Autologous adipose-derived stromal vascular fraction and platelet concentrates for the treatment of complex perianal fistulas.

BACKGROUND: Complex perianal fistulas are a major challenge for modern surgery since 10-35% of patients have functional problems after treatment. Sphincter-saving techniques have a wide range of efficacy (10-80%). We hypothesised that autologous adipose-derived stromal vascular fraction in combination with platelet rich plasma is a new therapeutic strategy with enhanced cure and function preservation rates. METHODS: Adult patients with complex cryptoglandular perianal fistulas were treated with injection of autologous adipose-derived stromal vascular fraction in combination with platelet rich plasma around and inside the fistulous tract between May 2018 and April 2019 at the General and Emergency Surgery Operative Unit of the University Hospital "P. Giaccone" of Palermo. Fistulas were confirmed by magnetic resonance imaging. Patients completed the Short Form-36 score on quality of life and the Wexner and Vaizey scores on faecal incontinence, and they were functionally studied using a three-dimensional anorectal manometry. The clinical and functional follow-up was performed at 1 year and 2 years after surgery. RESULTS: Nine patients (4 males, 5 females; median age 42 years [19-63 years]) with high trans-sphincteric or horseshoe fistulas were treated. The average number of previous surgeries per patient was 4.8. At 1 year follow-up, 77.7% of patients were cured, while at 2 years there was 1case of relapse. The variation in Short Form-36 score in cured patients was not significant (p = 0.0936). No statistically significant differences were found in continence scores. CONCLUSIONS: The proposed treatment is a treatment option that preserves sphincter integrity and function, potentially avoiding postoperative incontinence and the need of repeated treatments.

Different distribution of antimicrobial resistance genes and virulence profiles of Staphylococcus aureus strains isolated from clinical mastitis in six countries.

Staphylococcus aureus is recognized worldwide as one of the main contagious mastitis agents in cattle and can express a set of antimicrobial resistance genes and virulence-associated genes that explain the wide range of outcomes of intramammary infections. Staphylococcus aureus strains are heterogeneous: their different resistance and virulence patterns, associated with host-level factors and treatment factors, are related to the severity of infection. The aim of this study was to determine phenotypic antibiotic susceptibility, occurrence of selected antimicrobial resistance genes and other virulence genes in 93 S. aureus strains isolated from clinical mastitis in 6 countries: Argentina, Brazil, Germany, Italy, the United States (New York State), and South Africa. These isolates were tested against a total of 16 drugs (amoxicillin-clavulanate, ampicillin, cefazolin, cefoperazone, cefquinome, enrofloxacin, erythromycin, gentamicin, kanamycin, lincomycin, oxacillin, penicillin, rifampin, spiramycin, sulfamethoxazole/trimethoprim, tylosin) by minimum inhibitory concentration (MIC) assay, and examined for the presence of 6 antibiotic-resistance genes (blaZ, mecA, mecC, ermA, ermB, ermC) and 6 virulence-associated genes (scn, chp, sak, hla, hlb, sea) via PCR analysis. The phenotypic results of this study revealed the presence of 19.4% penicillin-resistant strains, whereas 22.6% of the strains were classified as having resistance (5.4%) or intermediate resistance (17.2%) to erythromycin. Most (96.8%) of the isolates were inhibited by cephalosporins, and all were susceptible to amoxicillin-clavulanate. Two strains (1 from Germany, 1 from Italy) were resistant to oxacillin and were positive for mecA. Among the other antimicrobial resistance genes, the most frequently detected was blaZ (46.2%), and 32.3% of the isolates were positive for erm genes: ermC (21.5%) and ermB (10.8%). The most prevalent virulence gene was hla (100%), followed by hlb (84.9%) and sea (65.6%). These results show a low prevalence of antibiotic multidrug resistance in S. aureus isolates, even if the detection of selected antimicrobial resistance genes did not always correspond with the occurrence of phenotypic antibiotic resistance; the immune evasion cluster gene prevalence was quite low in the samples analyzed.

Pharmacokinetic and pharmacodynamic evaluations of a 10 mg/kg enrofloxacin intramuscular administration in bearded dragons (Pogona vitticeps): a preliminary assessment.

