Antimicrobial peptide RP-1 structure and interactions with anionic versus zwitterionic micelles

Topologically, platelet factor-4 kinocidins consist of distinct N-terminal extended, C-terminal helical, and interposing gamma-core structural domains. The C-terminal alpha-helices autonomously confer direct microbicidal activity, and the synthetic antimicrobial peptide RP-1 is modeled upon these domains. In this study, the structure of RP-1 was assessed using several complementary techniques. The high-resolution structure of RP-1 was determined by NMR in anionic sodium dodecyl sulfate (SDS) and zwitterionic dodecylphosphocholine (DPC) micelles, which approximate prokaryotic and eukaryotic membranes, respectively. NMR data indicate the peptide assumes an amphipathic alpha-helical backbone conformation in both micelle environments. However, small differences were observed in the side-chain orientations of lysine, tyrosine, and phenylalanine residues in SDS versus DPC environments. NMR experiments with a paramagnetic probe indicated differences in positioning of the peptide within the two micelle types. Molecular dynamics (MD) simulations of the peptide in both micelle types were also performed to add insight into the peptide/micelle interactions and to assess the validity of this technique to predict the structure of peptides in complex with micelles. MD independently predicted RP-1 to interact only peripherally with the DPC micelle, leaving its spherical shape intact. In contrast, RP-1 entered deeply into and significantly distorted the SDS micelle. Overall, the experimental and MD results support a preferential specificity of RP-1 for anionic membranes over zwitterionic membranes. This specificity likely derives from differences in RP-1 interaction with distinct lipid systems, including subtle differences in side chain orientations, rather than gross changes in RP-1 structure in the two lipid environments.     

Toxic heavy metals and other trace elements in foodstuffs from 12 different countries

A research program related to the assessment of toxic heavy metals and essential trace elements in foodstuffs has been carried out in 12 countries under the auspices of the IAEA. The main purpose of this program was to obtain data on the elemental concentrations of potentially toxic elements in foodstuffs in various countries, and to compare them with the maximum permissible levels specified in national legislation and international guidelines. High-priority elements for this study were As, Cd, Cr, Pb, Hg, and Se. Also of interest, but of lower priority, were Sb Cu, and Zn/ Emphasis was placed on the use of nuclear and nuclear-related analytical techniques, complemented by conventional methods, and on quality assurance.     

Gastrointestinal gas.

Complaints related to gastrointestinal gas are commonly encountered in clinical practice. Various therapies have been proposed, yet none has appeared to be extremely effective. A review of the literature revealed little hard evidence to support the use of simethicone, pancreatic enzymes, anticholinergic agents or antibiotics. Evidence supporting the use of prokinetic agents has been the strongest, and there may be a pathophysiologic basis for the use of these agents if the complaints are related to abnormal intestinal motility. The use of activated charcoal for adsorbing intestinal gas has been effective in healthy subjects but has not been properly investigated in patients with gas complaints. Dietary modification may be beneficial in certain cases. Additional controlled trials are necessary to clarify the issues in the treatment of this common problem.     

Strain persistence of invasive Candida albicans in chronic hyperplastic candidosis that underwent malignant change

Objectives: The aim of this study was to assess persistence and tissue invasion of Candida albicans strains isolated from a 65 year‐old patient with chronic hyperplastic candidosis (CHC), that subsequently developed into squamous cell carcinoma (SCC). Materials and Methods: C. albicans (n=7) were recovered from the oral cavity of the patient over seven years. Confirmation of CHC and SCC in this patient was achieved by histopathological examination of incisional biopsy tissue. DNA fingerprinting was performed on the seven isolates from the CHC patient together with a further eight isolates from patients with normal oral mucosa (n=2), chronic atrophic candidosis (n=1), SCC (n=1) and CHC (n=4). Genotyping involved the use of inter‐repeat PCR using the eukaryotic repeat primer 1251. Characterisation of the tissue invasive abilities of the isolates was achieved by infecting a commercially available reconstituted human oral epithelium (RHE; SkinEthic, Nice, France). After 24 h. C. albicans tissue invasion was assessed by histopathological examination. Results: DNA fingerprinting demonstrated strain persistence of C. albicans in the CHC patient over a seven year period despite provision of systemic antifungal therapy. The strain of C. albicans isolated from this patient was categorised as a high invader within the RHE compared to other isolates. Conclusions: Candidal strain persistence was evident in a patient with CHC over seven years. This persistence may be due to incomplete eradication from the oral cavity following antifungal therapy or subsequent recolonisation from other body sites or separate exogenous sources. The demonstration of enhanced in vitro tissue invasion by this particular strain may, in part, explain the progression to carcinoma.     

A Retrospective Study of Dermatophyte Infection in Newfoundland for the Period 1962-1968

The results of a survey of dermatophyte infection in New-foundland for the period 1962 to 1968 are presented. A steady annual rise in the number of specimen submissions is noted, with positive findings in an average of 21.7%. The contribution by source of specimens is recorded, and species distribution indicates that Microsporum canis has behaved in epidemic form whereas other species appear endemic. Trichophyton rubrum infection shows a steady annual increase. No cases of favus have been noted. The distribution of species by anatomical site is indicated.     

Comparison of two ActiGraph accelerometer generations in the assessment of physical activity in free living conditions

ABSTRACT: BACKGROUND: The aim of this study was to compare physical activity measured using GT1M ActiGraph and GT3X ActiGraph accelerometers in free living conditions. FINDINGS: Twenty-five adults wore GT1M and GT3X Actigraph accelerometers simultaneously during a typical weekday of activity. Data were uploaded from the monitor to a computer at the end of test (one day). Previously established thresholds were used for defining time spent at each level of physical activity, physical activity was assessed at varying intensities comparing data from the two accelerometers by ANOVA and Bland and Altman statistical analysis. The concordance correlation coefficient between accelerometers at each intensity level was 0.99. There were no significant differences between accelerometers at any of the activity levels. Differences between data obtained in minutes with the GT1M accelerometer and the GT3X monitor were to 0.56, 0.36, 0.52 and 0.44% for sedentary, light, moderate and vigorous, respectively. The Bland and Altman method showed good agreement between data obtained for the two accelerometers. CONCLUSIONS: Findings suggest that the two accelerometers provided similar results and therefore the GT3X may be used in clinical and epidemiological studies without additional calibration or validation studies.