Surviving sudden cardiac arrest-successes, challenges, and opportunities.

Sudden cardiac arrest (SCA) is the most common cause of death in the world. This manuscript highlights the various challenges in prevention and early management of SCA and also discusses the current state of SCA awareness. The manuscript also outlines the various national and international initiatives in improving SCA awareness and their impact on improving outcomes in SCA. Various campaigns have strived for widespread dissemination of cardiopulmonary resuscitation training and advocated for broader public access defibrillator availability. Finally, the manuscript describes future directions including harnessing technology with voice command and artificial intelligence to allow lay person deliver effective CPR, to improve EMS response times, and to allow wider CPR knowledge dissemination in schools and places of employment. Future research should be focused on optimizing SCA outcomes among vulnerable populations and minorities. Advancements in resuscitation science and use of big data for improvement of EMS services will improve outcomes in SCA.

Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.

Large-scale gene expression analysis of legacy* and emerging** brominated flame retardants were conducted in the male Harlan Sprague Dawley rat [1]. Each animal was dosed for 5 days with the chemical at concentrations of 0.1 - 1000 µmol/kg body weight per day. Following the last dose, a specimen of the left liver was removed for RNA extraction. The amplified RNA (aRNA) was fragmented and then hybridized to Affymetrix Rat Genome 230 2.0 Arrays. Each GeneChip® array was scanned using an Affymetrix GeneChip® Scanner 3000 7 G to generate raw expression level data (.CEL files). Statistical contrasts were used to find pairwise gene expression differences between the control group and each dose group using the R/maanova package [2]. The transcriptomic data can be used to provide insights into the degree of toxicity, toxic mechanisms, disease pathways activated by exposure, and for benchmark dose analysis. The gene expression data for each of the nine flame retardants discussed here accompanies the research article entitled, "Comparative Toxicity and Liver Transcriptomics of Legacy and Emerging Brominated Flame Retardants following 5-Day Exposure in the Rat" [1]. * polybrominated diphenyl ether 47 (PBDE 47), decabromodiphenyl ether (decaBDE), hexabromocyclododecane (HBCD); ** 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB); bis(2-ethylhexyl) tetrabromophthalate (TBPH); tetrabromobisphenol A-bis(2,3-dibromopropyl ether (TBBPA-DBPE); 1,2-bis(tribromophenoxy)ethane (BTBPE); decabromodiphenylethane (DBDPE); hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO).

Comparative toxicity and liver transcriptomics of legacy and emerging brominated flame retardants following 5-day exposure in the rat.

The relative toxicity of three legacy and six emerging brominated flame retardants* was studied in the male Harlan Sprague Dawley rat. The hepatocellular and thyroid toxicity of each flame retardant was evaluated following five-day exposure to each of the nine flame retardants (oral gavage in corn oil) at 0.1-1000 µmol/kg body weight per day. Histopathology and transcriptomic analysis were performed on the left liver lobe. Centrilobular hypertrophy of hepatocytes and increases in liver weight were seen following exposure to two legacy (PBDE-47, HBCD) and to one emerging flame retardant (HCDBCO). Total thyroxine (TT4) concentrations were reduced to the greatest extent after PBDE-47 exposure. The PBDE-47, decaBDE, and HBCD liver transcriptomes were characterized by upregulation of liver disease-related and/or metabolic transcripts. Fewer liver disease or metabolic transcript changes were detected for the other flame retardants studied (TBB, TBPH, TBBPA-DBPE, BTBPE, DBDPE, or HCDBCO). PBDE-47 exhibited the most disruption of hepatocellular toxic endpoints, with the Nrf2 antioxidant pathway transcripts upregulated to the greatest extent, although some activation of this pathway also occurred after decaBDE, HBCD, TBB, and HCBCO exposure. These studies provide information that can be used for prioritizing the need for more in-depth brominated flame retardant toxicity studies.

Preclinical toxicity evaluation of JD5037, a peripherally restricted CB1 receptor inverse agonist, in rats and dogs for treatment of nonalcoholic steatohepatitis.

