Brain Magnetic Resonance Imaging Abnormalities in Acute Flaccid Myelitis.

BACKGROUND: Acute flaccid myelitis (AFM) presents with acute onset of flaccid paralysis with involvement of the gray matter on magnetic resonance imaging (MRI) of the spinal cord. Studies have reported brain MRI abnormalities, but the characteristics have not been fully defined. In this multicenter study, we assessed the acute features and evolution of brain MRI abnormalities in AFM. METHODS: We reviewed brain MRIs of patients with AFM who presented to four referral hospitals between 2012 and 2018. Cases met established criteria for AFM. We analyzed the initial and follow-up brain MRIs. Areas were divided into supratentorial, infratentorial, and subdivisions within those regions. RESULTS: A total of 66 patients were included. Brain MRI abnormalities were present in 34 (52%). Infratentorial abnormalities were more common, occurring in 33 (97%) cases with the dorsal pons being the most frequently affected area (88%). Abnormalities were also present in the medulla (74%), cerebellum (41%), and midbrain (38%). Nine subjects (26%) exhibited both supratentorial and infratentorial abnormalities, whereas isolated supratentorial changes were present in only one (3%). Contrast-enhancing abnormalities were encountered in 9% of cases and meningeal involvement in 6%. On follow-up, most abnormalities, 20 of 24 (83%), were stable, improving, or had resolved. CONCLUSIONS: Brain MRI abnormalities occur in about half of the cases of AFM and commonly resolve with time. Dorsal pontine involvement is a characteristic MRI feature, whereas isolated supratentorial abnormalities are rare. Clinicians should consider that brain imaging abnormalities do not exclude a diagnosis of AFM in patients with typical presentations.

Effect of botulinum toxin type A in functionality, synkinesis and quality of life in peripheral facial palsy sequelae.

OBJECTIVES: This study aimed to assess the effects of botulinum toxin A (BTX-A) infiltration on face muscle function, synkinesis, and quality of life in patients with sequelae of peripheral facial palsy (PFP). MATERIAL AND METHODS: We present the results of a prospective study including a sample of 20 patients with sequelae of PFP (15 women, 5 men) who underwent BTX-A (Botox© or Xeomin©) infiltration. All patients had previously received personalised treatment with neuromuscular retraining. A clinical assessment was performed before BTX-A infiltration and 4 weeks after treatment. The effect of BTX-A on face muscle function, quality of life, and synkinesis was evaluated using the Sunnybrook Facial Grading System (SFGS), the Facial Clinimetric Evaluation (FaCE) questionnaire, and the Synkinesis Assessment Questionnaire (SAQ), respectively. RESULTS: Mean SFGS scores increased from 64.8 to 69.9 after BTX-A infiltration (P=.004). Increases were also observed in mean total FaCE scores (from 52.42 to 64.5; P<.001) and the mean score on the FaCE social function subscale (from 61.15 to 78.44; P<.001). Mean SAQ scores decreased from 46.22 to 37.55 after BTX-A infiltration (P=.001). CONCLUSIONS: BTX-A infiltration increases face muscle function, improves quality of life, and reduces synkinesis in patients with sequelae of PFP.

FTIR-ATR detection method for emerging C3-plants-derivated adulterants in honey: Beet, dates, and carob syrups.

