Characterization of the dystrophin-associated protein complex by mass spectrometry.

The dystrophin-associated protein complex (DAPC) is a highly organized multiprotein complex that plays a pivotal role in muscle fiber structure integrity and cell signaling. The complex is composed of three distinct interacting subgroups, intracellular peripheral proteins, transmembrane glycoproteins, and extracellular glycoproteins subcomplexes. Dystrophin protein nucleates the DAPC and is important for connecting the intracellular actin cytoskeletal filaments to the sarcolemma glycoprotein complex that is connected to the extracellular matrix via laminin, thus stabilizing the sarcolemma during muscle fiber contraction and relaxation. Genetic mutations that lead to lack of expression or altered expression of any of the DAPC proteins are associated with different types of muscle diseases. Hence characterization of this complex in healthy and dystrophic muscle might bring insights into its role in muscle pathogenesis. This review highlights the role of mass spectrometry in characterizing the DAPC interactome as well as post-translational glycan modifications of some of its components such as α-dystroglycan. Detection and quantification of dystrophin using targeted mass spectrometry are also discussed in the context of healthy versus dystrophic skeletal muscle.

Diuretics in States of Volume Overload: Core Curriculum 2022.

Volume overload, defined as excess total body sodium and water with expansion of extracellular fluid volume, characterizes common disorders such as congestive heart failure, end-stage liver disease, chronic kidney disease, and nephrotic syndrome. Diuretics are the cornerstone of therapy for volume overload and comprise several classes whose mechanisms of action, pharmacokinetics, indications, and adverse effects are essential principles of nephrology. Loop diuretics are typically the first-line treatment in the management of hypervolemia, with additional drug classes indicated in cases of diuretic resistance and electrolyte or acid-base disorders. Separately, clinical trials highlight improved outcomes in some states of volume overload, such as loop diuretics and sodium/glucose cotransporter 2 inhibitors in patients with congestive heart failure. Resistance to diuretics is a frequent, multifactorial clinical challenge that requires creative and physiology-based solutions. In this installment of AJKD's Core Curriculum in Nephrology, we discuss the pharmacology and therapeutic use of diuretics in states of volume overload and strategies to overcome diuretic resistance.

Multi-jet fusion for additive manufacturing of radiotherapy immobilization devices: Effects of color, thickness, and orientation on surface dose and tensile strength.

Immobilization devices are used to obtain reproducible patient setup during radiotherapy treatment, improving accuracy, and reducing damage to surrounding healthy tissue. Additive manufacturing is emerging as a viable method for manufacturing and personalizing such devices. The goal of this study was to investigate the dosimetric and mechanical properties of a recent additive technology called multi-jet fusion (MJF) for radiotherapy applications, including the ability for this process to produce full color parts. Skin dose testing included 50 samples with dimensions 100 mm × 100 mm with five different thicknesses (1 mm, 2 mm, 3 mm, 4 mm, and 5 mm) and grouped into colored (cyan, magenta, yellow, and black (CMYK) additives) and non-colored (white) samples. Results using a 6 MV beam found that surface dose readings were predominantly independent of the colored additives. However, for an 18 MV beam, the additives affected the surface dose, with black recording significantly lower surface dose readings compare to other colors. The accompanying tensile testing of 175 samples designed to ASTM D638 type I standards found that the black agent resulted in the lowest ultimate tensile strength (UTS) for each thickness of 1-5 mm. It was also found that the print orientation had influence on the skin dose and mechanical properties of the samples. When all data were combined and analyzed using a multiple-criteria decision-making technique, magenta was found to offer the best balance between high UTS and low surface dose across different thicknesses and orientations, making it an optimal choice for immobilization devices. This is the first study to consider the use of color MJF for radiotherapy immobilization devices, and suggests that color additives can affect both dosimetry and mechanical performance. This is important as industrial additive technologies like MJF become increasingly adopted in the health and medical sectors.

3D Printing: An Alternative Microfabrication Approach with Unprecedented Opportunities in Design.

