Viral infections in interferon-gamma receptor deficiency.

Interferon-gamma receptor deficiency is a recently described immunodeficiency that is associated with onset of severe mycobacterial infections in childhood. We describe the occurrence of symptomatic and often severe viral infections in 4 patients with interferon-gamma receptor deficiency and mycobacterial disease. The viral pathogens included herpes viruses, parainfluenza virus type 3, and respiratory syncytial virus. We conclude that patients with interferon-gamma receptor deficiency and mycobacterial disease have increased susceptibility to some viral pathogens

Microbial Shifts During Dental Biofilm Re-Development in the Absence of Oral Hygiene in Periodontal Health and Disease

Aim to monitor microbial shifts during dental biofilm re-development Methods Supra and subgingival plaque samples were taken separately from 28 teeth in 38 healthy and 17 periodontitis subjects at baseline and immediately after tooth cleaning. Samples were taken again from 7 teeth in randomly selected quadrants during 1, 2, 4 and 7 days of no oral hygiene. Samples were analyzed using checkerboard DNA-DNA hybridization. Species counts were averaged within subjects at each time point. Significant differences in counts between healthy and periodontitis subjects were sought using the Mann-Whitney test. Results Total supra and subgingival counts were significantly higher in periodontitis on entry and reached or exceeded baseline values after day 2. Supragingival counts of Veillonella parvula, Fusobacterium nucleatum ss vincentii and Neisseria mucosa increased from 2 to 7 days. Subgingival counts were greater for Actinomyces, green and orange complex species. Significant differences between groups in supragingival counts occurred for 17 of 41 species at entry, 0 at day 7; for subgingival plaque these values were 39/41 taxa at entry, 17/41 at day 7. Conclusions Supragingival plaque re-development was similar in periodontitis and health, but subgingival species recolonization was more marked in periodontitis

Early Microbial Succession in Re-Developing Dental Biofilms in Periodontal Health and Disease

Objective To determine the order of bacterial species succession in re-developing supra and subgingival biofilms. Methods Supra and subgingival plaque samples were taken separately from 28 teeth in 38 healthy and 17 periodontitis subjects immediately after professional cleaning. Samples were taken again from 7 teeth in randomly selected quadrants after 1, 2, 4 and 7 days of no oral hygiene and analyzed using checkerboard DNA-DNA hybridization. % DNA probe counts were averaged within subjects at each time point. Ecological succession was determined using a modified moving window analysis. Results Succession in supragingival biofilms from periodontitis and health was similar. At 1 day, Streptococcus mitis and Neisseria mucosa showed increased proportions, followed by Capnocytophaga gingivalis, Eikenella corrodens, Veillonella parvula and Streptococcus oralis at 1–4 days. At 4–7 days, Campylobacter rectus, Campylobacter showae, Prevotella melaninogenica and Prevotella nigrescens became elevated. Subgingival plaque redevelopment was slower and very different from supragingival. Increased proportions were first observed for S. mitis, followed by V. parvula and C. gingivalis and, at 7 days by Capnocytophaga sputigena and P. nigrescens. No significant increase in proportions of periodontal pathogens was observed in any of the clinical groups or locations. Conclusions There is a defined order in bacterial species succession in early supra and subgingival biofilm re-development after professional cleaning

Developments in injectable multiphasic biomaterials. The performance of microporous biphasic calcium phosphate granules and hydrogels

Calcium phosphate bioceramic granules associated with hydrosoluble polymers were developed as bone substitutes for various maxillofacial and orthopaedic applications. These injectable bone substitutes, support and regenerate bone tissue and resorb after implantation. The efficiency of these multiphasic materials is due to the osteogenic and osteoconductive properties of the microporous biphasic calcium phosphate. The associated hydrosoluble polymers are considered as carriers in order to achieve the rheological properties of injectable bone substitutes (IBS). In this study, we used 2 semi synthetic hydrosoluble polymers of polysaccharidic origin. The hydroxy propyl methyl cellulose (HPMC), with and without silane, was combined with microporous BCP granules. The presence of silane induced considerable gelation of the suspension. The 2 IBS used (without gelation, IBS1, with gelation, IBS2) were implanted in critical size femoral epiphysis defects in rabbits. No foreign body reactions were observed in either sample. However, because of the higher density from gelation, cell colonisation followed by bone tissue ingrowth was delayed over time with IBS2 compared to the IBS1 without gelation. The results showed resorption of the BCP granule and bone ingrowth at the expense of both IBS with different kinetics. This study demonstrates that the hydrogel cannot be considered merely as a carrier. The gelation process delayed cell and tissue colonisation by slow degradation of the HPMC Si, compared to the faster release of HPMC with IBS1, in turn inducing faster permeability and spaces for tissue ingrowth between the BCP granules

