In vitro evaluation of novel antimicrobial coatings for surgical sutures using octenidine

Background: Sutures colonized by bacteria represent a challenge in surgery due to their potential to cause surgical site infections. In order to reduce these type of infections antimicrobially coated surgical sutures are currently under development. In this study, we investigated the antimicrobial drug octenidine as a coating agent for surgical sutures. To achieve high antimicrobial efficacy and required biocompatibility for medical devices, we focused on optimizing octenidine coatings based on fatty acids. For this purpose, antimicrobial sutures were prepared with either octenidine-laurate or octenidine-palmitate at 11, 22, and 33 mu g/cm drug concentration normalized per length of sutures. Octenidine containing sutures were compared to the commercial triclosan-coated suture Vicryl (R) Plus. The release of octenidine into aqueous solution was analyzed and long-term antimicrobial efficacy was assessed via agar diffusion tests using Staphylococcus aureus. For determining biocompatibility, cytotoxicity assays (WST-1) were performed using L-929 mouse fibroblasts. Results: In a 7 days elution experiment, octenidine-palmitate coated sutures demonstrated much slower drug release (11 mu g/cm: 7 %;22 mu g/cm: 5 %;33 mu g/cm: 33 %) than octenidine-laurate sutures (11 mu g/cm: 82 %;22 mu g/cm: 88 %;33 mu g/cm: 87 %). Furthermore sutures at 11 mu g/cm drug content were associated with acceptable cytotoxicity according to ISO 10993-5 standard and showed, similar to Vicryl (R) Plus, relevant efficacy to inhibit surrounding bacterial growth for up to 9 days. Conclusions: Octenidine coated sutures with a concentration of 11 mu g/cm revealed high antimicrobial efficacy and biocompatibility. Due to their delayed release, palmitate carriers should be preferred. Such coatings are candidates for clinical testing in regard to their safety and efficacy

Effect of a Novel Nonviral Gene Delivery of BMP-2 on Bone Healing

Background. Gene therapeutic drug delivery approaches have been introduced to improve the efficiency of growth factors at the site of interest. This study investigated the efficacy and safety of a new nonviral copolymer-protected gene vector (COPROG) for the stimulation of bone healing. Methods. In vitro, rat osteoblasts were transfected with COPROG + luciferase plasmid or COPROG + hBMP-2 plasmid. In vivo, rat tibial fractures were intramedullary stabilized with uncoated versus COPROG+hBMP-2-plasmid-coated titanium K-wires. The tibiae were prepared for biomechanical and histological analyses at days 28 and 42 and for transfection/safety study at days 2, 4, 7, 28, and 42. Results. In vitro results showed luciferase expression until day 21, and hBMP-2-protein was measured from day 2 – day 10. In vivo, the local application of hBMP-2-plasmid showed a significantly higher maximum load after 42 days compared to that in the control. The histomorphometric analysis revealed a significantly less mineralized periosteal callus area in the BMP-2 group compared to the control at day 28. The rt-PCR showed no systemic biodistribution of luciferase RNA. Conclusion. A positive effect on fracture healing by nonviral BMP-2 plasmid application from COPROG-coated implants could be shown in this study; however, the effect of the vector may be improved with higher plasmid concentrations. Transfection showed no biodistribution to distant organs and was considered to be safe

Predictors of pneumococcal carriage and the effect of the 13-valent pneumococcal conjugate vaccination in the Western Australian Aboriginal population

Background: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced to prevent invasive pneumococcal disease (IPD) in Western Australian (WA) Aboriginal people in 2001. PCV13 replaced PCV7 in July 2011, covering six additional pneumococcal serotypes; however, IPD rates remained high in Aboriginal people in WA. Upper respiratory tract pneumococcal carriage can precede IPD, and PCVs alter serotype distribution. Methods: To assess the impact of PCV13 introduction, identify emerging serotypes, and assess risk factors for carriage, nasopharyngeal swabs and information on demographic characteristics, health, medication and living conditions from Aboriginal children and adults across WA from August 2008 to November 2014 were collected. Bacteria were cultured using selective media and pneumococcal isolates were serotyped by Quellung reaction. Risk factors were analysed by multivariable logistic regression. Results: One thousand five hundred swabs pre- and 1385 swabs post-PCV13 introduction were collected. Pneumococcal carriage was detected in 66.8% of children 53.2% of 5–14 year-olds post-PCV13, compared with pre-PCV13 prevalence of 72.2% and 49.4%, respectively. The prevalence of PCV13-non-PCV7 serotypes decreased in children 13.5% pre-PCV13 to 5.8% post-PCV13 (p \u3c 0.01), and from 8.4% to 6.1% in children 5–14 years old (p \u3e 0.05). The most common serotypes post-PCV13 were 11A (prevalence 4.0%), 15B (3.5%), 16F (3.5%), and 19F (3.2%). Risk of detection of pneumococcal carriage increased until age 12 months (odds ratio [OR] 4.19, 95% confidence interval [CI] 2.39–7.33), with nasal discharge (OR 2.49 [95% CI 2.00–3.09]), residence in a remote community (OR 2.21 [95% CI 1.67–2.92]) and household crowding (OR 1.36 [95% CI 1.11–1.67]). Recent antibiotic use was negatively associated with pneumococcal carriage (OR 0.48 [95% CI 0.33–0.69]). Complete resistance to penicillin was present among isolates of serotypes 19A (6.0%), 19F (2.3%) and non-serotypeable isolates (1.9%). Serotype 23F and newly emerged serotype 7B isolates showed high rates of resistance to cotrimoxazole, erythromycin and tetracycline (86.9%, 86.9%, 82.0%, respectively for 23F, 100.0%, 100.0% and 93.3% for 7B). Conclusion: Since PCV13 replaced PCV7, carriage of PCV13-non-PCV7 serotypes decreased significantly among childrenold, those most likely to have received PCV13, and to a lesser extent in older people. Known risk factors for carriage including crowding and young age remain in the Aboriginal population