In the past decade, 3D printing technologies have been adopted for the fabrication of microfluidic devices. Extrusion-based approaches including fused filament fabrication (FFF), jetting technologies including inkjet 3D printing, and vat photopolymerization techniques including stereolithography (SLA) and digital light projection (DLP) are the 3D printing methods most frequently adopted by the microfluidic community. Each printing technique has merits toward the fabrication of microfluidic devices. Inkjet printing offers a good selection of materials and multimaterial printing, and the large build space provides manufacturing throughput, while FFF offers a great selection of materials and multimaterial printing but at lower throughput compared to inkjet 3D printing. Technical and material developments adopted from adjacent research fields and developed by the microfluidic community underpin the printing of sub-100 µm enclosed microchannels by DLP, but challenges remain in multimaterial printing throughput. With the feasibility of 3D printed microfluidics established, we look ahead at trends in 3D printing to gain insights toward the future of this technology beyond the sole prism of being an alternative fabrication approach. A shift in emphasis from using 3D printing for prototyping, to mimic conventionally manufactured outputs, toward integrated approaches from a design perspective is critically developed.

Mitochondrial dysfunction and role of harakiri in the pathogenesis of myositis.

The etiology of myositis is unknown. Although attempts to identify viruses in myositis skeletal muscle have failed, several studies have identified the presence of a viral signature in myositis patients. Here we postulate that in individuals with susceptible genetic backgrounds, viral infection alters the epigenome to activate the pathological pathways leading to disease onset. To identify epigenetic changes, methylation profiling of Coxsackie B infected human myotubes and muscle biopsies from polymyositis (PM) and dermatomyositis (DM) patients were compared to changes in global transcript expression induced by in vitro Coxsackie B infection. Gene and protein expression analysis and live cell imaging were performed to examine the mechanisms. Analysis of methylation and gene expression changes identified that a mitochondria-localized activator of apoptosis - harakiri (HRK) - is upregulated in myositis skeletal muscle cells. Muscle cells with higher HRK expression have reduced mitochondrial potential and poor ability to repair from injury as compared to controls. In cells from myositis patient toll-like receptor 7 (TLR7) activates and sustains high HRK expression. Forced over expression of HRK in healthy muscle cells is sufficient to compromise their membrane repair ability. Endurance exercise that is associated with improved muscle and mitochondrial function in PM and DM patients decreased TLR7 and HRK expression identifying these as therapeutic targets. Increased HRK and TLR7 expression causes mitochondrial damage leading to poor myofiber repair, myofiber death and muscle weakness in myositis patients and exercise induced reduction of HRK and TLR7 expression in patients is associated with disease amelioration. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Morpholino-induced exon skipping stimulates cell-mediated and humoral responses to dystrophin in mdx mice.

Exon skipping is a promising genetic therapeutic strategy for restoring dystrophin expression in the treatment of Duchenne muscular dystrophy (DMD). The potential for newly synthesized dystrophin to trigger an immune response in DMD patients, however, is not well established. We have evaluated the effect of chronic phosphorodiamidate morpholino oligomer (PMO) treatment on skeletal muscle pathology and asked whether sustained dystrophin expression elicits a dystrophin-specific autoimmune response. Here, two independent cohorts of dystrophic mdx mice were treated chronically with either 800 mg/kg/month PMO for 6 months (n = 8) or 100 mg/kg/week PMO for 12 weeks (n = 11). We found that significant muscle inflammation persisted after exon skipping in skeletal muscle. Evaluation of humoral responses showed serum-circulating antibodies directed against de novo dystrophin in a subset of mice, as assessed both by Western blotting and immunofluorescent staining; however, no dystrophin-specific antibodies were observed in the control saline-treated mdx cohorts (n = 8) or in aged (12-month-old) mdx mice with expanded 'revertant' dystrophin-expressing fibers. Reactive antibodies recognized both full-length and truncated exon-skipped dystrophin isoforms in mouse skeletal muscle. We found more antigen-specific T-cell cytokine responses (e.g. IFN-g, IL-2) in dystrophin antibody-positive mice than in dystrophin antibody-negative mice. We also found expression of major histocompatibility complex class I on some of the dystrophin-expressing fibers along with CD8+ and perforin-positive T cells in the vicinity, suggesting an activation of cell-mediated damage had occurred in the muscle. Evaluation of complement membrane attack complex (MAC) deposition on the muscle fibers further revealed lower MAC deposition on muscle fibers of dystrophin antibody-negative mice than on those of dystrophin antibody-positive mice. Our results indicate that de novo dystrophin expression after exon skipping can trigger both cell-mediated and humoral immune responses in mdx mice. Our data highlights the need to further investigate the autoimmune response and its long-term consequences after exon-skipping therapy. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Membrane Repair Deficit in Facioscapulohumeral Muscular Dystrophy.

Deficits in plasma membrane repair have been identified in dysferlinopathy and Duchenne Muscular Dystrophy, and contribute to progressive myopathy. Although Facioscapulohumeral Muscular Dystrophy (FSHD) shares clinicopathological features with these muscular dystrophies, it is unknown if FSHD is characterized by plasma membrane repair deficits. Therefore, we exposed immortalized human FSHD myoblasts, immortalized myoblasts from unaffected siblings, and myofibers from a murine model of FSHD (FLExDUX4) to focal, pulsed laser ablation of the sarcolemma. Repair kinetics and success were determined from the accumulation of intracellular FM1-43 dye post-injury. We subsequently treated FSHD myoblasts with a DUX4-targeting antisense oligonucleotide (AON) to reduce DUX4 expression, and with the antioxidant Trolox to determine the role of DUX4 expression and oxidative stress in membrane repair. Compared to unaffected myoblasts, FSHD myoblasts demonstrate poor repair and a greater percentage of cells that failed to repair, which was mitigated by AON and Trolox treatments. Similar repair deficits were identified in FLExDUX4 myofibers. This is the first study to identify plasma membrane repair deficits in myoblasts from individuals with FSHD, and in myofibers from a murine model of FSHD. Our results suggest that DUX4 expression and oxidative stress may be important targets for future membrane-repair therapies.

Effects of Periodic Intensive Insulin Therapy: An Updated Review.

BACKGROUND: Traditional insulin treatment for diabetes mellitus with insulin administered subcutaneously yields nonpulsatile plasma insulin concentrations that represent a fraction of normal portal vein levels. Oral hypoglycemic medications result in the same lack of pulsatile insulin response to blood glucose levels. Intensive treatments of significant complications of diabetes are not recommended due to complicated multidrug regimens, significant weight gain, and the high risk of hypoglycemic complications. Consequently, advanced complications of diabetes do not have an effective treatment option because conventional therapy is not sufficient. Intensive insulin therapy (IIT) simulates normal pancreatic function by closely matching the periodicity and amplitude of insulin secretion in healthy subjects; however, the mechanisms involved with the observed improvement are not clearly understood. OBJECTIVE: The current review aims to analyze the pathophysiology of insulin secretion, discuss current therapies for the management of diabetes, provides an updates on the recent advancements of IIT, and proposes its mechanism of action. METHODS: A literature search on PubMed, MEDLINE, Embase, and CrossRef databases was performed on multiple key words regarding the history and current variations of pulsatile and IIT for diabetes treatment. Articles reporting the physiology of insulin secretion, advantages of pulsatile insulin delivery in patients with diabetes patients, efficacy and adverse effects of current conventional insulin therapies for the management of diabetes, benefits and shortcomings of pancreas and islet transplantation, or clinical trials on patients with diabetes treated with pulsed insulin therapy or advanced IIT were included for a qualitative analysis and categorized into the following topics: mechanism of insulin secretion in normal subjects and patients with diabetes and current therapies for the management of diabetes, including oral hypoglycemic agents, insulin therapy, pancreas and islet transplantation, pulsed insulin therapy, and advances in IIT. RESULTS: Our review of the literature shows that IIT improves the resolution of diabetic ulcers, neuropathy, and nephropathy, and reduces emergency room visits. The likely mechanism responsible for this improvement is increased insulin sensitivity from adipocytes, as well as increased insulin receptor expression. CONCLUSIONS: Recent advancements show that IIT is an effective option for both type 1 diabetes mellitus and type 2 diabetes mellitus patient populations. This treatment resembles normal pancreatic function so closely that it has significantly reduced the effects of relatively common complications of diabetes in comparison to standard treatments. Thus, this new treatment is a promising advancement in the management of diabetes. (Curr Ther Res Clin Exp. 2019; 80:XXX-XXX).

