Homozygous CADPS2 Mutations Cause Neurodegenerative Disease with Lewy Body-like Pathology in Parrots.

BACKGROUND: Several genetic models that recapitulate neurodegenerative features of Parkinson's disease (PD) exist, which have been largely based on genes discovered in monogenic PD families. However, spontaneous genetic mutations have not been linked to the pathological hallmarks of PD in non-human vertebrates. OBJECTIVE: To describe the genetic and pathological findings of three Yellow-crowned parrot (Amazona ochrocepahala) siblings with a severe and rapidly progressive neurological phenotype. METHODS: The phenotype of the three parrots included severe ataxia, rigidity, and tremor, while their parents were phenotypically normal. Tests to identify avian viral infections and brain imaging studies were all negative. Due to their severe impairment, they were all euthanized at age 3 months and their brains underwent neuropathological examination and proteasome activity assays. Whole genome sequencing (WGS) was performed on the three affected parrots and their parents. RESULTS: The brains of affected parrots exhibited neuronal loss, spongiosis, and widespread Lewy body-like inclusions in many regions including the midbrain, basal ganglia, and neocortex. Proteasome activity was significantly reduced in these animals compared to a control (P < 0.05). WGS identified a single homozygous missense mutation (p.V559L) in a highly conserved amino acid within the pleckstrin homology (PH) domain of the calcium-dependent secretion activator 2 (CADPS2) gene. CONCLUSIONS: Our data suggest that a homozygous mutation in the CADPS2 gene causes a severe neurodegenerative phenotype with Lewy body-like pathology in parrots. Although CADPS2 variants have not been reported to cause PD, further investigation of the gene might provide important insights into the pathophysiology of Lewy body disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Autologous platelet gel to treat chronic decubital ulcers: a randomized, blind controlled clinical trial in dogs.

OBJECTIVE: To determine the efficacy of topical application of the autologous platelet gel (PG) in canine chronic protracted decubital ulcers. STUDY DESIGN: Prospective, randomized, blind controlled clinical trial. ANIMALS: Dogs (n = 18) with bilateral chronic wounds caused by protracted decubitus ulcers. METHODS: For each dog, wound side was randomized to receive either platelet gel (group PG) every 5 days for 5 dressing changes, or paraffin gauzes dressings (group C), as negative control. Wound healing and wound surfaces were compared at admission and then evaluated every 5th day, until day 25. Outcome variables were: open wound area, reduction of open wound surface compared to admission and to each preceding dressing change, time to complete epithelialization. RESULTS: Significant differences in healing process were observed at day 5 and continued throughout the entire study period (P < .00001). At 25 days, mean percent reduction in wound area was 93.5% in group PG and 13.2% in group C (P < .00001). CONCLUSIONS: Appropriately prepared autologous PG, an inexpensive, readily available blood derivative, applied topically results in more rapid healing of chronic non-healing decubital ulcers in dogs than those treated by use of paraffin-impregnated gauzes.

Evaluation of Mud Worm (Polydora spp.) Infestation in Cupped (Crassostrea gigas) and Flat Oyster (Ostrea edulis) Broodstocks: Comparison between Magnetic Resonance Imaging and Computed Tomography.

The Polichete worms of the genus Polydora are considered very destructive for oysters, excavating channels in their shell and inducing oysters to create mud blisters in response to the irritation, interfering with their physiology and ethology. The parasite also causes important economic damage for oyster farmers, as products with a high degree of infestation cannot be commercialized. The present study aims to evaluate whether two non-invasive advanced diagnostic techniques, computed tomography scans (CT) and magnetic resonance imaging (MRI), are suitable to show the alterations induced by this parasite on live Crassostrea gigas and Ostrea edulis oyster broodstocks. A CT scan is also able to identify small lesions in the shell during the first stage of infection. MRI allows for the visualization of the advanced status of the lesions when blisters occupy the inner surface of the shell and can impact the health status and the economic value of the mollusk. Both techniques resulted in satisfactory spatial resolution, and no motion artifacts were reported, thus enabling the authors to faithfully visualize in vivo the damage caused by the parasite.

