Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive

Clinical trials of Treg therapy in transplantation are currently entering phases IIa and IIb, with the majority of these employing polyclonal Treg populations that harbor a broad specificity. Enhancing Treg specificity is possible with the use of chimeric antigen receptors (CARs), which can be customized to respond to a specific human leukocyte antigen (HLA). In this study, we build on our previous work in the development of HLA-A2 CAR-Tregs by further equipping cells with the constitutive expression of interleukin 10 (IL-10) and an imaging reporter as additional payloads. Cells were engineered to express combinations of these domains and assessed for phenotype and function. Cells expressing the full construct maintained a stable phenotype after transduction, were specifically activated by HLA-A2, and suppressed alloresponses potently. The addition of IL-10 provided an additional advantage to suppressive capacity. This study therefore provides an important proof-of-principle for this cell engineering approach for next-generation Treg therapy in transplantation.     

Severe Herpes Zoster Requiring Intravenous Antiviral Treatment in Allogeneic Hematopoietic Cell Transplantation Recipients on Standard Acyclovir Prophylaxis

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. The incidence, timing, and risk factors for severe herpes zoster (HZ) are not well described in the era of acyclovir (ACV) prophylaxis. We performed a retrospective cohort study of all patients who underwent first allogeneic HCT between October 2006 and December 2015 at our institution. Patients were followed until December 2017 for the development of severe HZ, defined as necessitating administration of i.v. antiviral medication. Out of 2163 patients who underwent allogeneic HCT, 22 (1.0%) developed severe HZ at a rate of 1 per 228 person-years, including dermatomal/multidermatomal disease (n = 5), disseminated skin disease (n = 5), HZ ophthalmicus (n = 4), meningitis/encephalitis (n = 4), pneumonia (n = 2), viremia (n = 1), and erythema multiforme (n = 1). Severe HZ infection occurred in a bimodal distribution during the early peri-HCT period and at 12 to 24 months post-HCT (median, 12.7 months). Twelve patients (54.5%) were compliant with ACV prophylaxis at the time of HZ diagnosis. Eleven patients (50%) died during the study period, only 2 of whom (9.1%) with active VZV infection. Mortality was higher in patients on immunosuppressive therapy (62.5% versus 16.7%; P = .045) and with concurrent graft-versus-host disease (75.0% versus 35.7%; P= .044). These data suggest that severe HZ remains an important consideration despite ACV prophylaxis.     

Potential Remineralization of Postorthodontic Demineralized Enamel and the Use of Enamel Microabrasion and Bleaching for Esthetics

Prevention of enamel demineralization during orthodontic treatment is of utmost importance. Should enamel demineralization occur (white spot lesions), early diagnosis and intervention is appropriate. Improved brushing with fluoridated dentifrice and over-the-counter fluoride rinses would be the first recommended intervention. If more aggressive intervention is considered to be necessary due to the extent of demineralized enamel or expected noncompliance with oral hygiene by the patient, professionally applied and/or prescribed fluorides are recommended. Likewise, casein phosphopeptide-amorphous calcium phosphate systems have demonstrated remineralization effects.     

Bacterial leakage along the implant-abutment interface of premachined or cast components

In recent clinical studies, contamination of the inner parts of dental implants through bacterial penetration along the implant components has been observed. The aim of the present in-vitro study was to investigate leakage of Fusobacterium nucleatum through the interface between implants and premachined or cast abutments. Both premachined (n=10) and cast (n=10) implant-abutment assemblies were inoculated with 3.0 microL of microbial inoculum. The assemblies were completely immersed in 5.0 mL of tryptic soy broth culture medium to observe leakage at the implant-abutment interface after 14 days of anaerobic incubation. Bacterial growth in the medium, indicative of microbial leakage, was found only in 1 out of 9 samples (11.1%) in each group. Both premachined and cast abutments connected to external hexagonal implants provide low percentages of bacterial leakage through the interface in in vitro unloaded conditions if the manufacturer's instructions and casting procedures are properly followed.     

Oral fluoride retention in saliva following toothbrushing with child and adult dentifrices with and without water rinsing

Ten healthy adult volunteers were recruited to participate in this double-blind randomised 18-leg crossover designed study. The subjects either rinsed their mouth with 10 ml de-ionised distilled water for 10 s or just spat out once after 1-min brushing with one of nine different toothpastes: NaF (500, 1,000 and 1,450 ppm F), SMFP (525, 1,000, 1,450 ppm F), AmF (250, 1,400 ppm F) or fluoride-free dentifrice. Samples of whole mixed unstimulated saliva were collected at different time intervals. The results showed that the use of the AmF toothpaste (1,400 ppm F) resulted in the highest fluoride content of saliva without water rinsing after 120 min (0.52 ppm F, CI 0.23, 0.81). Two hours after brushing with fluoride toothpaste containing AmF and NaF, the salivary fluoride levels were still higher than baseline levels.     

Microscopic qualitative evaluation of fixation time and decalcification media in rat maxillary periodontium

The rat model is widely used in periodontal research and the quality of histological sections is essential. The purpose of this study was to evaluate the histological characteristics of periodontal tissues in Wistar rat maxillae, with different times of fixation and decalcified by nitric acid or formic acid (Anna Morse Solution). Fifteen rats were used. Fixation was performed for 24, 48 and 72 hours. The maxillae were hemi-sectioned and each part was decalcified either in nitric acid for 7 days or in Anna Morse solution for 35 days. Two trained and blinded examiners performed the evaluation. Fourty eight hours of fixation and decalcification with Anna Morse solution showed more clear characteristics of the epithelium-connective tissue interface and of the periodontal structures. Mean measurements between the cementum-enamel junction and the bone crest varied in the different experimental times from 176.5 (+/- 60.45) to 210.94 (+/- 39.33) pixels on the buccal aspect, and from 199.69 (+/- 38.33) to 298.55 (+/-70.81) pixels on the palatal aspect, with no statistically significant differences (ANOVA, p > 0.05). In the same fixation period, decalcification with nitric acid or Anna Morse solution did not display any statistically significant differences. It may be concluded that for a qualitative histological analysis, fixation should preferably be for 48 hours and the demineralization should be made by Anna Morse solution. For a histomorphometric analysis, the decalcification solution does not interfere in the results.