Evaluation of soluble P-selectin as a predictive biomarker in acute symptomatic pulmonary embolism: Insights from a prospective observational study.

BACKGROUND: Soluble P-selectin (sP-selectin) has been proposed as a potential biomarker for venous thromboembolism (VTE) diagnosis with interesting results. However, its role in predicting early mortality in pulmonary embolism (PE) remains unexplored. METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 or older with confirmed acute symptomatic PE and no prior anticoagulation. The study aims to assess the prognostic capacity of sP-selectin measured at the time of PE diagnosis for short-term mortality and major bleeding. RESULTS: A total of 196 patients, with a mean age of 69.1 years (SD 17), were included, of whom 52.6% were male. Within 30 days, 9.7% of patients (n = 19) died, and 5.1% (n = 10) suffered major bleeding. PE risk stratification revealed 4.6% (n = 9) with high-risk PE, 34.7% (n = 68) with intermediate-high-risk PE, 38.3% (n = 75) with intermediate-low-risk PE, and 22.5% (n = 44) with low-risk PE according to the European Society of Cardiology score. Mean plasma sP-selectin levels were comparable between survivors and non-survivors (489.7 ng/mL ±63 vs. 497.3 ng/mL ±51; p = .9). The ROC curve for 30-day all-cause mortality and major bleeding yielded an AUC of 0.49 (95% CI 0.36-0.63) and 0.46 (95% CI 0.24-0.68), respectively. Multivariate and survival analyses were precluded due to lack of significance. CONCLUSIONS: sP-selectin was not useful for predicting short-term mortality or major bleeding in patients with acute symptomatic pulmonary embolism. Further studies are required to clarify the role of sP-selectin in VTE, particularly in prognosticating PE outcomes.

Platypnea-Orthodeoxia Syndrome and COVID-19 Successfully Treated With Percutaneous Patent Foramen Ovale Closure: A Report of Two Cases and Literature Review.

Platypnea-orthodeoxia syndrome (POS) is a rare clinical condition characterized by positional dyspnea and/or hypoxia. We report two cases of patients with COVID-19 bronchopneumonia with a torpid evolution. Due to clinical suspicion of POS, a diagnostic workup was performed, including a bubble echocardiography, which revealed a patent foramen ovale (PFO) with early and massive passage of bubbles to the left cavities. Both patients underwent percutaneous PFO closure with a resolution of POS. Here, we present the second and third cases of POS associated with PFO successfully closed during the acute phase of COVID-19. This suggests that PFO closure could be a potential treatment option for this condition.

Efficacy of Omalizumab for the treatment of Bullous Pemphigoid. Spanish multicenter real-world experience.

BACKGROUND: Bullous Pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are elderly and associate multiple comorbidities. Topical and systemic corticosteroids are considered as the first-line treatment for BP and immunosuppressors are used as steroid-sparing treatments but both have side effects and contraindications which are even more common in this elderly population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease this side effects while achieving equal or better effectiveness response rates.Omalizumab is a monoclonal antibody that targets IgE that has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. OBJECTIVES AND METHODOLOGY: To assess the efficacy and security of Omalizumab for the treatment of BP, we carried out a multicenter, retrospective, observational study including patients diagnosed of BP who received omalizumab for at least 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment was measured and we evaluate the possible correlation with clinical response. We excluded patients treated with Omalizumab for less than 3 months as we consider this duration is insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment we used the percentage of BSA improvement. RESULTS: We included 36 patients. The vast majority associate multiple comorbidities and all patients had used other systemic therapies apart from corticoids before Omalizumab.83% experienced some kind of treatment response and 42% of all patient treated achieved complete response.We did not find any correlation between higher levels and a better response (p=0,1791).All patients tolerated Omalizumab without reported side-effects. CONCLUSIONS: Omalizumab is a good therapeutic alternative for BP as it obtained clinical response in most patients and nearly half of the cases achieving complete response. It showed no side effects which is crucial in elderly patients suffering from BP.

Evolution of spontaneous portosystemic shunts over time and following aetiological intervention in patients with cirrhosis.

