Quantification and Influence of IL-1ß on Pain and Inflammatory Response after Placement of a Cement-Screw-Retained Restoration.

Background: The objective of this study was to evaluate the pain and inflammatory response in soft tissues using healing and prosthetic abutments of different diameters and lengths. Methods: The study population was rehabilitated with Astra Tech EV single implants (Dentsply Sirona, Atlantis, Dentsply Sirona S.A., Barcelona, Spain) of 4.2 and 4.8 millimetres in diameter in the upper and lower maxilla and loaded with custom abutments digitally designed using Dentsply Sirona's Virtual Atlantis Design software (Atlantis WebOrder, Dentsply Sirona S.A., Barcelona, Spain), version 4.6.5. The custom abutments had a larger diameter than the healing abutments to evaluate for biomarkers through ELISA. Results: Rehabilitations in the mandible and with healing abutments with diameters less than 4.29 mm and rehabilitators with diameters less than 2.18 mm elicited a higher pain and inflammatory response and, in turn, higher interleukin-1ß values. Conclusions: Greater inflammation was evident in cases in which healing abutments with reduced diameter were used compared to the same subsequent rehabilitation with prosthetic abutments with larger diameters.

Retrospective Case-Control Study Genes Related to Bone Metabolism That Justify the Condition of Periodontal Disease and Failure of Dental Implants in Patients with down Syndrome.

Down syndrome patients show success rates in dental implants much lower than those observed in the general population. This retrospective case-control study aimed to identify possible genes that are related to the regulation of inflammatory responses and bone metabolism related to periimplantitis and implant loss, as well as genes related to bone quality. This process involved using the functional analysis of the gene expression software Transcriptome Analysis Console (TAC version 4.0 Applied BiosystemsTM, Thermo Fisher Scientific, Waltham, MA, USA) and a search for possible candidate genes involved. The focus was placed on the 93 genes related to periodontitis, periimplantitis, bone loss, implant loss, and genes related to bone quality and regulators underlying the establishment and maintenance of osseointegration. Five genes showed statistically significant results (p < 0.05) in our comparison. Four of them, IL1B (p = 0.023), IL1RN (p = 0.048), BGLAP (p = 0.0372) and PTK2 (p = 0.0075) were down-regulated in the periodontal disease and implant rejection group, and only one was overexpressed: FOXO1A (p = 0.0552). The genes with statistically significant alterations described in this article determine that the group of Down syndrome patients with periodontal disease and implant failure is a group of patients genetically susceptible to suffering from both conditions together.

Detection of NOTCH1 mutations in paraffin samples in patients with potentially malignant lesions.

Background: On certain occasions, oral cancer is preceded by potentially malignant lesions. The degree of dysplasia in Guinea pigs attempts to determine the risk of developing a malignant lesion. The search for genetic mutations, biomarkers, as a more truthful and reproducible diagnostic tool, tries to fill the gaps in the anatomopathological study. In this line, the present retrospective case-control study is based on the detection of known mutations of the NOTCH1 gene in biopsied samples of potentially malignant lesions from 22 patients who attend the Oral and Maxillofacial Surgery service of the Virgen del Rocío University Hospital. Material and Methods: DNA extraction after dewaxing of the samples using the Minikit QIAamp DNA FFPE tissue extraction kit with extraction kit (reference 56404) of QIAGEN. Subsequently, with the DNA obtained, 4 amplification reactions were carried out using enzyme polymerase. Before sequencing the samples, they were purified with the ExoSAP-IT for PCR product cleaning kit of the INVITROGEN brand. Finally, to detect somatic mutations in NOTCH1, TaqMan Mutation Detection Assays was used and for the analysis of mutations we worked with the Mutation Detector software. Results: The mutation for NOTCH1 is not detected, the studied sample does not present the mutation, or it is below the limits of detection of the software. Conclusions: In the clinical setting of the sample, the NOTCH1 mutation seems to be not very frequent, although NOTCH1 has been described as a gene related to oral cancer in other geographical settings. Key words:Oral cancer, NOTCH1, mutations.

Metallothioneins in Dental Implant Treatment Failure and Periodontitis in Patients with Down's Syndrome: Validation of Results.

