A Protocol for Systematic Review

This work is financed by national funds through the FCT—Foundation for Science and Technology, I.P., under the project UIDB/04585/2020.Obstructive sleep apnea is a sleep disorder with a high prevalence in the world population. The mandibular advancement device is one of the options for treating obstructive sleep apnea. Neck computed tomography and drug-induced sleep endoscopy are complementary diagnostic tests that may help predict the effectiveness of mandibular advancement devices. This study aims to analyze the best method for predicting the effectiveness of mandibular advancement devices in the therapeutic approach to obstructive sleep apnea. PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection databases will be comprehensively searched. We will include randomized clinical trials, non-randomized prospective or retrospective clinical studies, case controls, cohort studies, and case series. Two authors will independently conduct data extraction and assess the literature quality of the studies. The analysis of the included literature will be conducted by Revman 5.3 software. The outcomes that will be analyzed are craniofacial characteristics, cephalometric assessments, site and type of obstruction of the upper airway, mean values of the apnea-hypopnea index, and SaO2 verified in the initial and follow-up polysomnography. This study will provide reliable, evidence-based support for the clinical application of mandibular advancement devices for obstructive sleep apnea.publishersversionpublishe

Retratos

Presentamos en este capítulo los retratos originales de las personalidades seleccionadas por su importancia en relación con los temas de esta obra

Evaluation of Poly(N-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells

MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells' function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects. To overcome these challenges, polymeric vehicles have attracted a lot of attention due to their ease of production with low costs, large payload, safety profiles, and minimal induction of the immune response. Poly(N-ethyl pyrrolidine methacrylamide) (EPA) copolymers have shown optimal DNA transfection efficiencies in fibroblasts. The present study aims to evaluate the potential of EPA polymers as miRNA carriers for neural cell lines and primary neuron cultures when they are copolymerized with different compounds. To achieve this aim, we synthesized and characterized different copolymers and evaluated their miRNA condensation ability, size, charge, cytotoxicity, cell binding and internalization ability, and endosomal escape capacity. Finally, we evaluated their miRNA transfection capability and efficacy in Neuro-2a cells and rat primary hippocampal neurons. The results indicate that EPA and its copolymers, incorporating β-cyclodextrins with or without polyethylene glycol acrylate derivatives, can be promising vehicles for miRNA administration to neural cells when all experiments on Neuro-2a cells and primary hippocampal neurons are considered together.This research was supported by the Council of Education, Culture and Sports of the Regional Government of Castilla La Mancha (Spain) and Co-financed by the European Union (FEDER) “A way to make Europe” (project references SBPLY/17/000376 and SBPLY/21/180501/000097) and by the Ministerio de Ciencia, Innovación y Universidades (RTI2018-096328-B-I00). Altea Soto was funded by the Council of Education, Culture and Sports of the Regional Government of Castilla La Mancha (Spain) M. Asunción Barreda-Manso is funded by the Council of Health of the Regional Government of Castilla La Mancha (Spain), through: “Convocatoria de Ayudas Regionales a la Investigación en Biomedicina y Ciencias de la Salud” (II-2020_05). Irene Novillo Algaba is funded by the Next Generation Funds of the European Union through the “Programa Investigo”.Peer reviewe

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Efeitos mutagênicos e citotóxicos do óleo essencial de Lantana camara usando Teste do Micronúcleo em medula óssea de camundongos

Este estudo objetivou avaliar as atividades mutagênicas e antimutagênicas, citotóxicas e anticitotóxicas do óleo essencial de Lantana camara através do teste do micronúcleo em medula óssea de camundongos. Foram utilizados 40 camundongos divididos em 8 grupos de 5 animais cada. Para a avaliação da mutagenicidade os camundongos receberam doses intraperitoneais de 300 mg/kg, 600 mg/kg e 1200 mg/kg do óleo essencial de Lantana camara. Para a avaliação da antimutagenicidade e anticitotoxicidade os animais receberam as mesmas doses do óleo essencial concomitantemente com doxorrubicina 2 mg/kg (controle positivo). O óleo de soja foi usado como controle negativo. A avaliação das atividades mutagênicas e antimutagênicas foi feita através da determinação da frequência de eritrócitos policromáticos micronucleados (EPCMN), enquanto que a avaliação das atividades citotóxicas e anticitotóxica ocorreu pela razão de eritrócitos policromáticos (ENC)/eritrócitos normocromáticos (ENC). Os resultados mostraram que na avaliação das atividades mutagênicas e citotóxicas, apenas as doses de 600 mg/kg e 1200 mg/kg apresentaram diferenças significativas em relação ao controle negativo. Nenhuma das três doses do óleo essencial administradas juntamente com doxorrubicina apresentou diferença significativa quando comparadas ao controle positivo. Concluiu-se que o óleo essencial de Lantana camara apresentou atividades mutagênicas e citotóxicas apenas nas doses de 600 mg/kg e 1200 mg/kg, porém nenhuma das doses testadas apresentou atividades antimutagênicas e anticitotóxicas

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved