Quantitative sensory testing in feline osteoarthritic pain - a systematic review and meta-analysis.

Quantitative sensory testing (QST) is a psychophysical test used to quantify somatosensory sensation under normal or pathological conditions including osteoarthritis (OA). OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of studies using QST in healthy and osteoarthritic cats, registered at Systematic Review Research Facility (#26-06-2017). DESIGN: Hierarchical models with random intercepts for each individual study extracted through the systematic review were fit to subject-level data; QST measures were contrasted between healthy and osteoarthritic cats. Four bibliographic databases were searched; quality and risk of bias assessment were performed using pre-established criteria. RESULTS: Six articles were included; most were of high quality and low risk of bias. Punctate tactile threshold (n = 70) and mechanical temporal summation (n = 35) were eligible for analysis. Cats with OA have lower punctate tactile threshold [mean difference (95%HDI): -44 (-60; -26) grams] and facilitated temporal summation of pain [hazard ratio (95%HDI): 5.32 (2.19; 14) times] when compared with healthy cats. The effect of sex and body weight on sensory sensitivity remained inconclusive throughout all analyses. Due to the correlation between age and OA status, it remains difficult to assess the effect of OA on sensory sensitivity, independently of age. CONCLUSIONS: Clear and transparent reporting using guidelines are warranted. Similar to people, centralized sensitization is a feature of OA in cats. Future studies should try to elucidate the age effect on feline OA. Research with natural OA in cats is promising with potential to benefit feline health and welfare, and improve translatability to clinical research.

Effect of body condition score and reuse of progesterone-releasing intravaginal devices on conception rate following timed artificial insemination in Nelore cows.

This study had the aim of investigating the efficiency of timed artificial insemination (TAI) through the progesterone-releasing intravaginal device (PRID), used in new condition and for the second and third times in Nelore cows. The effects of device reuse and body condition score (BCS) on the conception rate (CR) were evaluated in 1,122 multiparous Nelore cows (mean BCS of 2.7 ± 0.4), which were randomly distributed into three groups that received new (n = 330), once (n = 439) and twice used (n = 353) PRID. Among the 1,122 females that underwent TAI, 573 became pregnant, thus representing an overall CR of 51.06%. Cows with BCS between 2.75 and 4.0 had greater (p < .0001) CR (69.75%) than cows with BSC of 2.0-2.5 (32.98%). It was observed that the CR through using PRID was 60.00%, 51.71% and 41.93% for new, once and twice used PRID, respectively, with difference between all groups (p < .0001). Under tropical conditions, animals with BCS greater than 2.5 had a higher CR, and the CR decreased proportionally with the number of times that the PRID had been used.

Effects of the naturally-occurring contaminant microcystins on the Azolla filiculoides-Anabaena azollae symbiosis.

Harmful algal blooms (HABs) contaminate aquatic ecosystems and are responsible for animal poisoning worldwide. We conducted a toxicity test with the aquatic fern and the biofertilizer, Azolla filiculoides. The sporophytes were exposed to three concentrations (0.01, 0.1 and 1µgmL(-1)) of a microcystin (MC) cyanobacterial crude extract and purified MC-LR. The growth of A. filiculoides decreased only at 1µgmL(-1) crude extract concentration while with MC-LR it decreased at all the tested concentrations, indicating that the presence of other compounds in the crude extract altered toxicity and stimulated the fern growth at lower concentrations (0.01 and 0.1µgmL(-1)). Both phycoerythrocyanin and allophycocyanin levels decreased in all the concentrations of crude extract and MC-LR. The phycocyanin had a marked increase at 0.1µgmL(-1) crude extract concentration and a marked decrease at 1µgmL(-1) MC-LR concentration. These changes in the phycobiliprotein content indicate a shift in the antenna pigments of the cyanobionts of A. filiculoides. The changes in two oxidative stress enzymes, glutathione reductase for the crude extract assay and glutathione peroxidase for MC-LR assay, points towards the induction of stress defense responses. The low bioconcentration factor in both crude extract and MC-LR treatments can suggest the low uptake of microcystins, and indicates that the aquatic fern can be used as a biofertilizer and as animal feed but is not suitable for MC phytoremediation.

Quantitative sensory testing in canine musculoskeletal pain: Findings from a systematic review, meta-analysis feasibility assessment, and limitations.

Quantitative sensory testing (QST) allows the study of pain mechanisms, patient phenotyping, and response to therapy. The goals of this study were to conduct a systematic review of the use of QST in dogs with musculoskeletal disease including osteoarthritis (OA), and to assess, by means of a meta-analysis, the ability of QST to differentiate affected dogs from healthy controls. The study protocol was registered; three bibliographic databases were screened. Studies involving QST in healthy dogs and those with musculoskeletal disease were included. Data were extracted using a standardized form. Assessment of quality and risk of bias were performed using the CAMARADES critical assessment tool. Twenty-nine articles met the inclusion criteria [systematic review (n = 11); meta-analysis (n = 28)]. In the systematic review, ten studies performed static QST: mechanical [punctate tactile (n = 6); mechanical pressure (n = 5)]; thermal [cold (n = 3); hot (n = 4)]; electrical (n = 1); and one study performed dynamic QST [conditioned pain modulation (n = 1)]. Most studies were of good scientific quality and showed low to moderate risk of bias. A meta-analysis was not possible due to numerous and severe issues of heterogeneity of data among studies. Methods to reduce risk of bias and use of reporting guidelines are some of the most needed improvements in QST research in dogs. Standardization of QST methodology is urgently needed in future studies to allow for data synthesis and a clear understanding of the sensory phenotype of dogs with and without chronic pain including OA.

Fully automated deep learning models with smartphone applicability for prediction of pain using the Feline Grimace Scale.

This study used deep neural networks and machine learning models to predict facial landmark positions and pain scores using the Feline Grimace Scale© (FGS). A total of 3447 face images of cats were annotated with 37 landmarks. Convolutional neural networks (CNN) were trained and selected according to size, prediction time, predictive performance (normalized root mean squared error, NRMSE) and suitability for smartphone technology. Geometric descriptors (n = 35) were computed. XGBoost models were trained and selected according to predictive performance (accuracy; mean square error, MSE). For prediction of facial landmarks, the best CNN model had NRMSE of 16.76% (ShuffleNetV2). For prediction of FGS scores, the best XGBoost model had accuracy of 95.5% and MSE of 0.0096. Models showed excellent predictive performance and accuracy to discriminate painful and non-painful cats. This technology can now be used for the development of an automated, smartphone application for acute pain assessment in cats.

Atherogenic dyslipidemia in patients with established coronary artery disease.

BACKGROUND AND AIMS: Patients with stable coronary heart disease (CHD) and atherogenic dyslipidemia (AD) have a high-risk of recurrence and are those who derive most benefit from treatment with lipid-lowering agents. The aim of this study was to examine the prevalence of AD in patients with stable coronary heart disease and to investigate associated factors. METHODS: Cross-sectional study involving 7823 subjects admitted for a coronary event between 6 months and 10 years previously. AD was considered to be the concurrent presence of low HDL-cholesterol (<1.03 mmol/L [40 mg/dL] in males, <1.29 mmol/L [50 mg/dL] in females) and elevated triglycerides (≥1.7 mmol/L [150 mg/dL]). RESULTS: Mean age was 65.3 (10.1) years, 73.6% were males and 80.3% were receiving treatment with statins. Low HDL-cholesterol was observed in 26.3% of the participants, 39.7% had elevated triglyceride concentration and 13.0% had AD. The percentage of AD in patients with criteria for metabolic syndrome was 30.9%. Factors associated directly and independently with the presence of AD in the multivariate analysis were female sex, history of coronary syndrome without ST elevation or coronary revascularization, presence of atrial fibrillation, body mass index, LDL-cholesterol, systolic blood pressure and blood glucose levels, while age and glomerular filtration rate were significantly and inversely associated with AD. CONCLUSION: A significant proportion of patients with coronary disease could benefit from interventions aimed at increasing HDL-cholesterol and reducing triglycerides.

Role of autologous mesenchymal stem cells associated with platelet-rich plasma on healing of cutaneous wounds in diabetic mice.

