Effect of common sedation agents on feline splenic size determined via ultrasonography.

AIMS: To evaluate the effect of IM administration of three sedative drugs, acepromazine, alfaxalone and dexmedetomidine, in combination with morphine, on the size of the feline spleen using ultrasonography. METHODS: Twenty-four client-owned cats undergoing elective de-sexing or minor procedures were recruited for a focused ultrasonographic examination of the spleen prior to and at 10, 20 and 30 minutes following administration of one of three randomly assigned IM sedation protocols: 0.05 mg/kg acepromazine (ACE group), 3 mg/kg alfaxalone (ALF group), or 10 µg/kg dexmedetomidine (DEX group), in combination with 0.5 mg/kg morphine. B-mode images of the spleen were collected and measured following a standardised protocol. Cardiorespiratory parameters and sedation score were also recorded. Mean thickness of the head, body and tail of the spleen for each group at 10, 20 and 30 minutes after drug administration was compared to baseline. RESULTS: Mean splenic thickness increased over time in the ACE group (thickness of body at T0 = 8.9 (SE 2.1) mm and at T30 = 10.5 (SE 2.0) mm; p = 0.001) and the ALF group (thickness of body at T0 = 8.8 (SE 1.0) mm and at T30 = 10.3 (SE 1.7) mm; p = 0.022) but not in the DEX group (thickness of body at T0 = 8.6 mm (1.2) and at T30 = 8.9 mm (0.6); p = 0.67). Mean arterial blood pressure in the DEX group was significantly higher than in the other groups (p = 0.002). Sedation scores in the DEX group were consistently high for the entire period. However, the sedation score in the ACE group increased over 30 minutes (p = 0.007). Sedation score in the ALF group was highest at 10 minutes but gradually decreased over the following 20 minutes (p = 0.003). CONCLUSIONS: Sedation with IM dexmedetomidine and morphine did not change splenic size, whereas acepromazine or alfaxalone and morphine increased it regardless of the degree of sedation. CLINICAL RELEVANCE: Where splenomegaly is identified in a cat sedated with acepromazine or alfaxalone, the effects of the sedation protocol could be considered as a possible cause.

Substantial long-term loss of alpha and gamma diversity of lake invertebrates in a landscape exposed to a drying climate.

Many regions across the globe are shifting to more arid climates. For shallow lakes, decreasing rainfall volume and timing, changing regional wind patterns and increased evaporation rates alter water regimes so that dry periods occur more frequently and for longer. Drier conditions may affect fauna directly and indirectly through altered physicochemical conditions in lakes. Although many studies have predicted negative effects of such changes on aquatic biodiversity, empirical studies demonstrating these effects are rare. Global warming has caused severe climatic drying in southwestern Australia since the 1970s, so we aimed to determine whether lakes in this region showed impacts on lake hydroperiod, water quality, and α, ß and γ diversity of lake invertebrates from 1998 to 2011. Seventeen lakes across a range of salinities were sampled biennially in spring in the Wheatbelt and Great Southern regions of Western Australia. Multivariate analyses were used to identify changes in α, ß and γ diversity and examine patterns in physicochemical data. Salinity and average rainfall partially explained patterns in invertebrate richness and assemblage composition. Climatic drying was associated with significant declines in lake depth, increased frequency of dry periods, and reduced α and γ diversity (γ declined from ~300 to ~100 taxa from 1998 to 2011 in the 17 wetlands). In contrast, ß diversity remained consistently high, because each lake retained a distinct fauna. Mean α diversity per-lake declined both in lakes that dried and lakes that did not dry out, but lakes which retained a greater proportion of their maximum depth retained more α diversity. Accumulated losses in α diversity caused the decline in γ diversity likely through shrinking habitat area, fewer stepping stones for dispersal and loss of specific habitat types. Biodiversity loss is thus likely from lakes in drying regions globally. Management actions will need to sustain water depth in lakes to prevent biodiversity loss.

An agenda for research and action toward diverse and just futures for life on Earth.

Decades of research and policy interventions on biodiversity have insufficiently addressed the dual issues of biodiversity degradation and social justice. New approaches are therefore needed. We devised a research and action agenda that calls for a collective task of revisiting biodiversity toward the goal of sustaining diverse and just futures for life on Earth. Revisiting biodiversity involves critically reflecting on past and present research, policy, and practice concerning biodiversity to inspire creative thinking about the future. The agenda was developed through a 2-year dialogue process that involved close to 300 experts from diverse disciplines and locations. This process was informed by social science insights that show biodiversity research and action is underpinned by choices about how problems are conceptualized. Recognizing knowledge, action, and ethics as inseparable, we synthesized a set of principles that help navigate the task of revisiting biodiversity. The agenda articulates 4 thematic areas for future research. First, researchers need to revisit biodiversity narratives by challenging conceptualizations that exclude diversity and entrench the separation of humans, cultures, economies, and societies from nature. Second, researchers should focus on the relationships between the Anthropocene, biodiversity, and culture by considering humanity and biodiversity as tied together in specific contexts. Third, researchers should focus on nature and economies by better accounting for the interacting structures of economic and financial systems as core drivers of biodiversity loss. Finally, researchers should enable transformative biodiversity research and action by reconfiguring relationships between human and nonhuman communities in and through science, policy, and practice. Revisiting biodiversity necessitates a renewed focus on dialogue among biodiversity communities and beyond that critically reflects on the past to channel research and action toward fostering just and diverse futures for human and nonhuman life on Earth.

