Proteomic Analysis of Salivary Extracellular Vesicles from COVID-19 Patients Reveals a Specific Anti-COVID-19 Response Protein Signature.

Despite the understanding of the coronavirus disease-19 (COVID-19), the role of salivary extracellular vesicles (sEVs) in COVID-19 remains unclear. Exploring the proteomic cargo of sEVs could prove valuable for diagnostic and prognostic purposes in assessing COVID-19. The proteomic cargo of sEVs from COVID-19(+) subjects and their healthy close contacts (HCC) was explored. sEVs were isolated by ultracentrifugation from unstimulated saliva samples, and subsequently characterized through nanoparticle tracking, transmission electron microscopy, and Western blot analyses. The proteomic cargo of sEVs was processed by LC-MS/MS. sEVs were morphologically compatible with EVs, with the presence of Syntenin-1 and CD81 EV markers. The sEV pellet showed 1417 proteins: 1288 in COVID-19(+) cases and 1382 in HCC. In total, 124 proteins were differentially expressed in sEVs from COVID-19(+) subjects. "Coronavirus-disease response", "complement and coagulation cascades", and "PMN extracellular trap formation" were the most enriched KEGG pathways in COVID-19(+) cases. The most represented biological processes were "Hemoglobin and haptoglobin binding" and "oxygen carrier activity", and the best-denoted molecular functions were "regulated exocytosis and secretion" and "leucocyte and PMN mediated immunity". sEV proteomic cargo in COVID-19(+) suggests activity related to immune response processes, oxygen transport, and antioxidant mechanisms. In contrast, in HCC, sEV signature profiles are mainly associated with epithelial homeostasis.

The Impact of Candida albicans in the Development, Kinetics, Structure, and Cell Viability of Biofilms on Implant Surfaces-An In Vitro Study with a Validated Multispecies Biofilm Model.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between the control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass and a significantly higher cell viability (p < 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

Periodontal diseases and cardiovascular diseases, diabetes, and respiratory diseases: Summary of the consensus report by the European Federation of Periodontology and WONCA Europe.

BACKGROUND: Periodontitis is a chronic inflammatory non-communicable disease (NCD) characterised by the destruction of the tooth-supporting apparatus (periodontium), including alveolar bone, the presence of periodontal pockets, and bleeding on probing. OBJECTIVES: To outline, for family doctors, the implications of the association between periodontal and systemic diseases; to explore the role of family doctors in managing periodontitis as an ubiquitous non-communicable disease (NCD). METHODS: The consensus reports of previous focused collaborative workshops between WONCA Europe and the European Federation of Periodontology (using previously undertaken systematic reviews), and a specifically commissioned systematic review formed the technical papers to underpin discussions. Working groups prepared proposals independently, and the proposals were subsequently discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19 complications. Treatment of periodontitis has been associated with improvements in systemic health outcomes. The article also presents evidence gaps. Oral health care professionals (OHPs) and family doctors should collaborate in managing these conditions, including implementing strategies for early case detection of periodontitis in primary medical care centres and of systemic NCDs in oral/dental care settings. There is a need to raise awareness of periodontal diseases, their consequences, and the associated risk factors amongst family doctors. CONCLUSION: Closer collaboration between OHPs and family doctors is important in the early case detection and management of NCDs like cardiovascular diseases, diabetes mellitus, and respiratory diseases. Strategies for early case detection/prevention of NCDs, including periodontitis, should be developed for family doctors, other health professionals (OHPs), and healthcare funders. Evidence-based information on the reported associations between periodontitis and other NCDs should be made available to family doctors, OHPs, healthcare funders, patients, and the general population.

Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19.Periodontal treatment for optimal outcomes improves diabetes outcomes and surrogate measures of cardiovascular risk.Closer collaboration between oral health care professionals and family doctors is important in the early case detection and management of non-communicable diseases.Information on the reported associations should be made available to family doctors, oral health professionals, healthcare funders, patients, and the general population.

Association of Early Childhood Wheeze and Asthma Diagnosis Documentation by Race, Ethnicity, and Language in Children.

