Strategies and tactics for the synthesis of lipid I and II and shortened analogues: functional building blocks of bacterial cell wall biosynthesis.

Covering: the literature up to 2022This study discusses various synthetic strategies for the synthesis of lipid II, the pivotal bacterial cell wall precursor. In detail, it examines different solution phase approaches, reviews various solid phase sequences, and evaluates enzymatic ventures. The underlying rationale, scope, limitations, and perspectives of these strategies are discussed. The focus is on the tactics and strategies towards the authentic peptidoglycan compound, as well as analogues thereof with shortened side chains, which are increasingly recognized as more beneficial surrogates with more favorable physicochemical properties.

Complications secondary to endotracheal intubation in dogs and cats: A questionnaire-based survey among veterinary anaesthesiologists.

OBJECTIVE: To investigate anaesthesiologists' attitudes towards endotracheal intubation and the perceived incidence of complications secondary to endotracheal intubation in dogs and cats. STUDY DESIGN: A cross-sectional online questionnaire-based study. METHODS: Using an online questionnaire distributed via electronic mail, the perceived incidence of complications secondary to endotracheal intubation in dogs and cats was investigated. Attitudes towards endotracheal intubation, average caseload and percentage of animals intubated were examined. The study population consisted of Diplomates, Residents, and residency trained members of the American and European Colleges of Veterinary An(a)esthesia and Analgesia. Univariate descriptive statistics were calculated. For each complication, a mean incidence score (MIS) was calculated, ranging from 1 (never) to 5 (always). Additionally, a Wilcoxon signed-rank test and binary regression analyses were performed. A p value ≤ 0.05 was considered significant. RESULTS: The overall response rate was 35.1%, with a completion rate of 26.6%. Most dogs and cats undergoing general anaesthesia were intubated. Endotracheal intubation was viewed as an integral part of modern anaesthesia. Significant differences were found in the incidence of 16 of the 24 examined complications between dogs and cats (p ≤ 0.001). The most frequently perceived complications were reported to be cuff leak (MIS 3.20) and coughing during intubation (MIS 3.10) in dogs, and coughing (MIS 3.01) and laryngeal spasm during intubation (MIS 2.91) in cats. Sociodemographic and practice-specific aspects did not appear to play a significant role in the reported incidence of complications. CONCLUSIONS AND CLINICAL RELEVANCE: Endotracheal intubation was considered a state-of-the-art technique by the respondents. It was associated with a perceived low incidence of major complications and more frequent minor ones. Differences between dogs and cats need to be accounted for. Considering the retrospective and self-reporting nature of this survey, true incidences might differ.

Pol5 is required for recycling of small subunit biogenesis factors and for formation of the peptide exit tunnel of the large ribosomal subunit.

More than 200 assembly factors (AFs) are required for the production of ribosomes in yeast. The stepwise association and dissociation of these AFs with the pre-ribosomal subunits occurs in a hierarchical manner to ensure correct maturation of the pre-rRNAs and assembly of the ribosomal proteins. Although decades of research have provided a wealth of insights into the functions of many AFs, others remain poorly characterized. Pol5 was initially classified with B-type DNA polymerases, however, several lines of evidence indicate the involvement of this protein in ribosome assembly. Here, we show that depletion of Pol5 affects the processing of pre-rRNAs destined for the both the large and small subunits. Furthermore, we identify binding sites for Pol5 in the 5' external transcribed spacer and within domain III of the 25S rRNA sequence. Consistent with this, we reveal that Pol5 is required for recruitment of ribosomal proteins that form the polypeptide exit tunnel in the LSU and that depletion of Pol5 impairs the release of 5' ETS fragments from early pre-40S particles. The dual functions of Pol5 in 60S assembly and recycling of pre-40S AFs suggest that this factor could contribute to ensuring the stoichiometric production of ribosomal subunits.

Stereoselective methadone disposition after administration of racemic methadone to anesthetized Shetland ponies assessed by capillary electrophoresis.