Metallothioneins (MTs) are low molecular weight cysteine-rich proteins that can bind up to seven zinc ions. Among their numerous functions, MTs appear to act as protectors against oxidative and inflammatory injury. In our first published study, we reported downregulation of the isoforms MT1B (fold distance (FD) -2. 95; p = 0.0024), MT1F (FD -1.72; p = 0.0276), MT1X (FD -3.09; p = 0.0021), MT1H (FD -2.39; p = 0.0018), MT1M (FD -2.37; p = 0.0092), MT1L (FD -2. 55; p = 0.0048), MT1E (FD -2.71; p = 0.0014), MT2A (FD -2.35; p = 0.0072), MT1G (FD -2.24; p = 0.0118), and MT1A (FD -2.82; p = 0.0023) by comparing Down's syndrome patients with periodontal disease and implant failure to those without periodontal disease and with a positive progression of their implants. In this gene validation study, we intended to verify the results of our first gene expression analysis. Materials and Methods: In our retrospective case-control study, we performed retrotranscription (RT-qPCR) of 11 RNA-to-cDNA samples using the SuperScript™ VILO™ kit (50; reference 1,176,605) from Thermo Fisher. We conducted the study using the real-time PCR technique on the q-PCR ViiA 7 platform from Thermo Fisher. We chose the format of the Taqman Array Plate 16 Plus (reference 4,413,261) from Thermo Fisher, which accommodates 12 genes plus four controls (GAPDH, 18S, ACTB, and HPRT1). We conducted the analysis of the plates using the Thermo Fisher Cloud Web Software. Results: The results obtained through gene validation analysis show that in PD+RI+ patients, the genes encoding the isoforms MT1F (FD 0.3; p = 0.039), MT1X (FD 338; p = 0.0078), MT1E (FD 307; p = 0.0358), and MT2A (FD 252; p = 0.0428) continue to show downregulation, whereas MT1B (FD 2.75; p = 0.580), MT1H (FD 281; p = 0.152), MT1L (FD 354; p = 0.0965), and MT1G (FD 336; p = 0.0749) no longer show statistically significant results.

Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept.

Effective testing is essential to control the coronavirus disease 2019 (COVID-19) transmission. Here we report a-proof-of-concept study on hyperspectral image analysis in the visible and near-infrared range for primary screening at the point-of-care of SARS-CoV-2. We apply spectral feature descriptors, partial least square-discriminant analysis, and artificial intelligence to extract information from optical diffuse reflectance measurements from 5 µL fluid samples at pixel, droplet, and patient levels. We discern preparations of engineered lentiviral particles pseudotyped with the spike protein of the SARS-CoV-2 from those with the G protein of the vesicular stomatitis virus in saline solution and artificial saliva. We report a quantitative analysis of 72 samples of nasopharyngeal exudate in a range of SARS-CoV-2 viral loads, and a descriptive study of another 32 fresh human saliva samples. Sensitivity for classification of exudates was 100% with peak specificity of 87.5% for discernment from PCR-negative but symptomatic cases. Proposed technology is reagent-free, fast, and scalable, and could substantially reduce the number of molecular tests currently required for COVID-19 mass screening strategies even in resource-limited settings.

Mutations in p53 Gene Exons in a Sample from the South of Spain in Oral Cancer.