The European Union Publications Office has recently presented a report on the European Union's coordinated action with the Joint Research Centre to determine certain fraudulent practices in the honey sector, in which it has been indicated that 74% of the samples analyzed, imported from China, and 93% of the samples analyzed, imported from Turkey, the two largest honey producers worldwide, presented at least one indicator of exogenous sugar or suspicion of being adulterated. This situation has revealed the critical state of the problem of honey adulteration worldwide and the need to develop analytical techniques for its detection. Even though the adulteration of honey is carried out in a general way with sweetened syrups derived from C4 plants, recent studies have indicated the emerging use of syrups derived from C3 plants for the adulteration of honey. This kind of adulteration makes it impossible to analyze its detection using official analysis techniques. In this work, we have developed a fast, simple, and economical method based on the Fourier transform infrared spectroscopy technique, with attenuated total reflectance, for the qualitative, quantitative, and simultaneous determination of beetroot, date, and carob syrups, derived from of C3 plants; whose available bibliography is very scarce and analytically not very conclusive for its use by the authorities. The proposed method has been based on the establishment of the spectral differences between honey and the mentioned syrups at eight different points in the spectral region between 1200 and 900 cm-1 of the mid-infrared, characteristic of the vibrational modes of carbohydrates in honey, which allows the pre-discrimination of the presence or absence of the syrups studied, and their subsequent quantification, with precision levels lower than 2.0% of the relative standard deviation and relative errors lower than 2.0% (m/m).

Honey polyphenols: regulators of human microbiota and health.

A comprehensive review of research over the last decade was conducted to carry out this work. The main objective of this work is to present relevant evidence of the effect of honey intake on the human intestinal microbiota and its relationship with the improvement of various chronic diseases, such as cirrhosis, metabolic syndrome, diabetes, and obesity, among others. Therefore, this work focuses on the health-improving honey dietary supplementation implications associated with specific changes in the human microbiota and their biochemical mechanisms to enhance the proliferation of beneficial microorganisms and the inhibition of pathogenic microorganisms. Consumption of honey polyphenols significantly improves people's health conditions, especially in patients with chronic disease. Hence, honey intake unequivocally constitutes an alternative way to enhance health and could be used to prevent some relevant chronic diseases.

Rapid, reliable and easy-to-perform chemometric-less method for rice syrup adulterated honey detection using FTIR-ATR.

The adulteration of honey (Apis mellifera) is a global problem due to its economic, commercial and health implications. The world's leading beekeeping organisation, APIMONDIA, considers that the detection of adulteration in honey is a problem that has not yet been resolved. This evidence of the importance of the intensive development of analytical techniques that allow the unequivocal detection of adulterants in honey, especially those whose use as honey adulterants has recently emerged. This work aims to develop a fast, easy-to-perform, low-cost analytical method to qualitatively and quantitatively determine rice syrup using the Fourier transform infrared spectroscopy (FTIR) technique with attenuated total reflectance (ATR) mode without complex mathematical procedures and sophisticated sample preparation. This study involved the analysis of 256 intentionally rice-syrup-adulterated honey samples and 92 pure honey samples of bee multifloral honey from Spain. The method, based strictly on the determination of the absorbance directly from the samples, at 1013 cm-1 The methodology used no need for previous treatments or preparations and demonstrated the scope for the unequivocal detection of rice syrup in adulterated honey containing equal to or higher than 3% (m/m) or more of this adulterant. Using the Exponential Plus Linear model (r = 0.998) shows high accuracy and precision, in terms of relative error (0.32%, m/m) and coefficient of variation (1.4%). The results of this study have led to the establishment of a maximum absorbance threshold of 0.670 for honey without rice syrup.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction.

OBJECTIVE: High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). DESIGN: Observational prospective study. SETTING: Five Intensive Care Units (ICU). PATIENTS: Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. INTERVENTIONS: Determination of serum caspase-8 levels when MMCAI was diagnosed. MAIN VARIABLES OF INTEREST: Mortality at 30 days and time until this event. RESULTS: Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%-91%; p<0.001) by serum caspase-8 levels. Kaplan-Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4-28.4; p<0.001). CONCLUSIONS: The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction / Asociación de niveles sanguíneos de caspasa-8 y mortalidad de pacientes con infarto maligno de la arteria cerebral media

Objective High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). Design Observational prospective study. Setting Five Intensive Care Units (ICU). Patients Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. Interventions Determination of serum caspase-8 levels when MMCAI was diagnosed. Main variables of interest Mortality at 30 days and time until this event. Results Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%–91%; p<0.001) by serum caspase-8 levels. Kaplan–Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4–28.4; p<0.001). Conclusions The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study (AU)