Comparison of Microbial Changes in Early Re-Developing Biofilms on Natural Teeth and Dentures

Background and objective Surfaces and fluids can affect oral bacterial colonization. The aim of this study was to compare re-developing biofilms on natural teeth and dentures. Methods Supragingival plaque samples were taken from 55 dentate subjects and the denture teeth of 62 edentulous subjects before and after professional cleaning. Also, samples from 7 “teeth” in randomly selected quadrants were collected after 1, 2, 4 and 7 days of no oral hygiene. Samples were analyzed using checkerboard DNA-DNA hybridization. Counts and proportions of 41 bacterial taxa were determined at each time point and significant differences were sought using the Mann-Whitney test. Ecological succession was determined using a modified moving window analysis. Results Mean total DNA probe counts were similar pre-cleaning but were higher in dentate subjects at all post-cleaning visits (pStreptococcus mitis, Streptococcus oralisand Streptococcus mutans, whereas dentate subjects had higher proportions of Tannerella forsythia, Selenomonas noxia and Neisseria mucosa. By 2 days, mean counts of all taxa were higher in natural teeth and most remained higher at 7 days (pS. mitis and S. oralis by 1 day. N. mucosa, Veillonella parvula and Eikenella corrodens increased in both groups but later in edentate samples. Conclusions “Mature” natural and denture teeth biofilms have similar total numbers of bacteria but different species proportions. Post-cleaning biofilm re-development is more rapid and more complex on natural than denture teeth

Mitochondrial Superoxide Dismutase Overexpression and Low Oxygen Conditioning Hormesis Improve the Performance of Irradiated Sterile Males

The Sterile Insect Technique (SIT) is a successful autocidal control method that uses ionizing radiation to sterilize insects. However, irradiation in normal atmospheric conditions can be damaging for males, because irradiation generates substantial biological oxidative stress that, combined with domestication and mass-rearing conditions, may reduce sterile male sexual competitiveness and quality. In this study, biological oxidative stress and antioxidant capacity were experimentally manipulated in Anastrepha suspensa using a combination of low-oxygen conditions and transgenic overexpression of mitochondrial superoxide dismutase (SOD2) to evaluate their role in the sexual behavior and quality of irradiated males. Our results showed that SOD2 overexpression enhances irradiated insect quality and improves male competitiveness in leks. However, the improvements in mating performance were modest, as normoxia-irradiated SOD2 males exhibited only a 22% improvement in mating success compared to normoxia-irradiated wild type males. Additionally, SOD2 overexpression did not synergistically improve the mating success of males irradiated in either hypoxia or severe hypoxia. Short-term hypoxic and severe-hypoxic conditioning hormesis, per se, increased antioxidant capacity and enhanced sexual competitiveness of irradiated males relative to non-irradiated males in leks. Our study provides valuable new information that antioxidant enzymes, particularly SOD2, have potential to improve the quality and lekking performance of sterile males used in SIT programs

Improved human observer performance in digital reconstructed radiograph verification in head and neck cancer radiotherapy.

Purpose: Digitally reconstructed radiographs (DRRs) are routinely used as an a priori reference for setup correction in radiotherapy. The spatial resolution of DRRs may be improved to reduce setup error in fractionated radiotherapy treatment protocols. The influence of finer CT slice thickness reconstruction (STR) and resultant increased resolution DRRs on physician setup accuracy was prospectively evaluated. Methods: Four head and neck patient CT-simulation images were acquired and used to create DRR cohorts by varying STRs at 0.5, 1, 2, 2.5, and 3 mm. DRRs were displaced relative to a fixed isocenter using 0–5 mm random shifts in the three cardinal axes. Physician observers reviewed DRRs of varying STRs and displacements and then aligned reference and test DRRs replicating daily KV imaging workflow. A total of 1,064 images were reviewed by four blinded physicians. Observer errors were analyzed using nonparametric statistics (Friedman’s test) to determine whether STR cohorts had detectably different displacement profiles. Post hoc bootstrap resampling was applied to evaluate potential generalizability. Results: The observer-based trial revealed a statistically significant difference between cohort means for observer displacement vector error (p = 0.02) and for Z-axis (p < 0.01). Bootstrap analysis suggests a 15% gain in isocenter translational setup error with reduction of STR from 3 mm to ≤2 mm, though interobserver variance was a larger feature than STR-associated measurement variance. Conclusions: Higher resolution DRRs generated using finer CT scan STR resulted in improved observer performance at shift detection and could decrease operator-dependent geometric error. Ideally, CT STRs ≤2 mm should be utilized for DRR generation in the head and break neck

Prevalence of trypanosomes, salivary gland hypertrophy virus and Wolbachia in wild populations of tsetse flies from West Africa

Background: Tsetse flies are vectors of African trypanosomes, protozoan parasites that cause sleeping sickness (or human African trypanosomosis) in humans and nagana (or animal African trypanosomosis) in livestock. In addition to trypanosomes, four symbiotic bacteria Wigglesworthia glossinidia, Sodalis glossinidius, Wolbachia, Spiroplasma and one pathogen, the salivary gland hypertrophy virus (SGHV), have been reported in different tsetse species. We evaluated the prevalence and coinfection dynamics between Wolbachia, trypanosomes, and SGHV in four tsetse species (Glossina palpalis gambiensis, G. tachinoides, G. morsitans submorsitans, and G. medicorum) that were collected between 2008 and 2015 from 46 geographical locations in West Africa, i.e. Burkina Faso, Mali, Ghana, Guinea, and Senegal. Results: The results indicated an overall low prevalence of SGHV and Wolbachia and a high prevalence of trypanosomes in the sampled wild tsetse populations. The prevalence of all three infections varied among tsetse species and sample origin. The highest trypanosome prevalence was found in Glossina tachinoides (61.1%) from Ghana and in Glossina palpalis gambiensis (43.7%) from Senegal. The trypanosome prevalence in the four species from Burkina Faso was lower, i.e. 39.6% in Glossina medicorum, 18.08%; in Glossina morsitans submorsitans, 16.8%; in Glossina tachinoides and 10.5% in Glossina palpalis gambiensis. The trypanosome prevalence in Glossina palpalis gambiensis was lowest in Mali (6.9%) and Guinea (2.2%). The prevalence of SGHV and Wolbachia was very low irrespective of location or tsetse species with an average of 1.7% for SGHV and 1.0% for Wolbachia. In some cases, mixed infections with different trypanosome species were detected. The highest prevalence of coinfection was Trypanosoma vivax and other Trypanosoma species (9.5%) followed by coinfection of T. congolense with other trypanosomes (7.5%). The prevalence of coinfection of T. vivax and T. congolense was (1.0%) and no mixed infection of trypanosomes, SGHV and Wolbachia was detected. Conclusion: The results indicated a high rate of trypanosome infection in tsetse wild populations in West African countries but lower infection rate of both Wolbachia and SGHV. Double or triple mixed trypanosome infections were found. In addition, mixed trypanosome and SGHV infections existed however no mixed infections of trypanosome and/or SGHV with Wolbachia were found

STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles

A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi, but compared to their CD57− PD-1hi counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57− PD-1+ counterparts, but have a prominent cytotoxic phenotype. By analysis of responses to STAT3-dependent cytokines and cells from patients with gain- or loss-of-function STAT3 mutations, we show that CD4+ T cell cytotoxicity is STAT3-dependent. TFH formation also requires STAT3, but paradoxically, once formed, PD-1hi cells become unresponsive to STAT3. These findings suggest that changes in blood and germinal center cytotoxicity might be affected by changes in STAT3 signaling, or modulation of PD-1 by therapy.This work was supported by National Health and Medical Research Council (Australia) program grants APP1016953 and APP427620 (CGV, CCG, SGT, MCC)