BACKGROUND: Cancer is a genetic disease caused by mutations in DNA and epigenetic alterations that control gene expression. The majority of epidermoid carcinomas develop within the fields of epithelial genetic alterations. The mechanisms underlying tumorigenesis of epidermoid carcinoma are as yet unknown; therefore, precise identification of the risk factors is needed. Aim: The main aim of this study is to analyse and identify the emergence of the mutations described in the literature of the p53 gene with regard to the emergence of cancer in a sample of dysplastic and cancerous lesions in oral cavity mucosa in the population of the south of Spain, in order to determine the presence of said mutations and the percentage of them in our population. MATERIAL AND METHODS: A cross-sectional study was carried out, with a sample size of 22 patients with potentially malignant oral lesions ancillary to biopsy. All were patients, of both sexes, over 18 years of age from the Virgen del Rocío University Hospital with potentially malignant lesions in oral mucosa ancillary to biopsy (leukoplakias, erythroplasias or leukoerythopkias). An anatomopathological study was performed on all the samples and the lesions were divided into three types: low-grade dysplasia, high-grade dysplasia and squamous cell carcinoma. In respect of the genome study process, a complete search or scan for mutations in exons 5, 6, 8 and 9 of the p 53 gene was carried out, given that in the IARC database we observed that the 5 and 6 as well as the 8 and 9 exon sizes can be scanned completely in this way, since they have amplificon sizes of 476 and 445 base pairs respectively. RESULTS: In the scan for the complete exons 5, 6, 8 and 9 only a single result of interest was found to be described. In patient NBI 57 a change was observed in the TAT triplet by ATT of EXON 6, the change being of the T nucleotide by the A and in both directions both in Forward and Reverse. The exact location in the NCBI is GR Ch 37 p13 on chromosome 17, EXON 6 of the P53 gene and the change is in the C.613 T>A nucleotide; NM_000546. CONCLUSIONS: On reviewing this genetic variant in different scientific databases, such as ENSEMBL among others, in at least 6 different biocomputing tools it is described as a pathogen, therefore we can conclude that it is a pathogenic mutation for this case in particular. The rest of the mutations described in the literature on exons 5, 6, 8 and 9 of the p53 gene have not been found in our sample. Key words:Oral cancer, p53, Mutations, Exon.

Using Genetics in Periodontal Disease to Justify Implant Failure in Down Syndrome Patients.

Peri-implant bone loss leading to dental implant failure does not develop in the same way across subjects who apparently present the same condition-specifically, in the case of Down syndrome patients with the same genetic disorder-given that they do not necessarily develop immune-inflammatory disorders to the same extent. METHODS: This retrospective case-control study was aimed at identifying the possible genes involved in implant failure in Down syndrome patients by matching the periodontal disease variable by means of a retrospective case-control study. This process involved using the functional analysis of gene expression software Transcriptome Analysis Console (TAC, Affymetrix, Thermo Fisher Scientific, Waltham, MA, USA) and a search for the possible candidate genes involved. Focus was placed on the 92 genes related to the inflammation identified from the TaqMan™ Array Plate Human Inflammation Kit (Thermo Fisher Scientific, Waltham, MA, USA). RESULTS: Six genes showed statistically significant results (p < 0.05) in our comparison. Three of them-PLCG2 (p = 0.0333), ALOX5 (p = 0.03) and LTAH4 (p = 0.0081)-were overexpressed in the implant reject group, and the following three were down-regulated: VCAM1 (p = 0.0182), PLA2G2A (p = 0.0034) and PLA2G10 (p = 0.047). CONCLUSION: Statistically significant differences exist in the gene expression involved in osteoclastogenesis, inflammatory response and host defensive response.

Oxidative Stress, Telomere Shortening, and Apoptosis Associated to Sarcopenia and Frailty in Patients with Multimorbidity.

BACKGROUND: The presence of oxidative stress, telomere shortening, and apoptosis in polypathological patients (PP) with sarcopenia and frailty remains unknown. METHODS: Multicentric prospective observational study in order to assess oxidative stress markers (catalase, glutathione reductase (GR), total antioxidant capacity to reactive oxygen species (TAC-ROS), and superoxide dismutase (SOD)), absolute telomere length (aTL), and apoptosis (DNA fragmentation) in peripheral blood samples of a hospital-based population of PP. Associations of these biomarkers to sarcopenia, frailty, functional status, and 12-month mortality were analyzed. RESULTS: Of the 444 recruited patients, 97 (21.8%), 278 (62.6%), and 80 (18%) were sarcopenic, frail, or both, respectively. Oxidative stress markers (lower TAC-ROS and higher SOD) were significantly enhanced and aTL significantly shortened in patients with sarcopenia, frailty or both syndromes. No evidence of apoptosis was detected in blood leukocytes of any of the patients. Both oxidative stress markers (GR, p = 0.04) and telomere shortening (p = 0.001) were associated to death risk and to less survival days. CONCLUSIONS: Oxidative stress markers and telomere length were enhanced and shortened, respectively, in blood samples of polypathological patients with sarcopenia and/or frailty. Both were associated to decreased survival. They could be useful in the clinical practice to assess vulnerable populations with multimorbidity and of potential interest as therapeutic targets.

Metallothioneins in Failure of Dental Implants and Periodontitis Down Syndrome Patients.

