Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents-In Vitro Evaluation against Breast Cancer Cells.

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.

Relevant domains, core outcome sets and measurements for implant dentistry clinical trials: The Implant Dentistry Core Outcome Set and Measurement (ID-COSM) international consensus report.

AIM: Lack of consistently reported outcomes limits progress in evidence-based implant dentistry and quality of care. The objective of this initiative was to develop a core outcome set (COS) and measurements for implant dentistry clinical trials (ID-COSM). MATERIALS AND METHODS: This Core Outcome Measures in Effectiveness Trials (COMET)-registered international initiative comprised six steps over 24 months: (i) systematic reviews of outcomes reported in the last 10 years; (ii) international patient focus groups; (iii) a Delphi project with a broad range of stakeholders (care providers, clinical researchers, methodologists, patients and industry representatives); (iv) expert group discussions organizing the outcomes in domains using a theoretical framework and identifying the COSs; (v) identification of valid measurement systems to capture the different domains and (vi) final consensus and formal approval involving experts and patients. The methods were modified from the best practice approach following the Outcome Measures in Rheumatoid Arthritis Clinical Trial and COMET manuals. RESULTS: The systematic reviews and patient focus groups identified 754 (665 + 89, respectively) relevant outcome measures. After elimination of redundancies and duplicates, 111 were formally assessed in the Delphi project. By applying pre-specified filters, the Delphi process identified 22 essential outcomes. These were reduced to 13 after aggregating alternative assessments of the same features. The expert committee organized them into four core outcome areas: (i) pathophysiology, (ii) implant/prosthesis lifespan, (iii) life impact and (iv) access to care. In each area, core outcomes were identified to capture both the benefits and harms of therapy. Mandatory outcome domains included assessment of surgical morbidity and complications, peri-implant tissue health status, intervention-related adverse events, complication-free survival and overall patient satisfaction and comfort. Outcomes deemed mandatory in specific circumstances comprised function (mastication, speech, aesthetics and denture retention), quality of life, effort for treatment and maintenance and cost effectiveness. Specialized COSs were identified for bone and soft-tissue augmentation procedures. The validity of measurement instruments ranged from international consensus (peri-implant tissue health status) to early identification of important outcomes (patient-reported outcomes identified by the focus groups). CONCLUSIONS: The ID-COSM initiative reached a consensus on a core set of mandatory outcomes for clinical trials in implant dentistry and/or soft tissue/bone augmentation. Adoption in future protocols and reporting on the respective domain areas by currently ongoing trials will contribute to improving evidence-informed implant dentistry and quality of care.

Relevant domains, core outcome sets and measurements for implant dentistry clinical trials: The Implant Dentistry Core Outcome Set and Measurement (ID-COSM) international consensus report.

AIM: Lack of consistently reported outcomes limits progress in evidence-based implant dentistry and quality of care. The objective of this initiative was to develop a core outcome set (COS) and measurements for implant dentistry clinical trials (ID-COSM). MATERIALS AND METHODS: This Core Outcome Measures in Effectiveness Trials (COMET)-registered international initiative comprised six steps over 24 months: (i) systematic reviews of outcomes reported in the last 10 years; (ii) international patient focus groups; (iii) a Delphi project with a broad range of stakeholders (care providers, clinical researchers, methodologists, patients and industry representatives); (iv) expert group discussions organizing the outcomes in domains using a theoretical framework and identifying the COSs; (v) identification of valid measurement systems to capture the different domains and (vi) final consensus and formal approval involving experts and patients. The methods were modified from the best practice approach following the Outcome Measures in Rheumatoid Arthritis Clinical Trial and COMET manuals. RESULTS: The systematic reviews and patient focus groups identified 754 (665 + 89, respectively) relevant outcome measures. After elimination of redundancies and duplicates, 111 were formally assessed in the Delphi project. By applying pre-specified filters, the Delphi process identified 22 essential outcomes. These were reduced to 13 after aggregating alternative assessments of the same features. The expert committee organized them into four core outcome areas: (i) pathophysiology, (ii) implant/prosthesis lifespan, (iii) life impact and (iv) access to care. In each area, core outcomes were identified to capture both the benefits and harms of therapy. Mandatory outcome domains included assessment of surgical morbidity and complications, peri-implant tissue health status, intervention-related adverse events, complication-free survival and overall patient satisfaction and comfort. Outcomes deemed mandatory in specific circumstances comprised function (mastication, speech, aesthetics and denture retention), quality of life, effort for treatment and maintenance and cost effectiveness. Specialized COSs were identified for bone and soft-tissue augmentation procedures. The validity of measurement instruments ranged from international consensus (peri-implant tissue health status) to early identification of important outcomes (patient-reported outcomes identified by the focus groups). CONCLUSIONS: The ID-COSM initiative reached a consensus on a core set of mandatory outcomes for clinical trials in implant dentistry and/or soft tissue/bone augmentation. Adoption in future protocols and reporting on the respective domain areas by currently ongoing trials will contribute to improving evidence-informed implant dentistry and quality of care.

Piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. In vitro antiviral activity evaluation against Zika and Dengue viruses.

Since 2011 Direct Acting antivirals (DAAs) drugs targeting different non-structural (NS) viral proteins (NS3, NS5A or NS5B inhibitors) have been approved for clinical use in HCV therapies. However, currently there are not licensed therapeutics to treat Flavivirus infections and the only licensed DENV vaccine, Dengvaxia, is restricted to patients with preexisting DENV immunity. Similarly to NS5 polymerase, the NS3 catalytic region is evolutionarily conserved among the Flaviviridae family sharing strong structural similarity with other proteases belonging to this family and therefore is an attractive target for the development of pan-flavivirus therapeutics. In this work we present a library of 34 piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. The library was developed through a privileged structures-based design and then biologically screened using a live virus phenotypic assay to determine the half-maximal inhibitor concentration (IC50) of each compound against ZIKV and DENV. Two lead compounds, 42 and 44, with promising broad-spectrum activity against ZIKV (IC50 6.6 µM and 1.9 µM respectively) and DENV (IC50 6.7 µM and 1.4 µM respectively) and a good security profile were identified. Besides, molecular docking calculations were performed to provide insights about key interactions with residues in NS3 proteases' active sites.

Clinical in-situ evaluation of the effect of rubber dam isolation on bond strength to enamel.

OBJECTIVE: To evaluate the effect of rubber dam isolation on shear bond strength of two different adhesive systems to enamel. MATERIALS AND METHODS: The mesial, distal, lingual, and vestibular enamel surfaces of thirty human third molars were prepared (total n = 120). A custom splint was made to fit a volunteer's maxilla, holding the specimens in place in the oral cavity. Four composite resin cylinders were bonded to each tooth with one of two bonding agents (OptiBond FL and Prime&Bond active) with or without rubber dam isolation. Shear bond strength was tested in a universal testing machine and failure modes were assessed. Significance level for statistical analyses was set at 5%. RESULTS: All pairwise comparisons revealed statistical differences (p < 0.05). The highest mean shear bond strength values were obtained in rubber dam experimental groups, regardless of the adhesive system. Group OptiBond FL with rubber dam presented the highest mean bond strength values. Fracture modes for specimens bonded without rubber dam isolation were adhesive and cohesive within enamel, while rubber dam experimental groups revealed only cohesive fractures. CONCLUSIONS: Absolute isolation with rubber dam increases bond strength to enamel, independent of the adhesive system. The three-step total-etch system OptiBond FL provided significantly higher bond strength values than Prime&Bond active under both experimental conditions. CLINICAL SIGNIFICANCE: Rubber dam isolation has a significant effect on bond strengths to enamel, independent of the adhesive system. Its application is, therefore, advised whenever adhesive procedures are performed. A filled three-step etch-and-rinse adhesive performed superiorly, with or without rubber dam isolation, when bonding to enamel compared to an isopropanol-based universal adhesive.

Rehabilitation of full-arch edentulism with fixed or removable dentures retained by root-form dental implants: A systematic review of outcomes and outcome measures used in clinical research in the last 10 years.

