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S Michael Roberts, Dmitri S Bezinover, Piotr K JanickiDepartment of Anesthesiology, Penn State College of Medicine, Penn State Milton S Hershey Medical Center, Hershey, PA, USAAbstract: Chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting are one of the most frequent but also very concerning consequences for patients undergoing chemotherapy or surgical procedures under general anesthesia. There are a variety of mechanisms involved in the activation of nausea and vomiting. Serotonin, a ubiquitous central and peripheral neurotransmitter, is thought to be the predominant mediator of the perception of nausea and triggering of the vomiting response in both the brain and the periphery via the 5-hydroxytryptamine type 3 (5-HT3) receptor pathways. 5-HT3 receptor antagonists disrupt this pathway, largely at the level of the vagal afferent pathways, to decrease nausea and vomiting. This review will focus on dolasetron, an older but sill commonly used 5-HT3 receptor antagonist and its multimodal mechanism of action, safety and tolerability, patient considerations, and a review of the current literature on its use to combat both chemotherapy-induced and postoperative nausea and vomiting in these two important patient populations.Keywords: dolasetron, 5-HT3 antagonists, postoperative, chemotherapy, nausea and vomiting

Roberts SM, Bezinover DS, Janicki PK. Cancer Management and Research. 2012; 4: 67–73.On the first page of the paper the incorrect DOI has been displayed. The correct DOI is: 10.2147/CMAR.S15545.Read the original article.

Infant oral mutilation is the practice of removing developing tooth germs, commonly the mandibular canine, in infants up to the age of 1 year. Subsequent complications include missing, impacted or hypoplastic permanent anterior and canine teeth. We report on a case of bilaterally missing lower canines thought to be due to infant oral mutilation. It is important that general dental practitioners are aware of this practice and resulting complications when treating families from sub-Saharan East Africa. [ABSTRACT FROM AUTHOR]

Objective: Traditional food systems in indigenous groups have historically had health-promoting benefits. The objectives of the present study were to determine if a traditional dietary pattern of Pacific Northwest Tribal Nations (PNwT) could be derived using reduced rank regression and if the pattern would be associated with lower BMI and current Dietary Reference Intakes.Design: The baseline data from the Communities Advancing the Studies of Tribal Nations Across the Lifespan (CoASTAL) cohort were used to derive dietary patterns for the total sample and those with plausibly reported energy intakes.Setting: Pacific Northwest Coast of Washington State, USA.Subjects: Adult PNwT members of the CoASTAL cohort with laboratory-measured weight and height and up to 4 d of dietary records (n 418).Results: A traditional dietary pattern did not evolve from the analysis. Moderate consumption of a sweet drinks dietary pattern was associated with lower BMI while higher consumption of a vegetarian-based dietary pattern was associated with higher BMI. The highest consumers of the vegetarian-based dietary pattern were almost six times more likely to meet the recommendations for dietary fibre.Conclusions: Distinct dietary patterns were found. Further exploration is needed to confirm whether the lack of finding a traditional pattern is due to methodology or the loss of a traditional dietary pattern among this population. Longitudinal assessment of the CoASTAL cohort's dietary patterns needs to continue. [ABSTRACT FROM AUTHOR]

Several soil ingestion studies have indicated that some children ingest substantial amounts of soil on given days. Although the U.S. Environmental Protection Agency (U.S. EPA) has assumed that 95 percent of children ingest 200 mg of soil per day or less for exposure assessment purposes, some children have been observed to ingest up to 25 to 60 g of soil during a single day. In light of the potential for children to ingest such large amounts of soil, an assessment was made of the possibility for soil pica episodes to result in acute intoxication from contaminant concentrations U.S. EPA regards as representing conservative screening values (i.e., U.S. EPA soil screening levels and U.S. EPA Region III risk-based concentrations for residential soils). For a set of 13 chemicals included in the analysis, contaminant doses resulting from a one-time soil pica episode (5 to 50 g of soil ingested) were compared with acute dosages shown to produce toxicity in humans in clinical studies or case reports. For four of these chemicals, a soil pica episode was found to result in a contaminant dose approximating or exceeding the acute human lethal dose. For five of the remaining chemicals, the contaminant dose from a soil pica episode was well within the reported dose range in humans for toxicity other than lethality. Because both the exposure episodes and the toxicological response information are derived from observations in humans, these findings are regarded as particularly relevant for human health risk assessment. They suggest that, for some chemicals, ostensibly conservative soil criteria based on chronic exposure using current U.S. EPA methodology may not be protective of children during acute soil pica episodes. [ABSTRACT FROM AUTHOR]