The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone hydrochloride; n = 6) or constant rate infusion (0.25 mg/kg bolus followed by 0.25 mg/kg/h methadone hydrochloride; n = 3) administration of racemic methadone. Plasma concentrations of l-methadone and d-methadone and their major metabolites, l- and d-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), respectively, were analyzed by CE with highly sulfated γ-cyclodextrin as chiral selector and electrokinetic analyte injection from liquid/liquid extracts prepared at alkaline pH. In both trials, the d-methadone concentrations were lower than those of l-methadone and the d-EDDP levels were lower than those of L-EDDP. For the case of a single intravenous bolus injection, the plasma concentration versus time profile of methadone enantiomers was analyzed with a two-compartment pharmacokinetic model. l-methadone showed a slower elimination rate constant, a lower body clearance, and a smaller steady-state volume of distribution than d-methadone. d-methadone and d-EDDP were eliminated faster than their respective l-enantiomers. This is the first study that outlines that the disposition of racemic methadone administered to anesthetized equines is enantioselective.

Tellura(benzo)bithiophenes: Synthesis, Oligomerization, and Phosphorescence.

A series of planar π-extended Te-containing heteroacenes, termed tellura(benzo)bithiophenes, were synthesized. This new structural class of heterocycle features a tellurophene ring fused to a benzobithiophene unit with aromatic side groups (either -C6H4iPr or -C6H4OCH3) positioned at the 2- and 5-positions of the tellurophene moiety. Although attempts to enhance molecular rigidity and extend ring-framework π-delocalization in a cumenyl (-C6H4iPr)-capped tellura(benzo)bithiophene led to oxidation (and Te-C bond scission) to form a diene-one, the formation of an oligomeric tellura(benzo)bithiophene was possible via Kumada catalyst-transfer polycondensation (KCTP). Furthermore, one tellura(benzo)bithiophene derivative exhibits orange-red phosphorescence at room temperature in air when incorporated into a poly(methyl methacrylate) host; accompanying TD-DFT computations provided insight into a potential mechanism for the observed phosphorescence.

Quantification of reservoir bags as airway pressure-limiting devices in a nonrebreathing system.

OBJECTIVE: To evaluate the influence of reservoir bag types, volumes and previous use on the peak pressures (Pmax) and the times to develop 30 cmH2O pressure (P30) within a nonrebreathing system with a closed adjustable pressure-limiting (APL) valve. STUDY DESIGN: In vitro study using three-way factorial design with repeated measure on one factor. SUBJECTS: A total of 75 new anesthesia reservoir bags (five types, three volumes, five bags from each type × volume). The bag types were reusable latex (RL), disposable latex (DL) and three disposable neoprene (DN-1, DN-2 and DN-3). METHODS: Each bag was tested three times (treatments): new, after prestretching and 1 week later. The bags were attached to a Bain system and anesthesia machine with closed APL valve and patient port with O2 flow 2 L minute-1 until Pmax was reached. The Pmax and time to reach P30 values were determined from recorded pressure traces. General linear mixed model analysis was used to examine the effects of bag type, volume and treatment. One-sided 95% upper prediction limits of Pmax were calculated to test the null hypothesis that predicted Pmax of new bags would be ≥ 50 cmH2O for each factor combination. RESULTS: RL bags were the least and DN-3 bags were the most compliant. Prestretching increased compliance in all bag types. Smaller bags of RL, DL and DN-1 were less compliant than larger ones. The predicted Pmax values were < 50 cmH2O only for DN-3 bags after prestretching. The time to reach P30 was critically low when using 0.5 L bags (median 17 seconds). CONCLUSIONS AND CLINICAL RELEVANCE: To minimize the risk of barotrauma, highly compliant reservoir bags (e.g. DN-3) are recommended and reusable bags should be avoided. Bags should be prestretched before first use, 0.5 L bags should be avoided and fresh gas flow minimized.

Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies.