Objetivo Se han encontrado altas concentraciones de caspasa-8 (principal caspasa iniciadora de la vía extrínseca de apoptosis) en el tejido cerebral de pacientes con traumatismo craneoencefálico y en la sangre de pacientes con diferentes enfermedades. Sin embargo, no hay datos sobre las concentraciones sanguíneas de caspasa-8 en pacientes con ictus isquémico. Por tanto, el objetivo de este estudio fue determinar si existe una asociación entre las concentraciones sanguíneas de caspasa-8 y la probabilidad y velocidad de mortalidad a 30días en pacientes con infarto maligno de la arteria cerebral media (MMCAI). Diseño Observacional y prospectivo. Ámbito Cinco unidades de cuidados intensivos (UCI). Pacientes Pacientes con MMCAI grave definido como infarto agudo en más del 50% de ese territorio y escala de coma de Glasgow (GCS)<9. Intervenciones Determinación de niveles séricos de caspasa-8 cuando se diagnosticó el MMCAI grave. Variables de interés principal Mortalidad hasta los 30dias y tiempo hasta este evento. Resultados Los pacientes fallecidos (n=28) en comparación con los supervivientes (n=28) mostraron mayores concentraciones séricas de caspasa-8 (p<0,001), menor recuento plaquetario (p=0,01) y menor GCS (p=0,002). Encontramos un área bajo la curva para la predicción de mortalidad del 78% (IC 95%: 65-91%; p<0,001) por los niveles séricos de caspasa-8. El análisis de Kaplan-Meier encontró una mayor tasa de mortalidad en pacientes con niveles séricos de caspasa-8>62,8ng/mL (hazard ratio: 11,2; IC 95%: 4,4-28,4; p<0,001). Conclusiones La asociación de elevadas concentraciones sanguíneas de caspasa-8 con la tasa y velocidad de mortalidad a 30días en pacientes con MMCAI es el principal hallazgo nuevo de nuestro estudio (AU)

A Polymorphism Cluster at the 2q12 locus May Predict Response to Piromelatine in Patients with Mild Alzheimer's Disease.

BACKGROUND: Piromelatine is a novel melatonin MT1/2/3 and serotonin 5-HT-1A/1D receptors agonist developed for mild Alzheimer's disease (AD). In a randomized, placebo-controlled, dose-ranging study (ReCognition) of piromelatine (5, 20, and 50 mg daily for 6 months) in participants with mild dementia due to AD (n=371, age 60-85 years), no statistically significant differences were found between the piromelatine and placebo-treated groups on the primary (i.e., computerized neuropsychological test battery (cNTB)) and secondary outcomes (ADCS-CGIC, ADCS-MCI-ADL, ADAS-cog14, NPI, and Pittsburgh Sleep Quality Index (PSQI)) nor were there safety concerns (https://clinicaltrials.gov/ct2/show/NCT02615002). OBJECTIVES: This study was aimed at identifying genetic markers predicting piromelatine treatment response using a genome-wide association approach (GWAS). DESIGN: Variant genotyping of a combined whole genome and whole exome sequencing was performed using DNA extracted from lymphocytes from consenting participants. The general case-control allelic test was performed on piromelatine-treated participants, taking "responders" (i.e., >0.125 change from baseline in the cNTB) as cases and "non responders" as controls, using a Cochran-Armitage trend test. SETTING: 58 outpatient clinics in the US. PARTICIPANTS: 371 participants were randomized in the trial; 107 provided informed consent for genotyping. RESULTS: The GWAS sample did not differ from the full study cohort in demographics, baseline characteristics, or response to piromelatine. Six single-nucleotide polymorphisms (SNPs) in chromosome 2q12 (2:107,510,000-107,540,000) were associated with response (p-value < 1x10 -4 each). Post hoc analyses suggested that the carriers of the 2q12 polymorphism cluster (27% of the GWAS sample) improved significantly on the cNTB on piromelatine as compared to placebo but significantly worsened on the ADAS-Cog14 and PSQI. By contrast, "non-carriers" improved significantly with piromelatine compared to placebo on the ADAS-Cog14 ( 2.91 (N=23) with piromelatine 20 mg vs 1.65 (N=19) with placebo (p=0.03)) and PSQI. CONCLUSIONS: The 2q12 (2:107,510,000-107,540,000) 5-6 SNPs cluster may predict efficacy of piromelatine for mild AD. These findings warrant further investigation in a larger, prospective early-stage AD clinical trial for patients who are non-carriers of the 2q12 polymorphism cluster.