Effect of genetic background on the dystrophic phenotype in mdx mice.

Genetic background significantly affects phenotype in multiple mouse models of human diseases, including muscular dystrophy. This phenotypic variability is partly attributed to genetic modifiers that regulate the disease process. Studies have demonstrated that introduction of the γ-sarcoglycan-null allele onto the DBA/2J background confers a more severe muscular dystrophy phenotype than the original strain, demonstrating the presence of genetic modifier loci in the DBA/2J background. To characterize the phenotype of dystrophin deficiency on the DBA/2J background, we created and phenotyped DBA/2J-congenic Dmdmdx mice (D2-mdx) and compared them with the original, C57BL/10ScSn-Dmdmdx (B10-mdx) model. These strains were compared with their respective control strains at multiple time points between 6 and 52 weeks of age. Skeletal and cardiac muscle function, inflammation, regeneration, histology and biochemistry were characterized. We found that D2-mdx mice showed significantly reduced skeletal muscle function as early as 7 weeks and reduced cardiac function by 28 weeks, suggesting that the disease phenotype is more severe than in B10-mdx mice. In addition, D2-mdx mice showed fewer central myonuclei and increased calcifications in the skeletal muscle, heart and diaphragm at 7 weeks, suggesting that their pathology is different from the B10-mdx mice. The new D2-mdx model with an earlier onset and more pronounced dystrophy phenotype may be useful for evaluating therapies that target cardiac and skeletal muscle function in dystrophin-deficient mice. Our data align the D2-mdx with Duchenne muscular dystrophy patients with the LTBP4 genetic modifier, making it one of the few instances of cross-species genetic modifiers of monogenic traits.

Dabigatran Reversal in a Patient With End-Stage Liver Disease and Acute Kidney Injury.

Dabigatran, a direct thrombin inhibitor and one of the new class of direct oral anticoagulants, is increasingly used in preference to warfarin because of its efficacy and ease of administration. However, because the drug is cleared by the kidneys, it can accumulate in plasma and increase the risk for bleeding in patients with decreased kidney function. We report a patient with end-stage liver disease who developed life-threatening hemorrhage and acute kidney injury while taking dabigatran, 150mg, twice daily. Although the patient received idarucizumab, an anti-dabigatran antibody fragment used as an antidote, hemostasis could not be achieved. Administration of vitamin K, fresh frozen plasma, desmopressin, octreotide, and pantoprazole did not arrest bleeding or affect coagulation parameters, and it was not possible to establish vascular access for hemodialysis. In patients with end-stage liver disease, who are at increased risk for both bleeding and acute kidney injury, dabigatran should be prescribed cautiously and at decreased dose.

Quantitative Antisense Screening and Optimization for Exon 51 Skipping in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder, is caused by mutations in the dystrophin (DMD) gene. Exon skipping is a therapeutic approach that uses antisense oligonucleotides (AOs) to modulate splicing and restore the reading frame, leading to truncated, yet functional protein expression. In 2016, the US Food and Drug Administration (FDA) conditionally approved the first phosphorodiamidate morpholino oligomer (morpholino)-based AO drug, eteplirsen, developed for DMD exon 51 skipping. Eteplirsen remains controversial with insufficient evidence of its therapeutic effect in patients. We recently developed an in silico tool to design antisense morpholino sequences for exon skipping. Here, we designed morpholino AOs targeting DMD exon 51 using the in silico tool and quantitatively evaluated the effects in immortalized DMD muscle cells in vitro. To our surprise, most of the newly designed morpholinos induced exon 51 skipping more efficiently compared with the eteplirsen sequence. The efficacy of exon 51 skipping and rescue of dystrophin protein expression were increased by up to more than 12-fold and 7-fold, respectively, compared with the eteplirsen sequence. Significant in vivo efficacy of the most effective morpholino, determined in vitro, was confirmed in mice carrying the human DMD gene. These findings underscore the importance of AO sequence optimization for exon skipping.