Enrofloxacin (E) is commonly used in veterinary medicine. It is necessary to perform pharmacokinetic/dynamic studies to minimize the selection of resistant mutants of bacteria and extend the efficacy of antimicrobial agents. Eight healthy adult Pogona vitticeps were assigned into two groups of equal size and treated with a single intramuscular injection of E at 10 mg/kg. Blood samples were withdrawn at different scheduled times for each group, and rectal swabs were collected. E and ciprofloxacin (active metabolite) blood concentrations were quantified by an HPLC validated method, while the in vitro antimicrobial susceptibility was evaluated by the Kirby-Bauer disc diffusion susceptibility test. The pharmacokinetic profiles of E gave similar pharmacokinetic parameters irrespective of the collection time schedule. Bacteria isolation showed the presence of both E. coli, Salmonella enterica subspecies enterica and subspecies 3a, Proteus spp., and Pseudomonas spp. The majority of isolated colonies were sensitive to E, but the treatment did not reduce the number of bacteria in faeces. Results suggest that E is able to reach blood concentrations high enough to kill susceptible bacteria (MIC < 0.9 µg/mL), but at the same time does not significantly affect intestinal bacteria.

In vitro enantioselective pharmacodynamics of Carprofen and Flunixin-meglumine in feedlot cattle.

The activity of the anti-inflammatory agents Flunixin-meglumine (FLU), RS (±) Carprofen (CPF) and S (+) CPF on bovine cyclooxygenases (COXs) has been characterized in feedlot calves using an in vitro whole blood model. The drugs showed equivalent efficacy in their inhibitory activity on COXs, and the rank order of potency for both COX-1 and COX-2 inhibition was FLU > S (+) CPF > RS (±) CPF. Our results indicated that FLU is a nonselective inhibitor of bovine COXs, whereas RS (±) CPF and S (+) CPF exhibited different degrees of preferential inhibition of COX-2 isoenzyme. The rank order of IC50 COX-1: IC50 COX-2 potency ratios was in fact S (+) CPF (51.882) > RS (±) CPF (13.964) > FLU (0.606), and the calculated percentage inhibition of COX-1 corresponding to COX-2 inhibition values comprised between 80% and 95% was comprised between 57.697 and 79.865 for FLU, 33.373 and 51.319 for RS (±) CPF, and 0.230 and 4.622 for S (+) CPF, respectively. These findings are discussed in relation to the prediction of the clinical relevance of COX inhibition by the test drugs in cattle.

Effects of flunixin meglumine and ketoprofen on mediator production in ex vivo and in vitro models of inflammation in healthy dairy cows.

In this study, ex vivo assays were carried out in dairy cows to evaluate the anti-inflammatory effects of two nonsteroidal anti-inflammatory drugs: ketoprofen (KETO) and flunixin meglumine (FM). Twelve healthy Holstein dairy cattle were randomly allocated to two groups (n=6): group 1 received FM and group 2 received KETO at recommended therapeutic dosages. The anti-inflammatory effects of both drugs were determined by measuring the production of coagulation-induced thromboxane B2 (TXB2 ), lipopolysaccharides (LPS) (10 µg/mL)-induced prostaglandin E2 (PGE2 ), and calcium ionophore (60 µm)-induced leukotrien B4 (LTB4 ). Cytokine production was assessed by measuring tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-8 (CXCL8) concentrations after incubation in the presence of 10 µg/mL LPS. The IC50 of FM and KETO was determined in vitro by determining the concentration of TXB2 and PGE2 in the presence of scalar drug concentrations (10(-9) -10(-3) m). Both FM and KETO inhibited the two COX isoforms in vitro, but showed a preference for COX-1. FM and KETO showed similar anti-inflammatory effects in the cow.

The Multidisciplinary Approach for the Diagnosis of Laryngohyoid Lesions: a Systematic Literature Review and Meta-Analysis.

Background: The diagnosis of neck lesions remains a medico-legal diagnostic challenge because of the complexity of the anatomical relationship of the neck's organs and their anthropometric morphological variability. We compared the multidisciplinary approach using autopsy and postmortem computed tomography (PMCT), postmortem fine preparation (PMFP), postmortem micro-computed tomography (micro-CT), and postmortem magnetic resonance (PMMR) with the performance of a single diagnostic method among them evaluating the significance of different results. The multidisciplinary approach significantly reduced the number of unidentified neck lesions. The analysis demonstrates the need to better define the scan protocols and compose forensic guidelines for radiological application. The results of this study point out the need to compare the different diagnostic approaches in deceased subjects to better define the radiological scan protocol based on a multidisciplinary approach, including autopsy and radiological methods and the radiological scan protocols. Methods: We performed a systematic electronic search of retrospective scientific articles in PubMed, the Scopus database, and the Cochrane Library. The following combinations of words were used: "hyoid fracture"; "comparison between PMCT AND autopsy"; "hyoid fracture PMCT AND autopsy"; "hyoid bone fracture AND forensic imaging"; "hyoid fracture AND PMCT"; "neck fracture PMCT AND autopsy"; "laryngohyoid lesions"; "postmortem CT AND autopsy in strangulation"; "postmortem AND strangulation Signs "; "strangulation virtopsy"; and "strangulation AND MRI". We selected 16 articles that were published between March 2003 and June 2020. We conducted a meta-analysis with R software to evaluate the rates. We obtained related confidence intervals and a forest plot. Results: Thyroid cartilage damages were significantly more common than hyoid bone fractures (61.7% vs 42.2%) in a sample of 128 subjects. The synergic uses of autopsy/PMCT, autopsy/PMFP, autopsy/microCT, and autopsy/PMMR revealed significantly higher rates than a single investigation. We analyzed the PMCT scan data. The scan parameters evaluated were as follows: row, scan sample, reconstruction, kernel, slice thickness, kVp, and mAs. A lack of uniformity in the application of the protocol was observed. Conclusion: Further studies are needed to better define the radiological scan protocols and to draw guidelines to identify the appropriate radiological methods in relation to the specific case.

Cisplatin-gemcitabine as palliative chemotherapy in advanced squamous vulvar carcinoma: report of two cases.

Vulvar cancer (VC) is a rare disease, usually diagnosed in a stage still amenable to potentially curative treatments, including surgery and/or radiation therapy with or without chemotherapy. Several patients however present at diagnosis with metastatic disease and another 30-50% will relapse. Prognosis of metastatic or recurrent disease not amenable to salvage surgery or radiotherapy is very poor. Evidence about the efficacy of chemotherapy in this setting is limited and its role still remains unclear. At present there is no standard treatment for advanced VC and patients are usually treated with schedules adopted for chemoradiation or extrapolated from cervical cancer. We report our experience using a cisplatin-gemcitabine regimen in two cases of metastatic squamous cell VC. No response was obtained with this schedule. No other data are available in the literature about the choice of a cisplatin-gemcitabine regimen in this patient subset. The paucity of evidence about the role of palliative chemotherapy in metastatic VC justifies any effort to implement knowledge. For this reason we think it is notable to also report a negative experience. It is not possible for us to conclude that this chemotherapy would be unable to provide any benefit in a larger sample of patients; nonetheless we think that new agents, rather than combinations of older drugs, could hopefully provide more benefit.

Validation of the Meet-URO score in patients with metastatic renal cell carcinoma receiving first-line nivolumab and ipilimumab in the Italian Expanded Access Program.

BACKGROUND: The Meet-URO score allowed a more accurate prognostication than the International Metastatic RCC Database Consortium (IMDC) for patients with pre-treated metastatic renal cell carcinoma (mRCC) by adding the pre-treatment neutrophil-to-lymphocyte ratio and presence of bone metastases. MATERIALS AND METHODS: A post hoc analysis was carried out to validate the Meet-URO score on the overall survival (OS) of patients with IMDC intermediate-poor-risk mRCC treated with first-line nivolumab plus ipilimumab within the prospective Italian Expanded Access Programme (EAP). We additionally considered progression-free survival (PFS) and disease response rates. Harrell's c-index was calculated to compare the accuracy of survival prediction. RESULTS: Overall the EAP included 306 patients, with a median follow-up of 12.2 months, median OS was not reached, 1-year OS was 66.8% and median PFS was 7.9 months. By univariable analysis, both the IMDC score and the two additional variables of the Meet-URO score were associated with either OS or PFS (P < 0.001 for all comparisons). The four Meet-URO risk groups (G) had 1-year OS of 92%, 72%, 50% and 21% for G2 (29.1% of patients), G3 (28.8%), G4 (33.0%) and G5 (9.1%), respectively. OS was significantly shorter in each consecutive G (P = 0.001 for G3, P < 0.001 for both G4 and G5 compared to G2). Similarly, Meet-URO Gs 2-5 showed decreasing median PFS and response rates. The Meet-URO score showed the highest c-index for both OS (0.73) and PFS (0.67). Limitations include the post hoc nature of this analysis and the lack of a comparative arm to assess predictive value. CONCLUSION: The Meet-URO score appeared to show better prognostic classification than the IMDC alone in patients with mRCC at IMDC intermediate-poor risk treated with first-line nivolumab and ipilimumab.

Prognostic outcome of routine clinical noninvasive multidetector-row computed tomography coronary angiography in patients with suspected coronary artery disease: a 2-year follow-up study.

PURPOSE: The aim of the study was to assess the prognostic value of multidetector-row CT coronary angiography (MDCT-CA) in patients with suspected coronary artery disease (CAD) in a routine clinical context. MATERIALS AND METHODS: A total of 125 patients (82 men, age 57.4±10.3 years) with suspected CAD underwent MDCT-CA. All patients were assessed for cardiovascular risk factors, symptoms and coronary calcium score. A 2-year follow-up study for the occurrence of major adverse cardiac events was performed. RESULTS: According to the Morise pretest score, 76 patients (60.8%) were at intermediate risk. Patients with suspected CAD presented the following prognostic outcome (p<0.0001): in 41 patients with normal coronary arteries at MDCT-CA, the event rate was 0%; five of 49 patients with nonobstructive CAD had major cardiac events; two of 35 patients with obstructive CAD suffered cardiac death and 19 underwent revascularisation. At multivariate analysis, the presence of obstructive CAD is the only significant independent prognostic variable (hazard ratio, 10.1393; 95% confidence interval 3.2189-31.9379; p<0.0001). CONCLUSIONS: Routine clinical MDCT-CA provides an excellent prognostic value at 2-year follow-up in patients with normal coronary arteries. The cardiac event rate increases with CAD severity.

Preliminary comparative serological evaluation of Histamine H2 receptors in dogs with an acute onset of vomiting treated with Ranitidine and healthy dogs.

Despite the lack of evidence of the ability to suppress gastric acid secretion in dogs, ranitidine (RT) is often used to control clinical signs in dogs with acute vomiting even if the way it happens it is still largely unknown. The aim of this study was thus to evaluate the therapeutic effect of ranitidine on H2 receptors in dogs with acute vomiting. To investigate the RT activity a preliminary study was performed in dogs which underwent gastroscopy analyses, demonstrating that the level of H2R observed in the serum and gastric wall tissue was the same [1.473(1.30; 1.79) ng/ml and 1.498 (1.33; 1.85) ng/ml, respectively]. After that H2R levels in the serum of 22 healthy dogs (Group 1) and in a group of 22 dogs with acute vomiting (Group 2) were compared both before (T0), after 7-10 days (T1) of 2 mg/kg twice a day ranitidine administration and after 11 days since the drug was discontinued (T2). Significant differences (p<0.001) were detected between the level of circulating H2R among Group 1: 0.41 ng/ml (0.28;0.54) and Group 2: 2.27 ng/ml (2.11;2.49) at T0. In Group 2, no difference in the level of H2R was detected in samples collected at T0 compared to those at T1 [T1: 2.32 ng/ml (2.14; 2.49)] and T2 [T2: 2.30 ng/ml (1.99;2.69)]. In Group 2 all patients but one displayed remission of symptoms attributable to inflammatory gastropathy at the first withdrawal (T1: 7-10 days), while at the second withdrawal (T2: after 21 days), remission was detected in all dogs. Our preliminary hypothesis is that the clinical efficacy of ranitidine is related to the greater expression of H2 receptors in patients with acute vomiting. This increased expression may be due to continuous pathological stimulus at the gastric level. Further studies with a wider population are needed to better investigate the activity of RT in dogs with acute onset of vomiting.

WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.

A human Wilms tumor cell line (RM1) was developed to test the tumor suppressor activity of WT1, a zinc finger transcription factor that is expressed in the developing human kidney and is mutationally inactivated in a subset of Wilms tumors. Transfection of each of four wild-type WT1 isoforms suppressed the growth of RM1 cells. The endogenous WT1 transcript in these cells was devoid of exon 2 sequences, a splicing alteration that was also detected in varying amounts in all Wilms tumors tested but not in normal kidney. Production of this abnormal transcript, which encodes a functionally altered protein, may represent a distinct mechanism for inactivating WT1 in Wilms tumors.

Videofluorography swallow study of patients with systemic sclerosis.

PURPOSE: This study was undertaken to evaluate the role of the videofluorographic (VFG) swallow study in patients with systemic sclerosis. MATERIALS AND METHODS: Over a 23-month period, 45 women (mean age 58 years, range 27-76 years) with a known diagnosis of systemic sclerosis and a history of dysphagia underwent a dynamic and morphological study of the oral, pharyngeal and oesophageal phases of swallowing with videofluorography. All examinations were performed with a remote-controlled digital C-arm device with 16-in image intensifier, 0.6- to 1.2-mm focal spot range and maximum tube voltage of 150 kVp in fluorography and 120 kVp in fluoroscopy. Cineradiographic sequences were acquired for the swallow study with 12 images per second and matrix 512 x 512 after the ingestion of boluses of high-density (250% weight/volume) barium. The evaluation of oesophageal peristalsis was documented with digital cineradiographic sequences with six images per second in the upright and supine positions during the swallowing of barium (60% weight/volume), and the water siphon test was performed with the patient in the supine position to evaluate the presence of gastro-oesophageal reflux disease (GORD). All patients subsequently underwent laryngoscopy, endoscopy and pH monitoring, and the data thus obtained were processed and compared. RESULTS: The VFG swallow study identified alterations of epiglottal tilting associated with intraswallowing laryngeal penetration in 26 patients (57.8%), pooling of contrast agent in the valleculae and pyriform sinuses in 23 (51.1%) and radiographic signs of nonspecific hypertrophy of the lingual and/or palatine tonsils in 18 (40%). The study of the oesophageal phase revealed the presence of altered peristalsis in all patients, and in particular, 36 patients (80%) showed signs of atony. Altered oesophageal clearing mechanisms were evident in all 45 patients, sliding hiatus hernia in 43 (93%) and GORD in 44 (97%). CONCLUSIONS: Our study demonstrated that in patients with systemic sclerosis, there is no primary alteration of the oral or pharyngeal phase of swallowing. In addition, alterations of epiglottal tilting associated with laryngeal penetration of contrast agent were found to be secondary to chronic GORD. Indeed, in 40% of patients, radiographic signs were found that indicated nonspecific hypertrophy of the lingual tonsil and/or palatine tonsils and nonspecific signs of chronic pharyngeal inflammation, and GORD was identified in 93% of patients, which in 40% of cases extended to the proximal third of the oesophagus. The data obtained were confirmed in 85% of cases with pH monitoring and in all cases with laryngoscopy.

Prevalence of myocardial bridging and correlation with coronary atherosclerosis studied with 64-slice CT coronary angiography.

PURPOSE: This study aimed to assess the prevalence and characteristics of myocardial bridging in patients who underwent multislice computed tomography coronary angiography (MSCT-CA) and to evaluate the correlation between bridged coronary segments and atherosclerosis. MATERIALS AND METHODS: A total of 277 patients (mean age 60+/-11 years) we consecutively examined with 64-slice MSCT-CA for suspected or known coronary atherosclerosis were retrospectively reviewed for myocardial bridging. Segments proximal and distal to the bridging were evaluated for atherosclerotic plaque, as were the remaining coronary segments. RESULTS: Myocardial bridging was present in 82 patients (30%, mean age 59+/-12). Bridges were of variable length (<1 cm 58%; 1-2 cm 32%; >2 cm 10%) and depth (superficial 69%, intramyocardial 31%) and frequently localised in the mid-distal segment of the left anterior descending artery (95%). Myocardial bridging cannot be considered a significant risk factor for coronary atherosclerosis (odds ratio 0.49) compared with traditional cardiovascular risk factors. Coronary segments proximal to the bridge showed no atherosclerotic disease (33%), positive remodelling (27%), <50% stenosis (20%) or >50% stenosis (20%). We identified 12 noncalcified, 32 mixed and 17 calcified plaques. The distal segments were significantly less affected (p<0.0001). CONCLUSIONS: MSCT-CA is a reliable, noninvasive method that is able to depict myocardial bridging and associated atherosclerotic plaque in the proximal segments.

Steroid and beta-adrenergic receptor modifications in target organs of broiler chickens fed with a diet containing beta2-adrenergic agents.

The illegal use of beta2-agonists as repartitioning agents to improve production performance and carcass composition can induce changes in various organs of exposed animals. The aim of the present study was to evaluate the effects induced by dietary beta-agonists on beta-AR, AnR and GR in male broiler target organs. Fifty-four male broiler chickens (Ross 508), 26 days old, were randomly divided into three homogeneous experimental groups and fed for 21 days with a standard diet containing placebo (group 1, control), 1ppm of clenbuterol (group 2) and 1ppm of cimaterol (group 3). Tissue samples of heart, lung, brain, testicle, spleen, thymus and Bursa of Fabricius were collected post-mortem then cytosol fractions were used for AnR (testicles) and GR (spleen, thymus and Bursa of Fabricius), and membrane fractions for beta-AR (all tissues but testicles) determination by binding assays. The dietary administration of beta-adrenergic agents as repartitioning agents induced a significant decrease in AnR concentration in the testicle, in GR levels in the lymphoid tissues and in beta-AR concentrations of different target organs of male chickens. Present data confirm those observed in female chickens and suggest that in poultry the regulation exerted by adrenergic stimulation on steroid receptor concentrations produces different effects than in mammals.

Cardiac rupture caused by traffic accident: Case reports and a literature review.

The commonest cause of blunt cardiac injuries is from traffic accidents followed by violent falls, sport activities, accidents or a fight but rupture of the heart is rare and lethal. The precise incidence of cardiac injury after a blunt chest trauma is unknown as rates vary greatly in the literature from between 7% and 76% of cases. Autopsy studies have shown that the right ventricle is the most frequently ruptured, followed by the left ventricle, right atrium, intraventricular septum, left atrium and interatrial septum with decreasing frequency. Post-mortem imaging is a rapidly advancing field of post-mortem investigations of trauma victims. The available literature dealing with the comparison of post-mortem computed tomography results with forensic autopsy indicates that conventional autopsy remains superior for the detection of organ and soft tissue injuries in all body regions.

Utility of post mortem computed tomography in clivus fracture diagnosis. Case illustration and literature review.

Clivus fractures are usually associated with head blunt trauma due to traffic accident and falls. A 23 - year-old man died immediately after a smash-up while he was stopping on his motorcycle. Post-mortem Computed tomography (PMCT), performed before autopsy, revealed a complex basilar skull base fractures associated with brainstem and cranio-vertebral junction injuries, improving the diagnostic performance of conventional autopsy. Imaging data were re-assessable and PMCT offers the possibility to perform multiplanar and volume rendered reconstructions, increasing forensic medicine knowledge related to traumatic injuries.

Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: potential use in companion animals.

Endocannabinoids have analgesic/anti-inflammatory properties. The biology of endocannabinoids, their receptors, signalling mechanisms and role in the regulation of physiological processes have been extensively reviewed. This review focuses on the role of palmitoylethanolamide (PEA), an endogenous fatty acid amide analogue of the endocannabinoid anandamide, in tissue protective mechanisms. PEA was first identified almost five decades ago in lipid extracts of various natural products, and its anti-inflammatory and antinociceptive effects were established later. Evidence exists that PEA is synthesised during inflammation and tissue damage and a number of beneficial effects, including the relief of inflammation and pruritus, have been shown to be useful in the control of neurogenic and neuropathic pain. The postulated hypotheses as to the mode of action of PEA include a possible local autacoid-like mediator activity regulating mast-cell activity and putative activation of cannabinoids and vanilloid TRPV1 receptors via "entourage" effects. The large number of scientific investigations into the effects of PEA and PEA-related compounds has given rise to new therapeutic opportunities. In spite of the multitude of therapies currently employed to control inflammation, pain, pruritus and tissue damage, the possibility of using a natural compound, such as PEA to manipulate endogenous protective mechanisms may be considered a beneficial novel therapeutic strategy in veterinary medicine.