These highlights focus on research published in the year 2022 and is divided into preoperative, intraoperative, and postoperative sections. The preoperative section includes research on the assessment and optimization of candidates for heart transplantation; donor optimization and the use of extended donors; organ protection systems; donation after circulatory death allografts; recipient factors including cannabis use, sex, race, and comorbidities such as obesity, diabetes mellitus, and peripartum cardiomyopathy; the effects of the 2018 heart allocation policy change on waitlist and postoperative mortality; updates on heart transplantation in patients with coronavirus disease 2019; in pediatric patients; and those who require a bridge to transplant. The intraoperative section includes the use of a multidisciplinary team, a proposed transfusion algorithm, bench surgery on the allograft, and size matching. The postoperative section focuses on the research on the development and management of tricuspid regurgitation, echocardiography, arrhythmia management, and, finally, xenotransplantation., Competing Interests: Declaration of competing interest The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (eg, honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (eg, personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Inspired by the cyclopentenone family of prostaglandins, a series of 4-aza, cross-conjugated cyclopentenones is described. Synthesised from N-protected (4R)-aza-cyclopentenone 5, the exocyclic alkene was installed using a modified Baylis-Hillman type aldol reaction, whereby carbon-carbon bond formation is accompanied by dehydration. In this manner octanal and octenal, for example, can be introduced to mimic the ω-group present in the natural prostaglandins. Similarly, a focused range of alternative substituents were introduced using different aldehydes and ketones. The presence of the tert-butyloxycarbonyl (Boc) group on the 4-amino-cyclopentenone substituent enabled subsequent derivatisation and various electrophiles were successfully incorporated. The ability of the family of 4-amino functionalised cross-conjugated cyclopentenones to block activation of nuclear factor-kappa B (NF-κB) was studied and compared with the natural prostanoid, Δ 12,14 -15-deoxy-PGJ 2 (2). Thereafter, the synthesis of a series of thiol adducts from these compounds were prepared and similarly evaluated biologically. The adducts showed comparable and, on occasion, more potent inhibition of NF-κB than their cyclopentenone precursors and generally demonstrated diminished cytotoxicity. For example, cross-conjugated dieneone 12 inhibited the activation of NF-κB with an IC 50 value of 6.2 μM, whereas its endocyclic N-Boc (27) and N-acetyl (28) cysteine adducts blocked NF-κB activity with values of 1.0 and 8.0 μM respectively., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Abstract: Over the previous 20 years, the use of extracorporeal membranous oxygenation (ECMO) as a bridge to durable left ventricular assist device (dLVAD) increased significantly. Additionally, emerging literature has demonstrated a protective effect of biventricular decompression while on ECMO, with one such strategy including a temporary LVAD and right ventricular assist device (RVAD). The complexity of these operations is increased by the frequency of re-sternotomies, which result in adhesions and difficult access to traditional cannulation sites. In this case report, we present a patient presenting for a re-sternotomy for dLVAD on biventricular support in whom the RVAD outflow cannula was spliced into the cardiopulmonary bypass venous reservoir by the cardiac anesthesiologist. This innovative cannulation strategy allowed for continuation of RVAD flows to prevent thrombosis and active venting of the pulmonary artery to facilitate a bloodless surgical field., (Copyright © 2024 Copyright: © 2024 Annals of Cardiac Anaesthesia.)

Background: The U.S. opioid overdose crisis persists. Outpatient behavioral health services (BHS) are essential components of a comprehensive response to opioid use disorder and overdose fatalities. The Helping to End Addiction Long-Term® (HEALing) Communities Study developed the Communities That HEAL (CTH) intervention to reduce opioid overdose deaths in 67 communities in Kentucky, Ohio, New York, and Massachusetts through the implementation of evidence-based practices (EBPs), including BHS. This paper compares the rate of individuals receiving outpatient BHS in Wave 1 intervention communities (n = 34) to waitlisted Wave 2 communities (n = 33)., Methods: Medicaid data included individuals ≥18 years of age receiving any of five BHS categories: intensive outpatient, outpatient, case management, peer support, and case management or peer support. Negative binomial regression models estimated the rate of receiving each BHS for Wave 1 and Wave 2. Effect modification analyses evaluated changes in the effect of the CTH intervention between Wave 1 and Wave 2 by research site, rurality, age, sex, and race/ethnicity., Results: No significant differences were detected between intervention and waitlisted communities in the rate of individuals receiving any of the five BHS categories. None of the interaction effects used to test the effect modification were significant., Conclusions: Several factors should be considered when interpreting results-no significant intervention effects were observed through Medicaid claims data, the best available data source but limited in terms of capturing individuals reached by the intervention. Also, the 12-month evaluation window may have been too brief to see improved outcomes considering the time required to stand-up BHS., Trial Registration: Clinical Trials.gov http://www., Clinicaltrials: gov: Identifier: NCT04111939., Competing Interests: Declaration of Competing Interest In last three years, MRL has served as a scientific consultant for treatments in development for substance use disorders to Journey Colab, Titan, Braeburn, and Berkshire Biomedical. RDW has consulted to Alkermes., (Copyright © 2024. Published by Elsevier B.V.)

Accurate characterization of soil contaminant concentrations is often crucial for assessing risks to human and ecological health. However, fine-scale assessments of large tracts of land can be cost prohibitive due to the number of samples needed. One solution to this problem is to extrapolate sampling results from one area to another unsampled area. In the absence of a validated extrapolation methodology, regulatory agencies have employed policy-based techniques for large sites, but the likelihood of decision errors resulting from these extrapolations is largely unexplored. This study describes the results of a simulation study aimed at guiding environmental sampling for sites where extrapolation concepts are of interest. The objective of this study is to provide practical recommendations to regulatory agencies for extrapolating sampling results on large tracts of land while minimizing errors that are detrimental to human health. A variety of site investigation scenarios representative of environmental conditions and sampling schemes were tested using adaptive sampling when collecting discrete samples or applying incremental sampling methodology (ISM). These simulations address extrapolation uncertainty in cases where a Pilot Study might result in either false noncompliance or false compliance conclusions. A wide range of plausible scenarios were used that reflect the variety of heterogeneity seen at large sites. This simulation study demonstrates that ISM can be reliably applied in a Pilot Study for purposes of extrapolating the outcome to a large area site because it decreases the likelihood of false non-compliance errors while also providing reliable estimates of true compliance across unsampled areas. The results demonstrate how errors depend on the magnitude of the 95% upper confidence limit for the mean concentration (95UCL) relative to the applicable action level, and that error rates are highest when the 95UCL is within 10%-40% of the action level. The false compliance rate can be reduced to less than 5% when 30% or more of the site is characterized with ISM. False compliance error rates using ISM are insensitive to the fraction of the decision units (DUs) that are characterized with three replicates (with a minimum of 10 percent), so long as 95UCLs are calculated for the DUs with one replicate using the average coefficient of variation from the three replicate DUs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Renin, an aspartate protease, regulates the renin-angiotensin system by cleaving its only known substrate angiotensinogen to angiotensin. Recent studies have suggested that renin may also cleave complement component C3 to activate complement or contribute to its dysregulation. Typically, C3 is cleaved by C3 convertase, a serine protease that uses the hydroxyl group of a serine residue as a nucleophile. Here, we provide seven lines of evidence to show that renin does not cleave C3. First, there is no association between renin plasma levels and C3 levels in patients with C3 Glomerulopathies (C3G) and atypical Hemolytic Uremic Syndrome (aHUS), implying that serum C3 consumption is not increased in the presence of high renin. Second, in vitro tests of C3 conversion to C3b do not detect differences when sera from patients with high renin levels are compared to sera from patients with normal/low renin levels. Third, aliskiren, a renin inhibitor, does not block abnormal complement activity introduced by nephritic factors in the fluid phase. Fourth, aliskiren does not block dysregulated complement activity on cell surfaces. Fifth, recombinant renin from different sources does not cleave C3 even after 24 hours of incubation at 37 °C. Sixth, direct spiking of recombinant renin into sera samples of patients with C3G and aHUS does not enhance complement activity in either the fluid phase or on cell surfaces. And seventh, molecular modeling and docking place C3 in the active site of renin in a position that is not consistent with a productive ground state complex for catalytic hydrolysis. Thus, our study does not support a role for renin in the activation of complement., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Understanding community responses to climate is critical for anticipating the future impacts of global change. However, despite increased research efforts in this field, models that explicitly include important biological mechanisms are lacking. Quantifying the potential impacts of climate change on species is complicated by the fact that the effects of climate variation may manifest at several points in the biological process. To this end, we extend a dynamic mechanistic model that combines population dynamics, such as species interactions, with species redistribution by allowing climate to affect both processes. We examine their relative contributions in an application to the changing biomass of a community of eight species in the Gulf of Maine using over 30 years of fisheries data from the Northeast Fishery Science Center. Our model suggests that the mechanisms driving biomass trends vary across space, time, and species. Phase space plots demonstrate that failing to account for the dynamic nature of the environmental and biologic system can yield theoretical estimates of population abundances that are not observed in empirical data. The stock assessments used by fisheries managers to set fishing targets and allocate quotas often ignore environmental effects. At the same time, research examining the effects of climate change on fish has largely focused on redistribution. Frameworks that combine multiple biological reactions to climate change are particularly necessary for marine researchers. This work is just one approach to modeling the complexity of natural systems and highlights the need to incorporate multiple and possibly interacting biological processes in future models., (© 2023 John Wiley & Sons Ltd.)