OBJECTIVE: To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies. STUDY DESIGN: Prospective single-group interventional study. ANIMALS: A group of six healthy adult research ponies (four mares, two geldings). METHODS: Ponies were sedated with intravenous (IV) detomidine (0.02 mg kg-1) and butorphanol (0.01 mg kg-1) for an unrelated study. Additional IV detomidine (0.004 mg kg-1) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg-1) and ketamine (2.2 mg kg-1). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken after 15 minutes of stable isoflurane anaesthesia. l-Methadone (0.25 mg kg-1) with fenpipramide (0.0125 mg kg-1) was then administered IV. Selected cardiorespiratory variables were recorded every 10 minutes and compared to baseline using the Wilcoxon signed-rank test. Adverse events were recorded. Arterial plasma samples for analysis of plasma concentrations and pharmacokinetics of l-methadone were collected throughout anaesthesia at predetermined time points. Data are shown as mean ± standard deviation or median and interquartile range (p < 0.05). RESULTS: Plasma concentrations of l-methadone showed a rapid initial distribution phase followed by a slower elimination phase which is best described with a two-compartment model. The terminal half-life was 44.3 ± 18.0 minutes, volume of distribution 0.43 ± 0.12 L kg-1 and plasma clearance 7.77 ± 1.98 mL minute-1 kg-1. Mean arterial blood pressure increased from 85 (±16) at baseline to 100 (±26) 10 minutes after l-methadone/fenpipramide administration (p = 0.031). Heart rate remained constant. In two ponies fasciculations occurred at different time points after l-methadone administration. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a l-methadone/fenpipramide combination to isoflurane anaesthetized ponies led to a transient increase in blood pressure without concurrent increases in heart rate. Pharmacokinetics of l-methadone were similar to those reported for conscious horses administered racemic methadone.

Cardiovascular function, pulmonary gas exchange and tissue oxygenation in isoflurane-anesthetized, mechanically ventilated Beagle dogs with four levels of positive end-expiratory pressure.

OBJECTIVES: To compare pulmonary gas exchange, tissue oxygenation and cardiovascular effects of four levels of end-expiratory pressure: no positive end-expiratory pressure (ZEEP), positive end-expiratory pressure (PEEP) of maximal respiratory system compliance (PEEPmaxCrs), PEEPmaxCrs + 2 cmH2O (PEEPmaxCrs+2), PEEPmaxCrs + 4 cmH2O (PEEPmaxCrs+4), in isoflurane-anesthetized dogs. STUDY DESIGN: Prospective randomized crossover study. ANIMALS: A total of seven healthy male Beagle dogs, aged 1 year and weighing 10.2 ± 0.7 kg (mean ± standard deviation). METHODS: The dogs were administered acepromazine and anesthesia was induced with propofol and maintained with isoflurane. Ventilation was controlled for 4 hours with ZEEP, PEEPmaxCrs, PEEPmaxCrs+2 or PEEPmaxCrs+4. Cardiovascular, pulmonary gas exchange and tissue oxygenation data were evaluated at 5, 60, 120, 180 and 240 minutes of ventilation and compared using a mixed-model anova followed by Bonferroni test. p < 0.05 was considered significant. RESULTS: Cardiac index (CI) and mean arterial pressure (MAP) were lower in all PEEP treatments at 5 minutes when compared with ZEEP. CI persisted lower throughout the 4 hours only in PEEPmaxCrs+4 with the lowest CI at 5 minutes (2.15 ± 0.70 versus 3.45 ± 0.94 L minute-1 m-2). At 180 and 240 minutes, MAP was lower in PEEPmaxCrs+4 than in PEEPmaxCrs, with the lowest value at 180 minutes (58 ± 7 versus 67 ± 7 mmHg). Oxygen delivery index (DO2I) was lower in PEEPmaxCrs+4 than in ZEEP at 5, 60, 120 and 180 minutes. Venous admixture was not different among treatments. CONCLUSION AND CLINICAL RELEVANCE: The use of PEEP caused a transient decrease in MAP and CI in lung-healthy dogs anesthetized with isoflurane, which improved after 60 minutes of ventilation in all levels of PEEP except PEEPmaxCrs+4. A clinically significant improvement in arterial oxygenation and DO2I was not observed with PEEPmaxCrs and PEEPmaxCrs+2 in comparison with ZEEP, whereas PEEPmaxCrs+4 decreased DO2I.

The old sheep: a convenient and suitable model for senile osteopenia.