Eficacia y seguridad de las vacunas contra el SARS-CoV-2 / Efficacy and safety of SARS-CoV-2 vaccines

Ha habido un esfuerzo extraordinario, tanto técnico como económico, para producir vacunas eficaces. Las vacunas de las que existen datos de eficacia son las que han publicado resultados de la fase 3. Se resumen los datos más relevantes de estos ensayos clínicos agrupados por tipo de vacuna. Mientras que los datos de eficacia se obtienen en ensayos clínicos, la efectividad ha de medirse en la vida real, teniendo en cuenta que las vacunas se han empezado a implementar en España el 27 de diciembre de 2020. Las vacunas para prevenir la infección por SARS-CoV-2 parecen seguras y eficaces, con una calidad de la evidencia moderada. En el momento actual se ha vacunado de forma universal a la población adulta (primer grupo en tener evidencias de eficacia y seguridad vacunal) con las vacunas disponibles y según grupos de riesgo establecidos por el Ministerio de Sanidad, posteriormente se han ido incorporando otros grupos como embarazadas y adolescentes, y recientemente se ha incorporado el grupo de escolares entre 5 y 11 años tras la publicación de eficacia y seguridad vacunal en esta franja de edad de una de las vacunas autorizadas en la Unión Europea. A pesar de las limitaciones que presentan los ensayos clínicos, la situación de pandemia actual con gran amenaza para la salud pública y la gran pérdida de vidas que produce la enfermedad por SARS-CoV-2, hace que el balance riesgo beneficio sea favorable a la vacunación (AU)

There has been an extraordinary effort, technical as well as economic to produce effective vaccines. The vaccines with known effectivity data are those that have published phase 3 results. The most relevant data of these clinical trials are resumed here grouped by type of vaccine. While data on effectivity are obtained from clinical trials, the effectiveness must be measured in real life, considering that vaccines have been implemented in Spain since December 27, 2020. The vaccines to prevent SARS-CoV-2 infections seem safe and effective, with a moderate quality of the evidence. Currently, the adult population has been vaccinated (first age group with evidence of effectivity and safety) with the available vaccines and according to risk groups established by the Health Ministry, afterwards other groups have been added such as pregnant women and adolescents, and recently the schoolers 5 to 11 years after the publication of effectivity and safety in this age group of one of the vaccines authorized in the European Union. Despite the limitations of the published clinical trials, the current pandemic situation means a great public health threat and an enormous loss of lives due to SARS-CoV-2, which makes the risk benefit balance favorable to vaccination. (AU)

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction.

OBJECTIVE: High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). DESIGN: Observational prospective study. SETTING: Five Intensive Care Units (ICU). PATIENTS: Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. INTERVENTIONS: Determination of serum caspase-8 levels when MMCAI was diagnosed. MAIN VARIABLES OF INTEREST: Mortality at 30 days and time until this event. RESULTS: Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%-91%; p<0.001) by serum caspase-8 levels. Kaplan-Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4-28.4; p<0.001). CONCLUSIONS: The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study.

