) from postnatal day (P) 1-21 which produces increases of dopamine D2 receptor sensitivity throughout the animal's lifetime. In Experiment 2, rats were neonatally treated with saline or the immune system stimulant polyinosinic:polycytidylic acid (Poly I:C) from P5-7. Neonatal Poly I:C treatment mimics immune system activation associated with SCHZ. In both experiments, rats were raised to P30 and administered a control diet or a novel TNFα inhibitor PD2024 (10 mg/kg) in the diet from P30 until P67. At P45-46 and from P60-67, animals were behaviorally tested on auditory sensorimotor gating as measured through prepulse inhibition (PPI). NQ or Poly I:C treatment resulted in PPI deficits, and PD2024 treatment alleviated PPI deficits in both models. Results also revealed that increased hippocampal and prefrontal cortex microglial activation produced by neonatal Poly I:C was significantly reduced to control levels by PD2024. In addition, a separate group of animals neonatally treated with saline or Poly I:C from P5-7 demonstrated increased TNFα protein levels in the hippocampus but not prefrontal cortex, verifying increased TNFα in the brain produced by Poly I:C. Results from this study suggests that that brain TNFα is a viable pharmacological target to treat the neuroinflammation known to be associated with SCHZ.

Transcriptional Inhibition of the F1F0-Type ATP Synthase Has Bactericidal Consequences on the Viability of Mycobacteria.

Bedaquiline, an inhibitor of the mycobacterial ATP synthase, has revolutionized the treatment of Mycobacterium tuberculosis infection. Although a potent inhibitor, it is characterized by poorly understood delayed time-dependent bactericidal activity. Here, we demonstrate that in contrast to bedaquiline, the transcriptional inhibition of the ATP synthase in M. tuberculosis and Mycobacterium smegmatis has rapid bactericidal activity. These results validate the mycobacterial ATP synthase as a drug target with the potential for rapid bactericidal activity.

Genome Sequence of the Siphoviridae Staphylococcus aureus Phage vB_SauS_BaqSau1.

Here, we report the genome sequence of a Siphoviridae phage named vB_SauS_BaqSau1 (BaqSau1), infecting Staphylococcus aureus Phage BaqSau1 was isolated from a sewage water treatment plant in Sahagún, Córdoba, Colombia. It has a double-stranded DNA (dsDNA) genome of 44,384 bp with 67 predicted genes, including a lysin containing a CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain.

Effects of an adenosine A2A agonist on the rewarding associative properties of nicotine and neural plasticity in a rodent model of schizophrenia.

BACKGROUND: Adenosine A2a receptors form a mutually inhibitory heteromeric complex with dopamine D2 receptors such that each receptor exhibits lower sensitivity to its agonist after the opposing receptor agonist is bound. This study analyzed the effects of CGS 21680, an adenosine A2A agonist, on nicotine conditioned place preference (CPP) in adolescence using a rodent model of schizophrenia (SZ). METHODS: Rats were treated from postnatal day (P) 1 to P21 with saline or the dopamine D2/D3 agonist quinpirole (NQ treatment) and raised to P41. After an initial preference test, rats were conditioned with saline or nicotine (0.6 mg/kg base) from P43 to P51. CGS 21680 (0.03 or 0.09 mg/kg) was given 15 minutes before nicotine was administered. The post-conditioning test was administered on P52. On P53, the nucleus accumbens (NAcc) was analyzed for brain-derived neurotrophic factor (BDNF) and glial cell-lined neurotrophic factor (GDNF). RESULTS: Results revealed that NQ treatment enhanced nicotine CPP, and both doses of CGS 21680 alleviated this enhancement. Nicotine also resulted in a CPP in controls, which was alleviated by both doses of CGS 21680. BDNF closely followed the behavioral results: CGS 21680 alleviated the enhancement in NAcc BDNF in NQ-treated animals, and eliminated the increase in NAcc BDNF produced by nicotine in controls. NQ-treated animals conditioned to nicotine resulted in an increase of NAcc GDNF, but this was eliminated by CGS 21680. Both BDNF and GDNF correlated with CPP performance. CONCLUSIONS: Results revealed that an adenosine A2A agonist decreased the rewarding aspects of nicotine and its accompanying neural plasticity changes in a model of SZ.

The Effect of Content Delivery Style on Student Performance in Anatomy.

The development of new technologies and ensuing pedagogical research has led many tertiary institutions to integrate and adopt online learning strategies. The authors of this study have incorporated online learning strategies into existing educational practices of a second year anatomy course, resulting in half of the course content delivered via face-to-face lectures, and half delivered online via tailored video vignettes, with accompanying worksheets and activities. The effect of the content delivery mode on student learning was analyzed by tailoring questions to content presented either face-to-face or online. Four practical tests were conducted across the semester with each consisting of four questions. Within each test, two questions were based on content delivered face-to-face, and two questions were based on content delivered online. Examination multiple choice questions were similarly divided and assessed. Findings indicate that student learning is consistent regardless of the mode of content delivery. However, student viewing habits had a significant impact on learning, with students who viewed videos multiple times achieving higher marks than those less engaged with the online content. Student comments also indicated that content delivery mode was not an influence on learning. Therefore student engagement, rather than the mode of content delivery, is a determinant of student learning and performance in human anatomy. Anat Sci Educ. © 2018 American Association of Anatomists.

Short-term microbial effects of a large-scale mine-tailing storage facility collapse on the local natural environment.

We investigated the impacts of the Mount Polley tailings impoundment failure on chemical, physical, and microbial properties of substrates within the affected watershed, comprised of 70 hectares of riparian wetlands and 40 km of stream and lake shore. We established a biomonitoring network in October of 2014, two months following the disturbance, and evaluated riparian and wetland substrates for microbial community composition and function via 16S and full metagenome sequencing. A total of 234 samples were collected from substrates at 3 depths and 1,650,752 sequences were recorded in a geodatabase framework. These data revealed a wealth of information regarding watershed-scale distribution of microbial community members, as well as community composition, structure, and response to disturbance. Substrates associated with the impact zone were distinct chemically as indicated by elevated pH, nitrate, and sulphate. The microbial community exhibited elevated metabolic capacity for selenate and sulfate reduction and an abundance of chemolithoautotrophs in the Thiobacillus thiophilus/T. denitrificans/T. thioparus clade that may contribute to nitrate attenuation within the affected watershed. The most impacted area (a 6 km stream connecting two lakes) exhibited 30% lower microbial diversity relative to the remaining sites. The tailings impoundment failure at Mount Polley Mine has provided a unique opportunity to evaluate functional and compositional diversity soon after a major catastrophic disturbance to assess metabolic potential for ecosystem recovery.

Stereoacuity outcomes following surgical correction of the nonaccommodative component in partially accommodative esotropia.

BACKGROUND: Previous studies of partially accommodative esotropia (PAET) have assessed factors requiring surgery and alignment outcomes. The purpose of the present study was to additionally evaluate stereoacuity in patients who required surgery for their nonaccommodative component. METHODS: The medical records of consecutive patients with PAET who underwent bilateral medial rectus recession from April 1990 to July 2010 to treat the nonaccommodative component were reviewed retrospectively. Preoperative data included visual acuity, stereoacuity, cycloplegic refraction, deviation at distance and near, and age at surgery. The primary outcomes were stereoacuity and alignment. RESULTS: A total of 84 patients were included. Stereopsis by the Titmus StereoTest was demonstrated in 51 (61%) by the final visit. The average follow-up time was 4.4 ± 2.8 years (range, 0.8-11.0 years). Fine stereopsis (100 arcsec or better) was appreciated in 29 patients (35%, 57% of those with stereopsis). Of those with residual esotropia, 11 (50%) demonstrated stereopsis, and 7 (32%) appreciated fine stereoacuity. No exotropic patient had stereopsis. There was a statistically significant correlation between age at time of surgery and stereopsis at 1 year (ρ = 0.233; P = 0.033) but not at the final visit (ρ = 0.106, P = 0.34). Of the 84 patients, 56 (67%) had a favorable alignment (within 10Δ of orthotropia) at the final visit; 22 (26%) had residual esotropia; and 6 (7%) had consecutive exotropia. CONCLUSIONS: In this subset of esotropic patients who required surgery for their nonaccommodative component, favorable sensory outcomes can be achieved. Furthermore, favorable stereoacuity can be found even when there is a residual esodeviation.

Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain in the hepatic sinusoids.

Liver-resident CD8+ T cells are highly motile cells that patrol the vasculature and provide protection against liver pathogens. A key question is: how can these liver CD8+ T cells be simultaneously present in the circulation and tissue-resident? Because liver-resident T cells do not express CD103 - a key integrin for T cell residence in epithelial tissues - we investigated other candidate adhesion molecules. Using intra-vital imaging we found that CD8+ T cell patrolling in the hepatic sinusoids is dependent upon LFA-1-ICAM-1 interactions. Interestingly, liver-resident CD8+ T cells up-regulate LFA-1 compared to effector-memory cells, presumably to facilitate this behavior. Finally, we found that LFA-1 deficient CD8+ T cells failed to form substantial liver-resident memory populations following Plasmodium or LCMV immunization. Collectively, our results demonstrate that it is adhesion through LFA-1 that allows liver-resident memory CD8+ T cells to patrol and remain in the hepatic sinusoids.