AIM: To evaluate outcome measures, methods of assessment, and analysis in clinical studies on the rehabilitation of full-arch edentulism with implant-supported fixed or removable prostheses. MATERIALS AND METHODS: A protocol-oriented search was conducted in MEDLINE via PubMed, EMBASE, and Cochrane Library (PROSPERO registration CRD42021265179) from 1 January 2011 to 27 July 2021 to identify longitudinal studies reporting on the rehabilitation of edentulous patients with implant-supported prostheses. The primary aim of this study was the collection of all objectively reported outcomes in each study. Secondary aims included the description of the methods of assessment and analytical methods. Risk of bias was applied according to the study design (randomized controlled trial, cohort study, or descriptive pre-post study). Individual study data were extracted into an outcomes matrix. Outcomes were grouped into domains and descriptively analysed. A network diagram was generated to establish relationships between domains. The present review follows the PRISMA statement. RESULTS: The screening and selection processes resulted in the identification of 491 publications, corresponding to 421 different studies (cohorts of patients). Only 24% of the studies reported the use of EQUATOR network guidelines. Implant failure/survival was the most reported outcome (270 studies), but the criterion to determine implant failure and/or survival was frequently not described or was ambiguous. Implant success was much less frequently reported (88) and was based on several heterogenous composite definitions. Marginal bone levels (233 studies), technical complications (158), and clinical outcomes (150), including peri-implant soft tissue and implant stability assessment, were also frequently reported. Patient-reported outcome measures (PROMs) (145) and function-based outcomes (40) were predominantly reported in isolation from other outcomes and most frequently in removable restorations. While quality of life was evaluated using valid instruments, patient satisfaction was evaluated based on a common sense concept of satisfaction. Economic outcomes were under-reported (13). CONCLUSIONS: There is great heterogeneity in the criteria to define implant failure or survival and implant success, which prevents the comparison of rates across studies. Even though studies frequently report multiple outcomes, PROMs are usually reported in isolation from other outcomes. It would be valuable to have a set of core outcome variables and standardized methods of measurement for future studies.

Scientific rationale for study: Consistent data on the outcomes of treatments for full-arch edentulism are fundamental for establishing high-quality clinical practices with effective impact on patients' lives. Principal findings: Despite the increasing number of studies assessing the rehabilitation of full-arch edentulism with implant-supported prostheses, there has been little adherence to reporting guidelines (EQUATOR network), resulting in high variability regarding the type of outcomes reported. The clinical performance of these restorations has been mostly evaluated using clinician-oriented and patient-reported outcomes. Assessment methods are frequently not described and vary across studies. Practical implications: It would be valuable to have a set of core outcome variables and standardized methods of measurement for future studies.

Rehabilitation of full-arch edentulism with fixed or removable dentures retained by root-form dental implants: A systematic review of outcomes and outcome measures used in clinical research in the last 10 years.

AIM: To evaluate outcome measures, methods of assessment, and analysis in clinical studies on the rehabilitation of full-arch edentulism with implant-supported fixed or removable prostheses. MATERIALS AND METHODS: A protocol-oriented search was conducted in MEDLINE via PubMed, EMBASE, and Cochrane Library (PROSPERO registration CRD42021265179) from 1 January 2011 to 27 July 2021 to identify longitudinal studies reporting on the rehabilitation of edentulous patients with implant-supported prostheses. The primary aim of this study was the collection of all objectively reported outcomes in each study. Secondary aims included the description of the methods of assessment and analytical methods. Risk of bias was applied according to the study design (randomized controlled trial, cohort study, or descriptive pre-post study). Individual study data were extracted into an outcomes matrix. Outcomes were grouped into domains and descriptively analysed. A network diagram was generated to establish relationships between domains. The present review follows the PRISMA statement. RESULTS: The screening and selection processes resulted in the identification of 491 publications, corresponding to 421 different studies (cohorts of patients). Only 24% of the studies reported the use of EQUATOR network guidelines. Implant failure/survival was the most reported outcome (270 studies), but the criterion to determine implant failure and/or survival was frequently not described or was ambiguous. Implant success was much less frequently reported (88) and was based on several heterogenous composite definitions. Marginal bone levels (233 studies), technical complications (158), and clinical outcomes (150), including peri-implant soft tissue and implant stability assessment, were also frequently reported. Patient-reported outcome measures (PROMs) (145) and function-based outcomes (40) were predominantly reported in isolation from other outcomes and most frequently in removable restorations. While quality of life was evaluated using valid instruments, patient satisfaction was evaluated based on a common sense concept of satisfaction. Economic outcomes were under-reported (13). CONCLUSIONS: There is great heterogeneity in the criteria to define implant failure or survival and implant success, which prevents the comparison of rates across studies. Even though studies frequently report multiple outcomes, PROMs are usually reported in isolation from other outcomes. It would be valuable to have a set of core outcome variables and standardized methods of measurement for future studies.

