Ivermectin toxicokinetics in rainbow trout (Oncorhynchus mykiss) following P-glycoprotein inhibition.

Changes to ivermectin (IVM [22,23-dihydro avermectin B1a + 22,23-dihydro avermectin B1b]) toxicokinetics (TK) with and without P-glycoprotein (P-gp) inhibition by cyclosporin A (CsA) were examined in rainbow trout (Oncorhynchus mykiss). Rainbow trout were injected with 175 μg/kg H-IVM (8.6 μCi/mg IVM) with or without co-administration of 480 μg/kg CsA into the caudal vasculature.

Potency and mechanism of p-glycoprotein chemosensitizers in rainbow trout (Oncorhynchus mykiss) hepatocytes.

The membrane efflux transporter P-glycoprotein (P-gp, [ABCB1, MDR1]) exports a wide range of xenobiotic compounds, resulting in a continuous first line of defense against toxicant accumulation at basal expression levels, and contributing to the multixenobiotic resistance (MXR) phenotype at elevated expression levels. Relatively little information exists on P-gp inhibition in fish by chemosensitizers, compounds which lower toxicity thresholds for harmful P-gp substrates in complex mixtures. The effects of four known mammalian chemosensitizers (cyclosporin A [CsA], quinidine, valspodar [PSC833], and verapamil) on the P-gp-mediated transport of rhodamine 123 (R123) and cortisol in primary cultures of rainbow trout (Oncorhynchus mykiss) hepatocytes were examined.

Measuring Implicit Bias in ICU Notes Using Word-Embedding Neural Network Models.

Background: Language in nonmedical data sets is known to transmit human-like biases when used in natural language processing (NLP) algorithms that can reinforce disparities. It is unclear if NLP algorithms of medical notes could lead to similar transmissions of biases.

Research Question: Can we identify implicit bias in clinical notes, and are biases stable across time and geography?

Study Design And Methods: To determine whether different racial and ethnic descriptors are similar contextually to stigmatizing language in ICU notes and whether these relationships are stable across time and geography, we identified notes on critically ill adults admitted to the University of California, San Francisco (UCSF), from 2012 through 2022 and to Beth Israel Deaconess Hospital (BIDMC) from 2001 through 2012.

Ivermectin Toxicokinetics in Rainbow Trout (Oncorhynchus mykiss) following P-glycoprotein Induction.

Alterations in ivermectin (IVM, 22,23-dihydro avermectin B1a+22,23-dihydro avermectin B1b) toxicokinetics following P-glycoprotein (P-gp) induction by clotrimazole (CTZ) were examined in rainbow trout (Oncorhynchus mykiss) to assess the potential importance of P-gp activity levels in xenobiotic distribution and kinetics in fish. Control and fish pretreated with CTZ (30 µmol/kg) were administered 175 µg/kg H-IVM into the caudal vasculature. At various time points (0.

Effects of the chemosensitizer verapamil on P-glycoprotein substrate efflux in rainbow trout hepatocytes.

The ATP-dependent membrane transporter P-glycoprotein (P-gp) is associated with resistance to a wide variety of chemical substrates, as well as the multi-drug resistance (MDR) phenotype in mammals. Less is known regarding P-gp's function and relevance in teleosts; this study expanded the range of known substrates and the inhibitory effects of a model chemosensitizer verapamil. The P-gp-mediated uptake and efflux dynamics of 5 known mammalian substrates (berberine, cortisol, doxorubicin, rhodamine 123 [R123], and vinorelbine) were examined in isolated rainbow trout (Oncorhynchus mykiss) hepatocytes with and without co-exposure to varying doses of verapamil.

The effects of SLICE®- and ivermectin-contaminated sediment on avoidance behaviour and oxygen consumption in marine benthic invertebrates.

Pest management strategies to reduce sea lice infestations in the salmon aquaculture industry include in-feed treatments with ivermectin (IVM) and SLICE® (active ingredient [AI] emamectin benzoate [EMB]), which can result in local contamination of the environment. These compounds partition to sediments, have moderate persistence, and may pose a risk to non-target benthic organisms. The sub-lethal effects of EMB, IVM and a combination of both (EMB/IVM) on the benthic amphipod Eohaustorius estuarius and polychaete Nereis virens at environmentally relevant sediment concentrations were examined in subchronic exposures (28-30-d).

The effects of P-glycoprotein induction on ivermectin-induced behavioural alterations in zebrafish (Danio rerio) under varying diets.

The neuroprotective effects of inducing the blood-brain barrier ATP-binding cassette protein transporter P-glycoprotein (P-gp) with clotrimazole (CTZ) in both fed and fasted zebrafish (Danio rerio) against the CNS-toxicant ivermectin (IVM, 22,23-dihydro avermectin B1a + 22,23-dihydro avermectin B1b) were examined. Zebrafish were administered 2 μmol/kg IVM intraperitoneally, and various behavioural assays (swimming performance, exploratory behaviour, olfactory responses, motor coordination, and escape responses) were used to measure neurological dysfunction. IVM administration alone caused a decrease in mean swim speed (91 % of controls), maximal speed (71 %), passage rate (81 %), 90° turns (81 %), and response to food stimulus (39 %).