Competing Interests: Conflict of Interest None.

Diversity of phage propagation, physical properties, and assembly promotes the use of phages in ecological studies and biomedicine. However, observed phage diversity is incomplete. Bacillus thuringiensis siphophage, 0105phi-7-2, first described here, significantly expands known phage diversity, as seen via in-plaque propagation, electron microscopy, whole genome sequencing/annotation, protein mass spectrometry, and native gel electrophoresis (AGE). Average plaque diameter vs. plaque-supporting agarose gel concentration plots reveal unusually steep conversion to large plaques as agarose concentration decreases below 0.2%. These large plaques sometimes have small satellites and are made larger by orthovanadate, an ATPase inhibitor. Phage head-host-cell binding is observed by electron microscopy. We hypothesize that this binding causes plaque size-increase via biofilm evolved, ATP stimulated ride-hitching on motile host cells by temporarily inactive phages. Phage 0105phi7-2 does not propagate in liquid culture. Genomic sequencing/annotation reveals history as temperate phage and distant similarity, in a virion-assembly gene cluster, to prototypical siphophage SPP1 of Bacillus subtilis . Phage 0105phi7-2 is distinct in (1) absence of head-assembly scaffolding via either separate protein or classically sized, head protein-embedded peptide, (2) producing partially condensed, head-expelled DNA, and (3) having a surface relatively poor in AGE-detected net negative charges, which is possibly correlated with observed low murine blood persistence.

Millions of lead (Pb) pipes are still used in the drinking water distribution systems in many regions in the world. Human exposure to Pb from contaminated drinking water continues to be of concern in the United States (U.S.), as illustrated by the widely publicized "Flint Water Crisis" in 2015. The Pb isotopic composition of Pb-pipes potentially can be useful to identify human exposure to Pb from lead service lines (LSLs). In addition, as the LSLs were likely manufactured from similar industrial Pb sources as other Pb objects and materials in the USA, the Pb-pipes isotope data can provide information about the overall isotopic composition of the U.S. industrial Pb. In this work we present high-precision Pb isotope data from Pb-pipes excavated from different U.S. municipalities. The Pb-pipes show an extremely wide range of Pb isotopic compositions, with 206 Pb/ 204 Pb ranging from 17.004 to 22.010, 207 Pb/ 204 Pb from 15.460 to 15.921, and 208 Pb/ 204 Pb from 36.687 to 41.120. The wide isotope range is observed even in a single town, suggesting that no regional Pb isotope patterns can be expected within the continental USA. However, the high-precision MC-ICP-MS Pb data form a clear linear trend that, depending on the context, can be used to identify human Pb exposure. Furthermore, as the linear trend is a result of utilization of Pb ores from different domestic and international sources and secondary recycling of metallic Pb, it is likely representative of the overall isotopic composition of the U.S. industrial Pb pool. Therefore, the identified trend is the most accurate isotope representation of the U.S. anthropogenic Pb at present and can be used as first-order evaluation to determine if a person with elevated blood Pb levels was exposed to U.S. industrial Pb sources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Preoperative cardiac evaluation is a cornerstone of the practice of anesthesiology. This consists of a thorough history and physical attempting to elucidate signs and symptoms of heart failure, angina or anginal equivalents, and valvular heart disease. Current guidelines rarely recommend preoperative echocardiography in the setting of an adequate functional capacity. Many patients may have poor functional capacity and/or have medical history such that echocardiographic data is available for review. Much focus is often placed on evaluating major valvular abnormalities and systolic function as measured by ejection fraction, but a key impactful component is often overlooked-diastolic function. A diagnosis of diastolic heart failure is an independent predictor of mortality and is not uncommon in patients with normal systolic function. This narrative review addresses the clinical relevance and management of diastolic dysfunction in the perioperative setting.

