Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that remains uncured. Its pathogenesis is characterized by the formation of ß-amyloid (Aß) plaques. The use of antigen-specific regulatory T cells (Tregs) through adoptive transfer has shown promise for the treatment of many inflammatory diseases, although the effectiveness of polyspecific Tregs is limited. Obtaining a sufficient number of antigen-specific Tregs from patients remains challenging. AIMS AND METHODS: To address this problem, we used an antibody-like single-chain variable fragment from a phage library and subsequently generated a chimeric antigen receptor (CAR) targeting ß-amyloid. RESULTS: The ß-amyloid-specific CARs obtained were stimulated by both recombinant and membrane-bound Aß isolated from the murine brain. The generated CAR-Tregs showed a normal Treg phenotype, were antigen-specific activatable, and had suppressive capacity. CONCLUSION: This study highlights the potential of CAR technology to generate antigen-specific Tregs and presents novel approaches for developing functional CARs.

Elizabethkingia miricola infection in multiple anuran species.

This report describes an outbreak of Elizabethkingia miricola in northern leopard frogs (Lithobates pipiens) and three other species of frogs and toads held in captivity in Germany. The authors examine several treatment options and underline the difficulties in treating larger numbers of individuals with antimicrobials applied through bathing. Whole genome sequencing of three bacterial isolates emphasizes their relatedness to other frog isolates and leads us to conclude that E. miricola is an emerging and difficult to treat pathogen with a broad host range across anuran species. Moreover, ambiguities in identification of flavobacteria associated with disease in frogs reported in the literature make it seem possible that E. miricola has been overlooked as an anuran pathogen in the past.

Effect of intraoperative positioning on postoperative neurological status in cats after perineal urethrostomy.

OBJECTIVES: The aim of this study was to evaluate and quantify the changes in neurological status in cats after perineal urethrostomy performed in dorsal and ventral recumbency. METHODS: This was a prospective, randomised study. Twenty male castrated cats with feline lower urinary tract disease presented for perineal urethrostomy were enrolled in this study. Surgery was performed in either dorsal recumbency (group A) or ventral recumbency (group B). Motor response of patellar tendon, gastrocnemius muscle, pelvic limb withdrawal and perineal reflexes, as well as the presence of spinal pain in the lumbosacral region, motor function of the tail and faecal continence, were examined before surgery, and 24 h and 14 days after surgery. RESULTS: The animals had a mean weight of 5.07 ± 1.08 kg, with a mean age of 6.12 ± 1.85 years. Weight and age were not significantly different between groups A and B (both P = 0.897). All tested parameters of the neurological examination performed prior to surgery were considered normal in both groups (P = 1). The comparison between neurological examinations (perineal reflex and spinal pain) before and 24 h after surgery revealed a significantly decreased briskness of the perineal reflex and an increased occurrence of spinal pain 24 h after surgery (P = 0.043 and P = 0.031, respectively). However, the changes of aforementioned parameters were statistically insignificant (P = 0.249 and P = 0.141) between groups A and B. The other parameters (patellar tendon, pelvic limb withdrawal and gastrocnemius muscle reflexes, motor function of the tail and faecal continence) were statistically insignificant (P = 1) before surgery and 24 h after surgery, as well as between groups A and B 24 h after surgery. Results of all tested parameters were statistically insignificant (P = 1) before surgery and 14 days after surgery, as well as between groups A and B 14 days after surgery. CONCLUSIONS AND RELEVANCE: The briskness of the perineal reflex was significantly decreased and the occurrence of spinal pain significantly increased 24 h after surgery. A parallel with a low-grade positioning-dependent nerve injury as described in human medicine may be drawn. However, no positioning method was proven to be superior to the other.

Repair of a Tibiotarsal Fracture in a Pomeranian Goose ( Anser anser) With a Locking Plate.

A 2-year-old Pomeranian goose ( Anser anser) weighing 8.1 kg was examined because of non-weight-bearing lameness of the right limb. A closed, transverse, diaphyseal fracture of the distal third of the right tibiotarsus with a craniolateral displacement of the distal fragment was diagnosed radiographically. Surgery under general anesthesia was performed to repair the fracture with a 14-hole, 2.7-mm locking plate fixed with 6 screws in a bicortical manner. Two days later, the bird was fully weight-bearing on the leg. Radiographs performed 4 and 8 weeks after surgery showed good healing of the affected bone with an appropriate callus formation bridging the fracture line. Sixteen weeks after surgery, the patient was readmitted because of lameness exhibited while staying outside exposed to subzero (°C) temperatures. On the basis of this finding, heat conduction was postulated as the possible cause of lameness because it disappeared after implant removal. To the best our knowledge, this case represents the first report of a surgical repair of a tibiotarsal fracture with a locking plate in waterfowl.

REPAIR OF A FEMORAL FRACTURE IN A CONGO AFRICAN GREY PARROT ( PSITTACUS ERITHACUS ERITHACUS) WITH A PARACORTICAL-CLAMP-CERCLAGE TECHNIQUE.

A 1-yr-old female Congo African grey parrot ( Psittacus erithacus erithacus) was admitted with a lameness of the right pelvic limb. On the radiographs a closed, caudolaterally displaced, comminuted, diaphyseal fracture of the femur was diagnosed. Surgery under general anesthesia was performed in order to repair the fracture with a paracortical-clamp-cerclage technique. This straightforward and effective technique has been developed as a low-cost treatment for simple and comminuted diaphyseal fractures in dogs and cats. Fixation is obtained with clamps, shaped during surgery, and attached to the bone shaft with cerclage wire. This technique led to immediate weight-bearing, appropriate bone healing, and permanent fixation of the implants in the patient. To the best of the authors' knowledge, this case represents the first report of a surgical repair of a femoral fracture with a paracortical-clamp-cerclage technique in a bird.