Proteomic study of CD44, Cyclin D1 and Galectin 9 as salivary biomarkers in potentially malignant disorders of the oral cavity

Los desórdenes potencialmente malignos (DPM) se caracterizan por presentar riesgo mayor de transformación maligna a carcinoma. Objetivos: Estudiar la expresión proteómica de las proteínas CD44, ciclina D1 y galectina 9 en fluido salival de pacientes con DPM respecto de un grupo control; correlacionar la concentración de estos biomarcadores con parámetros clínicos y anatomopatológicos; averiguar si su sobreexpresión es útil como indicador de riesgo de progresión a malignidad. Se realizará un estudio transverso con una muestra por conveniencia de pacientes con DPM y un grupo control de 20 pacientes sanos. Se realizará una historia clínica completa, muestra de saliva, analizada posteriormente por espectrometría de masa. Se compararán los niveles de la expresión de las proteínas entre la muestra de pacientes con DPM y el grupo control. Se correlacionarán los niveles de expresión de las proteínas y el grado de displasia epitelial en pacientes sometidos a biopsia por no responder al tratamiento convencional.Potentially malignant disorders (MPD) are characterized by a higher risk of malignant transformation to carcinoma. Objectives: To study the proteomic expression of the proteins CD44, cyclin D1 and galectin 9 in the salivary use of patients with MPD with respect to a control group; correlate the concentration of these biomarkers with clinical and anatomopathological parameters; Find out if overexpression is useful as an indicator of the risk of progression to malignancy. A transverse study was performed with a convenience sample of patients with MPD and a control group of 20 healthy patients. A complete clinical history was made, saliva sample, analyzed later by mass spectrometry. The expression levels of the proteins are compared between the sample of patients with MPD and the control group. The expression levels of the proteins and the degree of epithelial dysplasia will be correlated in patients undergoing a non-responder biopsy to conventional conventionalism.Facultad de Odontologí

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294

Proteomic study of CD44, Cyclin D1 and Galectin 9 as salivary biomarkers in potentially malignant disorders of the oral cavity

Los desórdenes potencialmente malignos (DPM) se caracterizan por presentar riesgo mayor de transformación maligna a carcinoma. Objetivos: Estudiar la expresión proteómica de las proteínas CD44, ciclina D1 y galectina 9 en fluido salival de pacientes con DPM respecto de un grupo control; correlacionar la concentración de estos biomarcadores con parámetros clínicos y anatomopatológicos; averiguar si su sobreexpresión es útil como indicador de riesgo de progresión a malignidad. Se realizará un estudio transverso con una muestra por conveniencia de pacientes con DPM y un grupo control de 20 pacientes sanos. Se realizará una historia clínica completa, muestra de saliva, analizada posteriormente por espectrometría de masa. Se compararán los niveles de la expresión de las proteínas entre la muestra de pacientes con DPM y el grupo control. Se correlacionarán los niveles de expresión de las proteínas y el grado de displasia epitelial en pacientes sometidos a biopsia por no responder al tratamiento convencional.Potentially malignant disorders (MPD) are characterized by a higher risk of malignant transformation to carcinoma. Objectives: To study the proteomic expression of the proteins CD44, cyclin D1 and galectin 9 in the salivary use of patients with MPD with respect to a control group; correlate the concentration of these biomarkers with clinical and anatomopathological parameters; Find out if overexpression is useful as an indicator of the risk of progression to malignancy. A transverse study was performed with a convenience sample of patients with MPD and a control group of 20 healthy patients. A complete clinical history was made, saliva sample, analyzed later by mass spectrometry. The expression levels of the proteins are compared between the sample of patients with MPD and the control group. The expression levels of the proteins and the degree of epithelial dysplasia will be correlated in patients undergoing a non-responder biopsy to conventional conventionalism.Facultad de Odontologí

Proteomic study of CD44, Cyclin D1 and Galectin 9 as salivary biomarkers in potentially malignant disorders of the oral cavity

Los desórdenes potencialmente malignos (DPM) se caracterizan por presentar riesgo mayor de transformación maligna a carcinoma. Objetivos: Estudiar la expresión proteómica de las proteínas CD44, ciclina D1 y galectina 9 en fluido salival de pacientes con DPM respecto de un grupo control; correlacionar la concentración de estos biomarcadores con parámetros clínicos y anatomopatológicos; averiguar si su sobreexpresión es útil como indicador de riesgo de progresión a malignidad. Se realizará un estudio transverso con una muestra por conveniencia de pacientes con DPM y un grupo control de 20 pacientes sanos. Se realizará una historia clínica completa, muestra de saliva, analizada posteriormente por espectrometría de masa. Se compararán los niveles de la expresión de las proteínas entre la muestra de pacientes con DPM y el grupo control. Se correlacionarán los niveles de expresión de las proteínas y el grado de displasia epitelial en pacientes sometidos a biopsia por no responder al tratamiento convencional.Potentially malignant disorders (MPD) are characterized by a higher risk of malignant transformation to carcinoma. Objectives: To study the proteomic expression of the proteins CD44, cyclin D1 and galectin 9 in the salivary use of patients with MPD with respect to a control group; correlate the concentration of these biomarkers with clinical and anatomopathological parameters; Find out if overexpression is useful as an indicator of the risk of progression to malignancy. A transverse study was performed with a convenience sample of patients with MPD and a control group of 20 healthy patients. A complete clinical history was made, saliva sample, analyzed later by mass spectrometry. The expression levels of the proteins are compared between the sample of patients with MPD and the control group. The expression levels of the proteins and the degree of epithelial dysplasia will be correlated in patients undergoing a non-responder biopsy to conventional conventionalism.Facultad de Odontologí

