In vitro evaluation of a hybrid negative pressure system for wound therapy.

OBJECTIVE: The objective of this study was to assess whether negative pressure could be maintained accurately and repeatably with a wall-suction-based hybrid negative pressure wound therapy (h-NPWT) system by comparing it with a commercial negative pressure wound therapy (NPWT) device. STUDY DESIGN: In vitro experimental study. METHODS: A commercial NPWT device (control) and three h-NPWT devices, with 0, 3, and 6 meters of additional tubing using the hospital-wall suction (groups 1, 2, and 3 respectively), were applied sequentially to a commercial NPWT dressing on a silicone skin substrate and set to run at a continuous pressure of -125 mmHg. The pressure within the wound space was monitored at 10 second intervals for 24 h. The process was repeated five times for each group. RESULTS: The commercial NPWT device produced an average pressure variance of 3.02 mmHg, and the h-NPWT produced average variances of 4.38, 4.24 and 4.20 mmHg for groups 1, 2 and 3, respectively. All groups produced an average pressure within 0.15 mmHg of -125 mmHg over the 24-hour period, and the h-NPWT systems produced the smallest range with all values remaining within a ±5% variation from -125 mmHg. CONCLUSION: The h-NPWT system achieved negative pressures that were comparable to those of a commercial control NPWT device. The addition of tubing between the skin substrate and the canister did not affect the pressure applied at the wound site. CLINICAL SIGNIFICANCE: The h-NPWT device tested in this study can be considered as an alternative for negative wound therapy when a commercial device cannot be used.

One-step design of a stable variant of the malaria invasion protein RH5 for use as a vaccine immunogen.

Many promising vaccine candidates from pathogenic viruses, bacteria, and parasites are unstable and cannot be produced cheaply for clinical use. For instance, Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is essential for erythrocyte invasion, is highly conserved among field isolates, and elicits antibodies that neutralize in vitro and protect in an animal model, making it a leading malaria vaccine candidate. However, functional RH5 is only expressible in eukaryotic systems and exhibits moderate temperature tolerance, limiting its usefulness in hot and low-income countries where malaria prevails. Current approaches to immunogen stabilization involve iterative application of rational or semirational design, random mutagenesis, and biochemical characterization. Typically, each round of optimization yields minor improvement in stability, and multiple rounds are required. In contrast, we developed a one-step design strategy using phylogenetic analysis and Rosetta atomistic calculations to design PfRH5 variants with improved packing and surface polarity. To demonstrate the robustness of this approach, we tested three PfRH5 designs, all of which showed improved stability relative to wild type. The best, bearing 18 mutations relative to PfRH5, expressed in a folded form in bacteria at >1 mg of protein per L of culture, and had 10-15 °C higher thermal tolerance than wild type, while also retaining ligand binding and immunogenic properties indistinguishable from wild type, proving its value as an immunogen for a future generation of vaccines against the malaria blood stage. We envision that this efficient computational stability design methodology will also be used to enhance the biophysical properties of other recalcitrant vaccine candidates from emerging pathogens.

Cross-tolerance to biotic and abiotic stresses in plants: a focus on resistance to aphid infestation.

Plants co-evolved with an enormous variety of microbial pathogens and insect herbivores under daily and seasonal variations in abiotic environmental conditions. Hence, plant cells display a high capacity to respond to diverse stresses through a flexible and finely balanced response network that involves components such as reduction-oxidation (redox) signalling pathways, stress hormones and growth regulators, as well as calcium and protein kinase cascades. Biotic and abiotic stress responses use common signals, pathways and triggers leading to cross-tolerance phenomena, whereby exposure to one type of stress can activate plant responses that facilitate tolerance to several different types of stress. While the acclimation mechanisms and adaptive responses that facilitate responses to single biotic and abiotic stresses have been extensively characterized, relatively little information is available on the dynamic aspects of combined biotic/abiotic stress response. In this review, we consider how the abiotic environment influences plant responses to attack by phloem-feeding aphids. Unravelling the signalling cascades that underpin cross-tolerance to biotic and abiotic stresses will allow the identification of new targets for increasing environmental resilience in crops.

The validation of computed tomography derived radiodensity measurements of bone healing using histopathology.

BACKGROUND: The early identification of delayed bone healing or a non-union is vital for prompt treatment and superior patient outcomes. Current techniques rely heavily on operator skill for interpretation and hence their reliability and repeatability may be inconsistent. This study assessed the application of computed tomography (CT) derived densiometric measurements as a quantitative tool for the assessment of bone healing. METHODS: This prospective, longitudinal, method comparison study was performed using a recognised sheep tibial ostectomy model. Secondary bone healing was assessed at 2, 4, 6, and 8 weeks after the ostectomy was performed. CT densiometric measures of bone healing (Hounsfield units) were taken of the cis, trans, cranial and caudal cortices relative to the bone plate, with histological measurements (percentage of ossification) sourced from the same areas. Cis cortical densiometric data points were excluded from analysis due to significant beam hardening artefact from the bone plate (P < 0.001). A univariable linear regression was performed on the remaining data using averaged radiodensity (independent variable) and histomorphometric (dependent variable) measurements. RESULTS: The two measurements were significantly correlated (R2 = 0.623, P = 0.020) with a clear positive trend identified. CONCLUSION: This study suggests that radiodensity measurements may be a useful diagnostic and management tool for the monitoring of indirect bone healing.

The effect of appearance and functionality concerns, and weight status, on negative body image mental health literacy in women.

Few studies have investigated community knowledge and beliefs about negative body image. Yet, low rates of recognition and help-seeking for body image concerns have been reported. Given the prevalence of body image problems and associated mental health risks in women, the current online study investigated negative body image mental health literacy in 260 women aged 18 to 64 years recruited via Prolific. The mental health literacy paradigm was employed in a 2 × 2 experimental design in which the effect of a target's domain of body image concern (appearance versus body functionality) and weight status ("normal weight" versus "overweight") was assessed on problem recognition, beliefs, and help-seeking recommendations. Overall, low symptom recognition was observed, and ratings for beliefs and help-seeking suggested low levels of stigma. However, significantly greater sympathy and lifestyle support recommendations were observed in the overweight compared to normal weight condition, and a domain × weight interaction suggested significantly fewer negative emotional reactions in the appearance overweight condition compared to appearance normal weight, and functionality overweight, conditions. The findings suggest a need for education about body image independent of weight status in women. Future research would benefit from examining diverse samples, broader functionality concerns, and stigma.