INTRODUCTION: Existing osteoporosis models in sheep exhibit some disadvantages, e.g., challenging surgical procedures, serious ethical concerns, failure of reliable induction of substantial bone loss, or lack of comparability to the human condition. This study aimed to compare bone morphological and mechanical properties of old and young sheep, and to evaluate the suitability of the old sheep as a model for senile osteopenia. MATERIALS AND METHODS: The lumbar vertebral body L3 of female merino sheep with two age ranges, i.e., old animals (6-10 years; n = 41) and young animals (2-4 years; n = 40), was analyzed concerning its morphological and mechanical properties by bone densitometry, quantitative histomorphometry, and biomechanical testing of the corticalis and/or central spongious region. RESULTS: In comparison with young sheep, old animals showed only marginally diminished bone mineral density of the vertebral bodies, but significantly decreased structural (bone volume, - 15.1%; ventral cortical thickness, - 11.8%; lateral cortical thickness, - 12.2%) and bone formation parameters (osteoid volume, osteoid surface, osteoid thickness, osteoblast surface, all - 100.0%), as well as significantly increased bone erosion (eroded surface, osteoclast surface). This resulted in numerically decreased biomechanical properties (compressive strength; - 6.4%). CONCLUSION: Old sheep may represent a suitable model of senile osteopenia with markedly diminished bone structure and formation, and substantially augmented bone erosion. The underlying physiological aging concept reduces challenging surgical procedures and ethical concerns and, due to complex alteration of different facets of bone turnover, may be well representative of the human condition.

Enantioselective capillary electrophoresis for pharmacokinetic analysis of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in equines anesthetized with ketamine and isoflurane.

An enantioselective assay for the determination of methadone and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in equine plasma based on capillary electrophoresis with highly sulfated γ-cyclodextrin as chiral selector and electrokinetic analyte injection is described. The assay is based on liquid/liquid extraction of the analytes at alkaline pH from 0.1 mL plasma followed by electrokinetic sample injection of the analytes from the extract across a buffer plug without chiral selector. Separation occurs cationically at normal polarity in a pH 3 phosphate buffer containing 0.16% (w/v) of highly sulfated γ-cyclodextrin. The developed assay is precise (intra- and interday RSD < 4% and < 7%, respectively), is capable to determine enantiomer levels of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in plasma down to 2.5 ng/mL, and was successfully applied to monitor enantiomer drug and metabolite levels in plasma of a pony that was anesthetized with racemic ketamine and isoflurane and received a bolus of racemic methadone and a bolus followed by constant rate infusion of racemic methadone. The data suggest that the assay is well suited for pharmacokinetic purposes.

Self-Assembly of Macrocyclic Boronic Esters Bearing Tellurophene Moieties and Their Guest-Responsive Phosphorescence.

Guest-controlled diastereoselective self-assembly of a diboryltellurophene and a chiral tetrol bearing an indacene backbone was achieved to give either hetero- or homochiral macrocyclic boronic esters, selectively. The heterochiral isomer (hetero-[2+2]Te ) exhibited a higher inclusion ability for electron-deficient aromatic guests, leading to effective quenching of phosphorescence from the diboryltellurophene moieties. The reported macrocycles collectively represent a promising arene sensing approach based on phosphorescence.

Monitoring changes in distribution of pulmonary ventilation by functional electrical impedance tomography in anaesthetized ponies.

OBJECTIVE: To assess changes in the distribution in pulmonary ventilation in anaesthetized ponies using electrical impedance tomography (EIT). STUDY DESIGN: Prospective experimental study. ANIMALS: A group of eight adult pony geldings. METHODS: General anaesthesia was induced and maintained using isoflurane in oxygen with volume-controlled ventilation [tidal volume (VT) (10 mL kg-1), respiratory rate (8-12 breaths minute-1)] to maintain end-tidal carbon dioxide between 35 and 40 mmHg (4.66-5.32 kPa). Regional distribution of ventilation was assessed with EIT (plane of fifth to sixth intercostal space) at 30, 60 and 90 minutes after intubation. The resulting functional images were divided into four regions of interest (ROI, A-D) to determine: 1) the ratio of VT distribution between dependent to nondependent lung (D/ND) and 2) changes in distribution within the lungs in the latero-lateral direction. The centre of ventilation (COV) was calculated. The dimension of the chest in the latero-lateral (W) and dorso-ventral (H) direction was measured at the height of the withers and the W/H ratio was calculated. The influence of time on the D/ND ratio, COV and ROI A-D were analysed with anova followed by post hoc Bonferroni tests. Pearson correlation coefficient and the coefficient of determination (r2) were calculated to evaluate the relationship between the W/H ratio and D/ND ratio, and COV. Statistical significance was set at p < 0.05. RESULTS: The median D/ND ratio (T30-T90) was 0.67 (0.40-1.01) and for COV 31.15% (11.20-45.20), confirming the expected uneven distribution of ventilation. The D/ND ratio had a moderate negative correlation with the W/H ratio (r = -0.68, r2 = 0.46, p < 0.001), while the COV did not correlate with the W/H ratio (r = -0.04). CONCLUSIONS AND CLINICAL RELEVANCE: Uneven ventilation in mechanically ventilated right laterally recumbent anaesthetized ponies occurs within 30 minutes and changed little over the following 60 minutes.