Many organisms use conspicuous colour patterns to advertise their toxicity or unpalatability, a strategy known as aposematism. Despite the recognized benefits of this anti-predator tactic, not all chemically defended species exhibit warning coloration. Here, we use a comparative approach to investigate which factors predict the evolution of conspicuousness in frogs, a group in which conspicuous coloration and toxicity have evolved multiple times. We extracted colour information from dorsal and ventral photos of 594 frog species for which chemical defence information was available. Our results show that chemically defended and diurnal species have higher internal chromatic contrast, both ventrally and dorsally, than chemically undefended and/or nocturnal species. Among species that are chemically defended, conspicuous coloration is more likely to occur if species are diurnal. Our results also suggest that the evolution of conspicuous colour is more likely to occur in chemically defended prey with smaller body size. We discuss potential explanations for this association and suggest that prey profitability (related to body size) could be an important force driving the macroevolution of warning signals., (© 2022 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.)

Objectives: The primary aim of this study was to assess interobserver variability in grading tricuspid regurgitation (TR) severity. The authors' secondary goals were to delineate which transesophageal echocardiographic (TEE) parameters best correlate with severity and how consistent the participants were at grading severity., Design: This was a prospective cohort study of how clinicians evaluated previously acquired TEE images and videos., Setting: The 19 TEE studies of patients with TR were recorded by 4 senior echocardiographers across 4 US academic institutions. The participants evaluated these cases on a novel, web-based, assessment environment designed specifically for this study., Participants: Twenty-nine fellowship-trained and board-certified cardiologists and cardiothoracic anesthesiologists volunteered to participate in the study as observers from 19 different institutions., Interventions: No interventions were performed on the participants., Measurements and Main Results: For each case, participants measured the vena contracta (VC), proximal isovelocity surface area (PISA), and jet area before giving a final classification on the severity of TR. Variation was highest for effective regurgitant orifice area and lowest for VC and PISA. The coefficient of variation, defined as the standard deviation from the mean divided by the mean, for all cases of trace, mild, moderate and severe TR were as follows: Jet Area-111%, 46%, 48%, 76%; VC-67%, 44%, 43%, 36%; PISA-52%, 48%, 31%, 35%; and effective regurgitant orifice area-127%, 95%, 66%, 58%., Conclusions: The interobserver variation in quantifying TEE parameters for TR is high, suggesting these may be difficult to measure reliably in a busy perioperative setting. Of the parameters assessed, VC and PISA radius had the highest interobserver agreement and the highest correlation with severity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Patients presenting with ulnar-sided wrist pain can pose a diagnostic and therapeutic challenge to physicians because there are several pathologies with similar signs and symptoms. In comparison with adult patients, other etiologies must be considered in the pediatric patient, given the skeletal immaturity and potential for known or unrecognized syndromes. In addition, these patients may not be able to articulate their symptoms as clearly as an adult patient, further stressing the importance of obtaining a pertinent history and performing a focused physical examination. Having a thorough understanding of the anatomy, the varying pathologies, and the indications for surgical and nonsurgical management will assist in improved patient outcomes., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

Recent findings indicate that incidental ingestion of soil by humans primarily involves soil particles <150 µm, rather than <250 µm-sized fraction previously used for most oral bioaccessibility and bioavailability studies. It was postulated that a greater soil surface area in the finer fraction (<150 versus <250 µm) might increase oral bioaccessibility of arsenic (As) in soil. Bioaccessibility and concentrations of As were compared in <150 and <250 µm fractions of 18 soil samples from a variety of arsenic-contaminated sites. The two methods used to measure bioaccessibility were compared - EPA Method 1340 and the California Arsenic Bioaccessibility (CAB) method. Arsenic concentrations were nearly the same or higher in the <150 fraction compared with <250 µm. EPA Method 1340 and the CAB method presented significantly different bioaccessibility results, as well as estimated relative oral bioavailability (RBA) based upon algorithms specific to the methods, but there was no marked difference for <150 and <250 µm soil fractions within either method. When compared with RBA determined previously for these soil samples in vivo in non-human primates, EPA Method 1340 was generally more predictive than the CAB method. Data suggest that soil- or site-specific factors control bioaccessibility under either method and that the test method selected is more important than the particle size fraction (<150 or <250) in using these in vitro methods to predict As RBA for use in risk assessment.

C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS) are two rare diseases caused by dysregulated activity of the alternative pathway of complement secondary to the presence of genetic and/or acquired factors. Complement factor I (FI) is a serine protease that downregulates complement activity in the fluid phase and/or on cell surfaces in conjunction with one of its cofactors, factor H (FH), complement receptor 1 (CR1/CD35), C4 binding protein (C4BP) or membrane cofactor protein (MCP/CD46). Because altered FI activity is causally related to the pathogenesis of C3G and aHUS, we sought to test functional activity of select CFI missense variants in these two patient cohorts. We identified 65 patients (16, C3G; 48, aHUS; 1 with both) with at least one rare variant in CFI (defined as a MAF < 0.1%). Eight C3G and eleven aHUS patients also carried rare variants in either another complement gene, ADAMTS13 or THBD . We performed comprehensive complement analyses including biomarker profiling, pathway activity and autoantibody testing, and developed a novel FI functional assay, which we completed on 40 patients. Seventy-eight percent of rare CFI variants (31/40) were associated with FI protein levels below the 25 th percentile; in 22 cases, FI levels were below the lower limit of normal (type 1 variants). Of the remaining nine variants, which associated with normal FI levels, two variants reduced FI activity (type 2 variants). No patients carried currently known autoantibodies (including FH autoantibodies and nephritic factors). We noted that while rare variants in CFI predispose to complement-mediated diseases, phenotypes are strongly contingent on the associated genetic background. As a general rule, in isolation, a rare CFI variant most frequently leads to aHUS, with the co-inheritance of a CD46 loss-of-function variant driving the onset of aHUS to the younger age group. In comparison, co-inheritance of a gain-of-function variant in C3 alters the phenotype to C3G. Defects in CFH (variants or fusion genes) are seen with both C3G and aHUS. This variability underscores the complexity and multifactorial nature of these two complement-mediated renal diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Goodfellow, Ghiringhelli Borsa, Dunlop, Presti, Meyer, Shao, Roberts, Jones, Pitcher, Taylor, Nester and Smith.)