BACKGROUND: Sometimes dental implants seem to be the only therapeutic alternative for the oral rehabilitation of patients with Down syndrome, given that they usually lose all their teeth early due to suffering aggressive periodontitis and they do not usually have the skills required to wear removable prostheses. However, the evolution of dental implants in these patients shows very adverse results. It is possible that basal genetic alterations, or at least some characteristics of these, may underlie these clinical results. The metabolic pathway of metallothioneins, molecules with an important influence on bone metabolism, could be one of the said alterations. AIMS: To determine whether the expression of metallothioneins (MTs) and their metabolic pathway may be identified and related to the periodontitis and lack of osseointegration of dental implants in Down syndrome patients. MATERIALS AND METHODS: Retrospective study of cases and controls by comparing patients with Down syndrome, periodontal disease, and implant failure (four patients, test group) with patients with Down syndrome, without periodontal disease, and without implant failure after two years of following (seven patients, control group), by extracting peripheral blood at the time of the dental examination to extract RNA and its subsequent processing in relation to gene expression of the metabolic pathway of metallothioneins. RESULTS: The results identified low expression in the group of patients with periodontal disease and implant failure of genes MT1E, MT1H, MT1X, MT1A, MT1B, MT1C, MT1L, MT2A, MT1M, and MT1G. CONCLUSIONS: The low MT1 and MT2 gene expression seems to be related to the onset of periodontal disease and implant rejection in Down syndrome patients, although more data are required to confirm whether this relationship is due to one of the two conditions, to both independently, or to the two jointly-this last option being indicated by our current study.

La autopublicación, un nuevo paradigma en la creación digital del libro / Self-publishing, a new paradigm in digital book creation

Se entiende por autopublicación la publicación de un libro o cualquier otro documento por parte del autor de la obra sin la intervención de un tercero o de un editor. Por tanto, el autor es responsable del control de todo el proceso, incluyendo el diseño (cubierta/interior), formatos, precio, distribución, marketing y relaciones públicas. Los autores pueden hacerlo todo o subcontratar la totalidad o parte del proceso con empresas que ofrecen estos servicios. El objetivo del trabajo consiste en el estudio del fenómeno de la autopublicación en el nuevo contexto digital, haciendo un análisis de las ventajas e inconvenientes de los sistemas de autopublicación. Asimismo, se proporcionan datos de la autopublicación en el mundo y se recogen los principales agentes en este mercado, que se aleja del tradicional "Vanity Publisher", para concurrir directamente en el mercado editorial en igualdad de condiciones que las establecidas para los circuitos convencionales.

Self-publishing is the publication of any book or other media by the author of the work, without the intervention of a third party established or publisher. The author is responsible for controlling the whole process, including design (covered indoor), formats, pricing, distribution, marketing and public relations. Authors can do it all themselves or outsource all or part of the process in companies that offer these services. The aim of this paper is analyze the phenomenon of self-publishing in the new digital environment. An analysis of the advantages and disadvantages of self-publishing systems, data are provided in the publishing world and reflects the main players in this market remains a vanity press to attend directly in the publishing market with unprecedented bestsellers.

Prolyl hydroxylase-dependent modulation of eukaryotic elongation factor 2 activity and protein translation under acute hypoxia.

Early adaptive responses to hypoxia are essential for cell survival, but their nature and underlying mechanisms are poorly known. We have studied the post-transcriptional changes in the proteome of mammalian cells elicited by acute hypoxia and found that phosphorylation of eukaryotic elongation factor 2 (eEF2), a ribosomal translocase whose phosphorylation inhibits protein synthesis, is under the precise and reversible control of O(2) tension. Upon exposure to hypoxia, phosphorylation of eEF2 at Thr(56) occurred rapidly (<15 min) and resulted in modest translational arrest, a fundamental homeostatic response to hypoxia that spares ATP and thus facilitates cell survival. Acute inhibitory eEF2 phosphorylation occurred without ATP depletion or AMP kinase activation. Furthermore, eEF2 phosphorylation was mimicked by prolyl hydroxylase (PHD) inhibition with dimethyloxalylglycine or by selective PHD2 siRNA silencing but was independent of hypoxia-inducible factor α stabilization. Moreover, overexpression of PHD2 blocked hypoxic accumulation of phosphorylated eEF2. Therefore, our findings suggest that eEF2 phosphorylation status (and, as a consequence, translation rate) is controlled by PHD2 activity. They unravel a novel pathway for cell adaptation to hypoxia that could have pathophysiologic relevance in tissue ischemia and cancer.