Probing the nature of peripheral boryl groups within luminescent tellurophenes.

In this article our attempts to tune the color of luminescence within a new class of aggregation-induced emission (AIE) active tellurophenes is reported along with computational details that include spin-orbit coupling effects so as to better understand the nature of emission in the phosphorescent tellurophene (B-Te-6-B). Despite not meeting some of the initial synthetic targets, the emission within a borylated tellurophene can be altered with the addition of an N-heterocyclic carbene.

Publication rate of studies presented at veterinary anaesthesia specialty meetings during the years 2003-2008.

OBJECTIVE: To assess publication rates, factors predicting publication, and discrepancies between conference abstracts and subsequent full-text publications of abstracts from the veterinary meetings of the American College of Veterinary Anesthesiologists and the Association of Veterinary Anaesthetists from 2003 to 2008. STUDY DESIGN: Retrospective cohort study. METHODS: A total of 607 abstracts were identified and a database search (Scopus, PubMed, CAB) was conducted to identify matching publications. Authors of nonmatching abstracts were contacted to participate in a confidential online survey. Risk ratios were used to assess factors predicting publication and these were tested for significance (p < 0.05) using Fisher's exact test. RESULTS: The overall publication rate was 63.3% and the mean (± SD) time to publication was 25 ± 19 months. Factors significantly associated with subsequent full publication (i.e. publication of a full manuscript in a peer-reviewed journal) were continent of origin (North America), study design (experimental studies), specialty (analgesia) and the presence of a source of funding. The principal reasons why studies remained unpublished were lack of time and responsibility lying with co-authors. Minor changes compared with the original abstract were found in 71.6% of all publications. Major changes were noted in 34.6% and the outcome of the study changed in 7.6%. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that some of the abstracts reported preliminary findings. Therefore, caution is warranted when quoting abstracts as references in scientific publications. To date, major veterinary journals have not issued recommendations in their author guidelines addressing the use of abstracts as a reference. The authors propose the inclusion of such a statement in author guidelines.

Development, implementation and impact of simple patient safety interventions in a university teaching hospital.

OBJECTIVE: To determine the incidence of anesthesia patient safety incidents at a university teaching hospital, develop interventions to address the most common incidents, and determine the effectiveness of these interventions. STUDY DESIGN: Pre-post intervention observational. ANIMALS: Four thousand, one hundred forty dogs and cats anesthetized by the anesthesia service. METHODS: The study was divided into two 11.5 month periods. During each period, incidents were logged (e.g. closed adjustable pressure limiting (APL) valve, esophageal intubation, and medication error). At the end of the first period, four countermeasures were incorporated into the service's protocols: 1) prior to any drug injection, the individual would read out aloud the drug name, patient name, and route of administration; 2) use of a uniquely colored occlusive wrap over arterial catheters; 3) a check box on the anesthesia record labeled "Technician Confirmed Intubation"; 4) a check box on the anesthesia record labeled "Technician Checked OR (operating room)". The number of patient safety incidents during period 1 and period 2 were compared using Fisher's Exact Test. RESULTS: During Period 1, there were 74 incidents documented in 2028 patients (3.6%) including 25 medication errors, 20 closed APL valves, and 16 of esophageal intubation. During Period 2, there were 30 incidents documented in 2112 patients (1.4%) including 14 medication errors, 5 closed APL valves, and 4 of esophageal intubation. The proportion of events during Period 2 was significantly smaller than during Period 1 (p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: Implementation of four simple interventions was associated with a significant decrease in the number of incidents.

Assessment of maxillary and infraorbital nerve blockade for rhinoscopy in sevoflurane anesthetized dogs.

OBJECTIVE: To investigate the efficacy of maxillary and infraorbital nerve blocks for prevention of cardiovascular and qualitative responses to rhinoscopy, as well as response to skin clamping after assigned nerve block placement. STUDY DESIGN: Randomized, blinded, placebo-controlled cross-over experimental study. ANIMALS: Eight random-source mixed breed dogs > 1 year old and weighing between 13 and 22 kg. METHODS: Within three anesthetic episodes, separated by at least 3 days, dogs were assigned to receive either 1 mL lidocaine 2% maxillary nerve block (ML); 0.5 mL lidocaine 2% infraorbital nerve block (IOL); or equal amounts of saline for maxillary or infraorbital nerve block combined as control treatment (S). Monitoring included temperature, respiratory rate, end-tidal CO2 , ECG, heart rate (HR), systolic, diastolic and mean arterial pressure (SAP, DAP, MAP). Posterior (pR) and anterior rhinoscopies (aR) were performed and scored. Differences from baseline for outcome parameters HR, SAP, DAP, MAP were analyzed using repeated-measures anova, and results reported as mean ± SD. Binary scores for rhinoscopy were analyzed using logistic regression, and odds ratio was reported. RESULTS: Changes from baseline for HR and SAP were significant for all treatments, besides ML for pR. Difference in changes from baseline among treatments was statistically significant for HR during pR with ML < S, and for SAP, DAP and MAP in right and left aR with ML < S and IOL > ML, except for DAP in left aR with only IOL > ML. Analysis of the binary score showed that the probability of a response for S and IOL treatments was nearly triple that of the ML treatment. None of the dogs, regardless of the treatments applied, responded to skin clamping. CONCLUSION AND CLINICAL RELEVANCE: Cardiovascular parameters do not seem to reflect the occurrence of adverse reactions during rhinoscopy. The maxillary nerve block is superior to the infraorbital nerve block, as applied in this study, in preventing adverse reactions during posterior rhinoscopy.

Pharmacodynamics of alfaxalone after single-dose intramuscular administration in red-eared sliders (Trachemys scripta elegans): a comparison of two different doses at two different ambient temperatures.

OBJECTIVE: This study compares the pharmacodynamics of two different doses of alfaxalone administered intramuscularly (IM) to red-eared sliders at two ambient temperatures. STUDY DESIGN: Prospective blinded crossover experimental study. ANIMALS: Nine adult female sliders (Trachemys scripta elegans). METHODS: Following a 2-week acclimation at 22-25 °C, nine sliders were randomly assigned to receive alfaxalone, 10 mg kg(-1) (W10), or 20 mg kg(-1) (W20) IM. Each turtle received each dose, with a minimum 7-day washout period. A blinded observer evaluated heart rate (HR), palpebral and corneal reflexes, muscle relaxation, handling, and response to toe pinch at the following points: pre-injection, and 5, 12, 20, 30, 45, 60, and 120 minutes post-injection. Turtles then acclimated to 18-20 °C for 63 days, and the experiment was repeated in this lower-temperature environment, with treatment groups C10 (alfaxalone 10 mg kg(-1)) and C20 (alfaxalone 20 mg kg(-1)) subjected to the same crossover design. RESULTS: C10 and C20 groups had significantly lower intraanesthetic HR than W10 or W20, respectively. C10 and W20 were significantly more relaxed and easier to handle than W10. No significant differences were observed in palpebral reflex, nor responsiveness to the toe pinch stimulus. None of the turtles lost corneal reflex. W20 and C20 had prolonged recoveries, compared to low-dose groups within the same temperature environment. Recovery was also longer at C20 and C10 compared to W10. CONCLUSIONS: Turtles given 10 mg kg(-1) were more relaxed and easier to handle in cold than warm conditions. Warm turtles were more relaxed and easier to handle when given 20 mg kg(-1) than those given 10 mg kg(-1). Cold conditions correlated with lower HR and longer recovery time for each dose category. CLINICAL RELEVANCE: The turtles had dose-dependent and inconsistent responses to alfaxalone. Lower ambient temperature augmented the behavioral effects of this drug.

A comparison of cardiopulmonary and anesthetic effects of an induction dose of alfaxalone or propofol in dogs.

OBJECTIVE: To compare the physiological parameters, arterial blood gas values, induction quality, and recovery quality after IV injection of alfaxalone or propofol in dogs. STUDY DESIGN: Prospective, randomized, blinded crossover. ANIMALS: Eight random-source adult female mixed-breed dogs weighing 18.7 ± 4.5 kg. METHODS: Dogs were assigned to receive up to 8 mg kg(-1) propofol or 4 mg kg(-1) alfaxalone, administered to effect, at 10% of the calculated dose every 10 seconds. They then received the alternate drug after a 6-day washout. Temperature, pulse rate, respiratory rate, direct blood pressure, and arterial blood gases were measured before induction, immediately post-induction, and at 5-minute intervals until extubation. Quality of induction, recovery, and ataxia were scored by a single blinded investigator. Duration of anesthesia and recovery, and adverse events were recorded. RESULTS: The mean doses required for induction were 2.6 ± 0.4 mg kg(-1) alfaxalone and 5.2 ± 0.8 mg kg(-1) propofol. After alfaxalone, temperature, respiration, and pH were significantly lower, and PaCO2 significantly higher post-induction compared to baseline (p < 0.03). After propofol, pH, PaO2 , and SaO2 were significantly lower, and PaCO2 , HCO3 , and PA-aO2 gradient significantly higher post-induction compared to baseline (p < 0.03). Post-induction and 5-minute physiologic and blood gas values were not significantly different between alfaxalone and propofol. Alfaxalone resulted in significantly longer times to achieve sternal recumbency (p = 0.0003) and standing (p = 0.0004) compared to propofol. Subjective scores for induction, recovery, and ataxia were not significantly different between treatments; however, dogs undergoing alfaxalone anesthesia were more likely to have ≥ 1 adverse event (p = 0.041). There were no serious adverse events in either treatment. CONCLUSIONS AND CLINICAL RELEVANCE: There were no clinically significant differences in cardiopulmonary effects between propofol and alfaxalone. A single bolus of propofol resulted in shorter recovery times and fewer adverse events than a single bolus of alfaxalone.

Disposable Airway Pressure Manometers for Endotracheal Tube Cuff Inflation.

This study aimed to assess the performance, accuracy, precision and repeatability of two single-use airway pressure manometers as a cost-effective alternative for inflation of endotracheal tubes with high-volume, low-pressure cuffs. The manometers were tested in a bench top model against a U-tube manometer. Eighteen units of each device were tested. Three consecutive measurements were performed at pressures of 20, 25 and 30 cmH2O each. The mean ± SD of the recorded pressures and maximum deviation from the target pressures were calculated for each device and each target pressure. For device A, the mean ± SD pressures were 19.6 ± 0.7, 23.6 ± 0.8 and 28.3 ± 0.8 cmH2O; for device B, the mean ± SD pressures were 19.3 ± 0.6, 24.3 ± 0.9 and 29.2 ± 0.67 cmH2O for target pressures of 20, 25 and 30 cmH2O, respectively. The bias for device A was -0.4, -1.4, and -1.7 cmH2O and for device B, -0.7, -0.7, and -0.8 cmH2O for target pressures of 20, 25, and 30 cmH2O, respectively. Both devices showed results comparable to those reported for commercial cuff manometers. They represent inexpensive tools that provide clinically sufficient accuracy, precision and repeatability for ETT cuff inflation between pressures of 20 and 30 cmH2O.

Non-radioactive In Vivo Labeling of RNA with 4-Thiouracil.

RNA molecules and their expression dynamics play essential roles in the establishment of complex cellular phenotypes and/or in the rapid cellular adaption to environmental changes. Accordingly, analyzing RNA expression remains an important step to understand the molecular basis controlling the formation of cellular phenotypes, cellular homeostasis or disease progression. Steady-state RNA levels in the cells are controlled by the sum of highly dynamic molecular processes contributing to RNA expression and can be classified in transcription, maturation and degradation. The main goal of analyzing RNA dynamics is to disentangle the individual contribution of these molecular processes to the life cycle of a given RNA under different physiological conditions. In the recent years, the use of nonradioactive nucleotide/nucleoside analogs and improved chemistry, in combination with time-dependent and high-throughput analysis, have greatly expanded our understanding of RNA metabolism across various cell types, organisms, and growth conditions.In this chapter, we describe a step-by-step protocol allowing pulse labeling of RNA with the nonradioactive nucleotide analog, 4-thiouracil , in the eukaryotic model organism Saccharomyces cerevisiae and the model archaeon Haloferax volcanii .