We present a case of kidney transplantation in a 28-year-old patient who received a heart transplant at 7 weeks of age due to hypoplastic left heart syndrome. The patient's renal insufficiency was the result of chronic immunosuppression and hypertension. The almost 28-year-old graft demonstrated very good function. This patient represents as one of the longest pediatric cardiac graft recipients living without any significant functional limitations., Competing Interests: There are no conflicts of interest., (Copyright © 2022 Joseph Licata et al.)

The U.S. Food and Drug Administration (US FDA) has identified dietary exposure to heavy metals as a public health concern, focusing particularly on arsenic, cadmium, lead, and mercury. One way to determine current risk is to compare established safe exposure limits (reference values) with current population-based dietary background levels. Information on reference values and dietary background exposures for these metals and chromium were critically evaluated in support of an interactive risk assessment screening tool (Heavy Meals Screening Tool [HMST]). Cadmium, arsenic, and mercury background exposures from food and water were found to be below current safe US regulatory limits based on non-cancer effects, while lead background exposures were nearly equivalent to the US FDA's newest interim reference level for children. Because detections of chromium in foods are infrequent and data on speciation (trivalent versus hexavalent) are limited, chromium was excluded from the HMST. The focus of this work was to present U.S. based reference and background exposure values, although the tool can use inputs that may be more appropriate for other countries, cultures, and situations. With emerging science, new health endpoints, and changes in food consumption trends, both reference values and background exposure levels are likely to evolve., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Single species distribution models (SSDMs) are typically used to understand and predict the distribution and abundance of marine fish by fitting distribution models for each species independently to a combination of abiotic environmental variables. However, species abundances and distributions are influenced by abiotic environmental preferences as well as biotic dependencies such as interspecific competition and predation. When species interact, a joint species distribution model (JSDM) will allow for valid inference of environmental effects. We built a joint species distribution model of marine fish and invertebrates of the Northeast US Continental Shelf, providing evidence on species relationships with the environment as well as the likelihood of species to covary. Predictive performance is similar to SSDMs but the Bayesian joint modeling approach provides two main advantages over single species modeling: (1) the JSDM directly estimates the significance of environmental effects; and (2) predicted species richness accounts for species dependencies. An additional value of JSDMs is that the conditional prediction of species distributions can use not only the environmental associations of species, but also the presence and abundance of other species when forecasting future climatic associations., (© 2022. The Author(s).)

Background: Creeping indigo (Indigofera spicata) toxicosis is an emerging problem among horses in Florida and bordering states., Objectives: To quantify the putative toxins l-indospicine (IND) and 3-nitropropionic acid (NPA) in creeping indigo collected from multiple sites and to measure plasma toxin concentrations in ponies fed creeping indigo and horses with presumptive creeping indigo toxicosis., Study Design: Experimental descriptive study with descriptive observational field investigation., Methods: Air-dried creeping indigo was assayed for IND and NPA content. Five ponies were fed chopped creeping indigo containing 1 mg/kg/day of IND and trace amounts of NPA for 5 days, then observed for 28 days. Blood samples from these ponies and from horses involved in a presumptive creeping indigo toxicosis were assayed for IND and NPA., Results: IND in creeping indigo plants was 0.4-3.5 mg/g dry matter whereas NPA was <0.01 to 0.03 mg/g. During creeping indigo feeding, clinical and laboratory signs were unchanged except for significant weight loss (median 6%, range 2%-9%; p = .04) and significant increase from baseline plasma protein concentration (median 16 g/L, range 8-25 g/L; p < .001). These changes could not definitively be ascribed to creeping indigo ingestion. Plasma IND rose to 3.9 ± 0.52 mg/L on day 6. Pharmacokinetic modelling indicated an elimination half-life of 25 days and a steady state plasma concentration of 22 mg/L. Plasma IND concentration in sick horses during an incident of creeping indigo toxicosis was approximately twice that of clinically normal pasture mates. Plasma NPA was <0.05 mg/L in all samples., Main Limitations: Creeping indigo used in the feeding trial may not be representative of plants involved in creeping indigo toxicosis. There was no control group without creeping indigo in the feeding trial., Conclusions: Indospicine can be detected in blood of horses consuming creeping indigo and the toxin accumulates in tissues and clears slowly. The role of NPA in the neurological signs of this syndrome is unclear., (© 2020 EVJ Ltd.)

Objectives: To determine if hemodynamic changes secondary to propofol administration are a result of direct myocardial depression as measured by global longitudinal strain (GLS). The authors hypothesized that propofol would cause a significant worsening in GLS, indicating direct myocardial depression., Design: Prospective, observational., Setting: Endoscopy suite at a single academic medical center., Participants: Patients undergoing outpatient, elective endoscopic procedures at an outpatient clinic of a single tertiary care academic medical center., Interventions: None., Measurements and Main Results: Limited transthoracic echocardiograms were performed before and after patients received propofol for endoscopic procedures. Post-processing measurements included GLS, 2D (dimensional) ejection fraction (2D EF), and 3D EF. Using paired sample Student's t test, no statistically significant change in GLS, 2D EF, or 3D EF was found despite statistically significant hypotension. In fact, there was a trend toward more negative GLS (improved myocardial function) in patients after receiving propofol., Conclusion: We found propofol did not cause a reduction in systolic function as measured by GLS, a sensitive measure of myocardial contractility. Therefore, decreases in blood pressure after a propofol bolus in spontaneously breathing patients are likely due to decreased vascular tone and not impaired left ventricular systolic function. These results should be considered in the management of propofol-induced hypotension for spontaneously breathing patients.

