Anti-infectives in Drug Delivery-Overcoming the Gram-Negative Bacterial Cell Envelope.

Infectious diseases are becoming a major menace to the state of health worldwide, with difficulties in effective treatment especially of nosocomial infections caused by Gram-negative bacteria being increasingly reported. Inadequate permeation of anti-infectives into or across the Gram-negative bacterial cell envelope, due to its intrinsic barrier function as well as barrier enhancement mediated by resistance mechanisms, can be identified as one of the major reasons for insufficient therapeutic effects. Several in vitro, in silico, and in cellulo models are currently employed to increase the knowledge of anti-infective transport processes into or across the bacterial cell envelope; however, all such models exhibit drawbacks or have limitations with respect to the information they are able to provide. Thus, new approaches which allow for more comprehensive characterization of anti-infective permeation processes (and as such, would be usable as screening methods in early drug discovery and development) are desperately needed. Furthermore, delivery methods or technologies capable of enhancing anti-infective permeation into or across the bacterial cell envelope are required. In this respect, particle-based carrier systems have already been shown to provide the opportunity to overcome compound-related difficulties and allow for targeted delivery. In addition, formulations combining efflux pump inhibitors or antimicrobial peptides with anti-infectives show promise in the restoration of antibiotic activity in resistant bacterial strains. Despite considerable progress in this field however, the design of carriers to specifically enhance transport across the bacterial envelope or to target difficult-to-treat (e.g., intracellular) infections remains an urgently needed area of improvement. What follows is a summary and evaluation of the state of the art of both bacterial permeation models and advanced anti-infective formulation strategies, together with an outlook for future directions in these fields

Current concept of abdominal sepsis : WSES position paper

Peer reviewe

Willingness to treat drug dependence and depression: comparisons of future health professionals

Brian K Ahmedani1,2, Sheryl Pimlott Kubiak2, Carlos F Rios-Bedoya3, Maureen Mickus4, James C Anthony51Center for Health Services Research, Henry Ford Health System, Detroit, MI, USA; 2School of Social Work, Michigan State University, East Lansing, MI, USA; 3Department of Family Medicine, Michigan State University, East Lansing, MI, USA; 4Occupational Therapy, Western Michigan University, Kalamazoo, MI, USA; 5Department of Epidemiology, Michigan State University, East Lansing, MI, USAPurpose: Stigma-related feelings, including degree of enthusiasm and willingness to work with alcohol, drug, and mental disorder (ADM) patients, as well as anticipated success in such work, will be required for the United States to be successful in its new initiatives for ADM screening, brief intervention, and effective referral to treatment and rehabilitation services (SBIRT). This study investigates students of medicine and social work with respect to their stigma-related feelings and degree of enthusiasm or willingness to treat patients affected by alcohol dependence, nicotine dependence, or major depression. Inference is strengthened by an anonymous online survey approach, with use of randomized reinforcers to gain at least partial experimental control of nonparticipation biases that otherwise are present in student survey data.Material and methods: All students on required course rosters were asked to participate in a two-part in-class and online assessment; 222 participated, with a gradient of participation induced via randomly drawn reinforcers for online survey participation. Between-group comparisons were made with a multivariate generalized linear model and generalized estimating equations approach that adjusts for covariates.Results: Medical and social work students did not differ from each other with respect to their willingness to treat patients affected by major depression, alcohol dependence, or nicotine dependence, but together were less willing to treat nicotine and alcohol dependence-affected patients as compared to depression-affected patients. Personal history was not associated with the students' willingness to treat, but men were less willing to treat. Drawing strength from the randomized reinforcer experimental design nested within this survey approach, the study evidence suggests potential nonparticipation bias in standard surveys on this topic.Conclusion: These results indicate that future health professionals may prefer to treat depression as opposed to drug dependence conditions. For SBIRT success, curriculum change with educational interventions may be needed to increase willingness to treat patients with neuropsychiatric conditions such as drug dependence. Future research requires attention to a possible problem of nonparticipation bias in surveys of this type.Keywords: alcohol dependence, nicotine dependence, depression, health professionals, stigma&nbsp

Improving the Efficiency of Electrical Stimulation Activities After Spinal Cord Injury

In order to enhance spinal cord injury (SCI) rehabilitation programs using neuromuscular electrical stimulation (NMES) and functional electrical stimulation (FES) it is important to examine the manner in which muscle fibers are recruited and the dose–response relationship. A review of the literature suggests that premature force decline and early fatigue with NMES and FES activities may be alleviated with decreased current frequency and increased current intensity. Dose–response relationships with NMES and FES are dependent on the goals of interest as reversing muscle atrophy can be achieved with activities 2–3 times per week for 6 or more weeks while increasing bone mass is more limited and requires more intense activity with greater exercise frequency and duration, e.g., 3–5 days per week for at least 6–12 months. The best known protocol to elicit neurological improvement is massed practice activities-based restorative therapies (ABRT) (3–5 h per day for several weeks)