Immunogenicity of BNT162b2 vaccine after two and three doses in health personnel and institutionalized elderly people not infected with SARS-CoV-2.

OBJECTIVE: The aim of our research was to compare the evolution of the immune response induced by the BNT162b2 vaccine after the administration of two and three doses in healthcare personnel and in institutionalized elderly people (>65 years of age) without previous SARS-CoV-2 infection. MATERIAL AND METHODS: A prospective observational study was carried out on a convenience sample made up of health workers and institutionalized elderly people, measuring antibodies against S and N proteins of SARS-CoV-2 two and six months after receiving the second vaccine dose, as well as two months after receiving the third dose. RESULTS: A significant reduction of the anti-S humoral immune response was reported six months after the second dose of vaccine in both health workers and residents. The administration of a third dose of vaccine induced a significant increase in this antibody response in both investigated groups reaching a similar proportion of responders two months after this third dose. CONCLUSIONS: Humoral immunity induced by two doses of the BNT162b2 vaccine in persons without prior SARS-CoV-2 infection wanes over time. The administration of a third dose significantly increases anti-S antibodies being highly recommended, especially in people over 65 years of age.

The implications of DNA methylation for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a complex and serious neurodegenerative disorder that develops in consequence of the progressive loss of the upper and lower motor neurons. Cases of ALS are classified as sporadic (sALS), or familial (fALS). Over 90% of cases are sALS, while roughly 10% are related to inherited genetic mutations (fALS). Approximately 70% of the genetic mutations that contribute to fALS have been identified. On the other hand, the majority of the sALS cases have an undetermined genetic contributor and few mutations have been described, despite the advanced genetic analysis methods. Also, several factors contribute to the onset and progression of ALS. Numerous lines of evidence indicate that epigenetic changes are linked to aging, as well as neurodegenerative disorders, such as ALS. In most cases, they act as the heritable regulation of transcription by DNA methylation, histone modification and expression of noncoding RNAs. Mechanisms involving aberrant DNA methylation could be relevant to human ALS pathobiology and therapeutic targeting. Despite advances in research to find factors associated with ALS and more effective treatments, this disease remains complex and has low patient survival. Here, we provide a narrative review of the role of DNA methylation for this complex neurodegenerative disorder.

Hierarchical Wilson-Cowan Models and Connection Matrices.

This work aims to study the interplay between the Wilson-Cowan model and connection matrices. These matrices describe cortical neural wiring, while Wilson-Cowan equations provide a dynamical description of neural interaction. We formulate Wilson-Cowan equations on locally compact Abelian groups. We show that the Cauchy problem is well posed. We then select a type of group that allows us to incorporate the experimental information provided by the connection matrices. We argue that the classical Wilson-Cowan model is incompatible with the small-world property. A necessary condition to have this property is that the Wilson-Cowan equations be formulated on a compact group. We propose a p-adic version of the Wilson-Cowan model, a hierarchical version in which the neurons are organized into an infinite rooted tree. We present several numerical simulations showing that the p-adic version matches the predictions of the classical version in relevant experiments. The p-adic version allows the incorporation of the connection matrices into the Wilson-Cowan model. We present several numerical simulations using a neural network model that incorporates a p-adic approximation of the connection matrix of the cat cortex.

Evaluation of the susceptibility of Tritrichomonas foetus to extracts of Lantana camara (Verbenaceae) by flow cytometry.

Bovine Trichomonosis (BT), a sexually transmitted disease endemic in countries with extensive cattle farming and natural service, is one of the most common causes of reproductive failure. 5-nitroimidazoles and their derivatives are used for its treatment, mainly metronidazole. The emergence of drug resistance mechanisms and treatment failures raise the need to investigate the effectiveness of new active compounds that contribute to parasite control. In this regard, extracts of Lantana camara (Verbenacea) have shown high biocidal potential against isolates of Trypanosoma cruzi and Leishmania braziliensis in vitro assays, although their effect on Tritrichomonas foetus has not been demonstrated yet. The available information on in vitro susceptibility of trichomonicidal drugs comes from the use of a diversity of methodologies and criteria, especially the observation of parasite motility under the optical microscope to assess their viability. Recently, in our laboratory, the use of flow cytometry has been described for the first time as a rapid and efficient method to evaluate the viability of T. foetus against metronidazole. The present study aimed to evaluate the cytostatic effect of L. camara extracts against T. foetus isolates by flow cytometry. Under aerobic conditions, IC50 values of 22.60 µg/mL were obtained on average. Under anaerobic conditions, the IC50 oscilated around 29.04 µg/mL. The results obtained allowed describing the susceptibility exhibited by these protozoa, being a valuable information for the development of potential BT treatments.