Background: Extremity weakness, fatigue, and postural instability often contribute to mobility deficits in persons after stroke. Wearable technologies are increasingly being utilized to track many health-related parameters across different patient populations. The purpose of this systematic review was to identify how wearable technologies have been used over the past decade to assess gait and mobility in persons with stroke., Methods: We performed a systematic search of Ovid MEDLINE, CINAHL, and Cochrane databases using select keywords. We identified a total of 354 articles, and 13 met inclusion/exclusion criteria. Included studies were quality assessed and data extracted included participant demographics, type of wearable technology utilized, gait parameters assessed, and reliability and validity metrics., Results: The majority of studies were performed in either hospital-based or inpatient settings. Accelerometers, activity monitors, and pressure sensors were the most commonly used wearable technologies to assess gait and mobility post-stroke. Among these devices, spatiotemporal parameters of gait that were most widely assessed were gait speed and cadence, and the most common mobility measures included step count and duration of activity. Only 4 studies reported on wearable technology validity and reliability metrics, with mixed results., Conclusion: The use of various wearable technologies has enabled researchers and clinicians to monitor patients' activity in a multitude of settings post-stroke. Using data from wearables may provide clinicians with insights into their patients' lived-experiences and enrich their evaluations and plans of care. However, more studies are needed to examine the impact of stroke on community mobility and to improve the accuracy of these devices for gait and mobility assessments amongst persons with altered gait post-stroke.

Reports of environmental and human health impacts of per- and polyfluoroalkyl substances (PFAS) have greatly increased in the peer-reviewed literature. The goals of the present review are to assess the state of the science regarding toxicological effects of PFAS and to develop strategies for advancing knowledge on the health effects of this large family of chemicals. Currently, much of the toxicity data available for PFAS are for a handful of chemicals, primarily legacy PFAS such as perfluorooctanoic acid and perfluorooctane sulfonate. Epidemiological studies have revealed associations between exposure to specific PFAS and a variety of health effects, including altered immune and thyroid function, liver disease, lipid and insulin dysregulation, kidney disease, adverse reproductive and developmental outcomes, and cancer. Concordance with experimental animal data exists for many of these effects. However, information on modes of action and adverse outcome pathways must be expanded, and profound differences in PFAS toxicokinetic properties must be considered in understanding differences in responses between the sexes and among species and life stages. With many health effects noted for a relatively few example compounds and hundreds of other PFAS in commerce lacking toxicity data, more contemporary and high-throughput approaches such as read-across, molecular dynamics, and protein modeling are proposed to accelerate the development of toxicity information on emerging and legacy PFAS, individually and as mixtures. In addition, an appropriate degree of precaution, given what is already known from the PFAS examples noted, may be needed to protect human health. Environ Toxicol Chem 2021;40:606-630. © 2020 SETAC., (© 2020 SETAC.)

Objective: Transcatheter aortic valve replacement (TAVR) with monitored anesthesia care (MAC) is well-tolerated and is growing in popularity. Differences in outcomes based on anesthetic agent choice with MAC has received less attention. The authors sought to determine whether differences in outcomes and cost exist based on whether patients receive dexmedetomidine or propofol when undergoing TAVR with MAC., Design: Retrospective cohort study., Setting: The Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania., Participants: The study comprised 161 patients who underwent TAVR with MAC between May 2014 and March 2019., Interventions: None., Measurements and Main Results: A propofol-only (n = 58) group and dexmedetomidine-only (n = 103) group were identified. No differences in in-hospital mortality or complication rate were identified when evaluating for stroke, transfusion, new arrhythmia, cardiac arrest, or bleeding and vascular complications (p > 0.05, all). Thirty-day outcomes were also equivalent, with no differences in mortality, stroke, vascular complication, new arrhythmia, or myocardial infarction (p > 0.05, all). The average amount of epinephrine, norepinephrine, or phenylephrine used intraoperatively was not significantly different. Overall median hospitalization costs were equivalent ($57,554.31 with dexmedetomidine v $58,538.08 with propofol, p = 0.97)., Conclusions: There were no significant differences in in-hospital outcomes, 30-day outcomes, or total cost of the patient's hospitalization, based on the use of dexmedetomidine versus propofol in patients undergoing TAVR., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Marine protected areas (MPAs) are valuable tools for marine conservation that aim to limit human impacts on marine systems and protect valuable species or habitats. However, as species distributions shift due to ocean warming, acidification, and oxygen depletion from climate change, the areas originally designated under MPAs may bear little resemblance to their past state. Different approaches have been suggested for coping with species on the move in conservation. Here, we test the effectiveness of different MPA designs, including dynamic, network, and different directional orientations on protecting shifting species under climate change through ecosystem modeling in a theoretical ecosystem. Our findings suggest that dynamic MPAs may benefit some species (e.g., whiting and anchovy) and fishing fleets, and these benefits can inform the design or adaptation of MPAs worldwide. In addition, we find that it is important to design MPAs with specific goals and to account for the effects of released fishing pressure and species interactions in MPA design., Competing Interests: The authors have declared that no competing interests exist.

Domoic acid (DA) is a marine neurotoxin that accumulates in filtering shellfish during harmful algal blooms. A health protection limit of 20 ppm DA in razor clams (RC) has been set based principally upon an episode of acute DA toxicity in humans that included Amnesic Shellfish Poisoning among survivors. The objective of this study was to determine the dose-response relationship between estimated DA exposure through RC consumption and memory loss in Washington state Native Americans from 2005 to 2015. Results from total learning recall (TLR) memory scores were compared before and after the highest DA exposures. A decrease in TLR was related to DA dose (p < 0.01) regardless whether the effect was assumed to be transient or lasting, and whether the dose was expressed as an average daily dose or an average dose per meal. Benchmark dose modeling identified BMDL 10 values of 167 ng/kg-day and 2740 ng/kg-meal assuming a transient effect, and 196 ng/kg-day and 2980 ng/kg-meal assuming no recovery of function occurs. These DA dose thresholds for a measurable memory function reduction observed in this study of clam consumers are well below the safe acute dose underpinning the current regulatory DA limit of 20 ppm (ca. 60 μg/kg)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Analyses of the impacts of climate change on fish species have primarily considered dynamic oceanographic variables that are the output of predictive models, yet fish species distributions are determined by much more than just variables such as ocean temperature. Functionally diverse species are differentially influenced by oceanographic as well as physiographic variables such as bottom substrate, thereby influencing their ability to shift distributions. Here, we show that fish species distributions that are more associated with bottom substrate than other dynamic environmental variables have shifted significantly less over the last 30 years than species whose distributions are associated with bottom salinity. Correspondingly, species whose distributions are primarily determined by bottom temperature or ocean salinity have shifted their mean centroid and southern and northern range boundaries significantly more than species whose distributions are determined by substrate or depth. The influence of oceanographic versus static variables differs by species functional group, as benthic species distributions are more associated with substrate and they have shifted significantly less than pelagic species whose distributions are primarily associated with ocean temperatures. In conclusion, benthic fish, that are more influenced by substrate, may prove much less likely to shift distributions under future climate change.