Background & Aims: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. Methods: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. Results: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n = 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n = 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122 mm2, p <0.001). Conclusions: The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased. Impact and implications: There is no information regarding the evolution of spontaneous portosystemic shunts (SPSS) during the course of cirrhosis, and especially after disease regression with aetiological interventions, such as HCV treatment with direct-acting antivirals or alcohol abstinence. These results are relevant for clinicians dealing with patients with cirrhosis and portal hypertension because they have important implications for the management of cirrhosis with SPSS after disease regression. From a practical point of view, physicians should be aware that in advanced cirrhosis with portal hypertension, after aetiological intervention, SPSS mostly persist despite liver function improvement, and complications related to SPSS may still develop.

Impact of Non-Surgical Periodontal Treatment on the Concentration and Level of MRP-8/14 (Calprotectin) as an Inflammatory Biomarker in Women with Periodontitis and Rheumatoid Arthritis: A Quasi-Experimental Study.

The aim of this study was to evaluate the impact of non-surgical periodontal treatment (NS-PT) on periodontal parameters and inflammatory biomarkers in the concentration and level of calprotectin (CLP) in women with periodontitis and rheumatoid arthritis (RA). In this quasi-experimental study, we evaluated 30 women (mean age: 52.0 ± 5.8 years) with periodontitis and RA who had been diagnosed and treated for RA for more than 3 years and whose activity markers remained at similar values without significant reduction over three consecutive months. Patients underwent NS-PT, which included plaque control, scaling, and root planing. Serum and saliva samples, periodontal indices, RA activity markers, Disease Activity Score-28 (DAS28), the erythrocyte sedimentation rate (ESR), and the C-reactive protein (CRP) and CLP contents were measured at the beginning of the study and 6 and 12 weeks after NS-PT. Parametric and nonparametric tests were used in the analysis. The mean age was 52.0 ± 5.8 years. Compared to the baseline results, all periodontal indices were significantly reduced 6 and 12 weeks after NS-PT (p < 0.001). DAS28 was also significantly reduced after 12 weeks (p < 0.0001). Similarly, the serum CLP concentration decreased 6 and 12 weeks after NS-PT (p < 0.0001). Of the patients, 100% presented lower levels of CRP and ESR (p < 0.0001). Overall, NS-PT reduced inflammation and disease activity, highlighting the importance of oral health in the control and treatment of systemic diseases such as RA and confirming that NS-PT effectively reduces periodontitis activity and plays a key role in modulating RA activity. Therefore, NS-PT should be considered as an adjunct treatment for RA.

Long non-coding RNA SNHG8 drives stress granule formation in tauopathies.

Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in the MAPT gene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream of MAPT mutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts >200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying a MAPT p.P301L, IVS10 + 16, or p.R406W mutation and CRISPR-corrected isogenic controls, we identified transcriptomic changes that occur as a function of the MAPT mutant allele. We identified 15 lncRNAs that were commonly differentially expressed across the three MAPT mutations. The commonly differentially expressed lncRNAs interact with RNA-binding proteins that regulate stress granule formation. Among these lncRNAs, SNHG8 was significantly reduced in a mouse model of tauopathy and in FTLD-tau, progressive supranuclear palsy, and Alzheimer's disease brains. We show that SNHG8 interacts with tau and stress granule-associated RNA-binding protein TIA1. Overexpression of mutant tau in vitro is sufficient to reduce SNHG8 expression and induce stress granule formation. Rescuing SNHG8 expression leads to reduced stress granule formation and reduced TIA1 levels in immortalized cells and in MAPT mutant neurons, suggesting that dysregulation of this non-coding RNA is a causal factor driving stress granule formation via TIA1 in tauopathies.

Bactericidal Activity of Silver Nanoparticles on Oral Biofilms Related to Patients with and without Periodontal Disease.

BACKGROUND AND OBJECTIVES: Periodontal disease (PD) is a multifactorial oral disease regularly caused by bacterial biofilms. Silver nanoparticles (AgNP) have offered good antimicrobial activity; moreover, there is no available scientific information related to their antimicrobial effects in biofilms from patients with PD. This study reports the bactericidal activity of AgNP against oral biofilms related to PD. MATERIALS AND METHODS: AgNP of two average particle sizes were prepared and characterized. Sixty biofilms were collected from patients with (30 subjects) and without PD (30 subjects). Minimal inhibitory concentrations of AgNP were calculated and the distribution of bacterial species was defined by polymerase chain reaction. RESULTS: Well-dispersed sizes of AgNP were obtained (5.4 ± 1.3 and 17.5 ± 3.4 nm) with an adequate electrical stability (-38.2 ± 5.8 and -32.6 ± 5.4 mV, respectively). AgNP showed antimicrobial activities for all oral samples; however, the smaller AgNP had significantly the most increased bactericidal effects (71.7 ± 39.1 µg/mL). The most resistant bacteria were found in biofilms from PD subjects (p < 0.05). P. gingivalis, T. denticola, and T. forsythia were present in all PD biofilms (100%). CONCLUSIONS: The AgNP showed efficient bactericidal properties as an alternative therapy for the control or progression of PD.