The development and use of a spatially explicit model for river otters to evaluate environmental hazards: a case study on the Department of Energy's Savannah River Site.

The Department of Energy's (DOE) Savannah River Site (SRS) faces a legacy of radionuclide and metal contamination from industrial processes that occurred throughout the site. Northern river otters (Lontra canadensis) are appropriate receptors for studying the effects of long-term, low-level contamination because they are long-lived, higher trophic level organisms susceptible to accumulating high levels of pollutants. The purpose of this study was to use latrine surveys to examine patterns of wetland latrine usage; explicitly model northern river otter resource selection on the landscape level; and utilize the model results within an ecological risk assessment (ERA) framework to assess potential effects of metals and radiocesium (137Cs) on the population for the SRS as a case study. River drainages and associated wetlands were surveyed for latrine sites and scats were collected and analyzed for 137Cs activity to validate model results. The spatially explicit resource model predicted otter drainage reach use and was used in an ERA to develop exposure models for nine heavy metals as well as 137Cs on the SRS population of river otters. The evaluation predicted that the only contaminant occurring at high enough levels to cause population effects was mercury and that the observed concentrations were probably not high enough to cause significant impairment. However, multiple metals were above action level thresholds. The field validation process showed an unexpected preference for one man-made treatment wetland that was heavily contaminated, showing that the ERA process is complex and must be approached using multiple scales.

Microbial community structure of a freshwater system receiving wastewater effluent.

Despite our dependency on treatment facilities to condition wastewater for eventual release to the environment, our knowledge regarding the effects of treated water on the local watershed is extremely limited. Responses of lotic systems to the treated wastewater effluent have been traditionally investigated by examining the benthic macroinvertebrate assemblages and community structure; however, these studies do not address the microbial diversity of the water systems. In the present study, planktonic and benthic bacterial community structure were examined at 14 sites (from 60 m upstream to 12,100 m downstream) and at two time points along an aquatic system receiving treated effluent from the Charleston Wastewater Treatment Plant (Charleston, IL). Total bacterial DNA was isolated and 16S rRNA sequences were analyzed using a metagenomics platform. The community structure in planktonic bacterial communities was significantly correlated with dissolved oxygen concentration. Benthic bacterial communities were not correlated with water quality but did have a significant geographic structuring. A local restructuring effect was observed in both planktonic and benthic communities near the treated wastewater effluent, which was characterized by an increase in abundance of sphingobacteria. Sites further downstream from the wastewater facility appeared to be less influenced by the effluent. Overall, the present study demonstrated the utility of targeted high-throughput sequencing as a tool to assess the effects of treated wastewater effluent on a receiving water system, and highlighted the potential for this technology to be used for routine monitoring by wastewater facilities.

Atrazine and glyphosate dynamics in a lotic ecosystem: the common snapping turtle as a sentinel species.

Atrazine and glyphosate are two of the most common pesticides used in the US Midwest that impact water quality via runoff, and the common snapping turtle (Chelydra serpentina) is an excellent indicator species to monitor these pesticides especially in lotic systems. The goals of this study were to (1) quantify atrazine, the atrazine metabolite diaminochlorotriazine (DACT), and glyphosate burdens in common snapping turtle tissue from individuals collected within the Embarras River in Illinois; (2) quantify atrazine, DACT, and glyphosate loads in water from the aquatic habitats in which common snapping turtles reside; and (3) investigate tissue loads based on turtle morphology and habitat choice. Concentrations of atrazine, DACT, and glyphosate in tissue did not show any relationship with lake habitat, carapace length, width, or mass. Both atrazine and glyphosate tissue samples varied as a function of site (river vs. lake), but DACT did not. Atrazine and glyphosate concentrations in water samples showed a linear effect on distance from the reservoir spillway and a deviation from linearity. Water column concentrations of all three contaminants varied across capture sites, but atrazine water concentration did not influence DACT water concentration nor did it exhibit a site interaction. Water atrazine and glyphosate concentrations were greater than tissue concentrations, whereas DACT water and tissue concentrations did not differ. This study showed that turtles are useful in long-term pesticide monitoring, and because DACT as a metabolite is less sensitive to variation, it should be considered as a preferred biomarker for pesticide runoff.