JD5037 is a novel peripherally restricted CB1 receptor (CB1R) inverse agonist being developed for the treatment of visceral obesity and its metabolic complications, including nonalcoholic fatty liver disease and dyslipidemia. JD5037 was administered by oral gavage at 10, 40, and 150 mg/kg/day dose levels for up to 34 days to Sprague Dawley rats, and at 5, 20, and 75 mg/kg/day dose levels for 28 consecutive days to Beagle dogs. In rats, higher incidences of stereotypic behaviors were observed in 10 mg/kg females and 40 mg/kg males, and slower responses for reflex and sensory tests were observed only in males at 10 and 40 mg/kg during neurobehavioral testing. Sporadic minimal incidences of decreased activity (males) and seizures (both sexes) were observed in rats during daily clinical observations, without any clear dose-relationship. Male dogs at 75 mg/kg during treatment period, but not recovery period, had an increased incidence of gut associated lymphoid tissue hyperplasia and inflammation in the intestine. In both species, highest dose resulted in lower AUCs indicative of non-linear kinetics. Free access to food increased the plasma AUC∞ by ~4.5-fold at 20 mg/kg in dogs, suggesting presence of food may help in systemic absorption of JD5037 in dogs. Based on the study results, 150 mg/kg/day in rats, and 20 and 75 mg/kg/day doses in male and female dogs, respectively, were determined to be the no-observed-adverse-effect-levels (NOAELs).

Impact of Obesity on Robot-Assisted Distal Pancreatectomy.

BACKGROUND: Obesity has been steadily increasing in the United States. The effect of body mass index (BMI) on surgical outcomes in pancreatic surgery is still controversial. Currently, there is no report related to obesity and robotic pancreatic surgery. The purpose of this study was to evaluate the impact of BMI on the surgical outcomes of both nonobese and obese patients undergoing robot-assisted distal pancreatectomy (RADP). METHODS: A prospectively collected database for RADP was retrieved for analysis. Patients were categorized as obese (BMI ≥30 kg/m(2)) and nonobese (BMI <30 kg/m(2)). Demographics, perioperative data, American Society of Anesthesiologists score, diagnosis, conversion rate, morbidity, surgical mortality, pancreatic fistula rate, and length of stay were compared. RESULTS: A total for 85 RADP were included, with 57 (67%) in the nonobese group and 28 (33%) in the obese group. No differences were found between nonobese and obese patients regarding demographic, preoperative risk, and perioperative parameters and mortality. There was a trend in the obese group associated with a higher rate of postoperative complications, but it was statistically insignificant. Clinically significant pancreatic fistula (grade B) occurred in 28.5% of obese patients and in 7% of nonobese patients, but without statistical significance (P = .064). CONCLUSIONS: Obesity does not have a significant impact on the perioperative outcomes and surgical risks for patients undergoing RADP, but high BMI may be a predictor for pancreatic fistula after RADP.

COMPARISON OF CHEMICAL AND SURGICAL VASECTOMY ON TESTICULAR ACTIVITY IN FREE-ROAMING HORSES (EQUUS CABALLUS).

Free-roaming horse (Equus caballus) management is a complex issue incorporating social, economic, emotional, political, and environmental factors. Currently, few proven field techniques exist for managing free-roaming horse population growth, which can reach 20-25% annually. Although there are several strategies available for sterilizing mares when managing free-roaming horse populations, surgical vasectomy is the only method used in the field for stallions. Some managers believe that surgically vasectomizing dominant stallions would have significant effects on reducing horse populations. However, sterilizing only dominant harem stallions results in a relatively modest reduction in population growth as substantial reproduction may occur even when 100% of the dominant harem stallions are sterilized if other males perform as little as 10% of the breeding. The overall goal of the current project was to evaluate the efficacy of a novel nonsurgical method for sterilizing free-roaming horses (chemical vasectomy). In September of 2013, stallions that had been previously surgically vasectomized (SURG, n = 25), previously chemically vasectomized (CHEM, n = 16), or untreated (CONT, n = 32) were captured and surgically castrated in preparation for adoption. When comparing both sterilization methods to CONT, serum testosterone and estrone sulfate concentrations did not differ (P > 0.05), suggesting that these methods for sterilizing free-roaming stallions would not disrupt herd social hierarchy. However, similar to the CONT, all CHEM stallions had sperm present within the vas deferens seminal fluid samples. CHEM stallions had more morphologically abnormal sperm than did CONT stallions but it is not known if this affected the actual fertility. Additional research is needed using alternative sclerosing agents for chemical vasectomy in free-roaming horse populations.

Fluorescence in robotic surgery.

Currently, there are several clinical applications for intraoperative ICG, such as identification of vascular and biliary anatomy, assessment of organ and tissue perfusion, lymph node mapping, and real-time identification of lesions. In this paper we present a review of the available literature related to the use of ICG fluorescence in robotic surgery in order to provide a better understanding of the current applications, show the rapid growth of this technique, and demonstrate the potential future applications.

Revisions after failed gastric band: sleeve gastrectomy and Roux-en-Y gastric bypass.

INTRODUCTION: Laparoscopic gastric band is an appealing bariatric operation due to its simplicity and good short-term outcomes; however, it is associated with complications (slippage, erosion, prolapse) and failure in reaching target weight loss. This study describes our experience with failed gastric bands that required a revisional procedure. MATERIALS AND METHODS: This single-center retrospective analysis includes all consecutive patients who underwent a gastric band removal and revisional surgery in our hospital from January 2008 to June 2014. A total of 81 patients were identified and divided in three groups: Group one included patients who just had the gastric band removed (43), group two consisted of patients who underwent a conversion to sleeve gastrectomy (SG) (26), and group three included patients who required a conversion to Roux-en Y gastric bypass (RYGB) (12). Patient demographics, date of gastric band placement, indications for revision, postoperative morbidity and mortality, operating time, blood loss, length of stay, and % excess weight loss (%EWL) were recorded. Perioperative and clinical outcomes were compared between conversions to SG and RYGB. RESULTS: In group two (n = 26), 21 conversions to SG were performed in concurrence with the band removal as a one-stage operation, while five procedures were performed in two-stages. There were no complications and no case was converted to open. Patients who underwent a one-stage procedure had a longer operative time, although it did not reach statistical significance. In group three, 12 patients underwent a conversion to RYGB as a revisional operation; 11 were performed as a one-stage procedure and only one patient underwent a two-stage procedure. CONCLUSIONS: SG and RYGB are safe options to revise a failed gastric band. Both groups who received either a SG or RYGB had a low complication rate and acceptable %EWL with no statistical difference between the two.

Carcinogenic and inflammatory effects of plutonium-nitrate retention in an exposed nuclear worker and beagle dogs.

PURPOSE: Plutonium-nitrate has a moderately rapid translocation rate from the lung to blood stream. Previous studies have shown an unexpected retention of soluble plutonium in the beagles and human case studied here. The inflammatory responses that may be associated with long-term exposure to ionizing radiation were characterized. These pathways include tissue injury, apoptosis, and gene expression modifications. Other protein modifications related to carcinogenesis and inflammation and the various factors that may play a role in orchestrating complex interactions which influence tissue integrity following irradiation were investigated. MATERIALS AND METHODS: We have examined numerous lung samples from a plutonium-exposed worker, a human control, and a variety of plutonium-exposed beagle dogs using immunohistochemistry and quantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). RESULTS: The exposed human showed interstitial fibrosis in peripheral regions of the lung, but no pulmonary tumors. Beagles with similar doses were diagnosed with tumors in bronchiolo-alveolar, peripheral and sub-pleural alveolar regions of the lung. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed an elevation of apoptosis in tracheal mucosa, tumor cells, and nuclear debris in the alveoli and lymph nodes of the beagles but not in the human case. In both the beagles and human there were statistically significant modifications in the expression of Fas ligand (FASLG), B-cell lymphoma 2 (BCL2), and Caspase 3 (CASP3). CONCLUSIONS: The data suggests that FASLG, BCL2, CASP3 and apoptosis play a role in the inflammatory responses following prolonged plutonium exposure. Utilizing these unique tissues revealed which pathways are triggered following the internal deposition and long-term retention of plutonium-nitrate in a human and a large animal model.

Fatal Caprine arthritis encephalitis virus-like infection in 4 Rocky Mountain goats (Oreamnos americanus).

Over a 3.5-year period, 4 Rocky Mountain goats (Oreamnos americanus), housed at a single facility, developed clinical disease attributed to infection by Caprine arthritis encephalitis virus (CAEV). Ages ranged from 1 to 10 years. Three of the goats, a 1-year-old female, a 2-year-old male, and a 5-year-old male, had been fed raw domestic goat milk from a single source that was later found to have CAEV on the premises. The fourth animal, a 10-year-old male, had not ingested domestic goat milk but had been housed with the other 3 Rocky Mountain goats. All 4 animals had clinical signs of pneumonia prior to death. At necropsy, findings in lungs included marked diffuse interstitial pneumonia characterized histologically by severe lymphoplasmacytic infiltrates with massive alveolar proteinosis, interstitial fibrosis, and type II pneumocyte hyperplasia. One animal also developed left-sided hemiparesis, and locally extensive lymphoplasmacytic myeloencephalitis was present in the cranial cervical spinal cord. Two animals had joint effusions, as well as severe lymphoplasmacytic and ulcerative synovitis. Immunohistochemical staining of fixed sections of lung tissue from all 4 goats, as well as spinal cord in 1 affected animal, and synovium from 2 affected animals were positive for CAEV antigen. Serology testing for anti-CAEV antibodies was positive in the 2 goats tested. The cases suggest that Rocky Mountain goats are susceptible to naturally occurring CAEV infection, that CAEV from domestic goats can be transmitted to this species through infected milk and by horizontal transmission, and that viral infection can result in clinically severe multisystemic disease.

Increased Survivorship and Altered Cytokine Profile from Treatment of Influenza A H1N1-Infected Mice with Ekybion: A Drug Complex of Natural Extracts and Inorganic Compounds.

Ekybion is a drug complex of 16 natural extracts and inorganic compounds designed to treat a variety of respiratory pathogens of bacterial and viral origin. It is licensed throughout Europe for the treatment of respiratory tract infections from equine parainfluenza type 3 and equine herpes virus type 1 in equine stables. The purpose of this paper was to test the efficacy of Ekybion on a well-developed animal model of influenza A infection and determine a mode of action. Experiments were performed with Balb/c mice infected with a lethal dose of influenza A/PR/8/34 H1N1 virus and treated with nebulized Ekybion every 8 h in a time-dependant or dose-dependant fashion. These experiments showed that mice treated prior to infection with Ekybion had a higher survival rates (~46%) compared with untreated animals (~0%). Paradoxically, these mice showed no significant difference in lung virus titer or weight loss. There was, however, a decrease in the level of GM-CSF, IL-6, and G-CSF cytokines in the lungs of Ekybion-treated, infected mice. It is possible that decreases in proinflammatory cytokines may have contributed to increased survivorship in Ekybion-treated influenza-infected mice.

Absence of the dens in a 9.5-year-old rottweiler with non-progressive clinical signs.

Absence of the dens is rarely described in large breed dogs. In this rottweiler, mild neurological deficits seen at 6 mo of age did not progress for the 9.5 y of the dog's life despite lack of surgical intervention. This finding underscores the marked differences between small and large breeds.

Aortic dissection associated with an obstructive aortic chondrosarcoma in a dog.

A 6-year-old, 35-kg, female spayed German wirehaired pointer was referred for evaluation of collapse/seizure-like activity and a suspected mediastinal mass. Echocardiographic examination revealed an obstructive, intraluminal aortic mass with aortic dissection. Gross and histopathological findings confirmed the aortic dissection with right pulmonary artery compression and an aortopulmonary fistula. The mass was histologically consistent with an intraluminal chondrosarcoma. To the authors knowledge this case represents only the second case of aortic chondrosarcoma in a dog, and interestingly the first case in either a dog or human to have aortic dissection associated with aortic obstruction by an intraluminal aortic tumor.

Fatal canine adenoviral pneumonia in two litters of Bulldogs.