Hérnias internas após bypass gástrico laparoscópico em Y-de-Roux: espaços intermesentéricos, sintomas e diagnóstico / Internal hernias after laparoscopic Roux-Y gastric bypass: intermesenteric spaces, symptoms and diagnosis

Introdução: Com o aumento da prevalência mundial de obesidade, operações para redução de peso vêm sendo cada vez mais frequentes, sendo o bypass gástrico laparoscópico a principal delas. Entretanto, existem complicações associadas, dentre elas, a formação de hérnias internas. Objetivos: Revisar o bypass gástrico e o desenvolvimento de hérnias internas, e discorrer sobre a importância do uso de tomografia no diagnóstico dessa complicação. Métodos: Revisão integrativa, envolvendo 646 artigos pesquisados nas bases de dados BVS e PubMed; deles, apenas 10 respeitaram os critérios de inclusão. Resultados: Atualmente o bypass gástrico é um dos principais métodos cirúrgicos utilizados em procedimentos que visam a redução de peso em obesos. Entretanto, a formação de hérnias internas em espaços mesentéricos criados durante o procedimento é uma possibilidade e resulta em sintomas inespecíficos, podendo levar a consequências graves. Nesse contexto, a tomografia computadorizada é instrumento diagnóstico muito útil. Conclusão: Em pronto-socorro, tomografia abdominal deve ser realizada em pacientes com queixa de dor abdominal inespecífica e com histórico de bypass gástrico, pois é útil no diagnóstico precoce das hérnias internas, diminuindo sua morbimortalidade.

Introduction: With the increase in the worldwide prevalence of obesity, operations to reduce weight are becoming more frequent, with laparoscopic gastric bypass being the main one. However, there are associated complications, among them, the formation of internal hernias. Objectives: To review gastric bypass and the development of internal hernias and discuss the importance of using tomography in the diagnosis of this complication. Methods: Integrative review, involving 646 articles searched in the BVS and PubMed databases; of them, only 10 met the inclusion criteria. Results: Currently, gastric bypass is one of the main surgical methods used in procedures aimed at reducing weight in obese people. However, the formation of internal hernias in mesenteric spaces created during the procedure is a possibility and results in nonspecific symptoms, which can lead to serious consequences. In this context, computed tomography is a very useful diagnostic tool. Conclusion: In an emergency room, abdominal tomography should be performed in patients complaining of nonspecific abdominal pain and with a history of gastric bypass, as it is useful in the early diagnosis of internal hernias, reducing their morbidity and mortality.

Importancia de los macrófagos cargados con hemosiderina en el diagnóstico de la hemorragia alveolar difusa / Importance of hemosiderin-loaded macrophages in diagnosis of diffuse alveolar hemorrhage / A importância dos macrófagos carregados com hemosiderina no diagnóstico de hemorragia alveolar difusa / Reconocimiento a la trayectoria del Prof. Dr. Juan Miguel Castagnino†

Resumen La hemorragia alveolar difusa (HAD) es un síndrome clínico con una alta mortalidad que compromete la función respiratoria. Su diagnóstico se basa en pruebas clínicas, radiológicas y citológicas. El objetivo del trabajo fue ratificar el valor de referencia de hemosiderófagos en lavados broncoalveolares (BAL) (hemosiderófagos ≥20%), correlacionar con la etiología y definir las condiciones preanalíticas para que la reacción de Perls alcance valores elevados de sensibilidad. De 109 muestras de pacientes con sospecha de HAD, se analizaron 90 por cumplir los criterios de inclusión; 36 resultaron positivas para HAD, 3 falsamente negativas y 51 resultaron negativas. La sensibilidad fue de 92% y la especificidad de 100%. La mediana de hemosiderófagos para muestras con diagnóstico de HAD fue de 70%. Se agruparon según la etiología: procesos infecciosos puros (PI), enfermedades autoinmunes puras (EA), enfermedades neoplásicas puras (EN), enfermedades autoinmunes más procesos infecciosos (EA+PI), enfermedades neoplásicas más procesos infecciosos (EN+PI), misceláneas (MI). La mediana de hemosiderófagos para cada grupo fue: PI (n=7) 50%, EA (n=15) 58%, EN (n=6) 73%, EA+PI (n=5) 80%, EN+PI (n=4) 80%, MI (n=2) 45% (p=0,57). El porcentaje de pacientes fallecidos fue de 49% (n=19), con una mediana de hemosiderófagos de 70%, en comparación con la de pacientes no fallecidos de 64% (p=0,25). Se ratificó el valor de referencia para establecer el diagnóstico de HAD en muestras de BAL obtenidas luego de las 36 h de comenzados los síntomas utilizando la reacción de Perls, la cual demuestra una alta sensibilidad y especificidad para dicho diagnóstico.