OBJECTIVE: To determine whether electronic health record (EHR) documentation of certain early childhood risk factors for asthma, such as wheeze differ by race, ethnicity, and language group, and whether these children have different subsequent asthma prevalences. METHODS: We used EHR data from the Accelerating Data Value Across a National Community Health Center (ADVANCE) Clinical Research Network from children receiving care in US community health centers (n = 71,259 children) across 21 states to examine the presence of ICD-coded documentation of early childhood wheeze and its association with subsequent asthma diagnosis documentation in the EHR by race/ethnicity/language. RESULTS: ICD-coded wheeze was present in 2 to 3% of each race/ethnicity/language group. Among the total sample, 18.5% had asthma diagnosed after age 4. The adjusted prevalence of subsequent asthma diagnosis was greater in children with wheeze than those without. Odds of asthma diagnosis did not differ among children in all race/ethnicity/language groups with early childhood wheeze. Non-Latino Black children without wheeze had higher odds of asthma (OR = 1.19, 95% CI = 1.08-1.32) compared with non-Latino White children without wheeze. DISCUSSION: In US community health centers which serve medically underserved populations, EHR documentation of early childhood wheeze was uncommon and did not differ significantly among race/ethnicity/language groups. Differences in asthma diagnosis in Latinos may not stem from differences in early-life wheeze documentation. However, our findings suggest that there may be opportunities for improvement in early asthma symptom recognition for non-Latino Black children, especially in those without early childhood wheeze.

Cross-sectional association between severe periodontitis and diabetes mellitus: A nation-wide cohort study.

AIM: To evaluate the cross-sectional association between severe periodontitis and diabetes mellitus (DM), in a representative sample of Spanish population. MATERIALS AND METHODS: The di@bet.es epidemiological study is a population-based cohort study aimed to determine the prevalence and incidence of DM in the adult population of Spain. The at-risk sample at the final examination (2016-2017) included 1751 subjects who completed an oral health questionnaire. This questionnaire, together with demographic and risk factors, had been previously validated to build an algorithm to predict severe periodontitis in the Spanish population. Logistic regression models were used to evaluate the association between severe periodontitis and DM with adjustment for confounding factors. RESULTS: In total, 144 subjects developed DM, which yielded 8.2% cumulative incidence. Severe periodontitis was detected in 59.0%, 54.7% or 68.8% of the subjects depending on three different selected criteria at the 2016-2017 exam. All criteria used to define severe periodontitis were associated with DM in unadjusted analysis, but the magnitude of the association decreased after adjusting for significant confounders. The criteria '≥50% of teeth with clinical attachment loss ≥5 mm' presented an odds ratio of 4.9 (95% confidence interval: 2.2-10.7; p ≤ .001) for DM. CONCLUSIONS: Severe periodontitis is associated with DM in the Spanish population.

Ibero-Panamerican Federation of Periodontology Delphi study on the trends of periodontology and periodontics by the year 2030. A Latin American consensus.

BACKGROUND AND OBJECTIVE: As elsewhere in the world, the prevalence of periodontitis in stages I-II is high in the Latin American population, this scenario emphasizes the need for identification of urgent needs for allocating adequate resources to provide diagnosis, prevention, and treatment of these diseases. The aim of this Delphi study was to predict the trends in periodontology/periodontics in the Latin American region by the year 2030. METHODS: A steering committee and an advisory group of experts in periodontology/periodontics were selected from 16 countries. An open questionnaire of 60 questions was validated and used following the Delphi methodology. RESULTS: Two hundred and twenty-five experts from Latin America answered the two rounds of the questionnaire. Moderate to strong consensus was reached on 45 questions (75%). The prediction was that the prevalence of gingivitis and periodontitis in stages I and II will be maintained, the importance of the link with systemic diseases will increase, and the impact of prevention and periodontal treatment will also increase, mainly in the private sector. There was a strong consensus that plastic and regenerative surgical procedures will increase, as well as the demand for training in the specialty of periodontology. CONCLUSIONS: The present study has provided relevant and useful information on predictions in periodontology/periodontics in Latin America, with important level of consensus among experts. It has been predicted that periodontitis will still be a highly prevalent disease, and its links with other medical conditions should demand more attention by health authorities to develop adequate prevention and management policies and strategies.

Colonic Anastomoses Reinforced With Ethyl-2-Cyanoacrylate Compared With Polydioxanone Sutures Alone in Fecal Peritonitis: An Experimental Study in Wistar Rats.