Serum caspase-3 levels during the first week of traumatic brain injury / Niveles séricos de caspasa-3 durante la primera semana de un traumatismo craneoencefálico

Objective: Confluence between the intrinsic and extrinsic apoptosis pathways is reached at the point of caspase-3 activation, which induces death cell. Higher serum caspase-3 levels have been recorded on day 1 of traumatic brain injury (TBI) in 30-day non-survivors compared to survivors. The objectives of this study therefore were to determine whether serum caspase-3 levels are persistently higher in non-survivors than in survivors, and whether these levels may be used to predict 30-day mortality.DesignA prospective observational study was carried out.SettingSix Spanish Intensive Care Units.PatientsPatients with severe isolated TBI (defined as Glasgow Coma Scale <9 points and non-cranial Injury Severity Score <10 points).InterventionsSerum caspase-3 concentrations were measured on days 1, 4 and 8 of TBI.Main variables of interestThirty-day mortality was considered as the study endpoint.ResultsIn comparison with non-survivors (n=34), 30-day survivors (n=90) showed lower serum caspase-3 levels on days 1 (p=0.001), 4 (p<0.001) and 8 (p<0.001) of TBI. Analysis of the ROC curves showed serum caspase-3 concentrations on days 1, 4 and 8 of TBI to have an AUC (95% CI) in predicting 30-day mortality of 0.70 (0.61–0.78; p=0.001), 0.83 (0.74–0.89; p<0.001) and 0.87 (0.79–0.93; p<0.001), respectively.ConclusionsThe novel findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivors and could predict 30-day mortality. (AU)

Objetivo: La vía intrínseca y extrínseca de la apoptosis confluyen en la activación de caspasa-3. Se han encontrado mayores niveles séricos de caspasa-3 en el día 1 del traumatismo craneoencefálico (TCE) en los pacientes que fallecen en los primeros 30 días que en supervivientes. Por tanto, los objetivos de este estudio es determinar si los niveles séricos de caspasa-3 se mantienen superiores en los pacientes fallecidos que en los supervivientes, y si podrían utilizarse para predecir la mortalidad a 30 días.DiseñoEstudio observacional y prospectivo.ÁmbitoSeis unidades de cuidados intensivos españolas.PacientesEnfermos con un TCE grave y aislado (definido como escala de coma de Glasgow <9 y puntuación de gravedad de la lesión Score en lesiones no craneales <10).IntervencionesSe midieron los niveles séricos de caspasa-3 en los días 1, 4 y 8 del TCE.Variables de interés principalesMortalidad a los 30 días.ResultadosLos pacientes supervivientes a los 30 días (n=90) presentan menores niveles séricos de caspasa-3 en los días 1 (p=0,001), 4 (p<0,001) y 8 (p<0,001) del TCE que los fallecidos (n=34). Los niveles séricos de caspasa-3 en los días 1, 4 y 8 del TCE tenían un área bajo la curva (intervalo de confianza del 95%) para predecir la mortalidad de 0,70 (0,61-0,78; p=0,001), 0,83 (0,74-0,89; p<0,001) y 0,87 (0,79-0,93; p<0,001), respectivamente.ConclusionesLos nuevos hallazgos de nuestro estudio fueron que los niveles séricos de caspasa-3 durante la primera semana del TCE fueron menores en los pacientes supervivientes, y que pueden predecir la mortalidad a los 30 días. (AU)

Effect of botulinum toxin typeA in functionality, synkinesis and quality of life in peripheral facial palsy sequelae. / Efecto de la toxina botulínica tipoA en la funcionalidad, las sincinesias y la calidad de vida en secuelas de parálisis facial periférica.

OBJECTIVES: This study aimed to assess the effects of botulinum toxin A (BTX-A) infiltration on face muscle function, synkinesis, and quality of life in patients with sequelae of peripheral facial palsy (PFP). MATERIAL AND METHODS: We present the results of a prospective study including a sample of 20 patients with sequelae of PFP (15 women, 5 men) who underwent BTX-A (Botox® or Xeomin®) infiltration. All patients had previously received personalised treatment with neuromuscular retraining. A clinical assessment was performed before BTX-A infiltration and 4weeks after treatment. The effect of BTX-A on face muscle function, quality of life, and synkinesis was evaluated using the Sunnybrook Facial Grading System (SFGS), the Facial Clinimetric Evaluation (FaCE) questionnaire, and the Synkinesis Assessment Questionnaire (SAQ), respectively. RESULTS: Mean SFGS scores increased from 64.8 to 69.9 after BTX-A infiltration (P=.004). Increases were also observed in mean total FaCE scores (from 52.42 to 64.5; P<.001) and the mean score on the FaCE social function subscale (from 61.15 to 78.44; P<.001). Mean SAQ scores decreased from 46.22 to 37.55 after BTX-A infiltration (P=.001). CONCLUSIONS: BTX-A infiltration increases face muscle function, improves quality of life, and reduces synkinesis in patients with sequelae of PFP.