Age matters: Comparing life-stage responses to diluted bitumen exposure in coho salmon (Oncorhynchus kisutch).

Millions of liters of diluted bitumen (dilbit), a crude oil product from Canada's oil sands region, is transported through critical Pacific salmon habitat each day. While the toxicity of the water-soluble fraction of dilbit (WSFd) to early life-stages of salmon is known, quantitative data on life-stage differences in sensitivity to WSFd is missing. To fill this knowledge gap, we exposed two juvenile life-stages of coho salmon (O.

P-glycoprotein inhibition affects ivermectin-induced behavioural alterations in fed and fasted zebrafish (Danio rerio).

The role of the blood-brain barrier ATP-binding cassette protein transporter P-glycoprotein (P-gp) in protecting zebrafish (Danio rerio) from the central nervous system neurotoxicant ivermectin (IVM, 22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b) was examined in the absence and presence of the competitive inhibitor cyclosporin A (CsA). Zebrafish injected intraperitoneally with 1, 2, 5, or 10 µmol/kg IVM exhibited mortality 30 min following administration at the highest dose. At sublethal doses > 1 µmol/kg, IVM altered the swimming performance, exploratory behaviour, motor coordination, escape response and olfactory response in exposed fish.

Diluted Bitumen Affects Multiple Physiological Systems in Sockeye Salmon (Oncorhynchus nerka) Embryo to Juvenile Life Stages.

An understanding of the risks associated with diluted bitumen (dilbit) transport through Pacific salmon habitat necessitates the identification and quantification of hazards posed to early life stages. Sockeye from the embryo to juvenile stage (8 months old) were exposed to four concentrations of the water-soluble fraction of Cold Lake dilbit (summer blend; concentrations of 0, 13.7, 34.

Diluted bitumen-induced alterations in aerobic capacity, swimming performance, and post-exercise recovery in juvenile sockeye salmon (Oncorhynchus nerka).

The transportation of heavy crudes such as diluted bitumen (dilbit) sourced from Canadian oil sands through freshwater habitat requires the generation of information that will contribute to risk assessments, spill modelling, management, and remediation for the protection of aquatic organisms. Juvenile sockeye salmon (Oncorhynchus nerka) were exposed acutely (96 h) or subchronically (28 d) to the water-soluble fraction (WSFd) of Cold Lake Blend dilbit at initial total polycyclic aromatic compound (TPAC) concentrations of 0, 13.7, 34.

A Focus on Amputation Level: Factors Preventing Length Preservation in the National Inpatient Sample.

Background: Diabetic lower-extremity disease is the primary driver of mortality in patients with diabetes. Amputations at the forefoot or ankle preserve limb length, increase function, and, ultimately, reduce deconditioning and mortality compared with higher-level amputations, such as below-the-knee amputations (BKAs). We sought to identify risk factors associated with amputation level to understand barriers to length-preserving amputations (LPAs).

Lethal and sublethal effects in Pink salmon (Oncorhynchus gorbuscha) following exposure to five aquaculture chemotherapeutants.

Early life stages of Pink salmon (Oncorhynchus gorbuscha) are at risk of exposure to the active ingredients of chemotherapeutant formulations (hydrogen peroxide [HP], azamethiphos [AZ], emamectin benzoate [EB], cypermethrin [CP] and deltamethrin [DM]) used to control sea lice in salmon aquaculture. LC50 values (95% confidence intervals) for acute 48-h water exposures in order of least to most toxic to seawater-adapted pink salmon fry were: HP (227 [138-418] mg/L), EB (1090 [676-2006] µg/L), AZ (80 [52-161] µg/L), CP (5.1 [3.

Environmental modulators of diluted bitumen effects in juvenile pink salmon (Oncorhynchus gorbuscha).

Recent and potential expansions in the transportation of diluted bitumen (dilbit) through marine terminals in coastal regions of British Columbia require the examination of potential risks to estuarine species such as Pacific salmon. The estuarine habitat of out-migrated pink salmon (Oncorhynchus gorbuscha) exhibits dynamic temperature and salinity regimes, possibly modifying dilbit exposure, bioavailability and/or its effects. To examine dilbit toxicity and its modification by environmental stressors, juvenile pinks were subchronically exposed for 3 months to the water-accommodated fraction (WAF) of Cold Lake Blend dilbit (winter) in seawater at three salinities (7, 14, and 28‰ [temperature 12.

Surgical Management of Lower Extremity Wounds in the Solid Organ Transplant Patient Population: Surgeon Beware.

To evaluate our institutional outcomes of surgical management of lower extremity (LE) wounds in the solid organ transplant recipient population. An 8-year retrospective review was conducted for all solid organ transplantation (SOT) recipients with LE wounds necessitating surgical management at our tertiary limb salvage center. Outcomes of interest included wound healing, surgical treatment, progression to amputation, and amputation level.

