Exploring the interdependence of calcium and chloride activation of O2 evolution in photosystem II.

Calcium and chloride are activators of oxygen evolution in photosystem II (PSII), the light-absorbing water oxidase of higher plants, algae, and cyanobacteria. Calcium is an essential part of the catalytic Mn4CaO5 cluster that carries out water oxidation and chloride has two nearby binding sites, one of which is associated with a major water channel. The co-activation of oxygen evolution by the two ions is examined in higher plant PSII lacking the extrinsic PsbP and PsbQ subunits using a bisubstrate enzyme kinetics approach. Analysis of three different preparations at pH 6.3 indicates that the Michaelis constant, KM, for each ion is less than the dissociation constant, KS, and that the affinity of PSII for Ca2+ is about ten-fold greater than for Cl-, in agreement with previous studies. Results are consistent with a sequential binding model in which either ion can bind first and each promotes the activation by the second ion. At pH 5.5, similar results are found, except with a higher affinity for Cl- and lower affinity for Ca2+. Observation of the slow-decaying Tyr Z radical, YZ•, at 77 K and the coupled S2YZ• radical at 10 K, which are both associated with Ca2+ depletion, shows that Cl- is necessary for their observation. Given the order of electron and proton transfer events, this indicates that chloride is required to reach the S3 state preceding Ca2+ loss and possibly for stabilization of YZ• after it forms. Interdependence through hydrogen bonding is considered in the context of the water environment that intervenes between Cl- at the Cl-1 site and the Ca2+/Tyr Z region.

The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses.

Introduction: Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Methods: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model. Results: Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature (p > 0.063). There was no significant effect of treatment on heart rate (p = 0.364). There was a significant effect of time (p = 0.003) on heart rate with overall heart rates being less than baseline at 64 h. Conclusions: Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied.

Detection of endometrial cancer in cervico-vaginal fluid and blood plasma: leveraging proteomics and machine learning for biomarker discovery.

BACKGROUND: The anatomical continuity between the uterine cavity and the lower genital tract allows for the exploitation of uterine-derived biomaterial in cervico-vaginal fluid for endometrial cancer detection based on non-invasive sampling methodologies. Plasma is an attractive biofluid for cancer detection due to its simplicity and ease of collection. In this biomarker discovery study, we aimed to identify proteomic signatures that accurately discriminate endometrial cancer from controls in cervico-vaginal fluid and blood plasma. METHODS: Blood plasma and Delphi Screener-collected cervico-vaginal fluid samples were acquired from symptomatic post-menopausal women with (n = 53) and without (n = 65) endometrial cancer. Digitised proteomic maps were derived for each sample using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning was employed to identify the most discriminatory proteins. The best diagnostic model was determined based on accuracy and model parsimony. FINDINGS: A protein signature derived from cervico-vaginal fluid more accurately discriminated cancer from control samples than one derived from plasma. A 5-biomarker panel of cervico-vaginal fluid derived proteins (HPT, LG3BP, FGA, LY6D and IGHM) predicted endometrial cancer with an AUC of 0.95 (0.91-0.98), sensitivity of 91% (83%-98%), and specificity of 86% (78%-95%). By contrast, a 3-marker panel of plasma proteins (APOD, PSMA7 and HPT) predicted endometrial cancer with an AUC of 0.87 (0.81-0.93), sensitivity of 75% (64%-86%), and specificity of 84% (75%-93%). The parsimonious model AUC values for detection of stage I endometrial cancer in cervico-vaginal fluid and blood plasma were 0.92 (0.87-0.97) and 0.88 (0.82-0.95) respectively. INTERPRETATION: Here, we leveraged the natural shed of endometrial tumours to potentially develop an innovative approach to endometrial cancer detection. We show proof of principle that endometrial cancers secrete unique protein signatures that can enable cancer detection via cervico-vaginal fluid assays. Confirmation in a larger independent cohort is warranted. FUNDING: Cancer Research UK, Blood Cancer UK, National Institute for Health Research.

Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses.

Background: Matrix type transdermal buprenorphine patches have not been investigated in horses and may provide an effective means of providing continuous pain control for extended period and eliminating venous catheterization. Objective: Assessment of the physiological variables (heart rate, respiratory rate, body temperature) and thermal nociceptive threshold testing, and describing the pharmacokinetic profile of transdermal buprenorphine matrix-type patch (20 µg h-1 and 40 µg h-1 dosing) in healthy adult horses. Study design: Randomised experimental study with a Latin-square design. Methods: Six adult healthy horses received each of the three treatments with a minimum 10 day washout period. BUP0 horses did not receive a patch (control). BUP20 horses received one patch (20 µg h-1) applied on the ventral aspect of the tail base resulting in a dose of 0.03-0.04 µg kg-1 h-1. BUP40 horses received two patches placed alongside each other (40 µg h-1) on the tail base resulting in a dose of 0.07-0.09 µg kg-1 h-1. Whole blood samples (for determination of buprenorphine concentration), physiological variables and thermal threshold testing were performed before (0 h) and at 2, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, and 96 h after patch application. The patches were removed 72 h following placement and were analyzed for residual buprenorphine content. Results: Between the three groups, there was no change in physiological variables across timepoints as compared to baseline (p > 0.1). With the higher dose, there was a significant increase in thermal thresholds from baseline values from 2 h until 48 h and these values were significantly higher than the group receiving the lower patch dose for multiple timepoints up to 40 h. 40 µg h-1 patch led to consistent measurable plasma concentrations starting at 2 h up to 96 h, with the mean plasma concentrations of > 0.1 ng/ml from 4 h to 40 h. Conclusions: 20 µg h-1 and 40 µg h-1 patch doses were well tolerated by all horses. At higher dose, plasma buprenorphine concentrations were more consistently measurable and blunted thermal thresholds for 48 h vs. 32 h with 20 µg h-1 dosing as compared to control.

Enhancing Nutrition Support for Esophageal Cancer Patients: Understanding Factors Influencing Feeding Tube Utilization.

Objective: We sought to identify factors that can predict esophageal cancer (EC) patients at high risk of requiring feeding tube insertion. Methods: A retrospective cohort review was conducted, including all patients diagnosed with EC at our cancer center from 2013 to 2018. Multivariate logistic regression was performed comparing the group that required a reactive feeding tube insertion to those who did not require any feeding tube insertion to identify risk factors. Results: A total of 350 patients were included in the study, and 132/350 (38%) patients received a feeding tube. 50 out of 132 (38%) patients had feeding tube inserted reactively. Severe dysphagia (OR 19.9, p < 0.001) at diagnosis and decision to undergo chemotherapy (OR 2.8, p = 0.008) appeared to be predictors for reactive feeding tube insertion. The reactive insertion group had a 7% higher rate of complications relating to feeding tube. Conclusion: Severe dysphagia at diagnosis and undergoing chemotherapy were identified as risk factors for requiring a feeding tube. Ultimately, the aim is to create a predictive tool that utilizes these risks factors to accurate identify high-risk patients who may benefit from prophylactic feeding tube insertion.

Evaluation of a rapid sequence induction technique in dogs with or without rocuronium.