Novel polypropylene-TiO2:Bi spherical floater for the efficient photocatalytic degradation of the recalcitrant 2,4,6-TCP herbicide.

In this work, spherical photocatalytic floaters were fabricated by depositing TiO2:Bi (TBi) particles on polypropylene (PP) spheres (recycled from beer cans). These particles were deposited on the sphere (TBi-sphere) by the spray coating technique and evaluated their performance for the photocatalytic degradation of 2,4,6-trichlorophenol (2,4,6-TCP) herbicide. SEM images demonstrated that the BTi powders consisted in conglomerated grains with sizes of 20-80 nm and the analysis by X-ray diffraction confirmed the presence of rutile and anatase phases in the BTi. The photocatalytic experiments showed that the TBi and TBi-sphere produced maximum degradation of 90 and 97% for 2,4,6-TCP, respectively, after 4 h under UV-Vis light. The photocatalytic powders/composites were reused 3 times and the loss of degradation efficiency was 3 and 16% for the TBi powder and TBi-sphere, respectively. This means that the TBi-sphere is more stable for the continuous degradation of the 2,4,6-TCP contaminant. The TiO2:Bi powder was compared with the commercial TiO2 (P25) and found that the TiO2:Bi powder had higher light absorption (≈42%) and higher surface area (≈105%) than the P25. Therefore, the degradation percentage for the 2,4,6-TCP was 52% higher in the sample doped with Bi. Also, scavenger experiments were carried out and found that the main oxidizing agents produced for the degradation of 2,4,6-TCP were •OH- radicals and •O2- anions. Other species such as h+ were also produced at lower amount. Hence, our results demonstrated that spherical/floatable photocatalytic composites are a viable option to remove herbicide residuals from the water, which is of interest in water-treatment-plants.

FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation.

SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 is linked to substantial inflammation, how SARS-CoV-2 triggers inflammation is not clear2. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D, leading to inflammatory death (pyroptosis) and the release of potent inflammatory mediators3. Here we show that about 6% of blood monocytes of patients with COVID-19 are infected with SARS-CoV-2. Monocyte infection depends on the uptake of antibody-opsonized virus by Fcγ receptors. The plasma of vaccine recipients does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in the supernatants of cultures of infected monocytes. Instead, infected cells undergo pyroptosis mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and gasdermin D. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from lung autopsies from patients with COVID-19 have activated inflammasomes. Taken together, these findings suggest that antibody-mediated SARS-CoV-2 uptake by monocytes and macrophages triggers inflammatory cell death that aborts the production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis.

Isolation and molecular identification of native As-resistant bacteria: As(III) and As(V) removal capacity and possible mechanism of detoxification.

The study of arsenic (As)-resistant microorganisms with high As removal capacity is fundamental for the development of economically sustainable technologies used for the treatment of water contaminated with metalloid. In the current study, four bacterial strains were isolated from As-contaminated water samples of the Xichu region, Mexico. Based on 16S rRNA gene sequencing and phylogenetic analysis of the isolated strains, Rhodococcus gordoniae, Microbacterium hydrocarbonoxydans, Exiguobacterium indicum, and Pseudomonas kribbensis were identified as potential As removal strains. R. gordoniae shows the highest growth capacity in both As(III) and As(V). R. gordoniae, M. hydrocarbonoxydans, and E. indicum removed approximately 81.6, 79.9, and 61.7% of As(III), as well as 77.2, 68.9, and 74.8% of As(V), respectively. P. kribbensis removed only about 80.2% of As(V). This study contributes to the possible detoxification mechanisms employed by these bacteria. Such insight could be crucial in the successful implementation of in situ bioremediation programs using these little-known bacteria.

SARS-CoV-2 infects blood monocytes to activate NLRP3 and AIM2 inflammasomes, pyroptosis and cytokine release.

