Poly(2-oxazoline)/saRNA Polyplexes for Targeted and Nonviral Gene Delivery.

RNA delivery has been demonstrated to be a potent method of vaccine delivery, as demonstrated by the recent success of the COVID-19 vaccines. Polymers have been shown to be effective vehicles for RNA delivery, with poly(ethylene imine) (PEI) being the current gold standard for delivery. Nonetheless, PEI has toxicity concerns, and so finding alternatives is desirable. Poly(2-oxazoline)s are a promising alternative to PEI, as they are generally biocompatible and offer a high degree of control over the polymer structure. Here, we have synthesized an ionizable primary amine 2-oxazoline and combined it with a double bond containing oxazoline to synthesize a small library of charged statistical and block copolymers. The pendant double bonds were reacted further to decorate the polymers with glucose via a thiol-ene click reaction. All polymers were shown to have excellent cell viability, and the synthesized block polymers showed promising complexation efficiencies for the saRNA, demonstrating a clear structure-property relationship. The polymer transfection potential was tested in various cell lines, and a polymer composition with an amine/glucose ratio of 9:27 has demonstrated the best transfection potential across all cell lines tested. Overall, the results suggest that block polymers with a cationic segment and high levels of glycosylation have the best complexation efficiency and RNA expression levels.

Polymers without Petrochemicals: Sustainable Routes to Conventional Monomers.

Access to a wide range of plastic materials has been rationalized by the increased demand from growing populations and the development of high-throughput production systems. Plastic materials at low costs with reliable properties have been utilized in many everyday products. Multibillion-dollar companies are established around these plastic materials, and each polymer takes years to optimize, secure intellectual property, comply with the regulatory bodies such as the Registration, Evaluation, Authorisation and Restriction of Chemicals and the Environmental Protection Agency and develop consumer confidence. Therefore, developing a fully sustainable new plastic material with even a slightly different chemical structure is a costly and long process. Hence, the production of the common plastic materials with exactly the same chemical structures that does not require any new registration processes better reflects the reality of how to address the critical future of sustainable plastics. In this review, we have highlighted the very recent examples on the synthesis of common monomers using chemicals from sustainable feedstocks that can be used as a like-for-like substitute to prepare conventional petrochemical-free thermoplastics.

Comparison of Veterinary Student Ability to Learn 1-Handed and 2-Handed Techniques for Surgical Knot Tying.

OBJECTIVE: To determine which type of surgical hand-tie trainee surgeons learn most readily in a laboratory setting, using a combination of audiovisual demonstration and one-on-one teaching. STUDY DESIGN: Randomized controlled learning trial. SAMPLE POPULATION: Year 4 veterinary students in their 1st year of clinical training (n = 58). METHODS: Veterinary students entering clinical rotations were randomly allocated to 2 learning groups: 1-handed (28 students) or 2-handed (30 students) surgical ties. Knot tying technique was taught followed by three 15-minute practice sessions with student progress recorded by filming each student tying a square knot (2 throws). All 3 knot tying attempts were scored for technique and knot formation. Data on potential confounding factors between groups, including age and gender, were recorded. RESULTS: There were no significant differences between group scores for each attempt (1st attempt P = .5; 2nd P = .2; 3rd P = .19). Initially, scores indicated more rapid learning in the 1-handed group but fewer individuals achieved a perfect technique and knot after 60 minutes of learning (29/30 for 2-handed; 24/28 for 1-handed group). The 1-handed group was the most error-prone (after 45 minutes P < .01; after 60 min P < .01). CONCLUSIONS: Over 95% of students in the 2-handed group performed the technique and knot perfectly after 60 minutes learning time; were significantly less error-prone and fewer students continued to make corrected errors after 60 minutes. This evidence indicates that the 2-handed technique allows students to achieve success in a manageable teaching time.

Abnormal reflex activation of hamstring muscles in dogs with cranial cruciate ligament rupture.

The mechanisms underlying cranial cruciate ligament rupture (CCLR) in dogs are poorly understood. In this study hamstring muscle reflexes in response to cranial tibial translation were analysed to determine whether these active stabilisers of the stifle joint are differently activated in dogs with CCLR compared to control dogs. In a prospective clinical study reflex muscle activity from the lateral and medial hamstring muscles (biceps femoris and semimembranosus) was recorded using surface electrodes in control dogs (n=21) and dogs with CCLR (n=22). These electromyographic recordings were analysed using an algorithm previously validated in humans. The hamstring reflex was reliably and reproducibly recorded in normal dogs. Both a short latency response (SLR, 17.6±2.1ms) and a medium latency response (MLR, 37.7±2.7ms) could be identified. In dogs with unilateral CCLR, the SLR and MLR were not significantly different between the affected and the unaffected limbs, but the MLR latency of both affected and unaffected limbs in CCLR dogs were significantly prolonged compared to controls. In conclusion, the hamstring reflex can be recorded in dogs and the MLR is prolonged in dogs with CCLR. Since both affected and unaffected limbs exhibit prolonged MLR, it is possible that abnormal hamstring reflex activation is a mechanism by which progressive CCL damage may occur. The methodology allows for further investigation of the relationship between neuromuscular imbalance and CCLR or limitations in functional recovery following surgical intervention.

Use of the cumulative summation technique to quantitatively assess a surgical learning curve: canine total hip replacement.

OBJECTIVE: To quantitatively assess a surgical "learning curve" using the cumulative summation (CUSUM) score technique. STUDY DESIGN: Application of a CUSUM technique to a consecutive series of surgical cases. ANIMALS: Consecutive primary cemented total hip replacement (THR; n=116) in 106 dogs. METHODS: Records of all dogs that had primary canine THR were reviewed. Data retrieved included date of surgery, postoperative complications, and duration of follow-up. The 12-week outcome was analyzed graphically and with a CUSUM technique. RESULTS: One hundred and one (87%) procedures were "successful" and 15 (13%) developed major complications within 12 weeks (failures). The CUSUM chart clearly demonstrated an initial "learning curve" of ∼44 THR. CONCLUSION: The CUSUM technique can be used to demonstrate the learning curve for canine THR surgery.

Does the degree of preoperative subluxation or soft tissue tension affect the incidence of postoperative luxation in dogs after total hip replacement?

OBJECTIVE: To investigate whether preexisting coxofemoral subluxation/luxation predisposes to postoperative total hip replacement (THR) luxation. STUDY DESIGN: Case series. ANIMALS: Dogs (n=100) that had cemented THR (n=109); 23 normal controls. METHODS: A preliminary study was performed to validate our methods of assessing luxation and laxity by comparing dogs with severe hip dysplasia with a control population of normal dogs. For the main study, the records and radiographs of all dogs that had primary THR were reviewed. Measurements taken from preoperative radiographs to quantify hip subluxation/laxity included the Norberg angle, subluxation index, and 2 new measures: acetabular depth ratio (ADR) and dorsal acetabular rim ratio (DARR). Differences between groups that had luxation within 8 weeks and those that did not were investigated. RESULTS: Postoperative luxation occurred in 13 dogs (12%) within 8 weeks of surgery. Luxation was significantly associated with various measurements (including Norberg angle, ADR, DARR) thought to reflect degree of subluxation/soft tissue tension. CONCLUSION: Luxation after canine THR is a multifactorial problem but preexisting subluxation/soft tissue laxity is a significant risk factor for this complication.