Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation. They are, likewise, involved in the induction and ...maintenance of immune tolerance in homeostatic conditions. Their phenotypic and functional heterogeneity points to their great plasticity and ability to modulate, according to their microenvironment, the acquired immune response and, at the same time, makes their precise classification complex and frequently subject to reviews and improvement. This review will present general aspects of the DC physiology and classification and will address their potential and actual uses in the management of human disease, more specifically cancer, as therapeutic and monitoring tools. New combination treatments with the participation of DC will be also discussed.
Ascariasis is the most prevalent zoonotic helminthic disease worldwide, and is responsible for nutritional deficiencies, particularly hindering the physical and neurological development of children. ...The appearance of anthelmintic resistance in Ascaris is a risk for the target of eliminating ascariasis as a public health problem by 2030 set by the World Health Organisation. The development of a vaccine could be key to achieving this target. Here we have applied an in silico approach to design a multi-epitope polypeptide that contains T-cell and B-cell epitopes of reported novel potential vaccination targets, alongside epitopes from established vaccination candidates. An artificial toll-like receptor-4 (TLR4) adjuvant (RS09) was added to improve immunogenicity. The constructed peptide was found to be non-allergic, non-toxic, with adequate antigenic and physicochemical characteristics, such as solubility and potential expression in Escherichia coli. A tertiary structure of the polypeptide was used to predict the presence of discontinuous B-cell epitopes and to confirm the molecular binding stability with TLR2 and TLR4 molecules. Immune simulations predicted an increase in B-cell and T-cell immune response after injection. This polypeptide can now be validated experimentally and compared to other vaccine candidates to assess its possible impact in human health.
Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly ...infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection. An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival. In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.
Summary
Background
Although the standard treatment for venous ulcers is compression, drugs may be used as adjunctive therapy. Simvastatin has shown potential wound‐healing properties; however, no ...studies have investigated its use in venous ulcers.
Objectives
To assess the efficacy and safety of simvastatin in venous ulcer healing when combined with standard treatment for ulcers.
Methods
This was a randomized, double‐blind, placebo‐controlled trial. Outcome measures were the proportion of healed ulcers, healing time, total surface area healed and Dermatology Life Quality Index (DLQI) scores.
Results
Sixty‐six patients were randomized into two groups: a simvastatin (n = 32) and a control (n = 34) group. Among ulcers ≤ 5 cm, 100% were healed in the simvastatin group, and 50% were healed in the control group relative risk (RR) 0·10, 95% confidence interval (CI) 0·0141–0·707. The average healing times for ulcers ≤ 5 cm were 6·89 ± 0·78 weeks and 8·40 ± 1·13 weeks for the simvastatin and control groups, respectively (P < 0·001). Among ulcers > 5 cm, 67% closed in the simvastatin group, with a mean healing time of 9·17 ± 1·07 weeks. No ulcers of this size closed in the control group (RR 0·33, 95% CI 0·132–0·840). The simvastatin group had lower DLQI scores (P < 0·001) post‐treatment. No adverse effects were documented.
Conclusions
Simvastatin 40 mg daily, in addition to standard wound care and compression, is associated with a significant improvement in healing rate and time, as well as an improved patient quality of life when compared with placebo in the management of venous ulcers.
What's already known about this topic?
The standard treatment for venous ulcers is compression therapy, but drugs may be used as adjunctive therapy to accelerate the healing process.
Statins are cholesterol‐lowering drugs that may also have pleiotropic effects, which accelerate wound healing. However, supporting evidence for this is mainly from animal studies.
There are no previous studies investigating the use of statins for venous ulcers.
What does this study add?
This is the first study to investigate the use of statins (simvastatin 40 mg daily) in venous ulcer healing.
This randomized, double‐blind, placebo‐controlled trial showed that simvastatin, in addition to standard wound care and compression, is associated with a significant improvement in healing rate and time, as well as an improved patient quality of life when compared with placebo in the management of venous ulcers. No adverse effects were documented.
Semiconductor quantum dot sensitized solar cells (QDSSCs) have rapidly been developed, and their efficiency has recently exceeded 9%. Their performances have mainly been achieved by focusing on ...improving short circuit photocurrent employing polysulfide electrolytes. However, the increase of open circuit photovoltage (V OC) cannot be expected with QDSSCs based on the polysulfide electrolytes owing to their relatively negative redox potential (around −0.65 V vs Ag/AgCl). Here, we demonstrate enhancement of the open circuit voltage by employing an alternative electrolyte, ferricyanide/ferrocyanide redox couple. The solar cell performance was optimized by investigating the influence of ferricyanide and ferrocyanide concentration on their interfacial charge transfer and transport kinetics. The optimized ferricyanide/ferrocyanide species concentrations (0.01/0.2 M) result in solar energy conversion efficiency of 2% with V OC of 0.8 V. Since the potential difference between the TiO2 conduction band edge at pH 7 and the electrolyte redox potential is about 0.79 V, although the conduction band edge shifts negatively under the negative bias application into the TiO2 electrode, the solar cell with the optimized electrolyte composition has nearly reached the theoretical maximum voltage. This study suggests a promising method to optimize an electrolyte composition for maximizing solar energy conversion efficiency.
The α4β7 integrin is a validated target in inflammatory bowel disease. This randomized, phase 2b, placebo-controlled, double-blind study evaluated the efficacy and safety of the anti-α4β7 antibody ...abrilumab in patients with moderate-to-severe ulcerative colitis despite treatment with conventional therapies.
Patients (total Mayo Score 6–12, recto-sigmoidoscopy score ≥2) with inadequate response or intolerance to conventional therapies were randomized to receive subcutaneous abrilumab (7, 21, or 70 mg) on day 1, weeks 2 and 4, and every 4 weeks; abrilumab 210 mg on day 1; or placebo. The primary end point was remission (total Mayo Score ≤2 points, no individual sub-score >1 point) for the 2 highest dosages at week 8. Key secondary end points were response and mucosal healing (centrally read) at week 8.
For 354 patients who received ≥1 dose of investigational product (placebo, n = 116; 7 mg, n = 21; 21 mg, n = 40; 70 mg, n = 98; 210 mg, n = 79), non-adjusted remission rates at week 8 were 4.3%, 13.3%, and 12.7% for the placebo and abrilumab 70-mg and 210-mg groups, respectively (P < .05 for 70 and 210 mg vs placebo); odds of achieving remission were significantly greater with abrilumab 70 mg (odds ratio 3.35; 90% CI 1.41–7.95; P = .021) and 210 mg (odds ratio 3.33; 90% confidence interval 1.34–8.26; P = .030) than with placebo. Response and mucosal healing rates with these dosages also were significantly greater than with placebo. Higher baseline α4β7 levels on naïve CD4+ T cells were a prognostic indicator for overall outcome, but not a predictive biomarker of abrilumab response. There were no cases of progressive multifocal leukoencephalopathy or deaths.
Abrilumab treatment for 8 weeks induced remission, clinical response, and mucosal healing in patients with moderate-to-severe ulcerative colitis. ClinicalTrials.gov, number NCT01694485.
Immunotherapy for cancer treatment has gained increased attention in recent years. Recently, our group reported the case of a patient with glioblastoma who underwent vaccination based on dendritic ...cells and experienced a strong Th1 immune response together with near-complete tumor remission. Here we report the results of a phase I/II prospective, non-controlled clinical trial with 37 patients harboring glioblastoma or grade 4 astrocytomas. At the time of first recurrence after surgery, patients began receiving monthly intradermal injections of allogenic DC-autologous tumor cell hybridomas. Overall survival, quality of life, and immunological profiles were assessed prospectively. Compared with patients in the Genomic Data Commons data bank, overall survival for vaccinated patients with glioblastoma was 27.6 ± 2.4 months (vs. 16.3 ± 0.7, log-rank
< 0.001, hazard ratio 0.53, 95%CI 0.36-0.78,
< 0.01), and it was 59.5 ± 15.9 for vaccinated astrocytoma grade 4 patients (vs. 19.8 ± 2.5, log-rank
< 0.05, hazard ratio 0.18, 95%CI 0.05-0.62,
< 0.01). Furthermore, seven vaccinated patients (two IDH-1-mutated and five wild type) remain alive at the time of this report (overall survival 47.9 months, SD 21.1, range: 25.4-78.6 months since diagnosis; and 34.2 months since recurrence, range: 17.8 to 40.7, SD 21.3). We believe that the data reported here can foster the improvement of treatment protocols for high-grade gliomas based on cellular immunotherapy.
Purpose
To investigate the direct and indirect pathways between verbal bullying and adverse oral conditions among school-aged children.
Methods
A cross-sectional survey was conducted with 8- to ...10-year-old children, enrolled in public schools in Southern Brazil. Verbal bullying was collected by self-reports. Independent variables included sociodemographic characteristics (sex, age, household income, and caregivers’ educational level) and oral conditions (anterior open bite, anterior teeth crowding, upper anterior diastema, large overjet, untreated dental caries, and PUFA index). The pathways between verbal bullying and the independent variables were analysed through structural equation modelling.
Results
1369 children were included. The prevalence of verbal bullying was 26.2% (95% confidence interval CI 23.9–28.6%). Verbal bullying was directly influenced by large overjet (standard coefficient SC 0.13,
P
< 0.01), untreated dental caries (SC 0.63,
P
= 0.01) and PUFA index (SC 0.75,
P
= 0.02). Sex (SC − 0.005,
P
= .04) and age (SC − 0.006,
P
< 0.01) indirectly influenced verbal bullying via untreated dental caries.
Conclusions
Verbal bullying was directly influenced by large overjet, untreated dental caries and PUFA index. Sex and age indirectly impacted verbal bullying through untreated dental caries.
The aim of this study was to compare periapical radiographs with cone beam CT (CBCT) imaging in detecting and localizing alveolar bone loss by comparing linear measurements of the height, depth and ...width of the defects and identifying combined bone defects in tomographic images.
The images were selected from a secondary database containing images of patients referred for periodontal evaluation. The sample consisted of 51 sites showing both horizontal and vertical bone loss, assessed by 3 trained examiners.
The results showed that there were no statistically significant differences between the imaging methods in terms of identification of the pattern of bone loss. However, there were differences between the two methods when the distance between the cemento-enamel junction (CEJ) and the alveolar crest (AC) was measured. When the distance between the CEJ and the deepest point and width of the defect were measured, the methods showed no statistically significant difference. In this study, 30.8% of the 39 teeth evaluated had combined bone defects.
The two methods differ when detecting the height of the alveolar bone crest but present similar views of the depth and width of bone defects. CBCT was the only method that allowed for an analysis of the buccal and lingual/palatal surfaces and an improved visualization of the morphology of the defect.
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