High Nasopharyngeal Carriage of Non-Vaccine Serotypes in Western Australian Aboriginal People Following 10 Years of Pneumococcal Conjugate Vaccination

BackgroundInvasive pneumococcal disease (IPD) continues to occur at high rates among Australian Aboriginal people. The seven-valent pneumococcal conjugate vaccine (7vPCV) was given in a 2-4-6-month schedule from 2001, with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster at 18 months, and replaced with 13vPCV in July 2011. Since carriage surveillance can supplement IPD surveillance, we have monitored pneumococcal carriage in western Australia (WA) since 2008 to assess the impact of the 10-year 7vPCV program. MethodsWe collected 1,500 nasopharyngeal specimens from Aboriginal people living in varied regions of WA from August 2008 until June 2011. Specimens were cultured on selective media. Pneumococcal isolates were serotyped by the quellung reaction. ResultsStreptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were carried by 71.9%, 63.2% and 63.3% respectively of children <5 years of age, and 34.6%, 22.4% and 27.2% of people ≥5 years. Of 43 pneumococcal serotypes identified, the most common were 19A, 16F and 6C in children <5 years, and 15B, 34 and 22F in older people. 7vPCV serotypes accounted for 14.5% of all serotypeable isolates, 13vPCV for 32.4% and 23vPPV for 49.9%, with little variation across all age groups. Serotypes 1 and 12F were rarely identified, despite causing recent IPD outbreaks in WA. Complete penicillin resistance (MIC ≥2µg/ml) was found in 1.6% of serotype 19A (5.2%), 19F (4.9%) and 16F (3.2%) isolates and reduced penicillin susceptibility (MIC ≥0.125µg/ml) in 24.9% of isolates, particularly 19F (92.7%), 19A (41.3%), 16F (29.0%). Multi-resistance to cotrimoxazole, tetracycline and erythromycin was found in 83.0% of 23F isolates. Among non-serotypeable isolates 76.0% had reduced susceptibility and 4.0% showed complete resistance to penicillin.ConclusionsTen years after introduction of 7vPCV for Aboriginal Australian children, 7vPCV serotypes account for a small proportion of carried pneumococci. A large proportion of circulating serotypes are not covered by any currently licensed vaccine

Phonological facilitation of grammatical gender retrieval.

In Dutch, the gender of nouns is marked by the definite articles de (common gender) and het (neuter gender). Most models of language production assume that gender information is retrieved via the noun's syntactic representation (or lemma). The authors test Caramazza's (1997) alternative proposal, according to which gender information is retrieved via the noun's phonological word form (or lexeme). In three picture-word experiments, which differed in the tasks to be performed (noun production, article+noun production, article production, and gender decision), clear phonological effects were obtained in tasks involving the retrieval of the noun's gender information. It is argued that traditional models of language production have difficulty in accounting for the occurrence and/or the size of these effects whereas they follow quite naturally from Caramazza's (1997) Independent Network model. © 2004 Psychology Press Ltd

A survey of participants in two internet support groups for people with hair-pulling

BACKGROUND: A substantial number of patients suffering from psychological problems or psychiatric disorders have turned to internet support groups for help. This paper reports on the perceived effectiveness of trichotillomania (TTM) internet support groups for people suffering from hair-pulling. METHODS: A questionnaire was sent via e-mail to all subscribers of two mailing lists devoted to TTM, each of which takes a somewhat different approach to the condition. The questionnaire addressed the possible benefits and problems associated with belonging to a TTM virtual support group. RESULTS: Subscribers had similar demographic features as clinical samples of trichotillomania patients. Subscribers to both internet lists found them helpful in terms of feeling supported and in obtaining information. The different approaches to TTM on the two lists were associated with differences in treatments attempted by participants. CONCLUSION: Internet support groups can potentially contribute to increasing awareness about and knowledge of psychiatric disorders such as TTM, as well as to their management. Nevertheless, additional effort is required to ensure that subscribers are able to make informed, evidence-based decisions

One naive T cell, multiple fates in CD8+ T cell differentiation

The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of the development of single naive T cells into different subsets, we have developed a technology that introduces unique genetic tags (barcodes) into naive T cells. By comparing the barcodes present in antigen-specific effector and memory T cell populations in systemic and local infection models, at different anatomical sites, and for TCR–pMHC interactions of different avidities, we demonstrate that under all conditions tested, individual naive T cells yield both effector and memory CD8+ T cell progeny. This indicates that effector and memory fate decisions are not determined by the nature of the priming antigen-presenting cell or the time of T cell priming. Instead, for both low and high avidity T cells, individual naive T cells have multiple fates and can differentiate into effector and memory T cell subsets