Una Agenda para la Investigación y la Acción hacia un Futuro Diverso y Justo para la Vida sobre la Tierra Resumen Las décadas de investigación e intervenciones políticas sobre la biodiversidad han tratado significativamente los temas de la degradación de la biodiversidad y la justicia social. Debido a esto, se requieren nuevas estrategias. Diseñamos una agenda de investigación y acción que llama a la labor colectiva de revisar la biodiversidad hacia el objetivo de sustentar un futuro diverso y justo para la vida sobre la Tierra. Cuando se revisa la biodiversidad, se requiere de una reflexión crítica sobre las investigaciones, políticas y prácticas presentes y pasadas sobre la biodiversidad para inspirar un pensamiento creativo acerca del futuro. Desarrollamos la agenda por medio de un proceso de diálogo de dos años que involucró a casi 300 expertos de diversas disciplinas y localidades. Este proceso estuvo orientado por el conocimiento de las ciencias sociales que muestra cómo la investigación y la acción para la biodiversidad están sostenidas por las opciones de cómo están conceptualizados los problemas. Reconocimos al conocimiento, la acción y la ética como inseparables y sintetizamos un conjunto de principios que ayuda a navegar la labor de revisar la biodiversidad. La agenda articula cuatro áreas temáticas para la investigación en el futuro. Primero, los investigadores necesitan revisar las narrativas de la biodiversidad mediante el cuestionamiento de las conceptualizaciones que excluyen a la diversidad y consolidan la separación entre humanos, culturas, economías y sociedades y la naturaleza. Segundo, los investigadores deberían enfocarse en las relaciones entre el antropoceno, la biodiversidad y la cultura al considerar a la humanidad y la biodiversidad como interconectadas en contextos específicos. Tercero, los investigadores deberían enfocarse en la naturaleza y las economías al tener en mejor cuenta la interacción de las estructuras de los sistemas económico y financiero como conductores nucleares de la pérdida de la biodiversidad. Finalmente, los investigadores deberían permitir la investigación y acción transformadoras de la biodiversidad al reconfigurar las relaciones entre las comunidades humanas y no humanas dentro y a través de la ciencia, la política y la práctica. La revisión de la biodiversidad necesita de un enfoque renovado sobre el diálogo entre las comunidades de la biodiversidad y más allá, que reflexione críticamente sobre el pasado para canalizar a la investigación y acción hacia el fomento del futuro justo y diverso para la vida humana y no humana sobre la Tierra.

Re-evaluating diagnostic thresholds for intrahepatic cholestasis of pregnancy: case-control and cohort study.

OBJECTIVE: To determine the optimal total serum bile acid (TSBA) threshold and sampling time for accurate intrahepatic cholestasis of pregnancy (ICP) diagnosis. DESIGN: Case-control, retrospective cohort studies. SETTING: Antenatal clinics, clinical research facilities. POPULATION: Women with ICP or uncomplicated pregnancies. METHODS: Serial TSBA measurements were performed pre-/postprandially in 42 women with ICP or uncomplicated pregnancy. Third-trimester non-fasting TSBA reference ranges were calculated from 561 women of black, south Asian and white ethnicity. Rates of adverse perinatal outcomes for women with ICP but peak non-fasting TSBA below the upper reference range limit were compared with those in healthy populations. MAIN OUTCOME MEASURES: Sensitivity and specificity of common TSBA thresholds for ICP diagnosis, using fasting and postprandial TSBA. Calculation of normal reference ranges of non-fasting TSBA. RESULTS: Concentrations of TSBA increased markedly postprandially in all groups, with overlap between healthy pregnancy and mild ICP (TSBA <40 µmol/l). The specificity of ICP diagnosis was higher when fasting, but corresponded to <30% sensitivity for diagnosis of mild disease. Using TSBA ≥40 µmol/l to define severe ICP, fasting measurements identified 9% (1/11), whereas non-fasting measurements detected over 91% with severe ICP. The highest upper limit of the non-fasting TSBA reference range was 18.3 µmol/l (95% confidence interval: 15.0-35.6 µmol/l). A re-evaluation of published ICP meta-analysis data demonstrated no increase in spontaneous preterm birth or stillbirth in women with TSBA <19 µmol/l. CONCLUSIONS: Postprandial TSBA levels are required to identify high-risk ICP pregnancies (TSBA ≥40 µmol/l). The postprandial rise in TSBA in normal pregnancy indicates that a non-fasting threshold of ≥19 µmol/l would improve diagnostic accuracy. TWEETABLE ABSTRACT: Non-fasting bile acids improve the diagnostic accuracy of intrahepatic cholestasis of pregnancy diagnosis.

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a secondary analysis of the PITCHES trial.

OBJECTIVE: To evaluate whether a particular group of women with intrahepatic cholestasis of pregnancy (ICP), based on their presenting characteristics, would benefit from treatment with ursodeoxycholic acid (UDCA). DESIGN: Secondary analysis of the PITCHES trial (ISRCTN91918806). SETTING: United Kingdom. POPULATION OR SAMPLE: 527 women with ICP. METHODS: Subgroup analyses were performed to determine whether baseline bile acid concentrations or baseline itch scores moderated a woman's response to treatment with UDCA. MAIN OUTCOME MEASURES: Bile acid concentration and itch score. RESULTS: In women with baseline bile acid concentrations less than 40 µmol/l, treatment with UDCA resulted in increased post-randomisation bile acid concentrations (geometric mean ratio 1.19, 95% CI 1.00-1.41, P = 0.048). A test of interaction showed no significance (P = 0.647). A small, clinically insignificant difference was seen in itch response in women with a high baseline itch score (-6.0 mm, 95% CI -11.80 to -0.21, P = 0.042), with a test of interaction not showing significance (P = 0.640). Further subgroup analyses showed no significance. Across all women there was a weak relationship between bile acid concentrations and itch severity. CONCLUSIONS: There was no subgroup of women with ICP in whom a beneficial effect of treatment with UDCA on bile acid concentration or itch score could be identified. This confirms that its routine use in women with this condition for improvement of bile acid concentration or itch score should be reconsidered. TWEETABLE ABSTRACT: PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus.

Heat hypersensitivity at a site proximal to a surgically induced osteochondral fracture in horses.

OBJECTIVE: To evaluate thermal nociceptive thresholds (TNTs) before and after inducing a standardized radiocarpal bone osteochondral fracture (OCF) in horses. STUDY DESIGN: Prospective, controlled, randomized, masked study. ANIMALS: A group of 10 Thoroughbred fillies aged 2 years. METHODS: Skin temperature and TNTs were measured on the skin over the triceps brachii muscle in both the thoracic limbs before (week 0) and weekly (weeks 1-8) after unilateral arthroscopic induction of a radiocarpal OCF (n = 4) or sham surgery (n = 6) followed by a standardized exercise programme. The contralateral, non-operated thoracic limb was used as a control within each horse. Percentage thermal excursion (%TE) defined as %TE = 100 ∗ (TNT - skin temperature)/(cut-off temperature - skin temperature) was calculated. Data were analysed with a mixed-effects model followed by Dunnett's and Tukey's tests for within and between-limbs comparisons, respectively; p < 0.05 was considered significant. RESULTS: Skin temperature in the control limb of OCF horses was significantly higher at week 7 than at week 0 (p = 0.0125). At week 1, TNTs and %TE values in operated limbs of OCF horses were significantly reduced compared with their baseline values at week 0 (p ≤ 0.0153) and their values in contralateral control limbs (p ≤ 0.0024) and operated limbs of sham-operated horses (p ≤ 0.0162). At week 2, TNTs and %TE values in operated limbs of OCF horses remained significantly reduced compared with values in operated limbs of sham-operated horses (p ≤ 0.0248). CONCLUSIONS AND CLINICAL RELEVANCE: Creation of an OCF in a radiocarpal bone induced transitory (<2 weeks) ipsilateral heat hypersensitivity proximal to the surgery site (skin over the triceps brachii muscle) in horses. Surgically induced OCF may cause somatosensory abnormalities consistent with secondary thermal hyperalgesia.

Indicators of dehydration in healthy 4- to 5-day-old dairy calves deprived of feed and water for 24 hours.

Our objective was to identify practical indicators of calf dehydration that could be used in an industry context. Eleven healthy 4-d-old commercial dairy calves were fed 2 L of mixed colostrum, then deprived of food and water for 24 h. Total body water was determined in the fed state using the deuterium dilution method. Body weight, along with a range of behavioral and physiological variables, was recorded 1 h after feeding, then at 90-min intervals through to 24 h. Blood samples were collected at every second sampling to assess changes in plasma hemoglobin, hematocrit, and osmolality. Linear mixed-effects models were used to explore associations between hydration status (% body water) and outcome variables. All calves remained bright and alert with good suckling reflexes throughout the 24-h period. After 24 h, total body water had decreased by an average of 8.4% (standard error 1.18), consistent with mild to moderate dehydration. Skin tent return time, capillary refill time, and detectable enophthalmos were associated with hydration status. Calves with skin tent return times of 3 s or longer were 4.4 percentage points less hydrated than those with return times of less than 3 s. Similarly, a capillary refill time of 3 s or longer was associated with a 4.3 percentage point reduction in hydration compared with refill times of less than 3 s. Calves with detectable enophthalmos (≥1 mm) were 3.5 percentage points less hydrated than those without enophthalmos. The skin tent, capillary refill, and enophthalmos tests are all relatively simple to perform and, although requiring the calf to be briefly restrained, can easily be performed by a single operator. The outcome of these tests was relatively consistent, in that calves above the threshold in any test were 3.5 to 4.5% less hydrated than calves below the threshold. As such, these tests may be of practical utility to identify calves with mild to moderate dehydration in an industry setting.

Effect of insulation with bubble wrap and an absorbent pad on heat loss in anaesthetised cats.