Abstract Difusse alveolar hemorrhage (DAH) is a clinical syndrome with high mortality. Its diagnosis is based on clinical, radiological and cytological tests. The objective of this study was to ratify the reference value of hemosiderophages in bronchoalveolar lavages (BAL) (hemosiderophagues ≥20%), to correlate with the etiology and define the pre-analytical conditions for the Perls reaction to reach high sensitivity values. Out of the 109 samples from patients with suspected ADH, 90 were analysed for meeting the inclusion criteria; 36 were positive for HAD, 3 were false negatives, and 51 were negative (sensitivity 92%; specificity 100%). The median number of hemosiderophagues for samples with a diagnosis of ADH was 70%; they were grouped according to etiology: pure infectious processes (PI), pure autoimmune diseases (AD), pure neoplastic diseases (ND), autoimmune diseases plus infectious processes (AD + PI), and miscellaneous (MI). The median number of hemosiderophagues for each group was: PI (n=7) 50%, AD (n=15) 58%, ND (n=6) 73%, AD + PI (n=5) 80%, ND + PI (n=4) 80%, MI (n=2) 45% (p=0.57). The percentage of deceased patients was 49% (n=19), with a median hemosiderophague of 70%, compared with 64% of non-deceased patients (p=0.25). The reference value to establish the diagnosis of ADH in BAL simples obtained 36 hours after the beginning of symptoms using the Perls reaction was ratified, which shows a high sensitivity and specificity to make the diagnosis of ADH.

Resumo A hemorragia alveolar difusa (HAD) é uma síndrome clínica com alta mortalidade que compromete a função respiratória. Seu diagnóstico se baseia em testes clínicos, radiológicos e citológicos. O objetivo do trabalho foi ratificar o valor de referência de hemossiderófagos em lavagens broncoalveolares (LBA) (hemossiderófagos ≥20%), relacioná-los com a etiologia e definir as condições pré-analíticas para que a reação de Perls alcance valores elevados de sensibilidade. De 109 amostras de pacientes com suspeita de HAD, 90 foram analisadas para cumprir com os critérios de inclusão; 36 resultaram positivas para HAD, 3 foram falsos negativos e 51 resultaram negativas. A sensibilidade foi de 92% e a especificidade de 100%. A média de hemossiderófagos para amostras com diagnóstico de HAD foi de 70%, eles foram agrupados de acordo com a etiologia: processos infecciosos puros (PI), doenças autoimunes puras (DA), doenças neoplásicas puras (DN), doenças autoimunes mais processos infecciosos (DA+PI), doenças neoplásicas mais processos infecciosos (DN+PI), miscelâneas (MI). A média de hemossiderófagos para cada grupo foi: PI (n=7) 50%, DA (n=15) 58%, DN (n=6) 73%, DA+PI (n=5) 80%, DN+PI (n=4) 80%, MI (n = 2) 45% (p= 0,57). A porcentagem de pacientes falecidos foi de 49% (n=19), com uma média de hemossiderófagos de 70%, em comparação com 64% de pacientes não falecidos (p=0,25). Foi ratificado o valor de referência para estabelecer o diagnóstico de HAD em amostras LBA obtidas 36 horas após o início dos sintomas através da reação de Perls, que apresenta alta sensibilidade e especificidade para esse diagnóstico.

Diffusion of Vanadium Ions in Artificial Saliva and Its Elimination from the Oral Cavity by Pharmacological Compounds Present in Mouthwashes.

In this study, diffusion coefficients of ammonium vanadate at tracer concentrations in artificial saliva with and without sodium fluoride, at different pH values, were measured using an experimental model based on the Taylor dispersion technique. Ternary mutual diffusion coefficients (D11, D22, D12, and D21) for four aqueous systems {NH4VO3 (component 1) + ß-cyclodextrin (ß-CD) (component 2),} {NH4VO3 (component 1) + ß-cyclodextrin (HP-ß-CD) (component 2)}, {NH4VO3 (component 1) + sodium dodecyl sulphate (SDS) (component 2)} and {NH4VO3 (component 1) + sodium hyaluronate (NaHy) (component 2)} at 25.00 °C were also measured by using the same technique. These data showed that diffusion of ammonium vanadate was strongly affected in all aqueous media studied. Furthermore, a significant coupled diffusion of this salt and ß-CD was observed through the non-zero values of the cross-diffusion coefficients, D12, allowing us to conclude that there is a strong interaction between these two components. This finding is very promising considering the removal, from the oral cavity, of vanadium resulting from tribocorrosion of Ti-6Al-4V prosthetic devices.

Consensus Report on Preventive Antibiotic Therapy in Dental Implant Procedures: Summary of Recommendations from the Spanish Society of Implants.

Current patterns of preventive antibiotic prescribing are encouraging the spread of antimicrobial resistance. Recently, the Spanish Society of Implants (SEI) developed the first clinical practice guidelines published to date, providing clear guidelines on how to prescribe responsible and informed preventive antibiotic therapy (PAT) based on the available scientific evidence on dental implant treatments (DIs). The present document aims to summarise and disseminate the recommendations established by this expert panel. These were based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were analysed using the Scottish Intercollegiate Guidelines Network (SIGN) checklist templates and ranked according to their level of evidence. They were then assigned a level of recommendation using the Grading of Recommendations, Assessment, Development and Evaluation system (GRADE). Guidelines were established on the type of PAT, antibiotic and dosage of administration in the placement of DIs without anatomical constraints, in bone augmentation with the placement of DIs in one or two stages, placement of immediate DIs, sinus elevations, implant prosthetic phase, as well as recommendations in patients allergic to penicillin. Therefore, the PAT must be adapted to the type of implant procedure to be performed.

Efficacy of Telemedicine and At-Home Telemonitoring following Hospital Discharge in Patients with COVID-19.

Aim: This work aims to evaluate the safety and utility of an at-home telemedicine with telemonitoring program for discharged COVID-19 patients. Methods: This is a retrospective cohort study of all patients discharged home in Galicia between 6 March 2020 and 15 February 2021. We evaluated a structured, proactive monitoring program conducted by the ASLAM (Área Sanitaria de Lugo, A Mariña y Monforte de Lemos) Healthcare Area team compared to patients discharged in the rest of the Autonomous Community of Galicia. Results: During the study period, 10,517 patients were hospitalized for COVID-19 and 8601 (81.8%) were discharged. Of them, 738 (8.6%) were discharged in ASLAM and 7863 (91.4%) were discharged in the rest of Galicia. Of those discharged in ASLAM, 475 (64.4%) patients were monitored. Compared to patients in the rest of Galicia, the group monitored via telemedicine had a significantly shorter first hospital stay (p < 0.0001), a lower readmission rate (p = 0.05), and a shorter second hospital stay (p = 0.04), with no differences in emergency department visits or 90-day all-cause mortality. Conclusion: A structured, proactive telemedicine with telemonitoring program for discharged COVID-19 patients is a safe, useful tool that reduces the mean length of hospital stay and readmissions.

Luting indirect restorations with resin cements versus composite resins: Effects of preheating and ultrasound energy on film thickness.

OBJECTIVE: This study aims to evaluate and compare the film thickness obtained with a resin cement and two composite resins, preheated and/or ultrasonically vibrated, as luting agents. MATERIALS AND METHODS: One hundred and twenty-six (126) pairs of resin discs were randomly assigned to six experimental groups (n = 21) according to luting agent (Variolink Esthetic LC, IPS Empress Direct or Estelite Omega) and cementation technique (preheating at 68°C and/or ultrasonic vibration). Specimens were luted by applying a controlled force. Following sectioning and film thickness measurement through field emission gun scanning electron microscopy, statistical analysis was carried out considering a 5% significance level. RESULTS: Statistically significant lower film thickness was observed in Variolink Esthetic LC group when compared to all composite resin groups (p < 0.001), except IPS Empress Direct preheated and ultrasonically vibrated group (p = 0.073). IPS Empress Direct with ultrasonic vibration yielded statistically lower film thickness values than Estelite Omega groups, regardless of luting technique (p < 0.05). Ultrasonically vibrated Estelite Omega groups showed statistically lower film thickness values than solely preheated groups (p < 0.05). CONCLUSIONS: Both Variolink Esthetic LC and IPS Empress Direct preheated and ultrasonically vibrated provided the lowest film thickness. The addition of ultrasonic vibration during cementation proved to be effective in reducing film thickness of both tested composite resins. CLINICAL SIGNIFICANCE: The cementation technique will have variable results depending on the luting material. Adhesive cementation protocols with composite resins should mainly consider ultrasonic vibration, but also preheating, as strategies for reducing film thickness. The tested resin cement, alongside with IPS Empress Direct composite resin preheated and ultrasonically vibrated, provided the lowest film thickness among the tested materials and techniques.