The Morscher Press-Fit Acetabular Component: An Independent Long-Term Review at 18-22 Years.

BACKGROUND: There are relatively few 20-year results of uncemented acetabular components, and most of these are modular designs. This study reports the 20-year results of a monoblock press-fit acetabular component. METHODS: A total of 122 total hip arthroplasties (111 patients) using the Morscher cup were reviewed at a mean of 19.7 years. The average age at implantation was 57.3 years (range, 36-74 years), and 81 (66%) were men. RESULTS: Twenty-two patients (25 hips) had died. Seven hips were revised, including 5 acetabular revisions. Six patients (6 hips) declined to participate but were known not to have been revised. The mean Oxford hip score was 41.1 (range, 22-48), and the mean reduced Western Ontario and McMaster Universities Osteoarthritis Index score was 5.7/48 (range, 0-24). Eccentric wear was seen in 13 (15.7%) and major osteolysis in 14 (17%) of 82 surviving hips with radiographs. The all-cause revision rate was 0.32 per 100 observed component years (95% confidence interval [CI], 0.13-0.66). The 20-year Kaplan-Meier survival was 93.4% (CI, 86.6-96.8) for all-cause revisions, 95.5% (CI, 89.4-98.1) for any acetabular revision, and 97.1% (CI, 91.2-99.1) for acetabular aseptic loosening, wear, or osteolysis. CONCLUSION: The Morscher acetabular component has continued to perform well at 20 years despite using conventional polyethylene with results that match or surpass other cementless acetabulae.

Response to Comment on "Worldwide evidence of a unimodal relationship between productivity and plant species richness".

Tredennick et al. criticize one of our statistical analyses and emphasize the low explanatory power of models relating productivity to diversity. These criticisms do not detract from our key findings, including evidence consistent with the unimodal constraint relationship predicted by the humped-back model and evidence of scale sensitivities in the form and strength of the relationship.

Forecasting climate change impacts on the distribution of wetland habitat in the Midwestern United states.

Shifting precipitation patterns brought on by climate change threaten to alter the future distribution of wetlands. We developed a set of models to understand the role climate plays in determining wetland formation on a landscape scale and to forecast changes in wetland distribution for the Midwestern United States. These models combined 35 climate variables with 21 geographic and anthropogenic factors thought to encapsulate other major drivers of wetland distribution for the Midwest. All models successfully recreated a majority of the variation in current wetland area within the Midwest, and showed that wetland area was significantly associated with climate, even when controlling for landscape context. Inferential (linear) models identified a consistent negative association between wetland area and isothermality. This is likely the result of regular inundation in areas where precipitation accumulates as snow, then melts faster than drainage capacity. Moisture index seasonality was identified as a key factor distinguishing between emergent and forested wetland types, where forested wetland area at the landscape scale is associated with a greater seasonal variation in water table depth. Forecasting models (neural networks) predicted an increase in potential wetland area in the coming century, with areas conducive to forested wetland formation expanding more rapidly than areas conducive to emergent wetlands. Local cluster analyses identified Iowa and Northeastern Missouri as areas of anticipated wetland expansion, indicating both a risk to crop production within the Midwest Corn Belt and an opportunity for wetland conservation, while Northern Minnesota and Michigan are potentially at risk of wetland losses under a future climate.

E6-AP facilitates efficient transcription at estrogen responsive promoters through recruitment of chromatin modifiers.

E6-AP is a known coactivator of the estrogen receptor alpha (ERα), however the coactivation mechanism of E6-AP is not clear. This work was undertaken to elucidate the coactivation mechanism of E6-AP. In order to examine the role of E6-AP in ERα signaling, we knocked-down the expression of E6-AP and examined the transactivation functions of ERα. Knockdown of E6-AP showed reduced mRNA production of the ERα target genes pS2 and GREB1 suggesting that E6-AP is required for their proper transcription facilitated by ERα. In order to study the mechanism(s) by which E6-AP regulates the transcriptional functions of ERα, we performed chromatin immunoprecipitation (ChIP) assays under E6-AP knockdown conditions. Our ChIP data suggest that knockdown of E6-AP leads to decreased recruitment of the histone acetylase p300 to the ERα target gene pS2 promoter as well as reduced histone modifications at the promoter. Although there was reduced p300 recruitment to the pS2 promoter, loss of p300 did not account fully for the loss of histone acetylation. Taken together our data suggest that E6-AP regulates the transactivation functions of ERα in part by complexing with p300 and other chromatin modifying enzymes at target gene promoters to create a transcriptionally active promoter environment.