OBJECTIVE: To determine, using a rapid sequence induction (RSI) technique, whether rocuronium improves the quality and speed of endotracheal intubation in healthy dogs. STUDY DESIGN: Randomized, crossover, experimental study. ANIMALS: Six adult intact male Beagles (12.3 ± 0.4 kg). METHODS: Dogs were premedicated with intravenous acepromazine (0.03 mg kg-1) and hydromorphone (0.1 mg kg-1). Ten minutes later, anesthesia was induced with intravenous propofol (2 mg kg-1 over 5 seconds), followed by saline (0.06 mL kg-1, CT group) or rocuronium (0.6 mg kg-1, RT group), with orotracheal intubation attempted after 45 seconds. Intubation time (IT) and conditions (IC) were assessed. PaO2, PaCO2, arterial blood pH and serum cortisol were obtained before and after RSI. After endotracheal intubation, saline (0.04 mL kg-1) or sugammadex (4 mg kg-1) were administered intravenously in CT or RT groups, respectively. Spontaneous ventilation restoration was noted. RESULTS: The IT was 54.3 ± 6.9 (mean ± SD) and 57.8 ± 5.2 seconds for CT and RT, respectively (p = 0.385). All laryngoscopies indicated good IC in both treatment groups. Heart rate was lower in CT group than in RT group (66 ± 16 versus 103 ± 39 beats minute-1, p = 0.016). PaCO2, pH, PaO2 and cortisol did not differ between treatments. Compared with baseline, PaCO2 increased from 47.7 ± 6.2 to 58.8 ± 5.8 (p < 0.001) and pH decreased from 7.35 ± 0.04 to 7.28 ± 0.04 (p = 0.003), independent of treatment. Dogs in both treatment groups returned to spontaneous ventilation within 30 seconds of RSI. CONCLUSIONS AND CLINICAL RELEVANCE: RSI resulted in respiratory acidosis without hypoxemia or increased cortisol. Rocuronium did not improve IT or IC. Spontaneous ventilation was observed immediately after administering saline or sugammadex. The co-administration of rocuronium showed no clinical benefits over propofol alone in RSI in healthy dogs.

A role for Shugoshin in human cilia?

We have recently described a novel role for the conserved centromeric/kinetochore protein and cohesin protector, Shugoshin, in cilia of C. elegans. Worms are unusual in that the sole Shugoshin protein ( SGO-1 ) is dispensable for chromosome segregation but required for cilia function in fully differentiated sensory neurons. Depletion of sgo-1 leads to an array of sensory defects observed in other cilia mutants with a compromised diffusion barrier. Accordingly, SGO-1 loads to the base of cilia in sensory neurons and can be observed occupying the transition zone, the critical ciliary domain that regulates trafficking in and out of ciliary compartments. Here we start to address a potential conserved role in cilia for vertebrate Shugoshin by asking whether human Shugoshin can: (1) localize to cilia and (2) rescue defects due to Shugoshin depletion in C. elegans . Our preliminary results suggest that human Shugoshin is detectable in the cilia base but show limited functional conservation when expressed in C. elegans sensory neurons.

Accuracy, precision, and interobserver and intraobserver agreements related to pressure-measurement devices.

OBJECTIVE: To evaluate the accuracy, precision, and observer agreement of three pressure measurement devices. STUDY DESIGN: In vitro model study. SAMPLE POPULATION: Water manometer with built-in gauge (WMg), arterial pressure transducer (APT), and Compass CT (CCT). METHODS: The model was set to five predetermined pressures (4, 8, 13, 17, and 24 cm H2 O) using a water manometer with a ruler (WMr) as the gold standard. Each device was tested at each pressure in a randomized order by three investigators. Bland-Altman plots were used to assess agreement between devices. Intraclass correlation coefficients (ICC) were calculated for interobserver and intraobserver agreements. RESULTS: The mean differences (cm H2 O) ± SEM in comparison with the set pressure were -0.020 ± 0.010 (WMg), -0.390 ± 0.077 (APT), and -1.267 ± 0.213 (CCT). Pressures measured by WMg did not differ from those measured by WMr. Pressures measured by all devices did not differ from each other (p > .062 for all comparisons). Interobserver agreement was excellent (1.000), and intraobserver agreement was excellent (0.985, 0.990, 0.998 for each observer). CONCLUSION: Compared to the WMr, the WMg was the most accurate and precise, followed by the APT; the CCT was the least accurate and precise. Interobserver and intraobserver agreements for all three devices were excellent. CLINICAL SIGNIFICANCE: The largest mean difference of all devices was within 1.3 cm H2 O of the set pressure, indicating possible clinical utility of any of the devices. However, WMr or WMg should be considered first due to their high precision and accuracy.