Ultrasound and Elastosonographic Features of the Patellar Ligament in Dogs Affected by Cranial Cruciate Ligament Disease.

This study aims to evaluate the morpho-functional change in the patellar ligament in dogs with cranial cruciate ligament disease. We hypothesized that it may show increased thickening and stiffness with increasing days from onset to diagnosis instead of trauma. Understanding this aspect has implications for the choice of timing for treating patients suffering from cranial cruciate ligament disease, as well as the contextualization of patellar ligament desmitis pictures after surgical treatment with tibial plateau leveling osteotomy or tibial tuberosity advancement. Thirty-three dogs affected by unilateral cranial cruciate disease were examined and divided into three groups based on the time elapsed from the onset of lameness to diagnosis: Group 1 (1-15 days), Group 2 (16-60 days), and Group 3 (over 60 days). Conventional B-mode ultrasonographic and elastosonographic examinations of the patellar ligament were performed without sedation for each dog. Upon ultrasonographic examination, all dogs showed modification in the echostructure of the patellar ligament. In addition, the patellar ligament tended to become harder with increasing days after disease, although there were no significant differences between groups. Our results show that as the time increases between the onset of cranial cruciate ligament disease and diagnosis and treatment, the patellar ligament progressively thickens and loses its elasticity.

Role of the Alteration in Calcium Homeostasis in Cell Death Induced by Clostridioides difficile Toxin A and Toxin B.

Clostridioides difficile (C. difficile), responsible for 15-25% of gastrointestinal infections, causes health problems mainly due to the toxic activity of toxins A and B (Tcds). These are responsible for its clinical manifestations, including diarrhea, pseudomembranous colitis, toxic megacolon and death, with a mortality of 5-30% in primary infection, that increase following relapses. Studies on Tcd-induced cell death have highlighted a key role of caspases, calpains, and cathepsins, with involvement of mitochondria and reactive oxygen species (ROS) in a complex signaling pathway network. The complex response in the execution of various types of cell death (apoptosis, necrosis, pyroptosis and pyknosis) depends on the amount of Tcd, cell types, and Tcd receptors involved, and could have as initial/precocious event the alterations in calcium homeostasis. The entities, peculiarities and cell types involved in these alterations will decide the signaling pathways activated and cell death type. Calcium homeostasis alterations can be caused by calcium influx through calcium channel activation, transient intracellular calcium oscillations, and leakage of calcium from intracellular stores. These increases in cytoplasmic calcium have important effects on all calcium-regulated molecules, which may play a direct role in several cell death types and/or activate other cell death effectors, such as caspases, calpains, ROS and proapoptotic Bcl-2 family members. Furthermore, some support for the possible role of the calcium homeostasis alteration in Tcd-induced cell death originates from the similarity with cytotoxic effects that cause pore-forming toxins, based mainly on calcium influx through plasma membrane pores.

Synovial Fluid Metabolome Can Differentiate between Healthy Joints and Joints Affected by Osteoarthritis in Horses.

Osteoarthritis (OA) is a common cause of lameness in sport horses with a significant economic impact. The prevention of OA is crucial since no effective treatment is available. This study aimed to apply untargeted metabolomic analysis to investigate the differences in synovial fluid (SF) composition between healthy and OA-affected joints in horses. SF collected from healthy (n.8) and OA (n.11) horses was analyzed using H-NMR analysis. Metabolomic analysis allowed 55 different metabolites to be identified and quantified in SF samples. Nineteen metabolites were found to be differently concentrated in OA compared to control horses. Synovial fluids from the OC group were found to be higher in 1,3-dihydroxyacetone but lower in tryptophan, phenylalanine, tyrosine, uridine, creatinine, creatine, glycine, choline, asparagine, glutamine, arginine, 3-hydroxybutyrate, valine, 2-hydroxyisovalerate, α-ketoisovaleric acid, 3-methyl-2-oxovalerate, 3-hydroxyisobutyrate, isoleucine, and methionine compared to the controls. A variety of SF metabolites significantly changed following joint disease, demonstrating the complex mechanism underlying osteoarthritis in horses and highlighting the value of applying the metabolomic approach in clinical research.

Fluorescent Light Energy in the Management of Multi Drug Resistant Canine Pyoderma: A Prospective Exploratory Study.

The increase in prevalence of staphylococcal antimicrobial resistance has been also associated with pyoderma in dogs, and prolonged antibiotic treatment, as often needed in severe cases of pyoderma, has been related to influencing possible development of multidrug resistance (MDR). Fluorescent light energy (FLE) has been indicated to improve pyoderma lesions as adjunct therapy to systemic antibiotics. In the present study, we evaluated the effect of FLE on clinical signs of MDR canine deep pyoderma (CDP) and interdigital furunculosis (CIF) when administered as solely management. Sixteen client-owned dogs affected by CIF (five dogs) and CDP (eleven dogs) were scored using a dedicated scoring system and received a single FLE applications twice weekly, until clinical resolution was achieved. Mean time to achieve complete resolution was 5.20 ± 3.56 weeks (median 3 weeks) for CIF cases and 4.18 ± 1.47 weeks (median 4 weeks) for CDP ones. FLE shows promise as an aid to managing clinical signs while reducing reliance on antibiotics for MDR CDP and CIF. In this study, FLE was responsible for the decrease in lesion scores and resolution of MDR pyoderma infection without any adjunct therapy, having a potential useful role to play in antibiotic stewardship programs, efficiently promoting complete clinical resolution of MDR lesions while optimizing the use of antibiotics.

Good Inter- and Intra-Observer Reliability for Assessment of Radiographic Femoral and Tibial Frontal and Sagittal Planes Joints Angles in Normal Cats.

OBJECTIVE: The aim of this study was to evaluate the inter- and intra-observer reliability of plain digital radiographs for assessing normal feline femoral and tibial joint reference angles in the sagittal and frontal planes. STUDY DESIGN: This was a cadaveric radiographic anatomical study. that involved 20 short-haired domestic adult cats. MATERIALS AND METHODS: Sagittal and frontal plane tibial and femoral joint angles of 40 limbs were measured twice by three observers with different levels of experience. Inter- and intraobserver reliability was determined by the intra-class correlation coefficient (ICC). An ICC > 0.75 was considered high correlation, 0.74 > ICC > 0.60 good correlation, 0.59 > ICC > 0.4 fair correlation and an ICC < 0.40 poor correlation. RESULTS: Mean ± standard deviation angles were anatomic lateral proximal femoral angle (aLPFA) 110.6 ± 3.6; anatomic lateral distal femoral angle (aLDFA) 91.9 ± 2.1; mechanical lateral proximal femoral angle; mLPFA (mLPFA) 107.3 ± 3.6; mechanical lateral distal femoral angle (mLDFA) 95.5 ± 1.7; femoral neck anteversion (FNA) 121.9 ± 4.1; anatomical caudal proximal femoral angle (aCPFA) 156.1 ± 3.9; anatomical caudal distal femoral angle (aCDFA) 101.4 ± 1.4; mechanical medial proximal tibial angle (mMPTA) 93.5 ± 1.2; mechanical medial distal tibial angle (mMDTA) 100.5 ± 2.3; mechanical cranial proximal tibial angle (mCrPTA) 113.1 ± 3.2; tibial plateau angle (TPA) 23.1 ± 3.2; mechanical cranial proximal tibial angle (mCrDTA) 86.7 ± 3.1.The intra-observer ICC indicated high correlation for 70% or more of the measurements. The inter-observer agreement among observers was high. These results show that the radiographic method for measuring femoral and tibial joint angles was good or high, except for FNA and mCrDTA. CONCLUSIONS: This study provides some radiographic anatomical and mechanical joint angles of the femurs and tibias of normal domestic short-haired cats. We found good reliability for both intra- and interobserver measurements.

Effects of Prunus cerasus L. Seeds and Juice on Liver Steatosis in an Animal Model of Diet-Induced Obesity.

The accumulation of adipose tissue increases the risk of several diseases. The fruits-intake, containing phytochemicals, is inversely correlated with their development. This study evaluated the effects of anthocyanin-rich tart cherries in diet-induced obese (DIO) rats. DIO rats were exposed to a high-fat diet with the supplementation of tart cherry seeds powder (DS) and seed powder plus juice (DJS). After 17 weeks, the DIO rats showed an increase of body weight, glycaemia, insulin, and systolic blood pressure. In the DS and DJS groups, there was a decrease of systolic blood pressure, glycaemia, triglycerides, and thiobarbituric reactive substances in the serum. In the DJS rats, computed tomography revealed a decrease in the spleen-to-liver attenuation ratio. Indeed, sections of the DIO rats presented hepatic injury characterized by steatosis, which was lower in the supplemented groups. In the liver of the DIO compared with rats fed with a standard diet (CHOW), a down-regulation of the GRP94 protein expression and a reduction of LC3- II/LC3-I ratio were found, indicating endoplasmic reticulum stress and impaired autophagy flux. Interestingly, tart cherry supplementation enhanced both unfolded protein response (UPR) and autophagy. This study suggests that tart cherry supplementation, although it did not reduce body weight in the DIO rats, prevented its related risk factors and liver steatosis.

Use of autologous platelet-rich plasma for a delayed consolidation of a tibial fracture in a young donkey.

A 9-month-old filly donkey was referred for a comminuted diaphyseal fracture of the right tibia. Surgical osteosynthesis, with multiple lag screws and a neutralization plate, was performed for anatomical reconstruction. Despite a good gait condition, delayed bone consolidation and a bone gap were evident on follow up radiographic evaluations. Due to delayed healing, autologous platelet-rich plasma (PRP) was injected on the surface of the tibia. Increased bone consolidation was evident on radiographs one month after the PRP injection. Progressive filling of both the fracture lines and bone gap continued during the six-month follow up. Clinical outcome was excellent. Autologous PRP should be considered as a practical adjuvant therapy in bone healing process in donkeys.

Bilateral cervical ribs in a mixed breed dog.

A 4-year-old intact female, mixed breed dog was presented with a complaint of dyspnea. Clinical examination revealed symptoms related to disease of the upper airways. Radiographic findings were consistent with tracheal collapse associated with anomalies involving the seventh cervical vertebra and the first ribs bilaterally. Radiographs were highly suggestive of cervical ribs; computed tomography and ultrasound examination allowed complete characterization and better localization of the anomalies with relationship to the adjacent muscle and vasculature. Cervical ribs are malformations widely described in human medicine, but only sporadically in dogs. Herein, we discuss etiological, clinical, diagnostic and therapeutic aspects of cervical ribs and possible correlations between the cervical ribs and other anatomical anomalies noted in this dog.

In vivo biocompatibility of p(HPMAm-lac)-PEG hydrogels hybridized with hyaluronan.

The present study reports on the biocompatibility in vivo after intramuscular and subcutaneous administration in Balb/c mice of vinyl sulphone bearing p(HPMAm-lac1-2)-PEG-p(HPMAm-lac1-2)/thiolated hyaluronic acid hydrogels, designed as novel injectable biomaterials for potential application in the fields of tissue engineering and regenerative medicine. Ultrasonography, used as a method to study hydrogel gelation and residence time in vivo, showed that, upon injection, the biomaterial efficiently formed a hydrogel by simultaneous thermal gelation and Michael Addition cross-linking forming a viscoelastic spherical depot at the injection site. The residence time in vivo (20 days) was found to be shorter than that observed in vitro (32 days), indicating that the injected hydrogel was resorbed not only by chemical hydrolysis but also by cellular metabolism and/or enzymatic activity. Systemic biocompatibility was tested by analysing routine haematological parameters at different time-points (7, 14 and 21 days after administration) and histology of the main organs, including the haematopoietic system. No statistically significant difference between parameters of the saline-treated group and those of the hydrogel-treated group was found. Importantly, a time-dependent decrease of important pro-inflammatory cytokines (TREM1 (Triggering Receptor Expressed on Myeloid cells-1), tumour necrosis factor-α and interleukin-1ß) in cultured bone marrow cells extracted from hydrogel treated mice was observed, possibly correlated to the anti-inflammatory effect of hyaluronic acid released in time as hydrogel degraded. Copyright © 2016 John Wiley & Sons, Ltd.