DNA and RNA oxidative damage are associated to mortality in patients with cerebral infarction.

OBJECTIVE: Secondary injury due to oxidation may occur during ischemic stroke, possibly leading to oxidative damage to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Higher blood concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) (through the oxidation of guanosine from DNA) have been found in ischemic stroke patients than in healthy subjects, and in patients with versus without post-ischemic stroke depression. The present study was carried out to explore the possible association between serum DNA and RNA oxidative damage and mortality in patients with cerebral infarction. METHODS: A prospective, multicenter observational study was carried out in the Intensive Care Units of 6 Spanish hospitals. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as ischemic changes evidenced by computed tomography in more than 50% of the middle cerebral artery territory and a Glasgow Coma Score (GCS)<9. Serum concentrations of the three oxidized guanine species (OGS) (8-hydroxyguanine from DNA or RNA, 8-hydroxyguanosine from RNA, and 8-OHdG from DNA) on the day of MMCAI diagnosis were determined. The study endpoint was 30-day mortality. RESULTS: We found higher serum OGS levels (p<0.001) in non-surviving (n=34) than in surviving patients (n=34). Logistic regression analyses showed serum OGS levels to be associated to 30-day mortality controlling for lactic acid, GCS and platelet count (OR=1.568; 95%CI=1.131-2.174; p=0.01). CONCLUSIONS: The novel observation in this study is the association between global serum OGS concentration and mortality in ischemic stroke patients.

Serum caspase-3 levels during the first week of traumatic brain injury.

OBJECTIVE: Confluence between the intrinsic and extrinsic apoptosis pathways is reached at the point of caspase-3 activation, which induces death cell. Higher serum caspase-3 levels have been recorded on day 1 of traumatic brain injury (TBI) in 30-day non-survivors compared to survivors. The objectives of this study therefore were to determine whether serum caspase-3 levels are persistently higher in non-survivors than in survivors, and whether these levels may be used to predict 30-day mortality. DESIGN: A prospective observational study was carried out. SETTING: Six Spanish Intensive Care Units. PATIENTS: Patients with severe isolated TBI (defined as Glasgow Coma Scale <9 points and non-cranial Injury Severity Score <10 points). INTERVENTIONS: Serum caspase-3 concentrations were measured on days 1, 4 and 8 of TBI. MAIN VARIABLES OF INTEREST: Thirty-day mortality was considered as the study endpoint. RESULTS: In comparison with non-survivors (n=34), 30-day survivors (n=90) showed lower serum caspase-3 levels on days 1 (p=0.001), 4 (p<0.001) and 8 (p<0.001) of TBI. Analysis of the ROC curves showed serum caspase-3 concentrations on days 1, 4 and 8 of TBI to have an AUC (95% CI) in predicting 30-day mortality of 0.70 (0.61-0.78; p=0.001), 0.83 (0.74-0.89; p<0.001) and 0.87 (0.79-0.93; p<0.001), respectively. CONCLUSIONS: The novel findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivors and could predict 30-day mortality.

MOG-IgG1 and co-existence of neuronal autoantibodies.

BACKGROUND: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood. OBJECTIVES: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients. METHODS: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG. RESULTS: A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2-39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy (p = 0.001), seizures (p = 0.045), and leptomeningeal enhancement (p = 0.045). CONCLUSION: NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.