SARS-CoV-2 causes acute respiratory distress that can progress to multiorgan failure and death in a minority of patients. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood. Monocytes and macrophages are sentinel immune cells in the blood and tissue, respectively, that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD) pores, leading to inflammatory death (pyroptosis) and processing and release of IL-1 family cytokines, potent inflammatory mediators. Here we show that expression quantitative trait loci (eQTLs) linked to higher GSDMD expression increase the risk of severe COVID-19 disease (odds ratio, 1.3, p<0.005). We find that about 10% of blood monocytes in COVID-19 patients are infected with SARS-CoV-2. Monocyte infection depends on viral antibody opsonization and uptake of opsonized virus by the Fc receptor CD16. After uptake, SARS-CoV-2 begins to replicate in monocytes, as evidenced by detection of double-stranded RNA and subgenomic RNA and expression of a fluorescent reporter gene. However, infection is aborted, and infectious virus is not detected in infected monocyte supernatants or patient plasma. Instead, infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of the NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD. Moreover, tissue-resident macrophages, but not infected epithelial cells, from COVID-19 lung autopsy specimens showed evidence of inflammasome activation. These findings taken together suggest that antibody-mediated SARS-CoV-2 infection of monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to severe COVID-19 disease pathogenesis.

SARS-CoV-2 infects blood monocytes to activate NLRP3 and AIM2 inflammasomes, pyroptosis and cytokine release.

SARS-CoV-2 causes acute respiratory distress that can progress to multiorgan failure and death in some patients. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood. Monocytes are sentinel blood cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD) pores, leading to inflammatory death (pyroptosis) and processing and release of IL-1 family cytokines, potent inflammatory mediators. Here we show that ~10% of blood monocytes in COVID-19 patients are dying and infected with SARS-CoV-2. Monocyte infection, which depends on antiviral antibodies, activates NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD cleavage and relocalization. Signs of pyroptosis (IL-1 family cytokines, LDH) in the plasma correlate with development of severe disease. Moreover, expression quantitative trait loci (eQTLs) linked to higher GSDMD expression increase the risk of severe COVID-19 disease (odds ratio, 1.3, p<0.005). These findings taken together suggest that antibody-mediated SARS-CoV-2 infection of monocytes triggers inflammation that contributes to severe COVID-19 disease pathogenesis. ONE SENTENCE SUMMARY: Antibody-mediated SARS-CoV-2 infection of monocytes activates inflammation and cytokine release.

Sentinel lymph node biopsy procedure in squamous vulvar cancer. 10 years follow-up analysis. / Biopsia selectiva de ganglio centinela en el carcinoma escamoso de vulva. Análisis de seguimiento a 10 años.

AIM: Application of sentinel lymph node biopsy (SLNB) procedure in early-stage vulvar cancer and analysis of results, recurrences and complications. MATERIAL AND METHODS: 40 patients with vulvar cancer and SLNB between 2008 and 2018 were retrospectively reviewed. During the surgical procedure the inguinofemoral lymph nodes were checked with a gamma probe to identify the sentinel nodes that were removed and referred for intraoperative pathological assessment. Subsequently, long-term patient follow-up was performed with analysis of complications, relapse and mortality. RESULTS: 40 patients (mean age: 72 years [47-86], the overall detection rate per patient was 95% and a total of 129 Sentinel Lymph Nodes (SLNs) were removed (3.22 SLN/patient). In 3 out of 25 patients with lateral tumour lesions drainage was bilateral and in 2 out of 15 with midline lesions drainage was unilateral. On lymphoscintigraphy, 16 out of 40 had bilateral drainage and 24 unilateral. A total of 119 SLN- and 10 SLN+ were obtained, in 8 out of 10 an inguinofemoral lymphadenectomy was performed. In the SLN- group, one case of lymphatic blockage and one false negative were included. In 12 out of 40 patients there were post-surgical complications, 4 of them lymphoedemas. In the median follow-up (40 months), 6 out of 10 with SLN+ (40% mortality) and 7 out of 30 SLN- (16% mortality) had recurrences. CONCLUSIONS: SLNB in vulvar cancer is the technique of choice for correct staging and locoregional therapy. Correct clinical lymph node staging is important before surgery in order to avoid potential blockage drainages which could induce a false negative SLN.

