Reference interval for the C-ACT activated clotting time test in healthy dogs using a water bath and manual assessment of clot formation.

AIMS: To establish a reference range for the canine C-ACT activated clotting time (ACT) test using a water bath and visual clot assessment technique. METHODS: Healthy, privately owned dogs (n = 48) were prospectively recruited to the study. Blood samples were collected via direct jugular venipuncture for complete blood count, serum biochemistry analysis and measurement of prothrombin time (PT) and activated partial thromboplastin time (aPTT). Five animals with major abnormalities or who became agitated during phlebotomy were excluded. For the 43 remaining animals, 2 mL of blood was collected via the cephalic vein and added directly to a C-ACT tube that was shaken vigorously before being placed in a water bath at 37°C. Tubes were visually assessed for clot formation and C-ACT was recorded in seconds when the magnet within the tube lodged in the clot. RESULTS: The nonparametric reference interval (capturing the central 95% of the data) was 50-80 seconds, with a 90% CI for the lower limit of 50-55 seconds and a 90% CI for the upper limit of 75-80 seconds. The C-ACT ACT test had a positive correlation with aPTT (0.42; 95% CI = 0.13-0.64). There was no evidence of a correlation between C-ACT ACT and age, weight, PT, haematocrit, white blood cell count, platelet count or total protein. CONCLUSIONS AND CLINICAL RELEVANCE: The results of this study suggest that the normal reference interval for ACT in dogs using C-ACT tubes in a 37°C water bath is 50-80 seconds. Care should be taken extrapolating the results of this study to the general population, as the smaller study design had less control for confounders than a larger study. However, when using the described analytical methods, C-ACT tube ACT test results >80 seconds should be considered prolonged in dogs and should prompt further investigation.

The Community Connection Model: implementation of best evidence into practice for self-management of chronic diseases.

OBJECTIVE: With chronic diseases becoming an increasing burden for healthcare systems worldwide, self-management support has gained traction in many health regions and organizations. However, the real-world application of the findings from clinical trials into actual community programming is not self-evident. The aim of this study was to present a model of programme implementation, namely the Community Connection Model. METHODS: The process of implementing a chronic disease self-management programme has been documented in detail from its initial inception through to a sustainable programme. This account includes a description of the strategic activities undertaken (e.g. alignment with local policy and the formation of community partnerships) and the specific steps taken on the path to programme implementation (e.g. a scoping literature review, an environmental scan and a pilot programme with an evaluation component). RESULTS: Reflection on this case example suggests that a cognizance of the interactions between policy, partnership, planning and programme could act as a useful tool to guide programme implementation, evaluation and sustainability. RESULTS: Multiple types of self-management support have been implemented (as part of the Living Health Champlain programme), and are being evaluated and adapted in response to new evidence, shifting priorities and direction from more partners. The widespread access means that self-management support programmes are becoming part of the culture of care in the study region. CONCLUSION: Establishing a connection around an important health problem, ensuring active partnerships, adequate planning and early implementation of a programme grounded on the principles of applying best-available evidence can lead to successful solutions. The Community Connection Model is proposed as a way of conceptualizing these processes.

Elective cricothyrotomy in a dog with transient laryngeal paralysis secondary to Australian paralysis tick (Ixodes holocyclus) envenomation.

The tube cricothyrotomy (CTT) has recently been introduced to small animal medicine as a viable surgical airway access procedure; however, there are no reports documenting its clinical use. The author's objective is to describe the clinical application, complications, and management of an elective CTT in a dog. Furthermore, the characteristics of CTT that may be clinically advantageous over temporary tube tracheostomy (TT) will be discussed. A 2-year-old female spayed German shepherd dog required mechanical ventilation (MV) due to unsustainable work of breathing as a result of tick paralysis and aspiration pneumonia. After successful weaning from MV, the dog was diagnosed with laryngeal paralysis. A surgical airway was performed using CTT to allow extubation and patient management whilst conscious. Complications included frequent tube suctioning due to accumulation of airway secretions in the tube and a single dislodgement event. The dog made an uneventful recovery with complete stoma healing by the second intention within 15 days. To the authors' knowledge, this is the first clinical report of an elective CTT performed to successfully manage upper airway obstruction in the dog. Its efficacy, clinical management and patient outcome are described.

Food for all: designing sustainable and secure future seafood systems.

Food from the sea can make a larger contribution to healthy and sustainable diets, and to addressing hunger and malnutrition, through improvements in production, distribution and equitable access to wild harvest and mariculture resources and products. The supply and consumption of seafood is influenced by a range of 'drivers' including ecosystem change and ocean regulation, the influence of corporations and evolving consumer demand, as well as the growing focus on the importance of seafood for meeting nutritional needs. These drivers need to be examined in a holistic way to develop an informed understanding of the needs, potential impacts and solutions that align seafood production and consumption with relevant 2030 Sustainable Development Goals (SDGs). This paper uses an evidence-based narrative approach to examine how the anticipated global trends for seafood might be experienced by people in different social, geographical and economic situations over the next ten years. Key drivers influencing seafood within the global food system are identified and used to construct a future scenario based on our current trajectory (Business-as-usual 2030). Descriptive pathways and actions are then presented for a more sustainable future scenario that strives towards achieving the SDGs as far as technically possible (More sustainable 2030). Prioritising actions that not only sustainably produce more seafood, but consider aspects of access and utilisation, particularly for people affected by food insecurity and malnutrition, is an essential part of designing sustainable and secure future seafood systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-021-09663-x.

Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, and seizures. The genetic cause of AS is the loss of expression of UBE3A (ubiquitin protein ligase E6-AP) in the brain, typically due to a deletion of the maternal 15q11-q13 region. Previous studies have been performed using a mouse model with a deletion of a single exon of Ube3a. Since three splice variants of Ube3a exist, this has led to a lack of consistent reports and the theory that perhaps not all mouse studies were assessing the effects of an absence of all functional UBE3A. Herein, we report the generation and functional characterization of a novel model of Angelman syndrome by deleting the entire Ube3a gene in the rat. We validated that this resulted in the first comprehensive gene deletion rodent model. Ultrasonic vocalizations from newborn Ube3am-/p+ were reduced in the maternal inherited deletion group with no observable change in the Ube3am+/p- paternal transmission cohort. We also discovered Ube3am-/p+ exhibited delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, and impaired touchscreen learning and memory in young adults. These behavioral deficits were large in effect size and easily apparent in the larger rodent species. Low social communication was detected using a playback task that is unique to rats. Structural imaging illustrated decreased brain volume in Ube3am-/p+ and a variety of intriguing neuroanatomical phenotypes while Ube3am+/p- did not exhibit altered neuroanatomy. Our report identifies, for the first time, unique AS relevant functional phenotypes and anatomical markers as preclinical outcomes to test various strategies for gene and molecular therapies in AS.

Plutonium speciation in water from mono lake, california.

The solubility of plutonium in Mono Lake water is enhanced by the presence of large concentrations of indigenous carbonate ions and moderate concentrations of fluoride ions. In spite of the complex chemical composition of this water, only a few ions govern the behavior of plutonium, as demonstrated by the fact that it was possible to duplicate plutonium speciation in a synthetic water containing only the principal components of Mono Lake water.

Neptunium and americium speciation in selected basalt, granite, shale, and tuff ground waters.

Neptunium and americium are relatively insoluble in ground waters containing high sulfate concentrations, particularly at 90 degrees C. The insoluble neptunium species is Np(IV); hence reducing waters should enhance its formation. Americium can exist only in the trivalent state under these conditions, and its solubility also should be representative of that of curium.

Cystic fibrosis liver disease: to transplant or not to transplant?