[HLA genetic polymorphisms and prognosis of patients with COVID-19]. / Polimorfismos genéticos de los HLA y pronóstico de pacientes con COVID-19.

OBJECTIVE: Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. DESIGN: Observational and prospective study. SETTING: Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). PATIENTS: COVID-19 patients admitted in ICU and healthy subjects. INTERVENTIONS: Determination of HLA genetic polymorphisms. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p=0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p=0.02) and HLA-C*16 (p=0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR=7.693; 95% CI=1.063-55.650; p=0.04) or APACHE-II (OR=11.858; 95% CI=1.524-92.273; p=0.02), the allele HLA-C*01 after controlling for SOFA (OR=11.182; 95% CI=1.053-118.700; p=0.04) or APACHE-II (OR=17.604; 95% CI=1.629-190.211; p=0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR=9.963; 95% CI=1.235-80.358; p=0.03). CONCLUSIONS: The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

HLA genetic polymorphisms and prognosis of patients with COVID-19.

Objective: Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. Design: Observational and prospective study. Setting: Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). Patients: COVID-19 patients admitted in ICU and healthy subjects. Interventions: Determination of HLA genetic polymorphisms. Main variable of interest: Mortality at 30 days. Results: A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p = 0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p = 0.02) and HLA-C*16 (p = 0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR = 7.693; 95% CI = 1.063-55.650; p = 0.04) or APACHE-II (OR = 11.858; 95% CI = 1.524-92.273; p = 0.02), the allele HLA-C*01 after controlling for SOFA (OR = 11.182; 95% CI = 1.053-118.700; p = 0.04) or APACHE-II (OR = 17.604; 95% CI = 1.629-190.211; p = 0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR = 9.963; 95% CI = 1.235-80.358; p = 0.03). Conclusions: The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

Objetivo: Diferentes polimorfismos genéticos de los antígenos leucocitarios humanos (HLA) están asociados con el riesgo y el pronóstico de enfermedades autoinmunes e infecciosas. Los objetivos de estudio fueron determinar si existe una asociación entre polimorfismos genéticos de HLA y la susceptibilidad y mortalidad de pacientes con la enfermedad del coronavirus 2019 (COVID-19). Diseño: Estudio observacional y prospectivo. Ámbito: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). Pacientes: Pacientes COVID-19 ingresados en la UCI y sujetos sanos. Intervenciones: Se determinaron los polimorfismos genéticos de los HLA. Variable de interés principal: Mortalidad a los 30 días. Resultados: Se incluyeron 3.886 sujetos sanos y 72 pacientes COVID-19 (10 fallecidos y 62 supervivientes a 30 días). Encontramos una tendencia a una mayor frecuencia de los alelos HLA-A*32 (p = 0,004) en sujetos sanos que en pacientes COVID-19, y de los alelos HLA-B*39 (p = 0,02) y HLA-C*16 (p = 0,02) en pacientes COVID-19 que en sujetos sanos; sin embargo, no fueron significativos al corregir por comparaciones múltiples. En la regresión logística encontramos que la presencia de ciertos alelos estuvo asociada con mayor mortalidad, como el alelo HLA-A*11 controlando por SOFA (OR= 7.693; IC del 95%= 1.063-55.650; p = 0,04) o APACHE-II (OR= 11.858; IC del 95%= 1.524-92.273; p = 0,02), el alelo HLA-C*01 controlando por SOFA (OR= 11.182; IC del 95%= 1.053-118.700; p = 0,04) o APACHE-II (OR= 17.604; IC del 95%= 1.629-190.211; p = 0,02) y el alelo HLA-DQB1*04 controlando por SOFA (OR= 9.963; IC del 95%= 1.235-80.358; p = 0,03). Conclusiones: Los nuevos hallazgos de nuestro preliminar estudio de pequeño tamaño muestral fueron que determinados polimorfismos genéticos de los HLA podrían estar asociados con la mortalidad de pacientes COVID-19; sin embargo, son necesarios estudios de mayor tamaño muestral para concluirlo definitivamente.