Aims: To evaluate the efficacy of insulating the limbs and thorax of cats with a combination of bubble wrap and an absorbent, plastic-lined pad in reducing heat loss during ovariohysterectomy. Methods: A preliminary study was performed to compare heat loss of 1 L bags of Hartmann's solution heated to 38°C which were either wrapped in two layers of bubble wrap and an absorbent pad (n = 6) or were unwrapped (n = 6). Bags were allowed to cool in a temperature-controlled room and the temperature of the bags was measured every 10 minutes for 60 minutes. The clinical study, included 16 intact female cats undergoing ovariohysterectomy. The cats were premedicated with I/M morphine and either medetomidine or dexmedetomidine, and anaesthesia was induced with I/V propofol and maintained with isoflurane in 100% oxygen. Cats were randomly assigned to either the treatment group (n = 8) whose limbs and thorax wrapped with two layers of bubble wrap and an absorbent pad immediately after induction, or the control group (n = 8) which were unwrapped. Body temperature (measured with an oesophageal temperature probe), heart rate, respiratory rate, mean arterial pressure and partial pressure of end-tidal CO2 were recorded immediately after induction (T start), before surgery started (T surgery), and at the end of isoflurane administration (T end). The times from T end to extubation, from T end to when the cat could maintain sternal recumbency and from T end to when the cat was able to stand, were also recorded. Results: In the preliminary study of heat loss by fluid bags, the mean temperature at 60 minutes was higher in wrapped bags (35.4 (SD 0.2)°C) compared to unwrapped bags (33.0 (SD 0.3)°C; p < 0.01). For cats undergoing ovariohysterectomy, mean body temperature of wrapped cats was higher than that of unwrapped cats both at T surgery (36.0 (SE 0.3) vs. 34.5 (SE 0.3)°C; p = 0.001) and at T end (37.2 (SE 0.5) vs. 36.0 (SE 0.5)°C; p = 0.01). Wrapped cats regained the ability to stand more rapidly that unwrapped cats (26.4 (SE 5.8) vs. 47.0 (SE 5.8) minutes p = 0.01). Conclusions: Wrapping the limbs and thorax of cats undergoing ovariohysterectomy in a combination of bubble wrap and absorbent pads reduced heat loss, which in turn improved recovery time from general anaesthesia. Clinical relevance: This inexpensive and practical method may reduce perioperative hypothermia, in cats undergoing abdominal surgery.

Enzymatic quantification of total serum bile acids as a monitoring strategy for women with intrahepatic cholestasis of pregnancy receiving ursodeoxycholic acid treatment: a cohort study.

OBJECTIVE: To evaluate enzymatic total serum bile acid quantification as a monitoring strategy for women with intrahepatic cholestasis of pregnancy (ICP) treated with ursodeoxycholic acid (UDCA). DESIGN: Cohort. SETTING: One UK university hospital. POPULATION: 29 ICP cases treated with UDCA. METHODS: Serial samples were collected prospectively throughout gestation. Total serum bile acids were measured enzymatically and individual bile acids by high-performance liquid chromatography-tandem mass spectrometry. Data were log-transformed and analysed with random effects generalised least square regression. MAIN OUTCOME MEASURES: The relationship between enzymatic total bile acid measurements and individual bile acid concentrations after UDCA treatment. RESULTS: In untreated women, cholic acid was the principal bile acid (51%) and UDCA concentrations were <0.5%, whereas UDCA constituted 60% (IQR 43-69) of serum bile acids following treatment and cholic acid fell to <20%. Changes in the total bile acid measurement reflected similar alterations in the concentrations of the pathologically elevated bile acids, e.g. a two-fold increase in enzymatic total bile acids is accompanied by approximately a two-fold increase in cholic acid and chenodeoxycholic acid at most UDCA doses (P < 0.001). Most of the effects of UDCA on cholic acid occur in the first week of treatment (60% relative reduction, P = 0.025, 95% CI 0.2-0.9, from 10 micromol/l (4.7-17.6) to 3.5 micromol/l (1.4-7.5). CONCLUSION: Ursodeoxycholic acid becomes the main component of the bile acid measurement after treatment. Enzymatic total bile acid assays are good predictors of both cholic acid and chenodeoxycholic acid, the primary bile acids that are raised prior to treatment. TWEETABLE ABSTRACT: Ursodeoxycholic acid constitutes approximately 60% of the bile acid measurement and reduces pathological cholic acid in treated women.

Analgesic efficacy of articaine hydrochloride for velvet antler removal in red deer (Cervus elaphus) and analysis of drug residues in the harvested velvet antlers.