Biliary cirrhosis complicates some adults with cystic fibrosis (CF) and may require transplantation. Cardio-respiratory disease severity varies such that patients may require liver transplantation, heart/lung/liver (triple) grafts or may be too ill for any procedure. A 15-year experience of adults with CF-related liver disease referred for liver transplantation is presented with patient survival as outcome. Twelve patients were listed for triple grafting. Four died of respiratory disease after prolonged waits (4-171 weeks). Eight underwent transplantation (median wait 62 weeks); 5-year actuarial survival was 37.5%. Four died perioperatively; only one is alive at 8-years. Eighteen patients underwent liver transplant alone (median wait 7 weeks); 1- and 5-year actuarial survival rates were 100% and 69%. Three long-term survivors required further organ replacement (two heart/lung and one renal). Two others were turned down for heart/lung transplantation and four have significant renal impairment. Results for triple grafting were poor with unacceptable waiting times. Results for liver transplant alone were satisfactory, with acceptable waiting times and survival. However, further grafts were required and renal impairment was frequent. The policy of early liver transplantation for adults with CF with a view to subsequent heart/lung or renal transplantation needs assessment in the context of long-term outcome.

A single centre experience of liver disease in adults with cystic fibrosis 1995-2006.

BACKGROUND: Liver disease is an important cause of death in adults with cystic fibrosis (CF). Ursodeoxycholic acid (UDCA) may slow progression. Managing varices and timely evaluation for liver transplantation are important. METHODS: Adults with CF underwent annual review. Abnormalities of liver function tests or ultrasound prompted referral to the CF/liver clinic where UDCA was commenced. Endoscopic surveillance for varices was undertaken if ultrasound suggested portal hypertension. RESULTS: 154 patients were followed for a median 5 years. 43 had significant liver disease, 29 had cirrhosis with portal hypertension and 14 had ultrasound evidence of cirrhosis without portal hypertension. All started UDCA. Only one patient developed chronic liver failure and none required liver transplantation. 27 underwent endoscopy; 1 required variceal banding, the others had insignificant varices. Ultrasound was normal in 97 patients while five had steatosis; nine further patients had splenomegaly but no other evidence of portal hypertension. Neither spleen size nor platelet count correlated with portal hypertension. CONCLUSIONS: Liver disease was common in adults with CF but disease progression was rare. Thus liver disease detected and closely monitored in adults appeared to have a milder course than childhood CF. Splenomegaly, unrelated to portal hypertension may be a consequence of CF.

Orthotopic liver transplantation for subacute hepatic failure following partial treatment of isoniazid-resistant tuberculosis.

The management of patients with pre-existing tuberculosis (TB) undergoing liver transplantation is challenging. Cautious immunosuppression is required to prevent reactivation of disease, and second-line anti-tuberculous treatment may be necessary to prevent graft hepatotoxicity. Furthermore, liver transplantation in the context of isoniazid-resistant TB has seldom been reported. We report on a 44-year-old man with recent isoniazid-resistant extra-pulmonary TB who developed subacute hepatic failure requiring emergency liver transplantation and treatment with second-line anti-tuberculous therapy. We demonstrate that patients who have pre-existing TB can be successfully treated with alternative anti-tuberculous medication while under immunosuppression post transplantation. Pre-existing TB, including resistant strains, should not be an absolute contraindication to liver transplantation.

Continuous Video Electroencephalographic (EEG) Monitoring for Electrographic Seizure Diagnosis in Neonates: A Single-Center Study.

The objective of this study was to determine the diagnostic yield of continuous video electroencephalographic (EEG) monitoring in critically ill neonates in the setting of a novel, university-based Neonatal Neurocritical Care Service. Patient demographic characteristics, indication for seizure monitoring, and presence of electrographic seizures were obtained by chart review. Among 595 patients cared for by the Neonatal Neurocritical Care Service, 400 (67%) received continuous video EEG. The median duration of continuous video EEG monitoring was 49 (interquartile range = 22-87) hours. Electrographic seizures were captured in 105 of 400 (26% of monitored patients) and of those, 25 of 105 (24%) had no clinical correlate. In addition, 52 of 400 subjects (13%) were monitored due to paroxysmal events concerning for seizures, but never had electrographic seizures. Continuous video EEG monitoring helped confirm or rule out ongoing seizures in more than one-third of the cases. This finding helps to support the use of continuous video EEG in critically ill neonates.

Inhibition of E. coli and S. aureus with selenium nanoparticles synthesized by pulsed laser ablation in deionized water.

Nosocomial diseases are mainly caused by two common pathogens, Escherichia coli and Staphylococcus aureus, which are becoming more and more resistant to conventional antibiotics. Therefore, it is becoming increasingly necessary to find other alternative treatments than commonly utilized drugs. A promising strategy is to use nanomaterials such as selenium nanoparticles. However, the ability to produce nanoparticles free of any contamination is very challenging, especially for nano-medical applications. This paper reports the successful synthesis of pure selenium nanoparticles by laser ablation in water and determines the minimal concentration required for ~50% inhibition of either E. coli or S. aureus after 24 hours to be at least ~50 ppm. Total inhibition of E. coli and S. aureus is expected to occur at 107±12 and 79±4 ppm, respectively. In this manner, this study reports for the first time an easy synthesis process for creating pure selenium to inhibit bacterial growth.

Molecular characterisation of Haemophilus influenzae type a and untypeable strains isolated simultaneously from cerebrospinal fluid and blood: novel use of quantitative real-time PCR based on the cap copy number to determine virulence.

This study investigated the genetic structure of the cap region of an isolate of Haemophilus influenzae serotype a (Hia) from the cerebrospinal fluid (CSF) of a child with meningitis. In addition, the genetic structure of the cap region of a non-serotypeable H. influenzae isolate, obtained simultaneously from the blood of the same patient, was determined. According to restriction fragment length polymorphism analysis, the CSF and blood isolates were identical, with the exception of a single band shift of c. 35 kb. PCR analyses suggested that the CSF isolate possessed the IS1016-bexA gene and cap region II, whereas the blood isolate only had the IS1016 element. Furthermore, Southern analysis of DNA from both isolates showed that the CSF isolate carried the cap gene(s), while the blood isolate did not. Using a novel quantitative real-time PCR approach for determining the cap copy number, it was demonstrated that the CSF isolate had two intact tandem repeats of the cap gene containing three copies of IS1016, whereas the blood isolate had only one copy of IS1016. This study provided evidence that H. influenzae serotypes other than serotype b can cause serious disease, and that the virulence of these non-serotype b strains relates primarily to the cap gene copy number and the structure of the cap locus. Therefore, the quantitative real-time PCR assay described in this study should be useful for the rapid and definitive identification of strains of H. influenzae type a that represent a risk for serious disease.

Cost-effectiveness of Veterans Administration hospital-based home care. A randomized clinical trial.

A randomized design was used to examine the cost-effectiveness of a Veterans Administration hospital-based home care program that case managed inpatient and outpatient care. Patients (N = 419) with two or more functional impairments or a terminal illness were randomized to hospital-based home care (n = 211) or customary care (n = 208). Functional status, satisfaction with care, and morale were measured at baseline and at 1 and 6 months after discharge from the hospital; health care utilization was tracked for 6 months. Findings included significantly higher (0.1 on a three-point scale) patient and caregiver satisfaction with care at 1 month and lower Veterans Administration and private sector hospital costs ($3000 vs $4245) for the experimental group. Net per person health care costs were also 13% lower in the experimental group. We conclude that this model of hospital-based home care is cost-effective and that its expansion to cover these two patient groups throughout the Veterans Administration system can improve patient care at no additional cost.

A retrospective 15-year review: survival advantage after switching to sirolimus in hepatitis C virus infected liver graft recipients.

BACKGROUND: The use of sirolimus-based immune suppression in liver transplantation, particularly in hepatitis C virus (HCV)-infected recipients, remains contentious. There is some evidence that sirolimus retards hepatic fibrosis, is renal sparing and may be of benefit in preventing hepatocellular carcinoma (HCC) recurrence. Sirolimus has not been adopted by many transplant centres because of persistent concerns regarding an increased risk of hepatic artery thrombosis, graft loss and death with de novo sirolimus. AIM: To review the impact of switching to sirolimus monotherapy in HCV-infected liver recipients with respect to survival, graft loss and hepatic fibrosis. METHODS: A retrospective review of 190 patients from a single centre undergoing first liver transplantation for HCV over 15 years. 113 patients were switched from calcineurin inhibitor (CNI)-based therapy to low-dose sirolimus monotherapy at a median of 15 months after transplantation for HCV-related fibrosis (72%), renal impairment (14%) or high-risk HCC (5%). RESULTS: Patients switched to sirolimus had improved survival (P < 0.001) and slower progression to cirrhosis (P = 0.001). In patients with HCC (n = 91), sirolimus duration rather than strategy was an independent predictor of survival (P = 0.001) and extended time to HCC recurrence (33 vs. 16 months). Patients switched for renal dysfunction showed improvement in serum creatinine (140-108 µmol/L, P = 0.001). Those remaining on CNI-therapy were more likely to develop post-transplant diabetes (P = 0.03). CONCLUSION: These data suggest selective switching to low-dose sirolimus monotherapy in HCV-positive liver recipients improves clinical outcome.

Molecular targeting of malignant gliomas with novel multiply-mutated interleukin 13-based cytotoxins.

A vast majority of high-grade gliomas over-express a receptor for interleukin 13 (IL13). This glioma-associated receptor for IL13 is interleukin 4 (IL4)-independent. This is in contrast to the physiological and IL4-shared receptor for the IL13, IL13/4 receptor, which is found on many normal organs. IL13-based Pseudomonas exotoxin (PE)-containing cytotoxic fusion proteins have been shown to be very potent anti-glioma agents. However, native IL13-based cytotoxins interact with both forms of the IL13 receptor. Therefore, mutations in IL13 were made in order to diminish/eliminate IL13's interaction with the shared IL13/4 receptor of normal tissue. These mutations encompassed amino acids located on alpha-helix A and C of IL13. We have engineered double or triple mutants of IL13 linked to various forms of PE. We found that these mutations could be successfully incorporated into IL13 without the loss of the protein's ability to selectively deliver the toxin to glioma cells while reducing their toxicity.

The gamma-subunit of the acetylcholine receptor is not expressed in the levator palpebrae superioris.

In extraocular muscle (EOM), expression of the gamma-subunit, which is associated with the fetal-type acetylcholine receptor (AChR), may offer a differential target for immune-mediated damage and could explain the preponderance of ocular manifestations caused by myasthenia gravis (MG). Using Poly(A)+ RNA hybridization, we investigated expression of the gamma-subunit in bovine levator palpebrae superioris (LP), a muscle also differentially involved by MG. There were no transcripts of the gamma-subunit of the AChR, but the epsilon-subunit, associated with the adult-type AChR, was present. The results indicate that the susceptibility of LP to MG is not mediated by gamma-subunit expression and suggest that multiterminal fibers in EOM may be the site of gamma-subunit expression.

Antibodies to soluble human T cell receptor beta chain recognize multiple epitopes on cell surface TcR.

The T cell receptor (TcR) is an integral membrane protein occurring as a disulfide linked heterodimer, non-covalently associated with CD3 on the surface of T lymphocytes. Antibodies to the TcR have been shown to be effective for treating autoimmune disorders in animals. We describe here a method for producing antibodies to cell surface determinants of the human TcR, using a soluble form of the receptor as antigen. Soluble V alpha 1.2, V beta 8.1, V beta 11 TcR chains are expressed from a construct in which the extracellular domains of the TcR are fused to the mouse gamma 2a heavy chain constant region lacking the CH1 domain. These chimeric molecules contain both immunoglobulin and TcR determinants, as revealed by antibody probes. Amino-terminal sequence analysis of a chimeric V beta 8.1 molecule indicates that the TcR leader peptide is correctly processed from the soluble form. Antibodies raised against the soluble human V beta 8.1 molecule recognize the native determinants on Jurkat cells, and on natural T cells derived from resting human peripheral blood lymphocytes. Epitope mapping studies using competitive binding assays suggest that the anti-V beta 8 antibodies produced using soluble antigen recognize multiple overlapping determinants on the cell surface form of the TcR.