Pre-exposure prophylaxis with hydroxychloroquine for COVID-19 : a double-blind, placebo-controlled randomized clinical trial

Background: Pre-exposure prophylaxis (PrEP) is a promising strategy to break COVID-19 transmission. Although hydroxychloroquine was evaluated for treatment and post-exposure prophylaxis, it is not evaluated for COVID-19 PrEP yet. The aim of this study was to evaluate the efficacy and safety of PrEP with hydroxychloroquine against placebo in healthcare workers at high risk of SARS-CoV-2 infection during an epidemic period. Methods: We conducted a double-blind placebo-controlled randomized clinical trial in three hospitals in Barcelona, Spain. From 350 adult healthcare workers screened, we included 269 participants with no active or past SARS-CoV-2 infection (determined by a negative nasopharyngeal SARS-CoV-2 PCR and a negative serology against SARS-CoV-2). Participants allocated in the intervention arm (PrEP) received 400 mg of hydroxychloroquine daily for the first four consecutive days and subsequently, 400 mg weekly during the study period. Participants in the control group followed the same treatment schedule with placebo tablets. Results: 52.8% (142/269) of participants were in the hydroxychloroquine arm and 47.2% (127/269) in the placebo arm. Given the national epidemic incidence decay, only one participant in each group was diagnosed with COVID-19. The trial was stopped due to futility and our study design was deemed underpowered to evaluate any benefit regarding PrEP efficacy. Both groups showed a similar proportion of participants experiencing at least one adverse event (AE) (p=0.548). No serious AEs were reported. Almost all AEs (96.4%, 106/110) were mild. Only mild gastrointestinal symptoms were significantly higher in the hydroxychloroquine arm compared to the placebo arm (27.4% (39/142) vs 15.7% (20/127), p=0.041). Conclusions: Although the efficacy of PrEP with hydroxychloroquine for preventing COVID-19 could not be evaluated, our study showed that PrEP with hydroxychloroquine at low doses is safe. Trial registration: ClinicalTrials.govNCT04331834. Registered on April 2, 2020

Proteomic study of salivary biomarkers in potentially malignant oral cavity disorders

Los desórdenes potencialmente malignos (DPM) se caracterizan por presentar riesgo mayor de transformación maligna a carcinoma. Objetivos: Estudiar la expresión proteómica de las proteínas CD44, Ciclina D1 y Galectina 9 en fluido salival de pacientes con DPM respecto de un grupo control; correlacionar la concentración de estos biomarcadores con parámetros clínicos y anatomopatológicos; averiguar si su sobreexpresión es útil como indicador de riesgo de progresión a malignidad. Se realizará un estudio transverso con una muestra por conveniencia de pacientes con DPM y un grupo control de 20 pacientes sanos. Se realizará una historia clínica completa, muestra de saliva, analizada posteriormente por espectrometría de masa. Se compararán los niveles de la expresión de las proteínas entre la muestra de pacientes con DPM y el grupo control. Se correlacionarán los niveles de expresión de las proteínas y el grado de displasia epitelial en pacientes sometidos a biopsia por no responder al tratamiento convencional.Potentially malignant disorders (MPD) are characterized by a higher risk of malignant transformation to carcinoma. Objectives: To study the proteomic expression of the proteins CD44, cyclin D1 and galectin 9 in the salivary use of patients with MPD with respect to a control group; correlate the concentration of these biomarkers with clinical and anatomopathological parameters; Find out if overexpression is useful as an indicator of the risk of progression to malignancy. A transverse study was performed with a convenience sample of patients with MPD and a control group of 20 healthy patients. A complete clinical history was made, saliva sample, analyzed later by mass spectrometry. The expression levels of the proteins are compared between the sample of patients with MPD and the control group. The expression levels of the proteins and the degree of epithelial dysplasia will be correlated in patients undergoing a non-responder biopsy to conventional conventionalism.Facultad de Odontologí

Demographic reconstruction from ancient DNA supports rapid extinction of the great auk

The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species’ geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation

Anti–Neutrophil Extracellular Trap Antibodies in Antiphospholipid Antibody–Positive Patients: Results From the Antiphospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Clinical Database and Repository

OBJECTIVE: This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti–neutrophil extracellular trap (anti-NET) antibodies in a multinational cohort of antiphospholipid (aPL) antibody–positive patients who did not have lupus. METHODS: Anti-NET IgG/IgM levels were measured in serum samples from 389 aPL-positive patients; 308 patients met the classification criteria for antiphospholipid syndrome. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n = 214), we profiled autoantibodies using an autoantigen microarray platform. RESULTS: We found elevated levels of anti-NET IgG and/or IgM in 45% of the aPL-positive patients. High anti-NET antibody levels are associated with more circulating myeloperoxidase (MPO)–DNA complexes, which are a biomarker of NETs. When considering clinical manifestations, positive anti-NET IgG was associated with lesions affecting the white matter of the brain, even after adjusting for demographic variables and aPL profiles. Anti-NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum samples containing high levels of anti-NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti-NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan sulfate proteoglycan, laminin, MPO–DNA complexes, and nucleosomes. Anti-NET IgM positivity was associated with autoantibodies targeting single-stranded DNA, double-stranded DNA, and proliferating cell nuclear antigen. CONCLUSION: These data reveal high levels of anti-NET antibodies in 45% of aPL-positive patients, where they potentially activate the complement cascade. While anti-NET IgM may especially recognize DNA in NETs, anti-NET IgG species appear to be more likely to target NET-associated protein antigens

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys