Stapling of Peptides Potentiates the Antibiotic Treatment of Acinetobacter baumannii In Vivo

The rising incidence of multidrug resistance in Gram-negative bacteria underlines the urgency for novel treatment options. One promising new approach is the synergistic combination of antibiotics with antimicrobial peptides. However, the use of such peptides is not straightforward; they are often sensitive to proteolytic degradation, which greatly limits their clinical potential. One approach to increase stability is to apply a hydrocarbon staple to the antimicrobial peptide, thereby fixing them in an α-helical conformation, which renders them less exposed to proteolytic activity. In this work we applied several different hydrocarbon staples to two previously described peptides shown to act on the outer membrane, L6 and L8, and tested their activity in a zebrafish embryo infection model using a clinical isolate of Acinetobacter baumannii as a pathogen. We show that the introduction of such a hydrocarbon staple to the peptide L8 improves its in vivo potentiating activity on antibiotic treatment, without increasing its in vivo antimicrobial activity, toxicity or hemolytic activity

Anabolic resistance of muscle protein turnover comes in various shapes and sizes

Anabolic resistance is defined by a blunted stimulation of muscle protein synthesis rates (MPS) to common anabolic stimuli in skeletal muscle tissue such as dietary protein and exercise. Generally, MPS is the target of most exercise and feeding interventions as muscle protein breakdown rates seem to be less responsive to these stimuli. Ultimately, the blunted responsiveness of MPS to dietary protein and exercise underpins the loss of the amount and quality of skeletal muscle mass leading to decrements in physical performance in these populations. The increase of both habitual physical activity (including structured exercise that targets general fitness characteristics) and protein dense food ingestion are frontline strategies utilized to support muscle mass, performance, and health. In this paper, we discuss anabolic resistance as a common denominator underpinning muscle mass loss with aging, obesity, and other disease states. Namely, we discuss the fact that anabolic resistance exists as a dimmer switch, capable of varying from higher to lower levels of resistance, to the main anabolic stimuli of feeding and exercise depending on the population. Moreover, we review the evidence on whether increased physical activity and targeted exercise can be leveraged to restore the sensitivity of skeletal muscle tissue to dietary amino acids regardless of the population

The Role of Age, Education, and Digital Health Literacy in the Usability of Internet-Based Cognitive Behavioral Therapy for Chronic Pain:Mixed Methods Study

Contains fulltext : 215537.pdf (publisher's version ) (Open Access)BACKGROUND: Internet-based cognitive behavior therapy (iCBT) can be effective in mental and somatic health care. Research on the feasibility of internet interventions in clinical practice is, however, still scarce. Studies with a focus on the patient regarding usability of interventions and digital health literacy skills are especially lacking. OBJECTIVE: The goal of this study was to assess the usability of an iCBT for chronic pain, Master Your Pain, and the relationship between its usability outcomes and the factors age, educational level, and digital health literacy skills. The aims were to determine what changes were needed in the program for sufficient usability and which individual characteristics were related to the usability of the program. METHODS: Patients were recruited from two mental health care practices. A mixed methods approach was used in this study. A qualitative observational study comprising performance tasks in the iCBT program was used to test usability. A quantitative questionnaire was used to measure possible related constructs. Usability was operationalized as the number of tasks that could be completed and the type and number of problems that occurred while doing so. Performance tasks were set up to measure 6 digital skills: (1) operating the computer and internet browser, (2) navigation and orientation, (3) using search strategies, (4) evaluating relevance of content, (5) adding personal content, and (6) protecting and respecting privacy. Participants were asked to think aloud while performing the tasks, and screen activities and webcam recordings were captured. The qualitative observational data was coded using inductive analysis by two independent researchers. Correlational analyses were performed to test how usability relates to sociodemographics and digital health literacy. RESULTS: A total of 32 patients participated, with a mean age of 49.9 years and 84% (27/32) being female. All performance tasks except one (fill in a diary registration) could be completed independently by more than 50% of the participants. On operational, navigation, and search levels, participants struggled most with logging in, logging out, and finding specific parts of the intervention. Half of the sample experienced problems evaluating the relevance and adding content to the program to some extent. Usability correlated moderately negatively with age and moderately positively with digital health literacy skills but not with educational level. CONCLUSIONS: The results provide insight into what is essential for proper usability regarding the design of an iCBT program considering variations in age, educational level, and digital health literacy. Furthermore, the results provide insight into what type of support is needed by patients to properly use the intervention. Tailoring support among the needs of certain age groups or skill levels could be beneficial and could range from no extra support (only online feedback, as intended) to practical support (an additional usability introduction session) to blended care (combined face-to-face sessions throughout the therapy)