A mathematical model of dynamics of cell populations in squamous epithelium after irradiation

Purpose: To develop multi-compartment mechanistic models of dynamics of stem and functional cell populations in epithelium after irradiation. Methods and materials: We present two models, with three (3C) and four (4C) compartments respectively. We use delay differential equations, and include accelerated proliferation, loss of division asymmetry, progressive death of abortive stem cells, and turnover of functional cells. The models are used to fit experimental data on the variations of the number of cells in mice mucosa after irradiation with 13 Gy and 20 Gy. Akaike information criteria (AIC) was used to evaluate the performance of each model. Results: Both 3C and 4C models provide good fits to experimental data for 13 Gy. Fits for 20 Gy are slightly poorer and may be affected by larger uncertainties and fluctuations of experimental data. Best fits are obtained by imposing constraints on the fitting parameters, so to have values that are within experimental ranges. There is some degeneration in the fits, as different sets of parameters provide similarly good fits. Conclusions: The models provide good fits to experimental data. Mechanistic approaches like this can facilitate the development of mucositis response models to nonstandard schedules/treatment combinations not covered by datasets to which phenomenological models have been fitted. Studying the dynamics of cell populations in multifraction treatments, and finding links with induced toxicity, is the next step of this work

Medication-related osteonecrosis of the jaw: a critical narrative review

Background: Nearly two decades have passed since a paradoxical reaction in the orofacial region to some bone modifying agents and other drugs was recognized, namely medication-related osteonecrosis of the jaw (MRONJ). Purpose: The aim of this manuscript was to critically review published data on MRONJ to provide an update on key terminology, concepts, and current trends in terms of prevention and diagnosis. In addition, our objective was to examine and evaluate the therapeutic options available for MRONJ. Methods: The authors perused the most relevant literature relating to MRONJ through a search in textbooks and published articles included in several databases for the years 2003–2021. Results and conclusions: A comprehensive update of the current understanding of these matters was elaborated, addressing these topics and identifying relevant gaps of knowledge. This review describes our updated view of the previous thematic blocks, highlights our current clinical directions, and emphasizes controversial aspects and barriers that may lead to extending the accumulating body of evidence related to this severe treatment sequela

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Identification of prognosis associated microRNAs in HNSCC subtypes based on TCGA dataset

Background and Objectives: Head and Neck Squamous Cell Carcinoma (HNSCC) includes cancers from the oral cavity, larynx, and oropharynx and is the sixth-most common cancer worldwide. MicroRNAs are small non-coding RNAs for which altered expression has been demonstrated in pathological processes, such as cancer. The objective of our study was to evaluate the different expression profile in HNSCC subtypes and the prognostic value that one or several miRNAs may have. Materials and Methods: Data from The Cancer Genome Atlas Program-Head and Neck Squamous Cell Carcinoma (TCGA-HNSCC) patients were collected. Differential expression analysis was conducted by edge R-powered TCGAbiolinks R package specific function. Enrichment analysis was developed with Diana Tool miRPath 3.0. Kaplan-Meier survival estimators were used, followed by log-rank tests to compute significance. Results: A total of 127 miRNAs were identified with differential expression level in HNSCC; 48 of them were site-specific and, surprisingly, only miR-383 showed a similar deregulation in all locations studied (tonsil, mouth, floor of mouth, cheek mucosa, lip, tongue, and base of tongue). The most probable affected pathways based on miRNAs interaction levels were protein processing in endoplasmic reticulum, proteoglycans in cancer (p < 0.01), Hippo signaling pathway (p < 0.01), and Transforming growth factor-beta (TGF-beta) signaling pathway (p < 0.01). The survival analysis highlighted 38 differentially expressed miRNAs as prognostic biomarkers. The miRNAs with a greater association between poor prognosis and altered expression (p < 0.001) were miR-137, miR-125b-2, miR-26c, and miR-1304. Conclusions: In this study we have determined miR-137, miR-125b-2, miR-26c, and miR-1304 as novel powerful prognosis biomarkers. Furthermore, we have depicted the miRNAs expression patterns in tumor patients compared with normal subjects using the TCGA-HNSCC cohort