Effect of Cobalt and Chromium Ions on the Chlorhexidine Digluconate as Seen by Intermolecular Diffusion.

Metal ions such as cobalt (II) and chromium (III) might be present in the oral cavity, as a consequence of the corrosion of Co-Cr dental alloys. The diffusion of such metal ions into the organism, carried by saliva, can cause health problems as a consequence of their toxicity, enhanced by a cumulative effect in the body. The effect of the chlorhexidine digluconate, which is commonly used in mouthwash formulations, on the transport of these salts is evaluated in this paper by using the Taylor dispersion technique, which will allow an assessment of how the presence of chlorhexidine digluconate (either in aqueous solution or in a commercial formulation) may affect the diffusion of metal ions. The ternary mutual diffusion coefficients of metal ions (Co and Cr) in the presence of chlorhexidine digluconate, in an artificial saliva media, were measured. Significant coupled diffusion of CoCl2 (and CrCl3) and chlorhexidine digluconate is observed by analysis of the non-zero values of the cross-diffusion coefficients, D12 and D21. The observed interactions between metal ions and chlorhexidine digluconate suggest that the latter might be considered as an advantageous therapeutic agent, once they contribute to the reduction of the concentration of those ions inside the mouth.

Efficacy of Telemedicine and Telemonitoring in At-Home Monitoring of Patients with COVID-19.

AIM: this work aims to assess if telemedicine and telemonitoring are clinically useful and safe for at-home monitoring of Coronavirus disease 2019 (COVID-19) patients. METHODS: This is a retrospective cohort study of all patients diagnosed with COVID-19 in Galicia (Northwestern Spain) between 26 December 2020 and 15 February 2021. The structured, proactive monitoring via telemonitoring (TELEA) of patients considered to be high-risk in the Lugo, A Mariña, and Monforte Healthcare Area (ASLAM) was evaluated compared to other models in the remaining healthcare areas of Galicia. RESULTS: Of the 47,053 COVID-19 patients, 4384 (9.3%) were in ASLAM. Of them, 1187 (27.1%) were monitored via TELEA, and the rest (3197 in ASLAM and 42,669 in the rest of Galicia) were monitored via other methods. Patients monitored in ASLAM via TELEA were older, consulted in the emergency department less frequently (p = 0.05), were hospitalized less frequently (p < 0.01), had shorter hospital stays (p < 0.0001), and had a lower mortality rate in their first hospitalization (p = 0.03). No at-home life-threatening emergencies were recorded. CONCLUSIONS: these data suggest that, for COVID-19 patients, a care model involving proactive at-home monitoring with telemedicine and telemonitoring is associated with reduced pressure on hospital services and a lower mortality rate.

Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol.

Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17, 20, 26, 34, 44, 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC50 from 2.47 to 5.75 µM) and low cytotoxicity (CC50 from 28.70 to >200 µM). In addition, our mechanistic assays revealed that compounds 20 and 44 might be targeting specifically the HAdV DNA replication process, and compound 66 would be targeting HAdV E1A mRNA transcription. For compounds 17, 20, 34 and 60, the mechanism of action seems to be associated with later steps after HAdV DNA replication.

Clinical and radiographic performance of self-locking conical connection implants in the posterior mandible: Five-year results of a two-centre prospective study.

OBJECTIVE: This prospective study aims to assess the 5-year clinical performance of implants with internal conical connection and platform-switched abutments in the posterior mandible. MATERIAL AND METHODS: Healthy adults missing at least two teeth in the posterior mandible and with a natural tooth mesial to the implant site received two or three adjacent implants. After a transmucosal healing period single crown restorations were cemented on platform-switched abutments. Changes in marginal bone levels were investigated in standardized periapical radiographs from surgery and loading (baseline) to 60-months post-loading. RESULTS: Twenty-four patients received 52 implants. Bone remodelling took place between surgery and loading (mean:-0.5, SD:±0.4 mm). From loading to 60 months, there was a mean bone change of 0.27 (SD:±0.47 mm) which stabilized 24 months after prosthesis delivery (mean:0.2, SD:±0.46 mm). 71.7% of all implants presented bone preservation at 60 months irrespective of the initial insertion depth. Two implants were lost after 5 years and the success rate was 95.1%. Patient enquiry revealed high satisfaction. CONCLUSION: Internal conical connection implants with platform-switched abutments presented a high success rate and preservation of marginal bone levels at the implant shoulder after 5 years of loading.