Longitudinal evaluation of fentanyl concentrations in equine plasma and synovial fluid following application of transdermal fentanyl patches over one carpal joint.

OBJECTIVE: To determine if transdermally delivered fentanyl can achieve greater concentrations of fentanyl in synovial fluid when applied over a synovial structure. STUDY DESIGN: Randomized, experimental study. ANIMALS: Six healthy adult horses. METHODS: Each horse had two 100 µg/h fentanyl matrix patches applied on the dorsal aspect of one, randomly assigned, carpometacarpal joint (CMCJ) for 48 h. Whole blood and bilateral synovial samples from the intercarpal joint were obtained at 0, 2, 6, 12, 24, 36 and 48 h. Fentanyl concentrations were measured with liquid chromatography-mass spectrometry. RESULTS: All subjects achieved detectable concentrations of fentanyl in both plasma and synovial fluid. Time to peak synovial and plasma concentration was 12 h. At 6 h, the synovial concentration in the untreated carpus (0.104 ng/mL ± 0.106) was lower than plasma fentanyl concentrations 0.31 ± 0.27 (p = .036). At 12 h, both treated (0.55 ng/mL ± 0.3) and untreated (0.53 ng/mL ± 0.28) synovial fluid fentanyl concentrations were lower than plasma (0.87 ng/mL ± 0.48) concentrations (p < .001 and p = .001, respectively). Synovial concentrations of fentanyl did not differ between treated and untreated joints (p > 0.608 for all time points). CONCLUSION: Application of fentanyl matrix patches directly over the CMCJ did not result in increased fentanyl concentrations in the synovial fluid of the treated intercarpal joint in normal horses. CLINICAL SIGNIFICANCE: There is likely no analgesic advantage to placing fentanyl patches directly over the affected joint, as it did not result in increased synovial concentrations at the tested site.

Post-anesthetic CPS and EQUUS-FAP scores in surgical and non-surgical equine patients: an observational study.

Background: Equine pain scoring may be affected by the residual effect of anesthetic drugs. Objectives: To compare pain scores in the hours immediately following anesthetic recovery to baseline pre-anesthetic scores in equine patients undergoing surgical and non-surgical procedures. Study design: Clinical observational study. Methods: Fifty adult horses undergoing anesthesia for surgical or non-surgical procedures were enrolled. Horses underwent pain scoring using the Composite Pain Score (CPS) and Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) prior to anesthesia (T0) and following anesthetic recovery to standing, every hour for 5 h (T1-T5). Data were analyzed using a generalized linear mixed effects model. A post-hoc Dunnett's test for multiple comparisons was performed for variables where an effect was detected. Results: Mean (95% confidence interval) CPS scores for T0-T5 were 1.6 (1.2-2.0), 6.8 (6.0-7.6), 5.1 (4.3-5.9), 4.3 (3.4-5.2), 3.7 (2.8-4.6), and 2.8 (2.0-3.6) and EQUUS-FAP scores were 0.6 (0.3-0.9), 3.0 (2.5-3.5), 1.9 (1.6-2.2), 1.1 (0.8-1.4), 0.6 (0.4-0.8), and 0.7 (0.4-1.0), respectively. For the CPS, scores greater than 5, and for the EQUUS-FAP scores greater than 3, are consistent with minor pain. There was no effect of type of procedure (surgical vs non-surgical) on CPS or EQUUS-FAP scores. There was an effect of time with CPS scores significantly greater than baseline at T1-T5 and EQUUS-FAP scores significantly greater than baseline at T1 and T2. Main limitations: Discomfort caused by hoisting was not quantified and it was difficult to ascertain if this affected the results. Conclusions: Post-anesthetic pain scores may be influenced by the residual effect of anesthetic agents for as long as 5 h and 2 h for the CPS and EQUUS-FAP, respectively.