Heavy metal transport and evolution of atmospheric aerosols in the Antarctic region.

Suspended particulate matter (SPM) measurements and backward air mass trajectory analysis using the HYSPLIT model were performed to better understand the main sources and transport pathways of heavy metals in atmospheric aerosols reaching the Antarctic region. Field campaigns were carried out during the austral summer 2016-2017 at the "Gabriel de Castilla" Spanish Antarctic Research Station, located on Deception Island. Aerosols were deposited in an air filter through a low-volume sampler and chemically analysed using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The study of air masses and high enrichment factor values of several elements (Hf, Zr, As, Cu, Sn, Zn, Pb) together with their correlations (Hf/Zr, V/As, Ti/Mn and Cu/Sn) suggests a potentially significant role of three main sources in this area: remote maritime traffic, local petrol combustion (generators and/or tourist cruises), and remote/local crust. Additionally, the investigation of atmospheric flow patterns through backward trajectory analysis revealed that Hf/Zr correlation was related to a remote crustal origin, V/As to anthropogenic local pollution, Ti/Mn to terrestrial inputs on the island and Cu/Sn to remote anthropogenic sources. Overall, the present study demonstrates the existence of anthropogenic pollution at this remote site from distant as well as local sources following the Antarctic circumpolar wind pattern.

Quantification of particulate matter, tracking the origin and relationship between elements for the environmental monitoring of the Antarctic region.

The present work reports on the analysis of atmospheric aerosols in the Antarctic region, Deception Island, collected during austral summer 2016-2017 by field measurements carried from Gabriel de Castilla Spanish Research Station. A low-volume sampler was used to capture the aerosols depositing them onto the air filters. A chemical analysis of the samples using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) and Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) provided the total carbon (TC), organic carbon (OC), elemental Carbon (EC) and elements such as Al, Ca, Fe, K, Mg, Na, P, S, Cu, Pb, Sr, Ti, Zn and Cr. The average mass concentration of particulate matter (PM10) originated by natural and anthropogenic activities was calculated as 10 ±â€¯4 µg/m3, although values such as 28.2 µg/m3 were also obtained which is very high even when compared to other places in the coast of the Antarctic region. In addition, high enrichment factors have been found for elements such as Pb, Cr, Cu and Zn showing a remote anthropogenic contribution to particulate matter in this region. Correlations were found between Na, Mg, Ca, Al, Ti and S, where Na/Mg displayed the influence of marine environments, S correspond to volcanic activities, Ca to penguin colonies and influence of sea whereas Al/Ti indicated the crustal origin. Polar contour graphical maps were obtained from meteorological data using chemometrics methods, which allowed reproducing wind maps revealing the distribution of the aerosols and possible emission sources of different elements in the area. Given that this island has not been previously studied for atmospheric contamination, this work provides an interesting insight about the site-specific characteristics of particulate matter.

Megapixel multi-elemental imaging by Laser-Induced Breakdown Spectroscopy, a technology with considerable potential for paleoclimate studies.

Paleoclimate studies play a crucial role in understanding past and future climates and their environmental impacts. Current methodologies for performing highly sensitive elemental analysis at micrometre spatial resolutions are restricted to the use of complex and/or not easily applied techniques, such as synchrotron radiation X-ray fluorescence micro-analysis (µ-SRXRF), nano secondary ion mass spectrometry (nano-SIMS) or laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Moreover, the analysis of large samples (>few cm²) with any of these methods remains very challenging due to their relatively low acquisition speed (~1-10 Hz), and because they must be operated in vacuum or controlled atmosphere. In this work, we proposed an imaging methodology based on laser-induced breakdown spectroscopy, to perform fast multi-elemental scanning of large geological samples with high performance in terms of sensitivity (ppm-level), lateral resolution (up to 10 µm) and operating speed (100 Hz). This method was successfully applied to obtain the first megapixel images of large geological samples and yielded new information, not accessible using other techniques. These results open a new perspective into the use of laser spectroscopy in a variety of geochemical applications.