A systematic review of the protein composition of whole saliva in subjects with healthy periodontium compared with chronic periodontitis.

CONTEXT: Periodontitis is a chronic multifactorial inflammatory disease linked to oral microbiota dysbiosis. This disease progresses to infection that stimulates a host immune/inflammatory response, with progressive destruction of the tooth-supporting structures. OBJECTIVE: This systematic review aims to present a robust critical evaluation of the evidence of salivary protein profiles for identifying oral diseases using proteomic approaches and summarize the use of these approaches to diagnose chronic periodontitis. DATA SOURCES: A systematic literature search was conducted from January 1st, 2010, to December 1st, 2022, based on PICO criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and by searching the three databases Science Direct, Scopus, and Springer Link. STUDY SELECTION: According to the inclusion criteria, eight studies were identified to analyze the proteins identified by proteomics. RESULTS: The protein family S100 was identified as the most abundant in patients with chronic periodontitis. In this family, an increased abundance of S100A8 and S100A9 from individuals with the active disease was observed, which strongly relates to the inflammatory response. Moreover, the ratio S100A8/S100A9 and the metalloproteinase-8 in saliva could differentiate distinct periodontitis groups. The changes in protein profile after non-surgical periodontal therapy improved the health of the buccal area. The results of this systematic review identified a set of proteins that could be used as a complementary tool for periodontitis diagnosis using salivary proteins. CONCLUSION: Biomarkers in saliva can be used to monitor an early stage of periodontitis and the progression of the disease following therapy.

Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation.

TREM2 is an innate immune receptor expressed by microglia in the adult brain. Genetic variation in the TREM2 gene has been implicated in risk for Alzheimer's disease and frontotemporal dementia, while homozygous TREM2 mutations cause a rare leukodystrophy, Nasu-Hakola disease (NHD). Despite extensive investigation, the role of TREM2 in NHD pathogenesis remains poorly understood. Here, we investigate the mechanisms by which a homozygous stop-gain TREM2 mutation (p.Q33X) contributes to NHD. Induced pluripotent stem cell (iPSC)-derived microglia (iMGLs) were generated from two NHD families: three homozygous TREM2 p.Q33X mutation carriers (termed NHD), two heterozygous mutation carriers, one related non-carrier, and two unrelated non-carriers. Transcriptomic and biochemical analyses revealed that iMGLs from NHD patients exhibited lysosomal dysfunction, downregulation of cholesterol genes, and reduced lipid droplets compared to controls. Also, NHD iMGLs displayed defective activation and HLA antigen presentation. This defective activation and lipid droplet content were restored by enhancing lysosomal biogenesis through mTOR-dependent and independent pathways. Alteration in lysosomal gene expression, such as decreased expression of genes implicated in lysosomal acidification (ATP6AP2) and chaperone mediated autophagy (LAMP2), together with reduction in lipid droplets were also observed in post-mortem brain tissues from NHD patients, thus closely recapitulating in vivo the phenotype observed in iMGLs in vitro. Our study provides the first cellular and molecular evidence that the TREM2 p.Q33X mutation in microglia leads to defects in lysosomal function and that compounds targeting lysosomal biogenesis restore a number of NHD microglial defects. A better understanding of how microglial lipid metabolism and lysosomal machinery are altered in NHD and how these defects impact microglia activation may provide new insights into mechanisms underlying NHD and other neurodegenerative diseases.

Long non-coding RNA SNHG8 drives stress granule formation in tauopathies.

Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in the MAPT gene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream of MAPT mutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts >200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying a MAPT p.P301L, IVS10+16, or p.R406W mutation, and CRISPR-corrected isogenic controls, we identified transcriptomic changes that occur as a function of the MAPT mutant allele. We identified 15 lncRNAs that were commonly differentially expressed across the three MAPT mutations. The commonly differentially expressed lncRNAs interact with RNA-binding proteins that regulate stress granule formation. Among these lncRNAs, SNHG8 was significantly reduced in a mouse model of tauopathy and in FTLD-tau, progressive supranuclear palsy, and Alzheimer’s disease brains. We show that SNHG8 interacts with tau and stress granule-associated RNA-binding protein TIA1. Overexpression of mutant tau in vitro is sufficient to reduce SNHG8 expression and induce stress granule formation. Rescuing SNHG8 expression leads to reduced stress granule formation and reduced TIA1 levels, suggesting that dysregulation of this non-coding RNA is a causal factor driving stress granule formation via TIA1 in tauopathies.