Assessing multiple endpoints of atrazine ingestion on gravid Northern Watersnakes (Nerodia sipedon) and their offspring.

Ecotoxicological studies that focus on a single endpoint might not accurately and completely represent the true ecological effects of a contaminant. Exposure to atrazine, a widely used herbicide, disrupts endocrine function and sexual development in amphibians, but studies involving live-bearing reptiles are lacking. This study tracks several effects of atrazine ingestion from female Northern Watersnakes (Nerodia sipedon) to their offspring exposed in utero. Twenty-five gravid N. sipedon were fed fish dosed with one of the four levels of atrazine (0, 2, 20, or 200 ppb) twice weekly for the entirety of their gestation period. Endpoints for the mothers included blood estradiol levels measured weekly and survival more than 3 months. Endpoints for the offspring included morphometrics, clutch sex ratio, stillbirth, and asymmetry of dorsal scales and jaw length. Through these multiple endpoints, we show that atrazine ingestion can disrupt estradiol production in mothers, increase the likelihood of mortality from infection, alter clutch sex ratio, cause a higher proportion of stillborn offspring, and affect scale symmetry. We emphasize the need for additional research involving other reptile species using multiple endpoints to determine the full range of impacts of contaminant exposure.

Toxicodynamic modeling of 137Cs to estimate white-tailed deer background levels for the Department of Energy's Savannah River Site.

The U.S. Department of Energy's (USDOE) Savannah River Site (SRS) is a former nuclear weapon material production and current research facility adjacent to the Savannah River in South Carolina, USA. The purpose of this study was to determine the background radiocesium ((137)Cs) body burden (e.g., from global fallout) for white-tailed deer (Odocoileus virginianus) inhabiting the SRS. To differentiate what the background burden is for the SRS versus (137)Cs obtained from SRS nuclear activities, data were analyzed spatially, temporally and compared to other off-site hunting areas near the SRS. The specific objectives of this study were: to compare SRS and offsite deer herds based on time and space; to interpret comparisons based on how data were collected as well as the effect of environmental and anthropogenic influences; to determine what the ecological half-life/decay rate is for (137)Cs in the SRS deer herd; and to give a recommendation to what should be considered the background (137)Cs level in the SRS deer herd. Based on the available information and analyses, it is recommended that the determination of what is considered background for the SRS deer herd be derived from data collected from the SRS deer herd itself and not offsite collections for a variety of reasons. Offsite data show extreme variability most likely due to environmental factors such as soil type and land-use patterns (e.g., forest, agriculture, residential activities). This can be seen from results where samples from offsite military bases (Fort Jackson and Fort Stewart) without anthropogenic (137)Cs sources were much higher than both the SRS and a nearby (Sandhills) study site. Moreover, deer from private hunting grounds have the potential to be baited with corn, thus artificially lowering their (137)Cs body burdens compared to other free-ranging deer. Additionally, sample size for offsite collections were not robust enough to calculate a temporal decay curve with an upper confidence level to determine if the herds are following predicted radioactive decay rates like the SRS or if the variability is due to those points described above. Using mean yearly values, the ecological half-life for (137)Cs body burdens for SRS white-tailed deer was determined to be 28.79 years--very close to the 30.2 years physical half-life.

Trophic dynamics of U, Ni, Hg and other contaminants of potential concern on the Department of Energy's Savannah River Site.

The Department of Energy's Savannah River Site is a former nuclear weapon material production and current research facility located in South Carolina, USA. Wastewater discharges from a fuel and nuclear reactor target manufacturing facility released depleted and natural U, as well as other metals into the Tims Branch-Steed Pond water system. We investigated the current dynamics of this system for the purposes of environmental monitoring and assessment by examining metal concentrations, bioavailability, and trophic transfer of contaminants in seven ponds. Biofilm, detritus, and Anuran and Anisopteran larvae were collected and analyzed for stable isotopes (δ (15)N, δ (13)C) and contaminants of potential concern (COPC) with a focus on Ni, U, and Hg, to examine metal mobility. Highest levels of Ni and U were found in biofilms U (147 and 332 mg kg(-1) DW, respectively), while highest Hg levels were found in tadpoles (1.1 mg kg(-1) DW). We found intraspecific biomagnification of COPCs as expressed through stable isotope analysis. Biofilms were the best indicators for contamination and Anuran larvae with the digestive tract removed were the best indicators of the specific bioavailability of the focal metals. Monitoring data showed that baseline δ (15)N values differed between ponds, but within a pond, values were stable throughout tadpole Gosner stage, strengthening the case to use this species for monitoring purposes. It is likely that there still is risk to ecosystem integrity as COPC metals are being assimilated into lower trophic organisms and even low levels of this mixture has shown to produce deleterious effects to some wildlife species.

Time-of-Flight MRA of Intracranial Aneurysms with Interval Surveillance, Clinical Segmentation and Annotations.

Intracranial aneurysms (IAs) are present in 2-6% of the global population and can be catastrophic upon rupture with a mortality rate of 30-50%. IAs are commonly detected through time-of-flight magnetic resonance angiography (TOF-MRA), however, this data is rarely available for research and training purposes. The provision of imaging resources such as TOF-MRA images is imperative to develop new strategies for IA detection, rupture prediction, and surgical training. To support efforts in addressing data availability bottlenecks, we provide an open-access TOF-MRA dataset comprising 63 patients, of which 24 underwent interval surveillance imaging by TOF-MRA. Patient scans were evaluated by a neuroradiologist, providing aneurysm and vessel segmentations, clinical annotations, 3D models, in addition to 3D Slicer software environments containing all this data for each patient. This dataset is the first to provide interval surveillance imaging for supporting the understanding of IA growth and stability. This dataset will support computational and experimental research into IA dynamics and assist surgical and radiology training in IA treatment.

Contrast-induced acute kidney injury following coronary angiography: a cohort study of hospitalized patients with or without chronic kidney disease.

BACKGROUND: Contrast-induced acute kidney injury (CIAKI) has been linked to unfavorable consequences. In routine clinical practice, small increases in serum creatinine (SCr) following coronary angiography tend to be underestimated, especially in patients without chronic kidney disease (CKD). METHODS: We conducted a retrospective observational cohort study to analyze in-hospital and long-term outcomes of CIAKI following coronary angiography in patients with or without CKD (eGFR ≥ 60 mL/min/1.73 m(2)) from January 2008 through December 2009. CIAKI was defined as SCr either ≥ 25% or ≥ 0.5 mg/dL from baseline within 72 h after contrast exposure. Multivariable logistic regression for in-hospital mortality and Cox proportional hazards calculations for long-term mortality and requirement for dialysis were performed. RESULTS: A total of 1160 patients were included in the study. CIAKI occurred in 19% of CKD patients and in 18% of non-CKD patients. In CKD and non-CKD patients, CIAKI was more frequent in patients requiring mechanical ventilation or inotropes or in those given furosemide, and it was associated with adverse in-hospital (prolonged hospitalization, acute dialysis and mortality) and long-term (increased creatinine, initiation of dialysis and mortality) outcomes. In multivariable analysis, CKD patients had greater in-hospital mortality if they developed CIAKI (adjusted OR 8, 95% CI 1.9-34.5, P = 0.005), and non-CKD patients had greater long-term mortality if they developed CIAKI (adjusted HR 2.2, 95% CI 1.2-4.1, P = 0.016). CONCLUSIONS: CIAKI following coronary angiography was associated with adverse in-hospital and long-term outcomes in both CKD and non-CKD patients.