Monetary valuation of recreational fishing in a restored estuary and implications for future management measures

Recreational fishing is considered a cultural ecosystem service, important in terms of the socio-economic benefits that it provides. In the Nerbioi estuary (northern Spain), investments in water treatment and the closure of polluting industries have led to several benefits such as improvements in water quality, fish abundance and richness and recreational fishing activity. Currently, this activity is performed along the whole estuary including areas that previously were severely polluted. Valuing the benefits of recreational fishing is crucial to support the management of the estuary. The economic valuation is performed using a multi-site travel cost analysis. In addition, the effect on welfare measures of future scenarios where environmental conditions and accessibility change is analysed. Results indicate that each recreational trip in Nerbioi has a use value of 14.98 euros, with an aggregate value of 1.12 M euros year-1 for the whole recreational fishers´ community. The simulated scenarios suggest that further environmental improvements would have a positive effect in the activity, increasing the current welfare by 7.5-11.5%. In contrast, worsening of environmental conditions and accessibility could translate into a welfare reduction up to 71%. The monetary use value of recreational fishing partially covers (4.7%) the costs of maintaining the environmental quality of the estuary (i.e. treatment plant maintenance costs)

Available patient-centered Internet information on peri-implantitis. Can our patients understand it?

Objectives: The aim of this study was to evaluate the quality, readability, and popularity of patient-oriented online information about peri-implantitis. Materials and methods: The term “peri-implantitis” was searched in Google® and in Yahoo!®. The first 100 websites of each search engine were considered for further analysis. Quality was measured by DISCERN tool, and JAMA benchmarks. Readability was analyzed by Flesch Reading Ease Score (FRES), Flesch-Kinkaid Reading Grade (FKRG), Gunning Fog index (GFI), and Simple Measure of Gobbledygook (SMOG) index. Popularity was assessed by Alexa Popularity Rank (APR). Results: Only 28 websites remained after applying the exclusion criteria. The median overall DISCERN rating was 2.0 [2.0–3.0], which demonstrates the low quality of the information related to peri-implantitis. None of the websites achieved all the four JAMA benchmarks. Legibility indices showed ranges within the scores of difficult to read (FRES, 37.3 [26.9–53.9]; FKRGL, 12.8 [10.5–15.4]; GFI, 15.3 [12.5–18.0]; and SMOG, 11.1 [8.8–13.0]). Median APR was 2,228,599.0 [302,352.0–8,125,885.5]. Conclusions: Available English-written e-health information on peri-implantitis is poor in terms of quality and the analyzed websites are beyond the reading level recommended for comprehension. The popularity measurement showed great divergences between different Web pages. Clinical relevance: Information about peri-implantitis on the Internet is difficult to read by patients, which they are not capable of understand

Autophagy in periodontal disease: Evidence from a literature review

Objective To summarize evidence and data relating to the implications of autophagy in periodontal disease (PD) and to describe potential nutraceuticals or pharmaceuticals that could modulate this cell death subtype. Design Literature searches of various electronic databases (Medline via PubMed, SCOPUS, Web of Science, and EMBASE) using appropriate keywords (e.g., periodontal disease, periodontitis, alveolar bone loss, periodontal infection, tooth loss, autophagy, programmed cell death, and type 2 cell death) were performed. Then, a comprehensive literature review of the current understanding of this link was elaborated. Results Autophagy plays a pivotal role in PD, and its regulation seems to be an interesting avenue for future periodontal research, according to several in vivo and in vitro reports. Conclusion Today’s research has ascertained the role of autophagy in PD, especially its role in the host’s defence against periodontal disease drivers. A bulk of the research recognised several pharmaceuticals and nutraceuticals that could potentially modulate this kind of cell death and serve as useful therapies. However, further research is warranted to reach a clinical translation, which could help in the discovery of novel host modulation therapies for PD