Mental illness and social exclusion: assessment of the risk of violence after release.

OBJECTIVES: To examine the predictive validity of the HCR-20 (The Historical Clinical Risk Management-20) to predict future violent incidents in a representative sample of patients with severe mental disorders and with a history of previous admission to prison, who after release are in a situation of extreme social exclusion. MATERIAL AND METHOD: The study sample was selected from the 235 patients treated by the Mental Health Street Team of Madrid (ECASAM) from June 2014 to June 2017, including those with a previous history of a previous internment in a penitentiary (about which, the HCR-20 was completed). RESULTS: Of the 44 patients included, 29.6% (n=13) ended up participating in a violent incident after the release. The ROC curves (Receiver Operating Characteristic) analysis indicated that the total score of HCR-20 (AUC 0.98, p=0.01) has a high predictive validity. CONCLUSIONS: The social and medical changes that take place after the release of patients with severe mental illness justify the need to reassess the risk of violence. In this evaluation, the HCR-20 guide is a useful tool for predicting the risk of involvement in future violent incidents, and the inclusion of factors such as social exclusion and its consequences, as well as problems with substance use is especially important.

Photo-assisted inactivation of Escherichia coli bacteria by silver functionalized titanate nanotubes, Ag/H2Ti2O5·H2O.

One-dimensional titanate nanotubes (H2Ti2O5·H2O) functionalized with silver nanoparticles (AgNPs) exhibited unique properties for the effective inactivation of the Gram-negative Escherichia coli within 45 minutes under irradiation using a 65 W halogen lamp. The pathway of the photo-assisted catalytic inactivation was examined by SEM and TEM using a reproducible biological protocol for sample preparations. The membrane integrity of the bacteria was damaged due to the oxidative stress caused by the reactive oxygen species, the bacteriostatic effect of the highly-dispersed-surface AgNPs (∼5 nm) and the sharp nanotube penetration that induced the cell death.

Germination sensitivity to water stress in four shrubby species across the Mediterranean Basin.

Mediterranean shrublands are generally water-limited and fire-driven ecosystems. Seed-based post-fire regeneration may be affected by varying rainfall patterns, depending on species sensitivity to germinate under water stress. In our study, we considered the germination response to water stress in four species from several sites across the Mediterranean Basin. Seeds of species with a hard coat (Cistus monspeliensis, C. salviifolius, Cistaceae, Calicotome villosa, Fabaceae) or soft coat (Erica arborea, Ericaceae), which were exposed or not to a heat shock and smoke (fire cues), were made to germinate under water stress. Final germination percentage, germination speed and viability of seeds were recorded. Germination was modelled using hydrotime analysis and correlated to the water balance characteristics of seed provenance. Water stress was found to decrease final germination in the three hard-seeded species, as well as reduce germination speed. Moreover, an interaction between fire cues and water stress was found, whereby fire cues increased sensitivity to water stress. Seed viability after germination under water stress also declined in two hard-seeded species. Conversely, E. arborea showed little sensitivity to water stress, independent of fire cues. Germination responses varied among populations of all species, and hydrotime parameters were not correlated to site water balance, except in E. arborea when not exposed to fire cues. In conclusion, the species studied differed in germination sensitivity to water stress; furthermore, fire cues increased this sensitivity in the three hard-seeded species, but not in E. arborea. Moreover, populations within species consistently differed among themselves, but these differences could only be related to the provenance locality in E. arborea in seeds not exposed to fire cues.

Disruptive behavior disorders and indicators of disinhibition in adolescents: The BRIEF-SR, anti-saccade task, and D-KEFS color-word interference test.

Disinhibition contributes to the development of disruptive behavior disorders (DBD) in adolescents. Self-reports and behavioral tasks are commonly used to assess disinhibition, each with their unique strengths and limitations. Accordingly, it is important to identify which measure, or combination thereof, is the most effective in predicting DBD symptoms. This study assessed the relationship between DBD (symptoms of ADHD/ODD/CD) and two behavioral disinhibition tasks: the anti-saccade task and the D-KEFS color-word interference test, as well as a self-report measure (the BRIEF-SR). The results indicated that the BRIEF-Inhibit scale accounted for the majority of the variance in the DBD sum score. The anti-saccade task and color-word interference test were also significantly associated with an increase in the number of DBD symptoms endorsed. These behavioral tasks accounted for 9% additional variance than the self-report alone. Therefore, combining self-report measures with behavioral disinhibition tasks may provide the most thorough assessment of adolescent DBD.