INTRODUCTION: The use of tissue adhesives has been proposed as an anastomosis reinforcement; however, their efficacy has not been evaluated in a contaminated environment. The objective of this study was to determine if the use of sutures reinforced with ethyl-2-cyanoacrylate for colonic anastomoses in the presence of fecal peritonitis, in a murine animal model, decreases the frequency of dehiscence. METHODS: Wistar rats were used. Fecal peritonitis was established until reaching 18 hours of evolution. Then, resection and anastomosis of the colon were performed with only polydioxanone (PDS) sutures in the control group and reinforcement with ethyl-2-cyanoacrylate in the experimental group. The dehiscence frequency and burst pressure were evaluated six days after the anastomosis was performed. RESULTS: We included 30 Wistar rats, all males, with a median age of five months and an average weight of 350.43 g. Anastomotic dehiscence was observed in 53.33% of the control group, in contrast with 13.33% of the experimental group (p = 0.020). There was no significant difference in burst pressure between the two groups. CONCLUSION: The use of ethyl-2-cyanoacrylate, in an experimental murine animal model, as reinforcement in colonic anastomoses in the presence of fecal peritonitis decreases the frequency of anastomotic dehiscence, although it does not increase resistance to burst pressure.

Material didáctico para el desarrollo de la competencia comunicativa audio-oral en la educación médica de posgrado

Fundamento: El conocimiento del inglés como el idioma empleado globalmente en diversos sectores, se ha convertido, junto a las tecnologías de la información y las comunicaciones, es una herramienta de formación, trabajo y entretenimiento indispensable; el dominio de este posibilita las relaciones de cooperación e intercambio de profesionales del sector de la salud en varios países. Objetivo: Diseñar un material didáctico para el desarrollo de la competencia comunicativa audio-oral en inglés en estudiantes de posgrado de la carrera de Medicina, mediante el empleo de tecnologías de la información y la comunicación. Metodología: Se realizó una investigación de desarrollo con enfoque mixto en la Universidad de Ciencias Médicas de Holguín durante el período marzo-julio de 2022. Se asumió el método dialéctico materialista como concepción general de la investigación y se emplearon otros del nivel teórico: histórico-lógico, análisis y síntesis e inducción deducción, sistémico-estructural-funcional y revisión documental; empíricos: encuesta, entrevista y observación participativa. Resultados: Las principales dificultades estuvieron relacionadas con el insuficiente tratamiento de la competencia comunicativa audio-oral en inglés, se constató la importancia de la misma dentro del proceso de enseñanza-aprendizaje del inglés, pues establece las pautas generales que se deben seguir para una comunicación efectiva y se instituye desde una mirada holística del acto comunicativo del profesional. Conclusiones: Los especialistas valoraron el material como adecuado por su estructura y factibilidad para su implementación. Después de su aplicación se evidenció su efectividad en la consolidación del aprendizaje en este nivel educacional a través de la preparación idiomática.

Background: Knowledge of English as the language used globally in various sectors, has increasingly become, together with information and communications technologies, an indispensable training, work and entertainment tool in the current era. Its domain enables cooperation relations and exchange of professionals in the health sector in various countries. Objective: To design a didactic material for the development of audio-oral communicative competence in English in postgraduate medical students, through the use of Information and Communication Technologies (ICT). Methods: A development research with a mixed approach was carried out at the Holguín University of Medical Sciences during the period March-July 2022. It was assumed the dialectical materialist method as the general conception of the research and others of the theoretical level: historical- logical, analysis and synthesis and induction deduction, systemic-structural-functional and documentary review; empirical: survey, interview and participatory observation. Results: The main difficulties were related to an insufficient treatment of audio-oral communicative competence in English, it was confirmed its importance within the teaching-learning process of English, since it establishes the general guidelines that must be followed for an effective communication. Moreover, it is instituted from a holistic view of the professional communicative act. Conclusions: The specialists assessed the material as adequate due to its structure and feasibility for its implementation. After its application, it was evidenced its effectiveness in consolidating learning in this educational level through language training.

Molecular cloning of the gene promoter encoding the human CaVγ2/Stargazin divergent transcript (CACNG2-DT): characterization and regulation by the cAMP-PKA/CREB signaling pathway.