AIMS: To investigate the analgesic efficacy of articaine hydrochloride for antler removal in red deer (Cervus elaphus) following S/C administration as a ring block, and to quantify the residue concentrations of articaine compared to lignocaine in the harvested antlers. METHODS: Articaine hydrochloride (40 mg/mL) was administered to 10 male red deer as a ring block around the base of each antler at 1 mL/cm of pedicle circumference. Analgesia was evaluated by determining the response to a saw cut test every 1-minute, until no response was observed. Behaviour during and following removal of antlers was also recorded. Twenty commercially harvested velvet antlers were also collected following S/C administration of 2% lignocaine hydrochloride. A liquid chromatography-mass spectrometry (LC-MS) method for quantification of residues of articaine and lignocaine in velvet antlers was developed and validated. RESULTS: In red deer administered 4% articaine hydrochloride as a ring block, the median interval to analgesia was 4 (min 3, max 5) minutes and no deer showed withdrawal responses during antler removal. There were no signs of toxicity or adverse effects up to 2 hours after administration. The sample preparation method developed for the LC-MS was simple and had acceptable extraction recoveries of articaine and lignocaine from the velvet antlers. The lower limits of quantification of lignocaine and articaine were 5 and 50 ng/g, respectively. Mean concentrations of articaine in antlers following ring block with 4% articaine hydrochloride were 1.50 (SD 1.09) mg/kg, and of lignocaine following ring block with 2% lignocaine hydrochloride were 0.66 (SD 0.71) mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: A ring block with 4% articaine hydrochloride at a dose of 1 mL/cm of pedicle circumference provided effective analgesia for velvet antler removal in red deer. The LC-MS method developed and validated to quantify articaine and lignocaine was simple and sensitive. Based on these results, articaine hydrochloride appears to be an effective alternative to lignocaine hydrochloride for velvet antler removal. However, further studies to evaluate the safety and residue concentrations of articaine and articainic acid are required before it can be recommended for use in deer.Abbreviations: DMA: 2,6-dimethylaniline; LC-MS: Liquid chromatography-mass spectrometry; MEGX: Monoethylglycinexylidide; MRL: Maximum residue level.

Next-Generation Sequencing for Characterizing Drug Resistance-Conferring Mycobacterium tuberculosis Genes from Clinical Isolates in the Ukraine.

The Ukraine ranks among the top 20 countries with the highest number of multidrug-resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis cases in the world. However, little is known of the genetic diversity, i.e., resistance signatures, in clinical isolates from this region. We analyzed seven of most prevalent MDR/XDR antibiotic resistance-conferring genes from clinical isolates (n = 75) collected from geographically diverse Ukrainian oblasts and the southern Crimean peninsula. Genomic analysis revealed that 6 (8%) were sensitive, 3 (4%) were resistant to at least one antibiotic but were not MDR, 40 (53%) were MDR, and 26 (35%) were XDR. The majority of isolates (81%) were of the Beijing-like lineage. This is the first study to use next-generation sequencing (NGS) of clinical isolates from the Ukraine to characterize mutations in genes conferring M. tuberculosis drug resistance. Several isolates harbored drug resistance signatures that have not been observed in other countries with high-burden tuberculosis. Most notably, the absence of inhA gene promoter mutations, a diversity of mutation types in the rpoB resistance-determining region, and detection of heteroresistance provide a broader understanding of MDR/XDR from this area of the world.

Establishing and prioritizing research questions for the prevention, diagnosis and treatment of hair loss (excluding alopecia areata): the Hair Loss Priority Setting Partnership.

BACKGROUND: Hair and scalp problems are common. Unfortunately, many uncertainties exist around the most effective management and treatment strategies for these disorders. OBJECTIVES: To identify uncertainties in hair-loss management, prevention, diagnosis and treatment that are important to both people with hair loss and healthcare professionals. METHODS: A Hair Loss Priority Setting Partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in hair loss. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants; following exclusions 884 uncertainties relating to hair loss (excluding alopecia areata) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that was taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for hair loss (excluding alopecia areata) to guide researchers and funding bodies to support studies important to both patients and clinicians.

IgA Antibodies Against Gliadin and Tissue Transglutaminase in Dogs With Chronic Enteritis and Intestinal T-Cell Lymphoma.

Molecular clonality analysis of T-cell receptor (TCR) genes for diagnosing T-cell lymphoma is widely used in veterinary medicine. However, differentiating chronic enteritis (CE) from intestinal lymphoma is challenging because of the incompatibility between histopathologic and clonality analysis results. On the basis of findings that canine intestinal T-cell lymphoma and celiac disease share some common features, we conducted serologic examinations in combination with histopathologic and T-cell receptor clonality analyses in 48 dogs diagnosed with either CE or intestinal lymphoma. Immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies against gliadin and tissue transglutaminase (tTG) were quantitatively measured using ELISA. The conditions were classified according to the histopathologic diagnosis, clonality analysis, and combined histopathologic/clonality analysis. Histopathologic analysis showed that dogs with intestinal lymphoma were likely to have high levels of serum IgA antibodies against gliadin and tTG, and serum IgG antibodies against tTG. No correlation between the diagnosed groups and control group was observed in the results of the clonality analysis and histopathologic/clonality analysis. It is interesting that dogs with intestinal lymphoma had a higher serum IgA titer against gliadin and tTG than did dogs with CE. These results suggest an association between repetitive inflammatory stimulation by gliadin peptides and subsequent intestinal lymphoma in dogs.

Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus).