GPR120/FFAR4 Pharmacology: Focus on Agonists in Type 2 Diabetes Mellitus Drug Discovery.

The G-protein coupled receptors (GPCRs) activated by free fatty acids (FFAs) have emerged as new and exciting drug targets, due to their plausible translation from pharmacology to medicines. This perspective aims to report recent research about GPR120/FFAR4 and its involvement in several diseases, including cancer, inflammatory conditions, and central nervous system disorders. The focus is to highlight the importance of GPR120 in Type 2 diabetes mellitus (T2DM). GPR120 agonists, useful in T2DM drug discovery, have been widely explored from a structure-activity relationship point of view. Since the identification of the first reported synthetic agonist TUG-891, the research has paved the way for the development of TUG-based molecules as well as new and different chemical entities. These molecules might represent the starting point for the future discovery of GPR120 agonists as antidiabetic drugs.

Genome-Wide Association of Stem Carbohydrate Accumulation and Remobilization during Grain Growth in Bread Wheat (Triticum aestivum L.) in Mediterranean Environments.

Water deficit represents an important challenge for wheat production in many regions of the world. Accumulation and remobilization of water-soluble carbohydrates (WSCs) in stems are part of the physiological responses regulated by plants to cope with water stress and, in turn, determine grain yield (GY). The genetic mechanisms underlying the variation in WSC are only partially understood. In this study, we aimed to identify Single Nucleotide Polymorphism (SNP) markers that account for variation in a suite of WSC and GY, evaluated in 225 cultivars and advanced lines of spring wheat. These genotypes were established in two sites in the Mediterranean region of Central Chile, under water-limited and full irrigation conditions, and assessed in two growing seasons, namely anthesis and maturity growth periods. A genome-wide association study (GWAS) was performed by using 3243 SNP markers. Genetic variance accounted for 5 to 52% of phenotypic variation of the assessed traits. A rapid linkage disequilibrium decay was observed across chromosomes (r2 ≤ 0.2 at 2.52 kbp). Marker-trait association tests identified 96 SNPs related to stem weight (SW), WSCs, and GY, among other traits, at the different sites, growing seasons, and growth periods. The percentage of SNPs that were part of the gene-coding regions was 34%. Most of these genes are involved in the defensive response to drought and biotic stress. A complimentary analysis detected significant effects of different haplotypes on WSC and SW, in anthesis and maturity. Our results evidence both genetic and environmental influence on WSC dynamics in spring wheat. At the same time, they provide a series of markers suitable for supporting assisted selection approaches and functional characterization of genes.

Collagenated Porcine Heterologous Bone Grafts: Histomorphometric Evaluation of Bone Formation Using Different Physical Forms in a Rabbit Cancellous Bone Model.

Collagenated porcine-derived bone graft materials exhibit osteoconductive properties and the development of different formulations intends to enhance bone regeneration. This study aims to evaluate bone healing in a rabbit cancellous bone defect in response to grafting with different physicochemical forms of heterologous porcine bone. Twenty-six adult male New Zealand White rabbits received two critical size femoral bone defects per animal (n = 52), each randomly assigned to one of the five tested materials (Apatos, Gen-Os, mp3, Putty, and Gel 40). Animals were sacrificed at 15- and 30-days post-surgery. Qualitative and quantitative (new bone, particle and connective tissue percentages) histological analyses were performed. Histomorphometry showed statistically significant differences in all evaluated parameters between mp3 and both Putty and Gel 40 groups, regardless of the timepoint (p < 0.05). Moreover, statistical differences were observed between Apatos and both Putty (p = 0.014) and Gel 40 (p = 0.007) groups, at 30 days, in regard to particle percentage. Within each group, regarding new bone formation, mp3 showed significant differences (p = 0.028) between 15 (40.93 ± 3.49%) and 30 (52.49 ± 11.04%) days. Additionally, intragroup analysis concerning the percentage of particles revealed a significant reduction in particle occupied area from 15 to 30 days in mp3 and Gen-Os groups (p = 0.009). All mp3, Gen-Os and Apatos exhibited promising results in terms of new bone formation, thus presenting suitable alternatives to be used in bone regeneration.