Five Bulldog pups, 4 weeks of age or younger, were presented over a 2-day period for postmortem examination and diagnostic evaluation. The pups originated from 2 different litters but had been cared for at a common facility since their birth. All 5 pups died after exhibiting symptoms consisting of lethargy, dyspnea, nasal discharge, anorexia, vomiting, diarrhea, and abdominal pain. Necropsy examination revealed locally extensive to diffusely red, firm, consolidated lungs in all pups. Histopathologically, the lungs were variably effaced by multifocal areas of necrosis. The alveolar lumens contained fibrin, edema fluid, macrophages, and neutrophils. Many of the bronchioles contained cellular debris and neutrophils admixed with sloughed bronchiolar epithelium, which often contained large intranuclear amphophilic inclusion bodies that peripherally displaced chromatin. Fluorescent antibody testing was positive for Canine adenovirus. An adenovirus isolated via cell culture was positive on direct fluorescent antibody test and was identified as Canine adenovirus serotype 2 via polymerase chain reaction. Electron microscopy revealed typical viral inclusions within bronchiolar epithelial cells. Hemolytic Escherichia coli was also isolated from the lungs in 3 of the 5 pups. The current case demonstrates a natural and rare fatal infection with a viral agent that is typically associated with immunosuppression in both animals and humans.

Treatment of human respiratory syncytial virus infected Balb/C mice with the proteasome inhibitor bortezomib (Velcade, PS-341) results in increased inflammation and mortality.

Human Respiratory Syncytial Virus (HRSV) is an important pathogen and is associated with mortality in the young, old, and immuno-compromised. Due to the lack of effective therapeutic antivirals or a vaccine, there is a critical need for continued research in this field. Here we tested the ability of the FDA approved proteasome inhibitor bortezomib to inhibit HRSV in vitro and in vivo. We observed significant inhibition of HRSV replication in Vero cells at bortezomib concentrations from 20 to 40 ng/ml. Bortezomib was well tolerated in mice when administered intranasally at concentrations of < or = 0.3 mg/kg or intraperitoneally at 1.0 mg/kg. However, treatment of HRSV-infected mice with doses as low as 0.01 mg/kg resulted in increased pulmonary inflammation and mortality compared to mock treated-infected control animals. Examination of cytokine expression levels from lungs of bortezomib treated HRSV-infected mice revealed an increase in G-CSF, IL-6, MCP-1, and RANTES levels and a decrease in total IL-12 compared to mock treated-infected control animals. These data indicate that treatment with bortezomib during HRSV infection may alter the immune response and could potentially create a risk for patients treated with bortezomib in the event of a respiratory tract infection.

Acute megakaryoblastic leukemia in a German Shepherd dog.

An 11-year-old spayed-female German Shepherd dog was presented to the Veterinary Medical Teaching Hospital at Kansas State University with a history of weight loss, anorexia, depression, and lethargy for 2-3 weeks. Radiographic examination revealed a mass in the spleen and several round radiodense foci in the liver. CBC results included normocytic normochromic anemia, marked thrombocytopenia, and low numbers of neoplastic cells that frequently had cytoplasmic projections or blebs. A bone marrow aspirate contained about 80% neoplastic megakaryoblasts with the same microscopic features as those observed in peripheral blood. Using flow cytometry, cells of large size were identified in peripheral blood that expressed CD41/61, CD45, CD61, and CD62P (P-selectin) and were negative for markers of T cells, B cells, monocyte/macrophages, and dendritic cells. Because of the poor prognosis, euthanasia and subsequently necropsy were performed. On histopathologic examination, neoplastic megakaryoblasts were identified in spleen, liver, mesenteric lymph node, and the pulmonary vasculature. Using immunohistochemistry, the neoplastic megakaryoblasts weakly expressed von Willebrand factor. Based on microscopic and immunophenotypic findings, a diagnosis of acute megakaryoblastic leukemia (AMegL) was made. To our knowledge, this is the first report of AMegL in a domestic animal in which immunophenotyping by flow cytometry and a panel of antibodies against CD41/61, CD61, and CD62P were used to support the diagnosis.

What is your diagnosis? Muculent pleural effusion from a dog.

Pleural effusion was examined from a 5-year-old, female Brittany Spaniel with a 7-day history of dyspnea, anorexia, and diarrhea. The fluid was yellow, cloudy, and slightly gelatinous, and had a total protein concentration of 2.8 g/dL, a total nucleated cell concentration of 1.1 x 10(3)/microL, and a triglyceride concentration of 177 mg/dL. A cytocentrifuged preparation contained a mixed inflammatory cell population with a predominance of small lymphocytes and abundant mucinous material in the background. The dog died 3 days later and a mass was found within the lumen and wall of the right auricle of the heart at necropsy. Histopathologic sections of the mass contained a population of anaplastic spindle cells diffusely suspended in a pale basophilic matrix, consistent with myxosarcoma. The cells were positive for vimentin and negative for cytokeratin, desmin, and von Willebrand factor VIII-related antigen. A myxoid matrix was confirmed by positive staining with Alcian blue. Myxosarcoma is a rare cardiac tumor in dogs that should be considered, along with mucus-producing carcinomas and bile, as a cause of muculent effusion.

Evaluation of local and systemic effects after intramuscular implantation of lead shot alternatives in rats.

OBJECTIVE: To evaluate the local and systemic effects of IM implantation of lead shot alternatives in rats. ANIMALS: 22 laboratory rats. PROCEDURES: Sterile IM implantation of shot metals was performed, with euthanasia and necropsy at 2, 8, 16, and 26 weeks after implantation. Skeletal muscle specimens were examined histologically and kidney specimens were tested for heavy metals. In vivo and in vitro evaluation of corrosion of metals was performed. RESULTS: Corrosion of susceptible metals was greatest at 2 weeks in vivo and in vitro. Inflammation associated with all pellet types was greatest 2 weeks after implantation. Nickel-plated steel incited significantly greater inflammation at 2 weeks, compared with bismuth alloy. Kidney iron concentration was significantly greater at 26 weeks, compared with other test periods. Local tissue deposition of iron was verified by use of Prussian blue staining for all iron-containing metals. Concentration of arsenic in kidneys was significantly greater at 8, 16, and 26 weeks after implantation, compared with 2 weeks. CLINICAL RELEVANCE AND IMPACT FOR HUMAN MEDICINE: Humans or dogs wounded with nickel-plated steel may require more aggressive initial monitoring than those wounded with other shot types. Monitoring of systemic arsenic concentrations may be indicated in patients wounded with shotgun pellets.

Rhodococcus equi-specific cytotoxic T lymphocytes in immune horses and development in asymptomatic foals.

Rhodococcus equi is an important cause of pneumonia in young horses; however, adult horses are immune due to their ability to mount protective recall responses. In this study, the hypothesis that R. equi-specific cytotoxic T lymphocytes (CTL) are present in the lung of immune horses was tested. Bronchoalveolar lavage (BAL)-derived pulmonary T lymphocytes stimulated with R. equi lysed infected alveolar macrophages and peripheral blood adherent cells (PBAC). As with CTL obtained from the blood, killing of R. equi-infected targets by pulmonary effectors was not restricted by equine lymphocyte alloantigen-A (ELA-A; classical major histocompatibility complex class I), suggesting a novel or nonclassical method of antigen presentation. To determine whether or not CTL activity coincided with the age-associated susceptibility to rhodococcal pneumonia, CTL were evaluated in foals. R. equi-stimulated peripheral blood mononuclear cells (PBMC) from 3-week-old foals were unable to lyse either autologous perinatal or mismatched adult PBAC targets. The defect was not with the perinatal targets, as adult CTL effectors efficiently killed infected targets from 3-week-old foals. In contrast, significant CTL activity was present in three of five foals at 6 weeks of age, and significant specific lysis was induced by PBMC from all foals at 8 weeks of age. As with adults, lysis was ELA-A unrestricted. Two previously described monoclonal antibodies, BCD1b3 and CD1F2/1B12.1, were used to examine the expression of CD1, a nonclassical antigen-presenting molecule, on CTL targets. These antibodies cross-reacted with both foal and adult PBAC. However, neither antibody bound alveolar macrophages, suggesting that the R. equi-specific, major histocompatibility complex-unrestricted lysis is not restricted by a surface molecule identified by these antibodies.