GDNF and protection of adult central catecholaminergic neurons.

Neurotrophic factors are small proteins necessary for neuron survival and maintenance of phenotype. They are considered as promising therapeutic tools for neurodegenerative diseases. The glial cell line-derived neurotrophic factor (GDNF) protects catecholaminergic cells from toxic insults; thus, its potential therapeutic applicability in Parkinson's disease has been intensely investigated. In recent years, there have been major advances in the analysis of GDNF signaling pathways in peripheral neurons and embryonic dopamine mesencephalic cells. However, the actual physiological role of GDNF in maintaining catecholaminergic central neurons during adulthood is only starting to be unraveled, and the mechanisms whereby GDNF protects central brain neurons are poorly known. In this study, we review the current knowledge of GDNF expression, signaling, and function in adult brain, with special emphasis on the genetic animal models with deficiency in the GDNF-dependent pathways.

Oxygen sensing in the carotid body.

The carotid body (CB) is a neural crest-derived organ whose function is to elicit hyperventilation in response to hypoxemia. The CB contains clusters of neuron-like glomus cells enveloped by glia-like sustentacular cells. CB responsiveness to acute hypoxia relies on the inhibition of O2-sensitive K+ channels in glomus cells, which leads to depolarization, Ca2+ entry and release of transmitters that activate afferent nerve fibers. The molecular mechanisms underlying K+ channel modulation by O2 tension are unknown. Putative hypoxia-sensing mechanisms can be studied in detail using genetically modified mice in conjunction with a thin carotid body slice preparation. We discuss here the role in CB oxygen sensing of the hypoxia-inducible factor 1alpha, the mitochondrial complex II subunit D, and heme oxygenase 2. In chronic hypoxia the CB grows with increase in glomus cell number. We identified CB stem cells of glial lineage, which can differentiate into functionally normal glomus cells.

Absolute requirement of GDNF for adult catecholaminergic neuron survival.

GDNF is a potent neurotrophic factor that protects catecholaminergic neurons from toxic damage and induces fiber outgrowth. However, the actual role of endogenous GDNF in the normal adult brain is unknown, even though GDNF-based therapies are considered promising for neurodegenerative disorders. We have generated a conditional GDNF-null mouse to suppress GDNF expression in adulthood, hence avoiding the developmental compensatory modifications masking its true physiologic action. After Gdnf ablation, mice showed a progressive hypokinesia and a selective decrease of brain tyrosine hydroxylase (Th) mRNA, accompanied by pronounced catecholaminergic cell death, affecting most notably the locus coeruleus, which practically disappears; the substantia nigra; and the ventral tegmental area. These data unequivocally demonstrate that GDNF is indispensable for adult catecholaminergic neuron survival and also show that, under physiologic conditions, downregulation of a single trophic factor can produce massive neuronal death.

Acute oxygen sensing in heme oxygenase-2 null mice.

Hemeoxygenase-2 (HO-2) is an antioxidant enzyme that can modulate recombinant maxi-K(+) channels and has been proposed to be the acute O(2) sensor in the carotid body (CB). We have tested the physiological contribution of this enzyme to O(2) sensing using HO-2 null mice. HO-2 deficiency leads to a CB phenotype characterized by organ growth and alteration in the expression of stress-dependent genes, including the maxi-K(+) channel alpha-subunit. However, sensitivity to hypoxia of CB is remarkably similar in HO-2 null animals and their control littermates. Moreover, the response to hypoxia in mouse and rat CB cells was maintained after blockade of maxi-K(+) channels with iberiotoxin. Hypoxia responsiveness of the adrenal medulla (AM) (another acutely responding O(2)-sensitive organ) was also unaltered by HO-2 deficiency. Our data suggest that redox disregulation resulting from HO-2 deficiency affects maxi-K(+) channel gene expression but it does not alter the intrinsic O(2) sensitivity of CB or AM cells. Therefore, HO-2 is not a universally used acute O(2) sensor.