Proteomic analysis identifies subgroups of patients with active systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a clinically and biologically heterogenous autoimmune disease. We aimed to investigate the plasma proteome of patients with active SLE to identify novel subgroups, or endotypes, of patients. METHOD: Plasma was collected from patients with active SLE who were enrolled in the British Isles Lupus Assessment Group Biologics Registry (BILAG-BR). The plasma proteome was analysed using a data-independent acquisition method, Sequential Window Acquisition of All theoretical mass spectra mass spectrometry (SWATH-MS). Unsupervised, data-driven clustering algorithms were used to delineate groups of patients with a shared proteomic profile. RESULTS: In 223 patients, six clusters were identified based on quantification of 581 proteins. Between the clusters, there were significant differences in age (p = 0.012) and ethnicity (p = 0.003). There was increased musculoskeletal disease activity in cluster 1 (C1), 19/27 (70.4%) (p = 0.002) and renal activity in cluster 6 (C6) 15/24 (62.5%) (p = 0.051). Anti-SSa/Ro was the only autoantibody that significantly differed between clusters (p = 0.017). C1 was associated with p21-activated kinases (PAK) and Phospholipase C (PLC) signalling. Within C1 there were two sub-clusters (C1A and C1B) defined by 49 proteins related to cytoskeletal protein binding. C2 and C6 demonstrated opposite Rho family GTPase and Rho GDI signalling. Three proteins (MZB1, SND1 and AGL) identified in C6 increased the classification of active renal disease although this did not reach statistical significance (p = 0.0617). CONCLUSIONS: Unsupervised proteomic analysis identifies clusters of patients with active SLE, that are associated with clinical and serological features, which may facilitate biomarker discovery. The observed proteomic heterogeneity further supports the need for a personalised approach to treatment in SLE.

Rocuronium-neuromuscular blockade does not influence the patient state index in anesthetized dogs.

OBJECTIVE: To evaluate the effects of rocuronium and sugammadex on the patient state index (PSI) in dogs anesthetized with propofol. ANIMALS: 6 intact healthy male Beagles. PROCEDURES: Anesthesia was induced with and maintained on a propofol infusion. The estimated plasma propofol concentration (ePC) was recorded. Baseline PSI and train-of-four ratio (TOFR) readings were collected for 2 minutes in stable general anesthesia. Neuromuscular blockade (NMB) was induced with 0.6 mg/kg, IV, rocuronium, and full NMB was confirmed with a TOFR of 0. After 5 minutes, the neuromuscular function was restored with 4 mg/kg sugammadex, IV (reversal), and monitored for 5 minutes. Throughout the data collection, ePC, PSI, and TOFR were recorded every 15 seconds and compared with mixed-effect ANOVA. RESULTS: Baseline ePC, PSI, and TOFR were 3.63 ± 0.38, 41 ± 6, and 0.97 ± 0.08 µg/mL, respectively. There was no difference between the baseline of ePC and PSI from NMB or reversal. Compared to the baseline, the TOFR decreased to 0 with NMB (P < .001) and returned to 0.96 ± 0.08 (P = .721) on reversal. After 5 minutes, sugammadex fully reversed 5 out of 6 dogs to TOFR > 0.90 and partially reversed 1 animal to TOFR = 0.80. CLINICAL RELEVANCE: There was no evidence that NMB with rocuronium and sugammadex-induced reversal interfered with PSI readings under steady-state total intravenous anesthesia with propofol. Further evaluation of PSI is warranted to assess its utility in a clinical population to detect changes in levels of consciousness during NMB.

The effect of adding a heated humidified breathing circuit on body temperature in healthy anesthetized dogs.

OBJECTIVE: To compare the effect of a circulating warm water blanket (WWB) in combination with a heated humidified breathing circuit (HHBC) heated to 45 °C on rectal temperature (RT) in dogs undergoing general anesthesia for elective ovariohysterectomies. ANIMALS: 29 healthy dogs. PROCEDURES: Dogs in the experimental group (n = 8) and dogs in the control group (21) were connected to an HHBC and a conventional rebreathing circuit, respectively. All dogs were placed on a WWB in the operating room (OR). The RT was recorded at baseline, premedication, induction, transfer to OR, every 15 minutes during maintenance of anesthesia, and extubation. Incidence of hypothermia (RT < 37 °C) at extubation was recorded. Data were analyzed using unpaired t tests, the Fisher exact test, and mixed-effect ANOVA. Statistical significance was defined as P < .05. RESULTS: There was no difference in RT during baseline, premedication, induction, and transfer to OR. The overall RT was higher for the HHBC group during anesthesia (P = .005) and at extubation (37.7 ± 0.6 °C) compared with the control group (36.6 ± 1.0 °C; P = .006). The incidence of hypothermia at extubation was 12.5% for the HHBC group and 66.7% for the control group (P = .014). CLINICAL RELEVANCE: The combination of HHBC and WWB can reduce the incidence of postanesthetic hypothermia in dogs. Use of an HHBC should be considered in veterinary patients.

Evaluation of the electroencephalogram in awake, sedated, and anesthetized dogs.

Sedation and anesthesia alter the raw electroencephalogram (EEG). Interpretation of the EEG is facilitated by measuring the patient state index (PSI), visual inspection of density spectral arrays (DSA), and power density analysis of the delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta plus gamma (12-40 Hz) frequency bands. Baseline data were recorded in six male intact Beagles before sedation with intravenous acepromazine (0.03 mg/kg) and hydromorphone (0.1 mg/kg). Anesthesia was induced and maintained for five minutes with intravenous propofol (1.5 mg/kg over five seconds followed by 12 mg/kg/h). Additional propofol (0.5-1.0 mg/kg and up to 16.7 mg/kg/h) was administered within this time frame if the PSI was above 50. The effects of sedation and anesthesia were evaluated with a mixed-effect model followed by Dunnett's test (alpha = 0.05). The average baseline PSI (95% confidence interval) was 93.0 (91.4-94.6) and decreased on sedation [88.7 (86.0-91.3); p = 0.039] and anesthesia [44.5 (40.8-48.2); p < 0.001]. The awake DSA showed dense power in all bands. The power density decreased with sedation. During anesthesia, the power density was reduced in frequencies above 12 Hz. The baseline power density on the delta, theta, alpha, and beta plus gamma bands was higher than sedation (p < 0.007). Compared to baseline, anesthesia had lower power on delta, and beta plus gamma bands (p < 0.002). The interpretation in awake, sedated, and anesthetized dogs of the EEG can be facilitated by processing and generating PSI and DSA.

Antinociceptive effects of bupivacaine injected within the internal abdominis rectus sheath in standing healthy horses.

OBJECTIVE: To evaluate a regional anesthetic technique for blocking the abdominal midline in horses. STUDY DESIGN: Anatomical description and prospective, crossover, placebo-controlled, blinded study. ANIMALS: Adult horses; two cadavers, six healthy animals. METHODS: In stage 1, 0.5% methylene blue with 0.25% bupivacaine (0.5 mL kg-1) was injected using ultrasonography into the internal rectus abdominis sheath (RAS) of two cadavers with a one-point or two-point technique. The dye spread was described after the dissection of the abdomens. In stage 2, each horse was injected with 1 mL kg-1 of 0.9% NaCl (treatment PT) or 0.2% bupivacaine (treatment BT) using a two-point technique. The abdominal midline mechanical nociceptive threshold (MNT) was measured with a 1 mm blunted probe tip and results analyzed with mixed-effect anova. Signs of pelvic limb weakness were recorded. RESULTS: The cadaver dissections showed staining of the ventral branches from the eleventh thoracic (T11) to the second lumbar (L2) nerve with the one-point technique and T9-L2 with the two-point technique. Baseline MNTs were, mean ± standard deviation, 12.6 ± 1.6 N and 12.4 ± 2.4 N in treatments PT and BT, respectively. MNT increased to 18.9 ± 5.8 N (p = 0.010) at 30 minutes, and MNT was between 9.4 ± 2.0 and 15.3 ± 3.4 N from 1 to 8 hours (p > 0.521) in treatment PT. MNTs in treatment BT were 21.1 ± 5.9 to 25.0 ± 0.1 N from 30 minutes to 8 hours (p < 0.001). MNTs after the RAS injections were higher in treatment BT than PT (p = 0.007). No pelvic limb weakness was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Antinociception of at least 8 hours without pelvic limb weakness was observed in the abdominal midline in standing horses after the RAS block. Further investigations are necessary to evaluate suitability for ventral celiotomies.

Performing an ovariohysterectomy at the time of c-section does not pose an increase in risk of mortality, intra- or postoperative complications, or decreased mothering ability of the bitch.

OBJECTIVE: Ovariohysterectomy (OVH) is frequently recommended at the time of c-section in canines, yet prior literature suggests poor mothering ability and increased morbidity to the bitch with c-section with concurrent OVH (CSOVH). The study objective was to compare maternal survival, complications, and mothering ability between bitches that underwent c-section alone (CS) or CSOVH. ANIMALS: 125 bitches. PROCEDURES: Medical records from 2014 through 2021 were retrospectively reviewed; owners were surveyed for information up to weaning. RESULTS: 80 bitches undergoing CS and 45 bitches undergoing CSOVH were identified. There was no difference in anesthesia duration, intraoperative complications, postoperative complications, mothering ability, puppy survival to weaning, or other variables compared between groups. CSOVH bitches had longer surgery times (P = .045; 54.4 ± 20.7 min vs 46.9 ± 16.6 min) and longer time from delivery to nursing (P = .028; 75.4 ± 22.3 min vs 65.2 ± 19.5 min). Ninety (72%) owners responded to the survey. All 90 bitches survived until puppy weaning. CSOVH bitches were more frequently perceived as painful postoperatively (P = .015). CLINICAL RELEVANCE: Performing an OVH at the time of c-section does not pose a significant increase in risk of mortality, intraoperative complications, postoperative complications, or decreased mothering ability of the bitch. The increased duration of surgery and increased time from delivery to nursing in the CSOVH group were clinically insignificant. Appropriate postoperative pain management should be emphasized post-CSOVH. Based on these results, OVH should be performed concurrently with c-section if indicated.

A Novel Blood Proteomic Signature for Prostate Cancer.

Prostate cancer is the most common malignant tumour in men. Improved testing for diagnosis, risk prediction, and response to treatment would improve care. Here, we identified a proteomic signature of prostate cancer in peripheral blood using data-independent acquisition mass spectrometry combined with machine learning. A highly predictive signature was derived, which was associated with relevant pathways, including the coagulation, complement, and clotting cascades, as well as plasma lipoprotein particle remodeling. We further validated the identified biomarkers against a second cohort, identifying a panel of five key markers (GP5, SERPINA5, ECM1, IGHG1, and THBS1) which retained most of the diagnostic power of the overall dataset, achieving an AUC of 0.91. Taken together, this study provides a proteomic signature complementary to PSA for the diagnosis of patients with localised prostate cancer, with the further potential for assessing risk of future development of prostate cancer. Data are available via ProteomeXchange with identifier PXD025484.

Quantitative SWATH-based proteomic profiling of urine for the identification of endometrial cancer biomarkers in symptomatic women.

BACKGROUND: A non-invasive endometrial cancer detection tool that can accurately triage symptomatic women for definitive testing would improve patient care. Urine is an attractive biofluid for cancer detection due to its simplicity and ease of collection. The aim of this study was to identify urine-based proteomic signatures that can discriminate endometrial cancer patients from symptomatic controls. METHODS: This was a prospective case-control study of symptomatic post-menopausal women (50 cancers, 54 controls). Voided self-collected urine samples were processed for mass spectrometry and run using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning techniques were used to identify important discriminatory proteins, which were subsequently combined in multi-marker panels using logistic regression. RESULTS: The top discriminatory proteins individually showed moderate accuracy (AUC > 0.70) for endometrial cancer detection. However, algorithms combining the most discriminatory proteins performed well with AUCs > 0.90. The best performing diagnostic model was a 10-marker panel combining SPRR1B, CRNN, CALML3, TXN, FABP5, C1RL, MMP9, ECM1, S100A7 and CFI and predicted endometrial cancer with an AUC of 0.92 (0.96-0.97). Urine-based protein signatures showed good accuracy for the detection of early-stage cancers (AUC 0.92 (0.86-0.9)). CONCLUSION: A patient-friendly, urine-based test could offer a non-invasive endometrial cancer detection tool in symptomatic women. Validation in a larger independent cohort is warranted.

"I didn't feel like I could trust her and that felt really risky": a phenomenographic exploration of how Australian Midwives describe intrapartum risk.

OBJECTIVE: Concepts of intrapartum risk are not well explored in the Australian context. In response to an increasing focus on risk in maternity care, we sought to obtain insight into what Australian midwives conceptualised as intrapartum risk. DESIGN: The research was conducted using a phenomenographic approach. Following ethical approval, in-depth semi-structured interviews were used to determine the qualitatively different ways midwives conceptualise intrapartum risk. SETTING: This project was undertaken across different midwifery practice settings in Australia. PARTICIPANTS: Australian midwives (n=14) with expertise in caring for women in the intrapartum period volunteered to participate in the study. FINDINGS: When discussing their experience of intrapartum risk, midwives focused on the external horizon of the woman as the risk, that included the internal horizons of being labelled as clinically high risk, working relationships within transdisciplinary risk and institutional risk. Risks were orientated toward the woman as well as to the midwives. KEY CONCLUSIONS: The midwives in this study conceptualised that intrapartum risk was associated with the woman including being labelled as high risk in addition to certain challenges within the midwife-woman relationship, particularly if there was a lack of reciprocal trust. IMPLICATIONS FOR PRACTICE: This study supports current evidence that improved collaborative professional relationships are integral to safety in maternity care. It reinforces continuity of midwifery care as important, and particularly as a way of mitigating intrapartum risk. Further research is required to inform what challenges experienced in the midwife-woman relationship contribute to concepts of risk.

Comparison of Traditional Lecture-Based Learning versus Interactive Electronic Book Learning in Veterinary Student Comprehension of Inhalant Anesthetic Administration, Uptake, and Elimination.

The administration, uptake, and elimination of inhalant anesthetics is a challenging topic in the veterinary curriculum, and lecture-based learning is often insufficient to ensure that students understand these concepts. We hypothesized that the use of an interactive electronic book (e-book) would enhance student comprehension of the material. Two sequential Doctorate of Veterinary Medicine student cohorts participated in a prospective controlled study. The first cohort received traditional lecture-based learning while the second cohort was taught the topic using an interactive e-book. Student comprehension of the material was assessed twice during the course via multiple-choice questions: five questions in a midcourse quiz and seven within the final exam. At the end of the course, students also completed a Likert survey assessing their confidence regarding the topic. Averaged across assessment types, students taught using the interactive e-book scored higher than those taught via the traditional method (p < .001). Final exam scores were significantly higher in the e-book cohort compared with the lecture-based cohort (p < .001). However, there was no difference in quiz scores between groups (p = .109). No significant difference was found between groups in responses to the Likert survey. In conclusion, students using the interactive e-book had better comprehension of the material than students in the traditional lecture group as measured by their scores on multiple-choice question assessments. Future studies are needed to determine whether this advantage persists later in the curriculum when students apply these concepts in the clinical year.