CaVγ2 (Stargazin or TARPγ2) is a protein expressed in various types of neurons whose function was initially associated with a decrease in the functional expression of voltage-gated presynaptic Ca2+ channels (CaV) and which is now known to promote the trafficking of the postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) towards the cell membrane. Alterations in CaVγ2 expression has been associated with several neurological disorders, such as absence epilepsy. However, its regulation at the transcriptional level has not been intensively addressed. It has been reported that the promoter of the Cacng2 gene, encoding the rat CaVγ2, is bidirectional and regulates the transcription of a long non-coding RNA (lncRNA) in the antisense direction. Here, we investigate the proximal promoter region of the human CACNG2 gene in the antisense direction and show that this region includes two functional cAMP response elements that regulate the expression of a lncRNA called CACNG2-DT. The activity of these sites is significantly enhanced by forskolin, an adenylate cyclase activator, and inhibited by H89, a protein kinase A (PKA) antagonist. Therefore, this regulatory mechanism implies the activation of G protein-coupled receptors and downstream phosphorylation. Interestingly, we also found that the expression of CACNG2-DT may increase the levels of the CaVγ2 subunit. Together, these data provide novel information on the organization of the human CACNG2-DT gene promoter, describe modulatory domains and mechanisms that can mediate various regulatory inputs, and provide initial information on the molecular mechanisms that regulate the functional expression of the CaVγ2 protein.

[Systolic blood pressure reduction in patients with intracranial hemorrhage and functional prognosis]. / Reducción de la presión arterial sistólica en pacientes con hemorragia intracraneal y pronóstico funcional.

Background: Acute intracerebral hemorrhage affects annually more than 1 million people worldwide. Chronic systemic arterial hypertension is the most important modifiable risk factor for spontaneous intracerebral hemorrhage. Objective: To determine the relationship between the decrease in systolic blood pressure (SBP) in patients with intracranial hemorrhage and their short-term functional prognosis. Material and methods: Observational, longitudinal, prospective study in patients with intraparenchymal hemorrhage secondary to hypertensive dyscontrol, older than 18 years, of both sexes. Blood pressure was recorded at admission, every hour during the first 6 hours and every two hours from 8 to 24 hours after admission. Functionality was assessed using the modified Rankin scale at admission, at 6 and 24 hours after admission. Results: 58 patients were included, in whom the reduction of systolic blood pressure at admission was 17.04% and at 24 hours was 31.3 mm Hg; the mean systolic blood pressure was 183.62 mm Hg as opposed to 152.3 mm Hg at discharge (p < 0.001). Conclusions: In the first 6 hours, reduction in ASR is significantly associated with hospital outcome in patients with intracranial hemorrhage. A linear association was observed with improvement and favorable functional prognosis as measured by the modified Rankin scale.

Introducción: la hemorragia intracerebral aguda afecta anualmente a más de un millón de personas en todo el mundo. La hipertensión arterial sistémica crónica es el factor de riesgo modificable más importante para la hemorragia intracerebral espontánea. Objetivo: determinar la relación entre la disminución de la presión arterial sistólica (TAS) en pacientes con hemorragia intracraneal y su pronóstico funcional a corto plazo. Métodos: estudio observacional, longitudinal, prospectivo, en pacientes con hemorragia intraparenquimatosa secundaria a descontrol hipertensivo, mayores de 18 años, de ambos sexos. Se realizaron registros de presión arterial al ingreso, cada hora durante las primeras seis horas y cada dos horas desde las ocho a las 24 horas posterior al ingreso. Se evaluó funcionalidad mediante escala de Rankin modificada al ingreso, a las seis y a las 24 horas después del ingreso. Resultados: se incluyeron 58 pacientes, en quienes la reducción de la TAS al ingreso fue de 17.04% y a las 24 horas fue de 31.3 mm Hg de la presión arterial sistólica; la media de la TAS fue de 183.62 mm Hg a diferencia de la registrada al egreso, que fue de 152.3 mm Hg (p < 0.001). Conclusiones: en las primeras seis horas, la reducción de la TAS está significativamente asociada con el resultado hospitalario en pacientes con hemorragia intracraneal. Se observó una asociación lineal con la mejoría y un pronóstico funcional favorable, medido por la escala de Rankin modificada.

Screening for Hepatitis C Among Community Health Center Patients by Ethnicity and Language Preference.

Introduction: Hepatitis C virus is associated with high morbidity and mortality-chronic liver disease is a leading cause of death among Latinos in the U.S. Screening for hepatitis C virus in community health center settings, which serve a disproportionate percentage of Latinos, is essential to eradicating hepatitis C virus infection. We assessed hepatitis C virus screening disparities in adults served by community health centers by ethnicity and language preference. Methods: This was an observational cohort study (spanning 2013-2017) of adults born in 1945-1965 in the Accelerating Data Value Across a National Community Health Center Network electronic health record data set. Our exposure of interest was race/ethnicity and language preference (non-Hispanic White, Latino English preferred, Latino Spanish preferred). Our primary outcome was the relative hazard of hepatitis C virus screening, estimated using multivariate Cox proportional hazards regression. Results: A total of 182,002 patients met the study criteria and included 60% non-Hispanic Whites, 29% Latino Spanish preferred, and 11% Latino English preferred. In total, 9% received hepatitis C virus screening, and 2.4% were diagnosed with hepatitis C virus. Latino English-preferred patients had lower rates of screening than both non-Hispanic Whites and Latino Spanish preferred (5.5% vs 9.4% vs 9.6%, respectively). Latino English preferred had lower hazards of hepatitis C virus screening than non-Hispanic Whites (adjusted hazard ratio=0.56, 95% CI=0.44, 0.72), and Latino Spanish preferred had similar hazards of hepatitis C virus screening (adjusted hazard ratio=1.11, 95% CI=0.88, 1.41). Conclusions: We found that in a large community health center network, adult Latinos who preferred English had lower hazards of hepatitis C virus screening than non-Hispanic Whites, whereas Latinos who preferred Spanish had hazards of screening similar to those of non-Hispanic Whites. The overall prevalence of hepatitis C virus screening was low. Further work on the role of language preference in hepatitis C virus screening is needed to better equip primary care providers to provide this recommended preventive service in culturally relevant ways.

Molecular detection of bovine leukosis virus in naturally infected dairy and dual-purpose cattle in Mexico.

The objective of this study was to determine the prevalence of bovine leukosis virus (BLV) in specialized and dual-purpose dairy cows located in the central zone of Veracruz state in Mexico, using endpoint polymerase chain reaction (PCR). The study population consisted of 307 specialized dairy cows and 95 dual-purpose cows from 13 municipalities located in the study area. All cows were apparently healthy and ≥ 3 years old. Cows were stratified by age (3 - 5, 6 - 8 and ≥ 9 years). The overall prevalence of infection was 6.96%; the calculated prevalence in dairy cows was 7.82% and in dual-purpose cows it was 4.21%. The municipality with the highest proportion was Acajete (14.28%), followed by Huatusco and Tomatlán (11.53%). The association analysis confirms the infection's independence to the cows' productive purpose. The results by age strata were 3 - 5 (4.60%), 6 - 8 (8.00%) and ≥ 9 (18.40%) with X2 = 9.96, with an odds ratio of 4.68 for the stratum ≥ 9 years with a significant difference. The present study determined the prevalence of proviral DNA of BLV in dairy and dual-purpose cows in six municipalities in the central zone of Veracruz state, Mexico, using endpoint PCR.

Uptake of a Cervical Cancer Clinical Decision Support Tool: A Mixed-Methods Study.

OBJECTIVES: Clinical decision support (CDS) tools that provide point-of-care reminders of patients' care needs may improve rates of guideline-concordant cervical cancer screening. However, uptake of such electronic health record (EHR)-based tools in primary care practices is often low. This study describes the frequency of factors associated with, and barriers and facilitators to adoption of a cervical cancer screening CDS tool (CC-tool) implemented in a network of community health centers. METHODS: This mixed-methods sequential explanatory study reports on CC-tool use among 480 community-based clinics, located across 18 states. Adoption of the CC-tool was measured as any instance of tool use (i.e., entry of cervical cancer screening results or follow-up plan) and as monthly tool use rates from November 1, 2018 (tool release date) to December 31, 2020. Adjusted odds and rates of tool use were evaluated using logistic and negative-binomial regression. Feedback from nine clinic staff representing six clinics during user-centered design sessions and semi-structured interviews with eight clinic staff from two additional clinics were conducted to assess barriers and facilitators to tool adoption. RESULTS: The CC-tool was used ≥1 time in 41% of study clinics during the analysis period. Clinics that ever used the tool and those with greater monthly tool use had, on average, more encounters, more patients from households at >138% federal poverty level, fewer pediatric encounters, higher up-to-date cervical cancer screening rates, and higher rates of abnormal cervical cancer screening results. Qualitative data indicated barriers to tool adoption, including lack of knowledge of the tool's existence, understanding of its functionalities, and training on its use. CONCLUSION: Without effective systems for informing users about new EHR functions, new or updated EHR tools are unlikely to be widely adopted, reducing their potential to improve health care quality and outcomes.

Design and validation of a quantitative polymerase chain reaction test for the identification and quantification of uncultivable bacteria associated with periodontitis.

OBJECTIVE: This study aimed to standardize a quantitative polymerase chain reaction (qPCR)-based test to identify and quantify the uncultivable bacteria associated with periodontitis. METHODS: The standardization of qPCR, the curves for the quantification of Eubacterium saphenum, Eubacterium brachy, Desulfobulbus oralis, and Filifactor alocis were developed by cloning the 16 S rRNA target gene fragment, using the GEMTEasy vector. The qPCRs were validated in 55 subgingival biofilm clinical samples, from different stages of periodontitis and from periodontally healthy/gingivitis individuals, which were previously evaluated by next-generation sequencing (NGS). The results obtained by the two methods were compared by the concordance of Cohen's Kappa index, and sensitivity, specificity, receiver operating characteristic (ROC) curve, and predictive values were established. RESULTS: obtained by the two methods were compared using the concordance of Cohen's Kappa index, and sensitivity, specificity, predictive values, and ROC curves were generated. The qPCR test was standardized with efficiencies between 90% and 100% and R2: 0.997-0.999. Concordance between the qPCR and NSG was moderate to F. alocis (agreement 78.2%; kappa 0.56, p < 0.05) and fair to the other microorganisms (agreement 67.27%-72.73; kappa 0.37-0.38, p < 0.05). qPCR exhibited a high sensitivity (82.2-100%) and specificity (100%) for E. brachy, E. saphenum, and F. alocis. Sensitivity was lower to D. oralis. Conversely, qPCR demonstrated higher sensitivity to E. saphenum than NSG (100 vs. 68.1). CONCLUSIONS: The uncultivable microorganisms associated with periodontitis, D. oralis, E. brachy, E. saphenum, and F. alocis can be detected and quantified with the newly developed and validates qPCR test.

D-galactose Supplementation for the Treatment of Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE): A Pilot Trial of Precision Medicine After Epilepsy Surgery.

MOGHE is defined as mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Approximately half of the patients with histopathologically confirmed MOGHE carry a brain somatic variant in the SLC35A2 gene encoding a UDP-galactose transporter. Previous research showed that D-galactose supplementation results in clinical improvement in patients with a congenital disorder of glycosylation due to germline variants in SLC35A2. We aimed to evaluate the effects of D-galactose supplementation in patients with histopathologically confirmed MOGHE, with uncontrolled seizures or cognitive impairment and epileptiform activity at the EEG after epilepsy surgery (NCT04833322). Patients were orally supplemented with D-galactose for 6 months in doses up to 1.5 g/kg/day and monitored for seizure frequency including 24-h video-EEG recording, cognition and behavioral scores, i.e., WISC, BRIEF-2, SNAP-IV, and SCQ, and quality of life measures, before and 6 months after treatment. Global response was defined by > 50% improvement of seizure frequency and/or cognition and behavior (clinical global impression of "much improved" or better). Twelve patients (aged 5-28 years) were included from three different centers. Neurosurgical tissue samples were available in all patients and revealed a brain somatic variant in SLC35A2 in six patients (non-present in the blood). After 6 months of supplementation, D-galactose was well tolerated with just two patients presenting abdominal discomfort, solved after dose spacing or reduction. There was a 50% reduction or higher of seizure frequency in 3/6 patients, with an improvement at EEG in 2/5 patients. One patient became seizure-free. An improvement of cognitive/behavioral features encompassing impulsivity (mean SNAP-IV - 3.19 [- 0.84; - 5.6]), social communication (mean SCQ - 2.08 [- 0.63; - 4.90]), and executive function (BRIEF-2 inhibit - 5.2 [- 1.23; - 9.2]) was observed. Global responder rate was 9/12 (6/6 in SLC35A2-positive). Our results suggest that supplementation with D-galactose in patients with MOGHE is safe and well tolerated and, although the efficacy data warrant larger studies, it might build a rationale for precision medicine after epilepsy surgery.