Conserved gene signatures shared among MAPT mutations reveal defects in calcium signaling.

Introduction: More than 50 mutations in the MAPT gene result in heterogeneous forms of frontotemporal lobar dementia with tau inclusions (FTLD-Tau). However, early pathogenic events that lead to disease and the degree to which they are common across MAPT mutations remain poorly understood. The goal of this study is to determine whether there is a common molecular signature of FTLD-Tau. Methods: We analyzed genes differentially expressed in induced pluripotent stem cell-derived neurons (iPSC-neurons) that represent the three major categories of MAPT mutations: splicing (IVS10 + 16), exon 10 (p.P301L), and C-terminal (p.R406W) compared with isogenic controls. The genes that were commonly differentially expressed in MAPT IVS10 + 16, p.P301L, and p.R406W neurons were enriched in trans-synaptic signaling, neuronal processes, and lysosomal function. Many of these pathways are sensitive to disruptions in calcium homeostasis. One gene, CALB1, was significantly reduced across the three MAPT mutant iPSC-neurons and in a mouse model of tau accumulation. We observed a significant reduction in calcium levels in MAPT mutant neurons compared with isogenic controls, pointing to a functional consequence of this disrupted gene expression. Finally, a subset of genes commonly differentially expressed across MAPT mutations were also dysregulated in brains from MAPT mutation carriers and to a lesser extent in brains from sporadic Alzheimer disease and progressive supranuclear palsy, suggesting that molecular signatures relevant to genetic and sporadic forms of tauopathy are captured in a dish. The results from this study demonstrate that iPSC-neurons capture molecular processes that occur in human brains and can be used to pinpoint common molecular pathways involving synaptic and lysosomal function and neuronal development, which may be regulated by disruptions in calcium homeostasis.

Cytomegalovirus reactivation in patients diagnosed with severe COVID-19: A point prevalence study in a general hospital / Reactivación de citomegalovirus en pacientes diagnosticados de COVID-19 grave: Un estudio de prevalencia en un hospital general

Purpose: To determine the prevalence of CMV reactivation in a population admitted for severe COVID-19 to a general hospital. Methods: Point prevalence study in all hospitalized patients with severe COVID-19 (admitted either to general wards or ICU). Determination of the presence of CMV DNA in circulating blood. COVID-19 was confirmed in patients with compatible clinical manifestations, usually with pneumonia and a positive nasopharyngeal PCR test. Results: We included 140 hospitalized patients with COVID-19 who consented to participate. A total of 16 patients (11.42%), had circulating CMV-DNA in peripheral blood at the time of the study. Patients with positive CMV viral load were mainly ICU patients (11/37 -29,7%) and only 5/103 cases (4,85%) were hospitalized into general wards. The accumulated doses of corticosteroids (prednisone equivalents) in the study day were (median and IQR) 987.50 mg (396.87-2,454.68) and 187.50 mg (75.00-818.12) respectively in CMV positive and negative patients (p < 0.001). A significant proportion of CMV positive patients were discovered because of the study and were clinically unsuspected by their physicians. The coinfected COVID-CMV positive population had a higher risk of accumulated secondary nosocomially-acquired infections and a worse prognosis. Conclusion: CMV reactivation should be systematically searched in patients in COVID-19 cases admitted to the ICU. (AU)