P-glycoprotein induction and its energetic costs in rainbow trout (Oncorhynchus mykiss).

Biological organisms are constantly challenged by xenobiotics and have evolved mechanisms to reduce, neutralize, or repair toxic outcomes. The various chemical defenses all utilize energy, but their specific costs and impacts on energy budgets are currently unknown. In this study, the energetic costs associated with the induction and substrate transport of the efflux transporter P-glycoprotein (P-gp [ABCB1, MDR1]) were examined in rainbow trout.

Short communication: Tissue-specific transcript expression of P-glycoprotein isoforms abcb1a and abcb1b in rainbow trout (Oncorhynchus mykiss) following induction with clotrimazole.

P-glycoprotein (P-gp) plays a pivotal role in cellular defense, aimed at reducing xenobiotic accumulation. As a member of the ABC family of proteins, expression of this protein confers the multixenobiotic resistant (MXR) phenotype in aquatic organisms, including fish. To identify tissues protected by or contributing to the elimination of xenobiotics via P-gp, tissue-specific P-gp isoforms abcb1a and abcb1b transcript expression were measured in rainbow trout (Oncorhynchus mykiss).

Quantitative Results of Perfusion Utilising Hyperspectral Imaging on Non-diabetics and Diabetics: A Pilot Study.

There is a paucity of quantitative measures of microvascular perfusion values in the skin. Newly developed, handheld hyperspectral imaging devices identify unique spectral fingerprints of oxygenated and deoxygenated haemoglobin in the superficial microvasculature. Establishing value ranges for healthy patients without vascular complications will subsequently help standardise assessments for perfusion defects.

Ankle Disarticulation: An Underutilized Approach to Staged Below Knee Amputation-Case Series and Surgical Technique.

The staged approach to below knee amputation has proven to be an effective method of achieving functionality after amputation and reducing risk for postamputation complications. Transtibial or "guillotine" amputations are often used as the first-stage amputation. Disarticulation at the ankle joint is an alternative method that can be used with favorable results and benefits.

Effects of diluted bitumen exposure and recovery on the seawater acclimation response of Atlantic salmon smolts.

Petrogenic chemicals are common and widespread contaminants in the aquatic environment. In Canada, increased extraction of bitumen from the oil sands and transport of the major crude oil export product, diluted bitumen (dilbit), amplifies the risk of a spill and contamination of Canadian waterways. Fish exposed to sublethal concentrations of crude oil can experience a variety of adverse physiological effects including osmoregulatory dysfunction.

Effects of diluted bitumen exposure on Atlantic salmon smolts: Molecular and metabolic responses in relation to swimming performance.

Canada's oil sands industry continues to expand and the volume of diluted bitumen (dilbit) transported across North America is increasing, adding to spill risk and environmental contamination. Dilbit exposure is known to cause adverse effects in fish, but linking molecular and cellular changes with ecologically-relevant individual performance metrics is needed to better understand the potential consequences of a dilbit spill into the aquatic environment. Therefore, this study examined the effects of dilbit exposure on subcellular responses in cardiac and skeletal muscle in relation to swimming performance in a migratory fish species at risk of exposure, Atlantic salmon.

Early Definitive Care Is as Effective as Staged Treatment Protocols for Open Ankle Fractures Caused by Rotational Mechanisms: A Retrospective Case-Control Study.

Objectives: To compare immediate internal fixation with primary wound closure to temporary fixation/stabilization with delayed fixation and wound closure protocols for management of open ankle fractures.

Design: Retrospective case-control study.

Setting: Level 1 trauma center.

Physiological disturbances in juvenile sockeye salmon (Oncorhynchus nerka) exposed to the water-soluble fraction of diluted bitumen.

Current and proposed transcontinental pipelines for the transport of diluted bitumen (dilbit) from the Canadian oil sands traverse the coastal watersheds of British Columbia, habitat essential to Pacific salmonids. To determine the potential risks posed to these keystone species, juvenile sockeye (Oncorhynchus nerka; 1+ parr) were acutely (24-96 h) or subchronically (21-42 d) exposed to 4 concentrations of the water-soluble fraction (WSF) of unweathered Cold Lake Blend dilbit (initial total PAC concentrations: 0, 13.7, 34.

Massive Thymic Hyperplasia Mimicking Anterior Mediastinal Neoplasia in Occult Graves' Disease.

 Thymic hyperplasia is a recognized complication of Graves' disease that can present radiologically as an anterior mediastinal mass.  We present a unique case of massive thymic hyperplasia occurring in a 24-year-old female without a known history of thyroid or other systemic disease in whom Graves' disease first manifested intraoperatively during thymectomy for presumed neoplasia.  We suggest that the work-up of all anterior mediastinal masses should include a comprehensive search for medical causes of reversible thymic enlargement.