AIM: To develop and validate a simple and sensitive method using liquid chromatography-mass spectrometry (LC-MS) for quantification of articaine, and its major metabolite articainic acid, in plasma of red deer (Cervus elaphus), and to investigate the pharmacokinetics of articaine hydrochloride and articainic acid in red deer following S/C administration of articaine hydrochloride as a complete ring block around the antler pedicle. METHODS: The LC-MS method was validated by determining linearity, sensitivity, recovery, carry-over and repeatability. Articaine hydrochloride (40 mg/mL) was administered S/C to six healthy male red deer, at a dose of 1 mL/cm of pedicle circumference, as a complete ring block around the base of each antler. Blood samples were collected at various times over the following 12 hours. Concentrations in plasma of articaine and articainic acid were quantified using the validated LC-MS method. Pharmacokinetic parameters of articaine and articainic acid were estimated using non-compartmental analysis. RESULTS: Calibration curves were linear for both articaine and articainic acid. The limits of quantifications for articaine and articainic acid were 5 and 10 ng/mL, respectively. Extraction recoveries were >72% for articaine and >68% for articainic acid. After S/C administration as a ring block around the base of each antler, mean maximum concentrations in plasma (Cmax) of articaine were 1,013.9 (SD 510.1) ng/mL, detected at 0.17 (SD 0.00) hours, and the Cmax for articainic acid was 762.6 (SD 95.4) ng/mL at 0.50 (SD 0.00) hours. The elimination half-lives of articaine hydrochloride and articainic acid were 1.12 (SD 0.17) and 0.90 (SD 0.07) hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The LC-MS method used for the quantification of articaine and its metabolite articainic acid in the plasma of red deer was simple, accurate and sensitive. Articaine hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite articainic acid, and eliminated following S/C administration as a ring block in red deer. These favourable pharmacokinetic properties suggest that articaine hydrochloride should be tested for efficacy as a local anaesthetic in red deer for removal of velvet antlers. Further studies to evaluate the safety and residues of articaine hydrochloride and articainic acid are required before articaine can be recommended for use as a local anaesthetic for this purpose.

A survey of dog and cat anaesthesia in a sample of veterinary practices in New Zealand.

AIMS: To survey current anaesthesia practices for dogs and cats in small and mixed animal practices in New Zealand in order to improve anaesthesia education. METHODS: A questionnaire was sent to 440 small and mixed animal practices, including questions regarding the type of practice, preanaesthetic examination, anaesthetic drugs and management, anaesthetic machines, monitoring and topics of interest for continuing professional development. RESULTS: Responses were obtained from 113/440 (26%) practices, with 78 (69%) respondents from small and 35 (31%) from mixed animal practices. A preanaesthetic physical examination was carried out by >95% of respondents and premedication was usually given to dogs (112/113; 99%) and cats (95/113; 85%). Acepromazine was the preferred sedative for dogs and cats, with morphine or buprenorphine. Propofol and alfaxalone were the preferred induction agents, and isoflurane was preferred for maintenance in both dogs and cats. A venous catheter was usually placed for anaesthesia in dogs (59/113; 52%), but less so in cats (39/113; 35%). Perioperative fluid was administered at 10 mL/kg/hour by 62/110 (56%) respondents. Intubation was usually used for anaesthesia in dogs (111/112; 99%), and cats (87/112; 78%). Almost 40% of respondents usually administered supplementary oxygen if patients were not intubated. Local analgesia was used by 69/111 (88%) respondents sometimes or always if applicable. Morphine or buprenorphine, and meloxicam were common choices for post-operative analgesia after neuter surgery in dogs and cats. A semiclosed (non-rebreathing) system was used in animals weighing <10 kg, and a Mapleson E or F non-rebreathing circuit was used by 66/109 (61%) practices. Only 15/111 (14%) practices had a ventilator in their practice. A dedicated anaesthetist was usually used by 104/113 (92%) practices, and apnoea alarms, pulse oximeters, thermometers and oesophageal stethoscopes were the main monitoring devices available in practices. Loco-regional block, pain management, and anaesthetic drugs were the main topics of interest for continuing education. CONCLUSIONS AND CLINICAL RELEVANCE: Responses by the veterinarians taking part in this survey indicated that they had a reasonably good standard of anaesthetic practice. A physical examination was carried out preanaesthesia, and premedication including analgesia was routinely administered to most patients. A dedicated anaesthetist usually monitored patients and most respondents reported they had access to basic anaesthetic monitoring equipment. Areas where changes could lead to improved anaesthetic practice were increased use of I/V catheterisation, endotracheal intubation, and supplementary oxygen, and reduced I/V fluid rates.

Helminth parasites and zoonotic risk associated with urban coyotes (Canis latrans) in Alberta, Canada.

Coyotes (Canis latrans) are resilient, adaptable, cosmopolitan omnivores that are increasingly prevalent in urban environments, where they interact with both humans and domestic dogs. Coyotes potentially transmit zoonotic parasites, including the tapeworm Echinococcus multilocularis, which appears to be increasing in prevalence in western North America. In this study, we analysed the carcasses of 23 urban coyotes in Edmonton, Alberta, Canada. Focusing primarily on the helminth community, we recovered three tapeworm species (E. multilocularis, Taenia pisiformis, T. serialis), four nematodes (Toxascaris leonina, Uncinaria stenocephala, Capillaria sp., Physaloptera sp.), and two trematodes (Alaria arisaemoides and A. americana). Compared to previous studies of urban coyotes conducted in North America, we report one of the highest levels of E. multilocularis infection in North America: 65.2% infection prevalence. These results amplify concerns expressed by others about the increasing prevalence of this zoonotic parasite and the role coyotes may play in parasite transmission. More research is needed to better understand how various ecological factors, urbanization and wildlife management practices influence the transmission of potentially zoonotic parasites such as E. multilocularis.