Objetivo: Determinar la prevalencia de reactivación del CMV en una población ingresada por COVID-19 grave en un hospital general. Métodos: Estudio de prevalencia en todos los pacientes hospitalizados con COVID-19 (ingresados en salas generales o UCI). Determinación de la presencia de ADN de CMV en sangre. COVID-19 fue confirmado en pacientes con manifestaciones clínicas compatibles, generalmente con neumonía y una prueba de PCR nasofaríngea positiva. Resultados: Se incluyeron 140 pacientes hospitalizados con COVID-19 que firmaron el consentimiento. Un total de 16 pacientes (11,42%), tenían ADN-CMV circulante en sangre periférica en el momento del estudio. Los pacientes con carga viral CMV positiva eran principalmente pacientes de UCI 11/37 (29,7%) y solo 5/103 casos (4,85%) fueron hospitalizados en salas generaleres. Las dosis acumuladas de corticoides (equivalentes de prednisona), en el día del estudio fueron (mediana y RIQ) 987,50 mg (396,87-2.454,68) y 187,50 mg (75,00-818,12) respectivamente en pacientes con CMV positivo y negativo (p< 0,001). Una proporción significativa de pacientes con CMV positivos fueron descubiertos debido al estudio y fueron clínicamente insospechados por sus médicos. La población coinfectada con COVID-CMV positivo tuvo un mayor riesgo de infecciones nosocomiales secundarias acumuladas y un peor pronóstico. Conclusión: La reactivación de CMV debe buscarse sistemáticamente en pacientes con COVID-19 ingresados en la UCI. (AU)

[External Quality Control in Immunohematology of National Medical Center's Blood Bank. History and present]. / Control de Calidad Externo en Inmunohematología del Banco de Sangre del Centro Médico Nacional. Historia y presente.

For the proper functioning of the Immunohematology Area, an External Quality Control was established since 1973 through a program that evaluates the performance of the laboratories of the Blood Bank and transfusion services that carry out immunohematology tests. This program consists of sending panel cells to participating blood banks or services, which are phenotyped erythrocyte samples previously studied as problem cases but whose results are unknown by the participating laboratories. The processes in which the program is of most importance are determination of the ABO group, determination of Rh, performance of the direct and indirect Coombs test, and pre-transfusion compatibility tests. It was carried out an observational and retrospective study of the results obtained in the 2020 period from 104 units participating in the Immunohematology Quality Control Program of the National Medical Center's Blood Bank. A panel of cells was sent for external quality control of immunohematology every 45 days, resulting in 9 panels for each unit in the studied period. Compliance with the program was observed in the general result (79.6%), i.e., there was a decrease in the participation of the registered units. Of a maximum score of 100% to be obtained, it was observed a general result of 95.3% compliance of the participating units. The results obtained confirm the good general training of the immunohematology laboratories of the participating units. Yet, as in any external control program, it becomes clear that obtaining an erroneous result is a risk that can occur in any laboratory.

Para el buen funcionamiento del Área de Inmunohematología, desde 1973 se instauró el Control de Calidad Externo con un programa que evalúa los laboratorios del Banco de Sangre y los servicios de transfusión que hacen pruebas de inmunohematología. El programa consiste en enviar a los bancos de sangre, o servicios participantes, células panel, que son muestras de eritrocitos fenotipados y previamente estudiados como casos problema, pero cuyos resultados son desconocidos por los laboratorios participantes. Los procesos en los que el programa es de suma importancia son determinación del grupo ABO, determinación del Rh, realización de la prueba de Coombs directa e indirecta y las pruebas de compatibilidad pretransfusionales. Se hizo un estudio observacional y retrospectivo de los resultados de 2020 de 104 unidades participantes en el Programa de Control de Calidad de Inmunohematología del Banco de Sangre del Centro Médico Nacional Siglo XXI. Se envió un panel de células para el control de calidad externo de inmunohematología cada 45 días y dio como resultado nueve paneles para cada unidad. El cumplimiento del programa se observó en el resultado general (79.6%), es decir, disminuyó la participación de las unidades inscritas. De una calificación máxima de 100%, hubo un resultado general de las unidades participantes del 95.3% de cumplimiento. Los resultados confirman la buena capacitación general de los laboratorios de inmunohematología de las unidades participantes. Aun así, como en cualquier programa de control externo, obtener un resultado erróneo es un riesgo que puede presentarse en cualquier laboratorio.

Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration.

Impaired proteostasis is associated with normal aging and is accelerated in neurodegeneration. This impairment may lead to the accumulation of protein, which can be toxic to cells and tissue. In a subset of frontotemporal lobar degeneration with tau pathology (FTLD-tau) cases, pathogenic mutations in the microtubule-associated protein tau (MAPT) gene are sufficient to cause tau accumulation and neurodegeneration. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. Here, we show that molecular networks associated with lysosomal biogenesis and autophagic function are disrupted in brains from FTLD-tau patients carrying a MAPT p.R406W mutation. We then used human induced pluripotent stem cell (iPSC)-derived neurons and 3D cerebral organoids from patients carrying the MAPT p.R406W mutation and CRISPR/Cas9, corrected controls to evaluate proteostasis. MAPT p.R406W was sufficient to induce morphological and functional deficits in the lysosomal pathway in iPSC-neurons. These phenotypes were reversed upon correction of the mutant allele with CRISPR/Cas9. Treatment with mTOR inhibitors led to tau degradation specifically in MAPT p.R406W neurons. Together, our findings suggest that MAPT p.R406W is sufficient to cause impaired lysosomal function, which may contribute to disease pathogenesis and serve as a cellular phenotype for drug screening.