BACKGROUND: Chronic cutaneous lesions affect 15% of human patients with diabetes, and the associated risk of limb amputations is 15-46 times greater than that of people with normal glycaemia. It is estimated that half of these limb amputations could be avoided by opportune treatment with somatic stem cells or platelet-rich plasma (PRP). METHODS: We evaluated the effects of autologous transplant of mesenchymal stem cells (MSCs) with or without combination with autologous PRP in the re-epithelialization of cutaneous lesions induced in diabetic mice. RESULTS: Animals treated with MSCs alone showed a similar level of re-epithelialization of cutaneous lesions to those treated with MSC plus PRP, and no significant difference was found between the two treatments. CONCLUSION: Both treatments gave better results than daily cleaning of the cutaneous lesions with saline or covering of the lesions with semipermeable adherent bandage.

[Prevalence of metabolic syndrome in patients with stable coronary disease: therapeutic objectives and utilization of cardiovascular drugs]. / Prevalencia de síndrome metabólico en pacientes con enfermedad coronaria estable: objetivos terapéuticos y utilización de fármacos cardiovasculares.

OBJECTIVE: The achievement of the therapeutic objectives in patients with ischemic heart disease and metabolic syndrome is unknown. This study has aimed to evaluate whether the prevalence of risk factors, the prescription rate of evidence-based cardiovascular therapies and the attainment of therapeutic goals differ in coronary patients with and without the metabolic syndrome (MS). METHODS: A multicenter, cross-sectional study carried out with the participation of 7,600 patients with stable coronary heart disease (mean age 65.3 years, 82% males, 37.7% with MS) attended in primary care. Data on drug prescription and goal attainment were extracted from clinical records. MS was defined according to the National Cholesterol Education Program (NCEP) criteria. RESULTS: Patients with MS had a higher prevalence of cardiovascular risk factors and cardiovascular disease. They also had a higher prescription rate of blood-pressure lowering drugs, statins and antidiabetic agents, without differences in the rate of use of antithrombotics and beta-blockers. After adjusting for cardiovascular risk factors and co-morbidity, only fibrates and angiotensin II receptor blockers were used more frequently in MS patients. A lower percentage of subjects with MS achieved therapeutic goals of LDL cholesterol (23.4% vs 27.7%, P<.001), blood pressure (29.1% vs 52.2%, P<.001) and, in diabetics, of glycated hemoglobin (54.7% vs 75.9%, P<.001). CONCLUSION: Patients with stable coronary disease and MS do not reach therapeutic objectives as frequently as those without MS, in spite of receiving a higher amount of cardiovascular drugs.

Ice therapy: cool, current and complicated.

This is the fourth Capsule review article provided by the WSAVA Global Pain Council and which discusses the use of ice or cold therapy as a non-pharmacologic modality for pain control in small animal practice. The physiological effects of cold therapy on tissues, receptors and ion channels are discussed; as well as indications, recommendations for, and limitations of use.

Intraperitoneal and incisional analgesia in small animals: simple, cost-effective techniques.

The World Small Animal Veterinary Association Global Pain Council (WSAVA-GPC) has recently published its first "capsule review" by Monteiro et al. These are short articles that present a brief assessment of the scientific evidence and practical recommendations on important, and sometimes controversial, subjects in pain management. The capsules will be published regularly in the Journal of Small Animal Practice, the official journal of the WSAVA. This second article discusses the use of intraperitoneal and incisional analgesia in small animal practice, including their limitations and recommendations by the authors.

Supplemental progesterone induces temporal changes in luteal development and endometrial transcription in beef cattle.

Long-acting injectable progesterone (iP4) supplementation during early diestrus is a strategy to increase conception rates in cow-calf beef operations. However, iP4 treatment causes early functional and structural regression of the corpus luteum (CL) in a proportion of iP4-treated animals, resulting in pregnancy loss. The hypothesis evaluated was that iP4 accelerates downregulation of sex-steroid receptors (PGR, ESR1, ESR2) during early to mid-diestrus and the upregulation of genes controlling PGF2α secretion (OXTR, PTGS2, AKR1B1) during late diestrus in the endometrium. Ovulations of cyclic, multiparous Nelore (Bos indicus) cows were synchronized, and cows were divided to receive placebo or 300 mg iP4 3 d postovulation (D3). Growth and vascularization of luteal tissue were evaluated by ultrasonography. Blood samples were collected from 3 d postovulation to 3 d after luteolysis, and P4 plasma concentrations were measured by radioimmunoassay. On days 3, 5, 7, 9, 11, 13, and 16 luminal endometrial samples were taken using a cytologic brush. Transcript abundance was measured by qPCR. Structural luteolysis occurred 3 d earlier in cows receiving iP4 compared to the control group. Analyzing only cows that received iP4, those that presented early luteolysis (ie, ≤ D16) showed a decrease in CL area and P4 concentration after D5, compared to the control group. Cows that presented early luteolysis showed a reduced abundance of transcripts on D5 for the ESR2 gene and a greater abundance of transcripts for OXTR and ESR1 on D16, compared to cows that did not present early luteolysis. The iP4-induced early luteolysis can be explained by two nonexclusive possibilities: the activation of uterine mechanisms that trigger early secretion of endometrial PGF pulses and the formation of a subfunctional CL that is prone to early regression.

Long-term use of non-steroidal anti-inflammatory drugs in cats with chronic kidney disease: from controversy to optimism.

This is the first of a series of capsule reviews published by the World Small Animal Veterinary Association - Global Pain Council (WSAVA-GPC). Each of these short articles provides a brisk assessment of the scientific evidence in specific aspects of pain management, including analgesic techniques, recommendations and controversies surrounding their use. In this first capsule review, the scientific evidence available on the long-term use of non-steroidal anti-inflammatory drugs in cats with concomitant chronic pain and chronic kidney disease is discussed.

Effects of physical exercise on skeletal muscles of rats with cerebral ischemia.

Physical exercise is a known preventive and therapeutic alternative for several cerebrovascular diseases. Therefore, the objective of the present study was to evaluate the motor performance and histomorphometry of the biceps brachii, soleus, and tibialis anterior muscles of rats submitted to a treadmill training program prior to the induction of cerebral ischemia via occlusion of the middle cerebral artery (OMCA). A total of 24 Wistar rats were distributed into four groups: Sham-Sed: sedentary control animals (n=6), who underwent sham surgery (in which OMCA did not occur); Sham+Ex: control animals exercised before the sham surgery (n=6); I-Sed: sedentary animals with cerebral ischemia (n=6); and I+Ex: animals exercised before the induction of ischemia (n=6). The physical exercise consisted of treadmill training for five weeks, 30 min/day (5 days/week), at a speed of 14 m/min. The results showed that the type-I fibers presented greater fiber area in the exercised ischemic group (I+Ex: 2347.96±202.77 µm2) compared to the other groups (Sham-Sed: 1676.46±132.21 µm2; Sham+Ex: 1647.63±191.09 µm2; I+Ex: 1566.93±185.09 µm2; P=0.0002). Our findings suggested that the angiogenesis process may have influenced muscle recovery and reduced muscle atrophy of type-I fibers in the animals that exercised before cerebral ischemia.

Profile of LH release in response to intramuscular treatment with kisspeptin in Bos indicus and Bos taurus prepubertal heifers.

The main objective of this study was to evaluate the effect of intramuscular (I.M.) administration of different doses of kisspeptin (Kp) on the pattern of luteinizing hormone (LH) release in Bos taurus and Bos indicus prepubertal heifers. Holstein heifers weighing 215.1 ±â€¯38.6 kg (n = 24; aged 5-8 mo) and Gyr heifers weighing 215.4 ±â€¯31.4 kg (n = 24; aged 6-10 mo) were enrolled in this study. The animals were confirmed as non-cyclical by absence of a corpus luteum (CL) as determined by ultrasound scanning of the ovaries and low circulating P4 concentrations (<1.0 ng/mL) evaluated at a 10-day interval (on day -10 and day 0). For each genetic group, heifers were randomly assigned to one of four treatments: Kp at 2.5 µg/kg body weight (Kp2.5), Kp at 5.0 µg/kg (Kp5), Kp at 10 µg/kg (Kp10), or gonadotropin-releasing hormone (GnRH) agonist (0.01 mg of buserelin acetate per heifer), all administered by I.M. injection. All animals responded to the treatments with an LH surge (P < 0.01). There was an effect of breed (P < 0.01) on induced LH release, with Holstein heifers having a greater area under the curve for LH (AUC; P < 0.01) and greater LH peak amplitude (P < 0.01) than Gyr heifers. Nevertheless, greater AUC for LH occurred in Kp10 heifers for both breeds. There was no effect of breed on LH AUC or LH peak amplitude after GnRH agonist treatment. For both breeds, heifers treated with Kp displayed an earlier (P < 0.01) LH peak with a reduced amplitude of the LH peak (P < 0.01) and reduced LH AUC (P < 0.01) compared to heifers treated with GnRH agonist. Thus, both zebu and taurus immature heifers treated with I.M. Kp injection responded with a rapid and dose-dependent LH surge, although even large doses of the native Kp-10 did not mimic the magnitude or duration of the LH surge produced by the GnRH agonist. The early onset of the LH surge after Kp treatment and the short duration suggest that the effects of Kp were likely due to pituitary rather than hypothalamic action. Finally, there seems to be a greater responsiveness to Kp in Bos taurus than in Bos indicus prepubertal heifers, although LH release after GnRH agonist treatment was similar for the two breeds.

Perceptions and opinions of Canadian pet owners about anaesthesia, pain and surgery in small animals.

OBJECTIVES: The aim of this study was to evaluate the perceptions and opinions of Canadian pet owners about anaesthesia, pain and surgery in dogs and cats. METHODS: Six Canadian veterinary hospitals participated. Each practice received 200 copies of a questionnaire that were distributed to pet owners. Questions regarding the use of analgesics, anaesthesia, surgery and onychectomy (cats) were included. Responses were transformed into ordinal scores and analysed with a Cochran-Mantel-Haenszel test. RESULTS: A total of 849 out of 1200 questionnaires were returned. Owners believed more frequently that analgesics are needed for surgical procedures than for the medical conditions. Owners rated as very important/important: "knowing what to expect during illness/injury/surgery" (99·3%), "being assured that all necessary analgesic drugs/techniques will be used" (98·6%), "being informed about procedures/risk" (98·5%), and having a board-certified anaesthesiologist (90·5%). Most owners agreed/partly agreed that pain impacts quality of life (94·2%), and affects their pet's behaviour (89·5%). Most respondents (69%) were women; they were significantly more concerned than men about anaesthesia, pain, cost and client-communication. Cat owners believed that analgesics were necessary for some procedures/conditions significantly more often than canine-only owners. Pet owners with previous surgery disagreed more frequently that "pain after surgery can be helpful" and that "pain in animals is easy to recognize" than those without previous surgery. Most owners think onychectomy should be banned in cats (56·4%). CLINICAL SIGNIFICANCE: This study identified important areas of client communication regarding pain and its control in pets.

Impact of progesterone and estradiol treatment before the onset of the breeding period on reproductive performance of Bos indicus beef heifers.

The present aimed to develop a hormonal therapy based on the insertion of a progesterone (P4) insert (PI) during 10 d plus an estradiol injection (E2) at PI removal before the onset of breeding of beef heifers. In Exp. 1, the plasma P4 profile of prepubertal heifers showed that the insertion of a PI or 24 d previously used P4 insert (UPI) sustained plasma P4 above 1 ng/mL for at least the first 7 d of the treatment. In Exp. 2 there was no positive effect of additional estradiol benzoate (EB) administered at the insertion of UPI on the proportion of heifers with a corpus luteum (CL/Treated) 30 d after UPI removal [UPI + EB = 85.3%(a) (n = 134); EB + UPI + EB = 80.8%(a) (n = 125)]; however, both were greater (P < 0.0001) than the Control group [60.3%(b) (n = 129)]. In Exp. 3, a positive effect (P=0.01) of UPI treatment and both E2 supplementations [EB and estradiol cypionate (EC); P = 0.10] at the UPI removal was observed on CL/Treated [Control = 42.5%(b) (n = 94); UPI = 58.5%(a) (n= 130); UPI + EB = 64.0%(a) (n = 128); UPI + EC = 67.2%(a) (n = 128)]. However, greater pregnancy per treated heifer (P/Treated) following artificial insemination (AI) upon estrus detection was achieved when EC was applied [Control = 20.2%(b); UPI = 29.2%(ab); UPI + EB = 26.6%(b); UPI + EC = 36.7%(a)]. In Exp. 4, the treatment prior to the timed AI (TAI) tended to improve pregnancy per TAI [P/AI; Control 43.6% (n = 298) vs. UPI+EC 51.9% (n = 342); P = 0.08], but increased P/Treated [26.5% vs. 43.3%; P < 0.001]. Thus, UPI + EC treatment were efficient in increasing the CL/Treated, tended to improve the P/AI and consequently enhanced P/Treated of zebu beef heifers.

Electrical activity of the orbicularis muscles before and after installation of ocular prostheses.

This study examined the electrical activity of the superior (SO) and inferior (IO) orbicularis oculi muscles before and after installing ocular prostheses in patients who had undergone unilateral enucleation. Twelve volunteers requiring prostheses were selected. Their electrical activity was monitored at rest and during normal opening and closing of the eyelids, rapid opening and closing of the eyelids, and squeezing. Data were recorded before and 7, 30, and 60 days after the ocular prosthesis was installed. Two-way analysis of variance was performed to verify whether there were any significant differences between the muscles and periods, and means were compared by Tukey-Kramer honestly significant difference (HSD) tests (P < 0.05). Results from the initial period differed significantly from those after prosthesis installation in all clinical situations. The SO had significantly higher electrical activity levels than the IO in all clinical situations but squeezing. The authors observed the same values during the initial period for the condition of rest (SO 8.42/IO 5.93) and the highest values for the condition of squeezing after 60 days (SO 131.50/IO 117.12). Rehabilitative treatment promoted an increase in the electrical activity of the orbicularis oculi muscles, restoring part of the muscle tone and motor function to muscles of the affected area.

Impact of puberty status and melengestrol acetate supplementation before the breeding period on reproductive efficiency of Bos indicus beef heifers.

Two experiments were designed to evaluate the impact of puberty status and the administration of melengestrol acetate (MGA) before onset of the breeding period on ovulatory responses (Exp. 1) and conception rate after AI performed on estrus detection during 10 d and the pregnancy rate through 80 d of breeding period (Exp. 2) of pasture-grazed beef heifers. In Exp. 1, heifers (15 pubertal and 15 prepubertal) received 0.5 mg per heifer/d -1 of MGA over 14 d. No differences in the ovulatory responses were found 10 d after the MGA administration (pubertal = 46.7% vs. prepubertal P = 53.3%; P = 0.72). In Exp. 2, 368 heifers were randomly assigned to groups according to pubertal status and the MGA treatment. All heifers were inseminated on estrus detection for up 10 d after MGA administration and following exposure to bulls between 20 and 80 d. The MGA-treated heifers exhibited a greater AI service rate than control heifers (72.1 vs. 41.6%;P < 0.01); however, heifers receiving MGA had lower conception results following AI (51.6 vs. 71.4%; P = 0.01). In addition, MGA-treated heifers were more likely to have a corpus luteum in the middle of the breeding period (95.3 vs. 87.5%;P < 0.01), although the Cox proportional hazard of pregnancy rate was similar (P = 0.29) at the end of the breeding period. At onset of the breeding period, pubertal heifers presented a greater pregnancy rate following AI (pubertal P = 42.2% vs. prepubertal P = 24.9%; P = 0.01). Therefore, pubertal heifers seem to have greater overall reproductive efficiency than prepubertal heifers, particularly at the beginning of the breeding period. Interestingly, administration of MGA before the onset of the breeding period increased AI service rate but did not alter the rate of pregnancy throughout the breeding period of pasture-grazed beef heifers.