The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism.

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

Electrochemical modification of gold electrodes with azobenzene derivatives by diazonium reduction.

An electrochemical study of Au electrodes electrografted with azobenzene (AB), Fast Garnet GBC (GBC) and Fast Black K (FBK) diazonium compounds is presented. Electrochemical quartz crystal microbalance, ellipsometry and atomic force microscopy investigations reveal the formation of multilayer films. The elemental composition of the aryl layers is examined by X-ray photoelectron spectroscopy. The electrochemical measurements reveal a quasi-reversible voltammogram of the Fe(CN)6 (3-/4-) redox couple on bare Au and a sigmoidal shape for the GBC- and FBK-modified Au electrodes, thus demonstrating that electron transfer is blocked due to the surface modification. The electrografted AB layer results in strongest inhibition of the Fe(CN)6 (3-/4-) response compared with other aryl layers. The same tendencies are observed for oxygen reduction; however, the blocking effect is not as strong as in the Fe(CN)6 (3-/4-) redox system. The electrochemical impedance spectroscopy measurements allowed the calculation of low charge-transfer rates to the Fe(CN)6 (3-) probe for the GBC- and FBK-modified Au electrodes in relation to bare Au. From these measurements it can be concluded that the FBK film is less compact or presents more pinholes than the electrografted GBC layer.

Impact of a cleaner-burning cookstove intervention on blood pressure in Nicaraguan women.

Few studies have evaluated the cardiovascular-related effects of indoor biomass burning or the role of characteristics such as age and obesity status, in this relationship. We examined the impact of a cleaner-burning cookstove intervention on blood pressure among Nicaraguan women using an open fire at baseline; we also evaluated heterogeneity of the impact by subgroups of the population. We evaluated changes in systolic and diastolic blood pressure from baseline to post-intervention (range: 273-383 days) among 74 female cooks. We measured indoor fine particulate matter (PM(2.5); N = 25), indoor carbon monoxide (CO; N = 32), and personal CO (N = 30) concentrations. Large mean reductions in pollutant concentrations were observed for all pollutants; for example, indoor PM(2.5) was reduced 77% following the intervention. However, pollution distributions (baseline and post-intervention) were wide and overlapping. Although substantial reductions in blood pressure were not observed among the entire population, a 5.9 mmHg reduction [95% confidence interval (CI): -11.3, -0.4] in systolic blood pressure was observed among women aged 40 or more years and a 4.6 mmHg reduction (95% CI: -10.0, 0.8) was observed among obese women. Results from this study provide an indication that certain subgroups may be more likely to experience improvements in blood pressure following a cookstove intervention.

Retroperitoneal cystic mature teratoma as the presenting clinical scenario of testicular carcinoma.

OBJECTIVE: To describe a case of retroperitoneal mature teratoma presenting as metastasis of a testicular mixed germ cell tumor in a thirty year old man who had lumbar and abdominal pain and mass sensation in the left hemiabdomen. METHODS: Abdominal ultrasound and thoracic-abdominal-pelvic CT multidetector scan were performed, and then after a Doppler ultrasound study of the testicles. Surgical treatment was performed: orchiectomy and retroperitoneal lesion resection. RESULTS: Imaging studies showed a big cystic lesion in the left retroperitoneal space, 13 × 12 × 11 cm, well defined, with thin septa, displacing the kidney; and a solid-cystic 4 cm left testicular tumor, with multiple septa, solid poles and arterial flows with low resistances. Thoracic extension study did not show any finding. The histopathologic results of the orchiectomy and retroperitoneal resection pieces were, respectively, testicular mixed germ cell tumor (seminoma, with intratubular seminoma foci and teratoma) and mature cystic teratoma. CONCLUSIONS: Germ cell tumors derive from multipotencial cells with a large capacity of differentiation, and the nodal paraaortic chains are a natural way of dissemination of these neoplasms. Because of that, in the presence of a retroperitoneal lesion in a young patient we have to rule out testicular tumor metastasis. The retroperitoneal mature cystic teratoma must be considered as a lesion with malignant potential.