Use and management of disinfectants by dentists in San Luis Potosi, Mexico, during the covid-19 pandemic / Uso y manejo de desinfectantes por odontólogos de San Luis Potosí, México durante la pandemia covid-19

Introduction: Chlorine, ethyl alcohol, and quaternary ammonium are disinfectants with antiviral activity against SARS-Cov2. However, there are no previous reports of their use and handling for cleaning and disinfection in dental offices. Objetive: To determine the use and management of disinfectants in critical and non-critical areas used by dentists in San Luis Potosí, Mexico, during the COVID-19 pandemic. Material and Methods: A validated cross-sectional survey was applied online to 100 dentists in San Luis Potosí between February and June 2021. Participants were informed about the handling of personal data according to the standard DOF regulations (DOF 07-05-2010). Results: A total of 100 dentists were included in the study, 63% female and 37% male, with a mean age of 26 years. The most widely used disinfectants during the pandemic in critical areas were Lysol® and 0.1% sodium hypochlorite in non-critical areas. Eighty-five percent of dentists know the adverse effects of inappropriate use of disinfectants, 72% did not have any sign or symptom associated with the use of disinfectants. The most used protection barrier was gloves (97%). Sixty-seven per cent of dentists disposed of disinfectant waste down the drain. Conclusion: Sodium hypochlorite and quaternary ammonium compounds and/or ethanol are used to clean non-critical and critical areas in dental offices. However, appropriate measures for their management are not adopted. It is necessary to implement educational strategies to improve the use and management of disinfectants in dental practice.

Introducción: Cloro, alcohol etílico y amonio cuaternario son desinfectantes que muestran actividad antiviral contra el SARS-Cov2, sin embargo, no existen reportes previos de su uso y manejo para la limpieza y desinfección en clínicas dentales. Objetivo: Determinar el uso y manejo de los desinfectantes en áreas críticas y no críticas empleados por los odontólogos en San Luis Potosí durante la COVID-19. Material y Métodos: Encuesta transversal validada y aplicada on-line a 100 odontólogos de San Luis Potosí durante febrero-junio 2021. Se informó a los participantes sobre el manejo de datos personales de acuerdo a la norma (DOF 05-07-2010). Resultados: Se incluyeron un total de 100 odontólogos, 63% del sexo femenino y 37% del sexo masculino, con una edad promedio de 26 años. Los desinfectantes más utilizados durante la pandemia en las áreas críticas fueron el Lysol® y el hipoclorito de sodio al 0.1% en áreas no críticas. El 85% de los odontólogos conocen los efectos adversos del uso inadecuado de los desinfectantes, 72% no tuvieron algún signo o síntoma asociado al uso de desinfectantes. La barrera de protección más utilizada fueron los guantes (97%). El 67% de los odontólogos eliminó los desechos de desinfectantes por la coladera. Conclusión: Para la limpieza de las áreas no críticas y críticas en las clínicas dentales se utilizan el hipoclorito de Sodio y compuestos de amonio cuaternario y/o etanol, sin embargo, no se utilizan las medidas adecuadas para su manejo. Es necesario implementar estrategias educativas para mejorar el uso y manejo de desinfectantes en la práctica dental.

Anti-Adherence and Antimicrobial Activities of Silver Nanoparticles against Serotypes C and K of Streptococcus mutans on Orthodontic Appliances.