Osteogenic differentiation of adipose-derived canine mesenchymal stem cells seeded in porous calcium-phosphate scaffolds.

Introduction: Engineered bone graft substitutes are a promising alternative and supplement to autologous bone grafts as treatments for bone healing impairment. Advances in human medicine extend an invitation to pursue these biomimetic strategies in animal patients, substantiated by the theory that specialized scaffolds, multipotent cells, and biological cues may be combined into a bioactive implant intended for the enhancement of tissue regeneration. Methods: This proof-of-concept study was designed to evaluate and validate the feasibility of beta-tricalcium phosphate foam scaffolds seeded with canine mesenchymal stem cells derived from adipose tissue. Cell-inoculated samples and sham controls were cultured statically for 72 hours in complete growth medium to evaluate seeding capacity, while a subset of loaded scaffolds was further induced with osteogenic culture medium for 21 days. Produced implants were characterized and validated with a combination of immunofluorescence and reflection confocal microscopy, scanning electron microscopy, and polymerase chain reaction to confirm osteogenic differentiation in tridimensional-induced samples. Results: After 72 hours of culture, all inoculated scaffolds presented widespread yet heterogeneous surface seeding, distinctively congregating stem cells around pore openings. Furthermore, at 21 days of osteogenic culture conditions, robust osteoblastic differentiation of the seeded cells was confirmed by the change of cell morphology and evident deposition of extra-cellular matrix, accompanied by mineralization and scaffold remodeling; furthermore, all induced cell-loaded implants lost specific stemness immunophenotype expression and simultaneously upregulated genomic expression of osteogenic genes Osterix and Ostecalcin. Conclusions: ß-TCP bio-ceramic foam scaffolds proved to be suitable carriers and hosts of canine adipose-derived MSCs, promoting not only surface attachment and proliferation, but also demonstrating strong in-vitro osteogenic potential. Although this research provides satisfactory in-vitro validation for the conceptualization and feasibility of a canine bio-active bone implant, further testing such as patient safety, large-scale reproducibility, and quality assessment are needed for regulatory compliance in future commercial clinical applications.

Europe's contribution to the evaluation of the use of systemic antimicrobials in the treatment of periodontitis.

This narrative review celebrates Europe's contribution to the current knowledge on systemically administered antimicrobials in periodontal treatment. Periodontitis is the most frequent chronic noncommunicable human disease. It is caused by dysbiotic bacterial biofilms and is commonly treated with subgingival instrumentation. However, some sites/patients do not respond adequately, and its limitations and shortcomings have been recognized. This has led to the development of alternative or adjunctive therapies. One is the use of antimicrobials to target bacteria in subgingival biofilms in the periodontal pocket, which can be targeted directly through the pocket entrance with a locally delivered antibiotic or systemically by oral, intravenous, or intramuscular methods. Since the early 20th century, several studies on systemic antibiotics have been undertaken and published, especially between 1990 and 2010. Europe's latest contribution to this topic is the first European Federation of Periodontology, S3-level Clinical Practice Guideline, which incorporates recommendations related to the use of adjuncts to treat stage I-III periodontitis. Understanding the etiopathogenesis of periodontal diseases, specifically periodontitis, has influenced the use of systemic periodontal antibiotic therapy. Randomized clinical trials and systematic reviews with meta-analyses have demonstrated the clinical advantages of adjunctive systemic antimicrobials. However, current recommendations are restrictive due to concerns about antibiotic misuse and the increase in microbial antibiotic resistance. European researchers have contributed to the use of systemic antimicrobials in the treatment of periodontitis through clinical trials and by providing rational guidelines. Nowadays, European researchers are exploring alternatives and directing clinical practice by providing evidence-based guidelines to limit the use of systemic antimicrobials.

Prevention and treatment of peri-implant diseases-The EFP S3 level clinical practice guideline.