Spatiotemporal analysis of spontaneous myogenic contractions in the urinary bladder of the rabbit: timing and patterns reflect reported electrophysiology.

The dynamics of propagating myogenic contractions in the wall of the resting ex vivo urinary bladder of the rabbit were characterized by spatiotemporal maps and related to cyclic variation in intravesical pressure (Pves). Patches of propagating contractions (PPCs) enlarged and involuted in near synchrony with peaks in Pves [mean 3.85 ± 0.3 cycles per minute (cpm)] and were preceded by regions of stretch. The maximum area of the bladder undergoing contraction (55.28 ± 2.65%) and the sizes of individual PPCs (42.61 ± 1.65 mm2) coincided with the peak in Pves PPCs originated and propagated within temporary patch domains (TPDs) and comprised groups of nearly synchronous cyclic propagating individual contractions (PICs). The TPDs were located principally along the vertical axis of the anterior surface of the bladder. The sites of origin of PICs within PPCs were inconsistent, consecutive contractions often propagating in opposite directions along linear maps of strain rate. Similar patterns of movement occurred in areas of the anterior bladder wall that had been stripped of mucosa. Pves varied cyclically with area of contraction and with the indices of aggregation of PPCs, indicating that they grew by peripheral enlargement and collision without annihilation. The synchronization of PICs within PPCs was sometimes lost, uncoordinated PICs then occurring irregularly (between 4 and 20 cpm) having little effect on Pves We postulate that the formation and involution of PPCs within a TPD resulted from cyclic variation in excitation that increased the incidence and distance over which component PICs propagated.

Establishing and prioritizing research questions for the treatment of alopecia areata: the Alopecia Areata Priority Setting Partnership.

BACKGROUND: Alopecia areata (AA) is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. OBJECTIVES: To identify uncertainties in AA management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. METHODS: An AA priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in AA. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to AA (and variants) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for AA to guide researchers and funding bodies to support studies important to both patients and clinicians.

Longitudinal hemodynamics in acute phase of treatment with labetalol in hypertensive pregnant women to predict need for vasodilatory therapy.

OBJECTIVE: Hypertensive pregnant women who do not respond to treatment with labetalol to control blood pressure (BP), but require vasodilatory therapy, progress rapidly to severe hypertension. This could be delayed by early recognition and individualized treatment. In this study, we sought to create prediction models from data at presentation and at 1 h and 24 h after commencement of treatment to identify patients who will not have a sustained response to labetalol and therefore need vasodilatory therapy. METHODS: The study population comprised 134 women presenting with hypertension at a UK hospital. Treatment with oral labetalol was administered when BP was > 150/100 mmHg or > 140/90 mmHg with systemic disease. BP and hemodynamic parameters were recorded at presentation and at 1 h and 24 h after commencement of treatment. Labetalol doses were titrated to maintain BP around 135/85 mmHg. Women with unresponsive BP, despite labetalol dose maximization (2400 mg/day), received additional vasodilatory therapy with nifedipine. Binary logistic and longitudinal (mixed-model) data analyses were performed to create prediction models anticipating the likelihood of hypertensive women needing vasodilatory therapy. The prediction models were created from data at presentation and at 1 h and 24 h after treatment, to assess the value of central hemodynamics relative to the predictive power of BP, heart rate and demographic variables at these intervals. RESULTS: Twenty-two percent of our cohort required additional vasodilatory therapy antenatally. These women had higher rates of severe hypertension and delivered smaller babies at earlier gestational ages. The unresponsive women were more likely to be of black ethnicity, had higher BP and peripheral vascular resistance (PVR), and lower heart rate and cardiac output (CO) at presentation. Those who needed vasodilatory therapy showed an initial decrease in BP and PVR, which rebounded at 24 h, whereas BP and PVR in those who responded to labetalol showed a sustained decrease at 1 h and 24 h. Stroke volume and CO did not decrease during the acute phase of treatment in either group. The best model for prediction of the need for vasodilators was provided at 24 h by combining ethnicity and longitudinal BP and heart rate changes. The model achieved a detection rate of 100% for a false-positive rate of 20% and an area under the receiver-operating characteristics curve of 0.97. CONCLUSION: Maternal demographics and hemodynamic changes in the acute phase of labetalol monotherapy provide a powerful tool to identify hypertensive pregnant patients who are unlikely to have their BP controlled by this therapy and will consequently need additional vasodilatory therapy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. RESUMEN OBJETIVO: Las embarazadas hipertensas que no responden al tratamiento con labetalol para el control de la presión arterial (PA), pero que requieren terapia vasodilatadora, evolucionan rápidamente hacia una hipertensión severa. Ésta se puede retrasar mediante un diagnóstico precoz y un tratamiento individual. En este estudio se ha tratado de crear modelos de predicción a partir de datos al inicio del tratamiento y al cabo de 1 hora y de 24 horas después del mismo, para identificar a las pacientes que no mostrarán una respuesta constante al labetalol y que por lo tanto necesitarán terapia vasodilatadora. MÉTODOS: La población de estudio incluyó 134 mujeres con hipertensión en un hospital del Reino Unido. El tratamiento con labetalol por vía oral se administró cuando la PA fue >150/100 mm de Hg o >140/90 mm de Hg con enfermedad multisistémica. Se registró la PA y los parámetros hemodinámicos tanto al inicio como al cabo de 1 h y de 24 h después del inicio del tratamiento. Las dosis de Labetalol se ajustaron para mantener la PA en torno a los 135/85 mm de Hg. Las mujeres cuya PA no produjo respuesta, a pesar de haberles administrado la dosis máxima de labetalol (2400 mg/día), recibieron terapia vasodilatadora adicional con nifedipino. Se realizaron análisis de datos mediante logística binaria y longitudinal (modelo mixto), para crear modelos de predicción con los que pronosticar la probabilidad de la necesidad de terapia vasodilatadora en mujeres hipertensas. Los modelos de predicción se crearon a partir de datos al inicio y al cabo de 1 hora y 24 horas del tratamiento, para evaluar el valor de los parámetros hemodinámicos principales con respecto a la capacidad predictiva de la PA, la frecuencia cardíaca y las variables demográficas en estos intervalos. RESULTADOS: El 22 % de la cohorte necesitó terapia vasodilatadora adicional antes del parto. Estas mujeres tuvieron tasas más altas de hipertensión grave y neonatos más pequeños en edades gestacionales más tempranas. Las mujeres que no respondieron al tratamiento fueron con más frecuencia de raza negra, tuvieron la PA y la resistencia vascular periférica (RVP) más alta, y la frecuencia cardíaca y el gasto cardíaco (GC) más bajos al inicio del tratamiento. Aquellas que necesitaron terapia vasodilatadora mostraron un descenso inicial de la PA y la RVP, que se recuperó al cabo de 24 h, mientras que la PA y la RVP en las que respondieron al labetalol mostraron una disminución constante al cabo de 1 h y de 24 h. El volumen sistólico y el GC no disminuyeron durante la fase aguda del tratamiento en ninguno de los grupos. El mejor modelo para la predicción de la necesidad de vasodilatadores se obtuvo a las 24 h mediante la combinación de la etnia con los cambios longitudinales de la PA y la frecuencia cardíaca. El modelo alcanzó una tasa de detección del 100% para una tasa de falsos positivos del 20% y un área bajo la curva de características operativas del receptor de 0,97. CONCLUSIÓN: Los datos demográficos maternos y los cambios hemodinámicos en la fase aguda de la monoterapia con labetalol constituyen una herramienta poderosa para identificar a las pacientes embarazadas hipertensas con pocas probabilidades de que se les pueda controlar su PA mediante esta terapia y que por lo tanto necesitarán terapia vasodilatadora adicional. : 、(blood pressure,BP),。。,1 h24 h,。 : 134。BP>150/100 mmHgBP>140/90 mmHg。1 h24 hBP。,BP135/85 mmHg。BP,()。logistic(),。1 h24 h,,BP、。 : 22%。。,BP(peripheral vascular resistance,PVR),(cardiac output,CO)。BPPVR,24 h,1 h24 hBPPVR。CO。24hBP。100%,20%,0.97。 : ,BP。.

Deposition, Clearance, and Reinduction of Amyloid A Amyloid in Interleukin 1 Receptor Antagonist Knockout Mice.

Amyloid A (AA) amyloidosis is characterized by the extracellular deposition of AA amyloid and results in the irreversible dysfunction of parenchymal organs. In experimental models, AA amyloid deposits are cleared following a decrease in circulating serum amyloid A (SAA) concentrations. Additional inflammatory stimuli during this recovery process may induce more severe amyloid redeposition. In the present study, we confirmed the deposition, clearance, and reinduction of AA amyloid deposits in interleukin 1 receptor antagonist knockout mice (IL-1raKO) and studied the SAA levels and amyloid-enhancing factor activity based on the time-dependent changes of amyloid deposition. Histopathologically, following initial (day 0) injection of amyloid-enhancing factor in combination with an inflammatory stimulus (silver nitrate [AgNO3]), amyloid deposition peaked by day 20, and its deposition gradually decreased after day 35. SAA concentrations in serum were precipitously elevated on day 1 but returned to normal levels by day 10, whereas the SAA dimer was detected in serum after day 45. An additional AgNO3 injection was administered to mice with amyloidosis on day 5, 10, 35, or 50, and all mice developed large amyloid deposits. Amyloid deposition was most severe in mice treated with AgNO3 on day 35. The inoculation of sera from mice with AA amyloidosis, combined with AgNO3, induced AA amyloidosis. Serum samples collected on days 35 and 50, which contained high concentrations of the SAA dimer, induced amyloidosis in a high proportion (83%) of mice. Therefore, increased SAA and/or its dimer in serum during the recovery process may markedly exacerbate the development of AA amyloidosis.