miRNAs expression of oral squamous cell carcinoma patients: validation of two putative biomarkers

microRNA expression patterns have provided new directions in the search of biomarkers with prognostic value and even in the search of novel therapeutic targets for several neoplasms. Specifically, miRNAs profiling in oral squamous cell carcinoma (OSCC) represents a web of intrigue in the study of oral carcinogenesis. The objective of the present study was twofold: 1. to analyze miRNA profiling and estimate related biological pathways and, 2. to assess miRNAs profiles prognostic values in a cohort of OSCC-affected patients. The first study phase comprised case-control groups: A) 8 OSCC-affected patients and 8 healthy controls. Microarray technology (Affymetrix miRNA Array Plate 4.1) was used for miRNAs expression profile. Deregulated miRNAs were studied using Diana Tools miRPath 3.0 to associate miRNA targets with molecular pathways via Kyoto Encyclopedia of Genes and Genomes (KEGG). In a second phase, 2 miRNAs chosen for the subsequent RT-qPCR validation were studied in a second OSSC cohort (n = 8). Microarray analysis identified 80 deregulated miRNAs (35 over-expressed and 45 under-expressed). Two miRNAs (miR-497-5p and miR-4417) were chosen for further validation via RT-qPCR. Prognostic analysis did not ascertain relevant relation between miR-497-5p or miR-4417 expression and clinical or pathological parameters, except high miR-4417 in the case of nodular affectation (P = .035) and diminished miR-497-5p radiotherapy-treated patients (P = .05). KEGG analysis revealed that deregulated miRNAs were implicated in several biological pathways such as Proteoglycans in cancer. Our data suggest an altered miRNAs profiling in OSCC-affected patients. We have verified the altered expression of miR-497-5p and miR-4417 in OSCC samples and related the deregulated miRNAs with the ‘proteoglycans in cancer’ pathway. Further longitudinal studies with large samples are warranted to confirm the present findings

miRNAs expression of oral squamous cell carcinoma patients: Validation of two putative biomarkers

microRNA expression patterns have provided new directions in the search of biomarkers with prognostic value and even in the search of novel therapeutic targets for several neoplasms. Specifically, miRNAs profiling in oral squamous cell carcinoma (OSCC) represents a web of intrigue in the study of oral carcinogenesis. The objective of the present study was twofold:The first study phase comprised case-control groups: A) 8 OSCC-affected patients and 8 healthy controls. Microarray technology (Affymetrix miRNA Array Plate 4.1) was used for miRNAs expression profile. Deregulated miRNAs were studied using Diana Tools miRPath 3.0 to associate miRNA targets with molecular pathways via Kyoto Encyclopedia of Genes and Genomes (KEGG). In a second phase, 2 miRNAs chosen for the subsequent RT-qPCR validation were studied in a second OSSC cohort (n = 8).Microarray analysis identified 80 deregulated miRNAs (35 over-expressed and 45 under-expressed). Two miRNAs (miR-497-5p and miR-4417) were chosen for further validation via RT-qPCR. Prognostic analysis did not ascertain relevant relation between miR-497-5p or miR-4417 expression and clinical or pathological parameters, except high miR-4417 in the case of nodular affectation (P = .035) and diminished miR-497-5p radiotherapy-treated patients (P = .05). KEGG analysis revealed that deregulated miRNAs were implicated in several biological pathways such as Proteoglycans in cancer.Our data suggest an altered miRNAs profiling in OSCC-affected patients. We have verified the altered expression of miR-497-5p and miR-4417 in OSCC samples and related the deregulated miRNAs with the 'proteoglycans in cancer' pathway. Further longitudinal studies with large samples are warranted to confirm the present findings