Background and Objectives: Streptococcus mutans (S. mutans) is the main microorganism associated with the presence of dental caries and specific serotypes of this bacteria have been related to several systemic diseases limiting general health. In orthodontics, white spot lesions (WSL), represent a great challenge for clinicians due to the great fluctuation of their prevalence and incidence during conventional orthodontic treatments. Although silver nanoparticles (AgNP) have been demonstrated to have great antimicrobial properties in several microorganisms, including S. mutans bacteria, there is no available information about anti adherence and antimicrobial properties of AgNP exposed to two of the most relevant serotypes of S. mutans adhered on orthodontic materials used for conventional therapeutics. The objective of this study was to determine anti-adherence and antimicrobial levels of AgNP against serotypes c and k of S. mutans on conventional orthodontic appliances. Materials and Methods: An AgNP solution was prepared and characterized using dispersion light scattering (DLS) and transmission electron microscopy (TEM). Antimicrobial and anti-adherence activities of AgNP were determined using minimal inhibitory concentrations (MIC) and bacterial adherence testing against serotypes c and k of S. mutans clinically isolated and confirmed by PCR assay. Results: The prepared AgNP had spherical shapes with a good size distribution (29.3 ± 0.7 nm) with negative and well-defined electrical charges (−36.5 ± 5.7 mV). AgNP had good bacterial growth (55.7 ± 19.3 µg/mL for serotype c, and 111.4 ± 38.6 µg/mL for serotype k) and adherence inhibitions for all bacterial strains and orthodontic wires (p < 0.05). The serotype k showed statistically the highest microbial adherence (p < 0.05). The SS wires promoted more bacterial adhesion (149.0 ± 253.6 UFC/mL × 104) than CuNiTi (3.3 ± 6.0 UFC/mL × 104) and NiTi (101.1 ± 108.5 UFC/mL × 104) arches. SEM analysis suggests CuNiTi wires demonstrated better topographical conditions for bacterial adherence while AFM evaluation determined cell wall irregularities in bacterial cells exposed to AgNP. Conclusions: This study suggests the widespread use of AgNP as a potential anti-adherent and antimicrobial agent for the prevention of WSL during conventional orthodontic therapies and, collaterally, other systemic diseases.

Management of Hepatic Encephalopathy Associated with Advanced Liver Disease.

Hepatic encephalopathy (HE) is a very prevalent condition in patients with advanced liver disease and has a high recurrence rate. The pathophysiology has a multifactorial origin where hyperammonaemia and inflammation become particularly relevant. There are no HE-specific diagnostic tests, and diagnosis is usually made by taking into account the presence of suggestive and compatible clinical symptoms, the existence of a predisposing liver condition and ruling out other causes with similar clinical manifestations. Once the diagnosis of HE is established, it is essential to carry out an adequate classification based on the underlying liver disease, the intensity of clinical manifestations, the temporal course of the disease and the presence or absence of precipitating factors. Treatment should be aimed at decreasing the duration, intensity and consequences of episodes, preventing recurrence and limiting the impact of the disease in patients and their relatives.

Hepatitis C eradication improves cognitive function in patients with or without cirrhosis: A prospective real-life study.

BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) infection is associated with neuropsychiatric disturbances that impact on functioning and health-related quality of life (HRQoL). Reversibility at different liver disease stages is unknown, particularly in cirrhosis. We aimed to evaluate cognition, functioning, and HRQoL following HCV eradication at different liver disease stages. METHODS: A random sample (n = 152) of consecutive patients treated with direct-acting antiviral agents (DAAs) between April 2015 and March 2017 were included. A comprehensive neuropsychological assessment, functioning and HRQoL questionnaires were applied at baseline, and 12 and 48 weeks after the end of antivirals. RESULTS: One-hundred thirty-five patients who achieved virological response completed the follow-up, of whom 44 had cirrhosis (27% decompensated). Twenty-one percent had cognitive impairment before starting DAAs (34.1% cirrhotic vs. 14.4% noncirrhotic, p < 0.011). Viral eradication was associated with a decrease in cognitive impairment to 23% of cirrhotic and 6% of noncirrhotic patients (p < 0.05). Interestingly, older patients (B = 0.11, 95% confidence interval [CI] = 0.03-0.19) with baseline cognitive impairment (B = 3.58, 95% CI = 1.54-5.62) were those with higher cognitive benefit, regardless of liver disease. Persistent cognitive impairment was associated with having higher cardiovascular risk, cirrhosis, lower education, and higher anxiety and depression scores. Functioning and HRQoL also improved after eradication but remained worse in the cirrhotic group. CONCLUSIONS: Viral eradication decreases the prevalence of cognitive impairment and improves functioning and HRQoL. Patients with lower brain reserve (older patients) and baseline cognitive impairment may benefit the most. Identification and treatment of HCV patients through screening programs may reduce the burden of cognitive disturbances beyond the prevention of liver disease progression.