Study Objective . Our objectives were to estimate the incidence of symptoms of peripheral nerve injury (sPNI) in thoracic surgical patients undergoing video-assisted thoracic surgery or open thoracotomy and to determine whether intraoperative somatosensory evoked potentials (SSEPs) waveform changes correlate with postoperative peripheral neuropathic symptoms. Methods . We conducted a prospective observational study in the operating room of a tertiary hospital. We measured SSEPs intraoperatively and assessed patients for sPNI postoperatively. Results . Forty-four patients consented. Six were excluded from analysis. We found that 42% (95% confidence interval [CI] = 26% to 57%) of patients undergoing thoracic surgery had significant changes in SSEP amplitude and latency. Furthermore, 16% (95% CI = 4% to 28%) of patients had new postoperative symptoms of sensory or motor deficits in an upper extremity. We calculated a sensitivity of 66.7% (95% CI = 29.0% to 100%) and a specificity of 50% (95% CI = 33% to 67.3%) for the identification of sPNI based on automated intraoperative SSEP changes. Conclusions . We identified the incidence of SSEP changes in thoracic surgery (42%) and the incidence of postoperative sPNI after thoracic surgery (16%). We identified a positive correlation between intraoperative SSEP changes and postoperative sPNI, which after multivariate analysis was not significant given the small sample size of the study. By the time sensory and/or motor changes are detected postoperatively, it may be too late to reverse the nerve damage. Future versions of the EPAD device could provide anesthesiologists a way to monitor for the development of sPNI, and make changes before a potential injury becomes permanent.

The leishmaniases, caused by Leishmania species of protozoan parasites, are neglected tropical diseases with millions of cases worldwide. Current therapeutic approaches are limited by toxicity, resistance, and cost. N -Myristoyltransferase (NMT), an enzyme ubiquitous and essential in all eukaryotes, has been validated via genetic and pharmacological methods as a promising anti-leishmanial target. Here we describe a comprehensive structure-activity relationship (SAR) study of a thienopyrimidine series previously identified in a high-throughput screen against Leishmania NMT, across 68 compounds in enzyme- and cell-based assay formats. Using a chemical tagging target engagement biomarker assay, we identify the first inhibitor in this series with on-target NMT activity in leishmania parasites. Furthermore, crystal structure analyses of 12 derivatives in complex with Leishmania major NMT revealed key factors important for future structure-guided optimization delivering IMP-105 ( 43 ), a compound with modest activity against Leishmania donovani intracellular amastigotes and excellent selectivity (>660-fold) for Leishmania NMT over human NMTs.

Acute type A aortic dissection (TAAD) with malperfusion syndrome remains a challenging diagnosis and optimal surgical management remains unsettled. We present a case and surgical approach employed for a patient with TAAD and malperfusion syndrome who presented with pulseless bilaterally extremities. Satisfactory outcomes can be achieved with early multidisciplinary collaboration and urgent repair of the aorta and simultaneous efforts to restore blood flow to ischemic tissue.

The Deepwater Horizon oil spill (April 20, 2010) caused concern regarding Gulf seafood safety. Communities were skeptical of governmental risk assessments because they did not take into account the higher consumption of seafood along coastal areas. The objective of this study was to perform a probabilistic risk assessment based on the consumption rates of high-end consumers of Gulf seafood. We utilized seafood consumption data from five communities across the northeastern Gulf of Mexico. This study collected finfish, shrimp, blue crab, and oysters from these communities and analyzed their tissues for polynuclear aromatic hydrocarbons (PAHs). A probabilistic risk assessment was performed using population-specific seafood consumption rates and body weights for commercial fishers, recreational fishers, and a Filipino-American community. For non-cancer effects, 95th percentile hazard quotients for these targeted populations ranged between 1.84E-04 to 5.39E-03 for individual seafood types. The 95th percentile hazard indices for total seafood consumption ranged from 3.45E-03 to 8.41E-03. Based on total seafood consumption, highest hazard indices were modeled for the Filipino-American community followed by commercial and recreational fishers. Despite higher consumption rates, hazard indices for the high-end consumers targeted in this study were two to three orders of magnitude below the regulatory limit of 1.

Objectives: To assess the concordance between transesophageal echocardiographic (TEE) and transthoracic echocardiograpic (TTE) measures of right ventricular (RV) function using standard 2-dimensional and Doppler methods. The authors hypothesized that there would be significant disagreement in tricuspid annular plane systolic excursion (TAPSE), fractional area change, right-sided index of myocardial performance, and tricuspid annular systolic velocity (S')., Design: Prospective observational., Setting: Cardiac operating room at a single academic medical center., Participants: All adult patients undergoing elective cardiac surgery at a single tertiary care academic medical center over 6 months., Interventions: None., Measurements and Main Results: The fractional area change, S', TAPSE, right-sided index of myocardial performance, and tricuspid annular diameter were measured with TEE and TTE to assess for concordance using the concordance correlation coefficient and paired t tests, including 95% confidence limits. The study demonstrated that quantitative measures of RV function by TEE correlate poorly with TTE measurements in close temporal proximity under similar hemodynamic conditions., Conclusions: When performing an assessment of RV function, transesophageal echocardiographers should exercise caution when extrapolating data validated by TTE to TEE studies. Measures of RV function by TEE tend to have fair agreement to TTE measurements obtained in close temporal proximity under similar hemodynamic conditions. Most importantly, the present study showed that TAPSE and S' values obtained from the modified transgastric RV inflow view tend to have lower values than those measured with TTE. Given the propensity for underestimating measurements from the modified transgastric RV inflow view, the authors conclude that values equal to or greater than established norms for tricuspid annular motion may be used to establish normal-but not abnormal-RV function., Competing Interests: Conflict of Interest There are no conflicts of interest for any of the authors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Perfluorohexane sulfonate (PFHxS) is a six-carbon perfluoroalkyl sulfonic acid that was used as an industrial surfactant, but is now found as an environmental contaminant worldwide. In addition to its use as an industrial surfactant, it is a legacy contaminant from the use of aqueous film-forming foams. Despite its widespread occurrence in the environment and evidence of biological activity associated with PFHxS and similar perfluoroalkyl sulfonic acids in rodents, there is no oral toxicity value currently available from the IRIS Database. To derive an oral reference dose (RfD) for PFHxS, available toxicity studies were reviewed using a weight-of-evidence approach. A 42-day mouse reproductive study was chosen as the critical study for the derivation of the oral RfD. Benchmark dose modeling was utilized to derive a point of departure (POD) for a reduction in litter size. A 95% lower confidence limit on the benchmark dose (BMDL) of 13,900 ng/mL (serum PFHxS) was modeled for a reduction in litter size. An oral RfD for PFHxS of 4.0 ng/kg/d was calculated by conversion of the BMDL to a human equivalent oral dose using a human half-life adjusted dosimetric conversion factor and the application of a total uncertainty factor of 300. Additional research is needed to better characterize the toxicity associated with oral exposure to PFHxS and refine the development of toxicity values., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Solvent organization is a key but underexploited contributor to the thermodynamics of protein-ligand recognition, with implications for ligand discovery, drug resistance, and protein engineering. Here, we explore the contribution of solvent to ligand binding in the Haemophilus influenzae virulence protein SiaP. By introducing a single mutation without direct ligand contacts, we observed a >1000-fold change in sialic acid binding affinity. Crystallographic and calorimetric data of wild-type and mutant SiaP showed that this change results from an enthalpically unfavorable perturbation of the solvent network. This disruption is reflected by changes in the normalized atomic displacement parameters of crystallographic water molecules. In SiaP's enclosed cavity, relative differences in water-network dynamics serve as a simple predictor of changes in the free energy of binding upon changing protein, ligand, or both. This suggests that solvent structure is an evolutionary constraint on protein sequence that contributes to ligand affinity and selectivity.

BACKGROUND Global longitudinal strain (GLS) detected by echocardiography has been shown to have a prognostic role in the evaluation of myocardial ischemia in several clinical settings. A case is presented where GLS was used to detect intraoperative myocardial ischemia in a high-risk patient undergoing open abdominal aortic aneurysm repair. CASE REPORT A 75-year-old Caucasian man with non-insulin dependent diabetes mellitus and a 60 pack-year smoking history presented with a one-week history of exertional chest pain. Two-dimensional (2D) speckle-tracking echocardiography was used to calculate myocardial velocities and deformation parameters, including GLS. A reduced baseline GLS of -18.2% was found with dysfunction of the basal anterior, inferior, and mid anterolateral wall of the left ventricle. During aortic cross-clamping, his basal segments became mildly hypokinetic, although his ejection fraction (EF) remained unchanged at 50-55%. Despite normal left ventricular systolic function on visual assessment, his GLS decreased to -14.2% during aortic cross-clamping with similar segmental changes noted in the baseline GLS analysis. After the release of the aortic cross-clamp, his basal segments returned to normal and his left ventricular systolic function improved with an EF of 60-65% and the GLS recovered to -18.4% with improvement in the basal segmental function. CONCLUSIONS This case report showed that detection of GLS by echocardiography was a sensitive indicator of myocardial dysfunction that was superior to regional ventricular wall assessment. Detection of early changes in myocardial function by evaluating GLS may assist in guiding anesthetic management in high-risk patients with ischemic heart disease.

Craniotomy in the sitting position entails risk for venous air embolism (VAE). A 50-year-old male underwent pineal region mass resection through a sitting position craniotomy. Intraoperative transesophageal echocardiography confirmed the absence of intracardiac shunt. During craniotomy, VAE was noted inside the patient's right heart, leading to hemodynamic instability. After repositioning to the supine position, significant crossover of air into the left heart was noted. Postoperatively, multiple small embolic strokes were noted. Patients who undergo craniotomy in the sitting position and are not found to have a patent foramen ovale (PFO) are not free of risk for paradoxical air embolism (PAE)., Competing Interests: The authors have declared that no competing interests exist.

Bioaccessibilities of PCDD/PCDF congeners contributing to cancer risk were determined in twelve soil samples from the American Creosote Works Superfund site in Florida. Based upon sample locations, congener profiles (i.e., the same dominant congeners), and total (Toxic Equivalent; TEQ) concentrations, each of these samples has PCDD/PCDF contamination reasonably attributable to the site. Bioaccessibility was determined using a 2-phase in vitro extraction method that included both simulated gastric and intestinal conditions of the human GI tract. Measured congener-specific bioaccessibility values ranged from 34.3 to 62.1%. There was no apparent relationship between the extent of chlorination of PCDD/PCDF congeners and their bioaccessibility. TEQ-weighted bioaccessibility values varied among individual soil samples, which is not unexpected based upon the literature. This variability could not be explained by differences in soil pH, composition, or organic carbon content. The average TEQ-weighted bioaccessibility value of 59% for the twelve samples was accepted as representing site-specific bioavailability of PCDD/PCDFs. This value is higher than most dioxin/furan bioaccessibility values reported in the literature and at the upper end of the range of relative oral bioavailability (RBA) values reported for PCDD/PCDFs from in vivo bioavailability studies. This study used a finer fraction of soil particles (<150 microns versus the more typical <250 microns) to better represent soil that is incidentally ingested. This finer fraction would be expected to have a greater surface area available for extraction of PCDD/PCDFs per unit mass, which might account for the greater than expected bioaccessibility., (Copyright © 2018 Elsevier Ltd. All rights reserved.)