BACKGROUND: The recently published Clinical Practice Guidelines (CPGs) for the treatment of stages I-IV periodontitis provided evidence-based recommendations for treating periodontitis patients, defined according to the 2018 classification. Peri-implant diseases were also re-defined in the 2018 classification. It is well established that both peri-implant mucositis and peri-implantitis are highly prevalent. In addition, peri-implantitis is particularly challenging to manage and is accompanied by significant morbidity. AIM: To develop an S3 level CPG for the prevention and treatment of peri-implant diseases, focusing on the implementation of interdisciplinary approaches required to prevent the development of peri-implant diseases or their recurrence, and to treat/rehabilitate patients with dental implants following the development of peri-implant diseases. MATERIALS AND METHODS: This S3 level CPG was developed by the European Federation of Periodontology, following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, formulation of specific recommendations, and a structured consensus process involving leading experts and a broad base of stakeholders. RESULTS: The S3 level CPG for the prevention and treatment of peri-implant diseases culminated in the recommendation for implementation of various different interventions before, during and after implant placement/loading. Prevention of peri-implant diseases should commence when dental implants are planned, surgically placed and prosthetically loaded. Once the implants are loaded and in function, a supportive peri-implant care programme should be structured, including periodical assessment of peri-implant tissue health. If peri-implant mucositis or peri-implantitis are detected, appropriate treatments for their management must be rendered. CONCLUSION: The present S3 level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to maintain healthy peri-implant tissues, and to manage peri-implant diseases, according to the available evidence at the time of publication.

Oral and systemic health: is there a "new" link with COVID-19?

OBJECTIVES: The objective of the present narrative review was to evaluate the evidence of a possible association between periodontitis and COVID-19, and its biological plausibility, using as models the potential associations with cardiovascular diseases, diabetes, and some respiratory diseases. METHODS: A recent systematic review was used as main reference to explore the associations of periodontitis with different respiratory diseases, including COVID-19, following two focussed questions: a PECOS question, aimed to explore epidemiological evidence, and a PICOS question, designed to explore the evidence derived from intervention studies. In addition to that evidence, other relevant scientific documents, including consensus papers, were carefully selected and appraised. FINDINGS: Convincing evidence was found to support the association of periodontitis and cardiovascular diseases, diabetes, and some respiratory diseases. The biological plausibility behind those associations is based on four factors: (1) bacteraemia of oral bacteria and periodontal pathogens, (2) increased systemic inflammation, (3) common genetic factors, and (4) common environmental risk factors. Limited initial evidence is available to support an association between periodontitis and COVID-19 complications. Among the proposed factors to explain the suggested association, a combination of the previously mentioned factors, plus additional factors related with SARS-CoV-2 characteristics and pathogenicity, has been suggested. CONCLUSIONS: Initial evidence suggests that periodontitis may be associated with a more severe COVID-19 and with a higher risk of death due to COVID-19. CLINICAL RELEVANCE: Due to the possible association between periodontitis and an increased severity for COVID-19, additional efforts should be made to improve oral and periodontal health, including the promotion of oral healthy habits, such as oral hygiene.

Molecular Mechanisms of Nuclear Transport of the Neuronal Voltage-gated Ca2+ Channel ß3 Auxiliary Subunit.

Previous studies have shown that in addition to its role within the voltage-gated calcium channel complex in the plasma membrane, the neuronal CaVß subunit can translocate to the cell nucleus. However, little is known regarding the role this protein could play in the nucleus, nor the molecular mechanism used by CaVß to enter this cell compartment. This report shows evidence that CaVß3 has nuclear localization signals (NLS) that are not functional, suggesting that the protein does not use a classical nuclear import pathway. Instead, its entry into the nucleus could be associated with another protein that would function as a carrier, using a mechanism known as a piggyback. Mass spectrometry assays and bioinformatic analysis allowed the identification of proteins that could be participating in the entry of CaVß3 into the nucleus. Likewise, through proximity ligation assays (PLA), it was found that members of the heterogeneous nuclear ribonucleoproteins (hnRNPs) and B56δ, a regulatory subunit of the protein phosphatase 2A (PP2A), could function as proteins that regulate this piggyback mechanism. On the other hand, bioinformatics and site-directed mutagenesis assays allowed the identification of a functional nuclear export signal (NES) that controls the exit of CaVß3 from the nucleus, which would allow the completion of the nuclear transport cycle of the protein. These results reveal a novel mechanism for the nuclear transport cycle of the neuronal CaVß3 subunit.