Infecciones orofaciales de origen odontogénico

La naturaleza polimicrobiana de las infecciones odontógenas así como la heterogeneidad de los cuadros clínicos asociados son consecuencia de la diversidad de la microbiota bucal y de la complejidad anatómica y funcional de la cavidad oral. Así mismo, estos procesos pueden dar lugar a múltiples complicaciones que pueden limitarse a afecciones locales o derivar hasta compromisos sistémicos. En el tratamiento farmacológico de estas infecciones es crucial la elección del antibiótico y la pauta posológica más eficaces. La farmacodinamia proporciona los parámetros que hacen posible valorar como varía la actividad de los antibióticos en función del tiempo. Como norma general, en el manejo inicial de las infecciones orofaciales en el adulto, incluidas las infecciones odontógenas, se utilizará amoxicilina/ac. Clavulánico en dosis de 875 mg de amoxicilina y 125 mg de ac. clavulánico pautado cada 8 horas. El cumplimiento terapéutico es clave para evitar la aparición de resistencias, por lo que se ha de maximizar la aceptación por parte de los pacientes. En este sentido se ha demostrado que la nueva presentación de 2000/125 mg de Augmentine Plus pautado cada 12 horas tanto en profilaxis como tratamiento disminuye significativamente la tasa de complicaciones infecciosas derivada de la extracción del tercer molar.The polymicrobial nature of the odontogenic infections as well as the variety of associated conditions are a consequence of the diversity of the buccal microbiota and the anatomical and functional complexity of the oral cavity. In addition to this, all these processes can give way to multiple complications which range from the local to the systemic level. The appropriate choice of antibiotic and posology is crucial in the successful management of these infections. Pharmacodynamics provides those parameters that make it possible to assess how antibiotics activity varies in time. As a general rule, the first step in the initial management of orofacial infections in adults, included odontogenic infections, will be the administration of 875 mg of amoxicillin and 125 mg of clavulanic every 8 hours. Therapeutic compliance is paramount to avoid resistance, therefore patient's acceptance must be sought. In this sense, it has been proved that Augmentine Plus (2000/125) every twelve hours both as profylaxis and as treatment significantly decreases the rate of infective complications associated to extraction of the third molar

Dynamic Excimer (DYNEX) Imaging of Lipid Droplets

This work was funded by grants CTQ2017-85658-R (MICIU/AEI/ERDF), FQM-337 (Junta de Andalucía), and PIUJA 2019-20 (Universidad de Jaén). We acknowledge the Universidad de Granada (Spain) microscopy central facilities (CIC-UGR) and computing time from CSIRC-UGR. M.C.G.-G. thanks MICIU/AEI for a predoctoral fellowship. Funding for open access charge: Universidad de Granada/CBUA. We are indebted to Prof. Reinhard Jahn for his generous support.Unraveling cellular physiological processes via luminescent probes that target specific cellular microenvironments is quite challenging due to the uneven distribution of probes. Herein, we designed a new dynamic excimer (DYNEX) imaging method that involves the sensitive detection of nanosecond-scale dynamic molecular contacts of a fluorescent acridone derivative and reveals the cell microenvironment polarity. Using our method, we specifically tracked cell lipid droplets in fibroblast colon carcinoma cells. These organelles play a central role in metabolic pathways, acting as energy reservoirs in regulatory processes. DYNEX imaging provides the inner polarity of cell lipid droplets, which can be related to lipid contents and metabolic dysfunctions. This new methodology will inspire development of novel multidimensional fluorescent sensors that are able to provide target-specific and orthogonal information at the nanosecond scale.CBUAMICIUUniversidad de GranadaUniversidad de JaénAgencia Estatal de InvestigaciónEuropean Regional Development Fund FQM-337Junta de Andalucía PIUJA 2019-2

Seeding and Growth of β-Amyloid Aggregates upon Interaction with Neuronal Cell Membranes

In recent years, the prevalence of amyloid neurodegenerative diseases such as Alzheimer’s disease (AD) has significantly increased in developed countries due to increased life expectancy. This amyloid disease is characterized by the presence of accumulations and deposits of β-amyloid peptide (Aβ) in neuronal tissue, leading to the formation of oligomers, fibers, and plaques. First, oligomeric intermediates that arise during the aggregation process are currently thought to be primarily responsible for cytotoxicity in cells. This work aims to provide further insights into the mechanisms of cytotoxicity by studying the interaction of Aβ aggregates with Neuro-2a (N2a) neuronal cells and the effects caused by this interaction. For this purpose, we have exploited the advantages of advanced, multidimensional fluorescence microscopy techniques to determine whether different types of Aβ are involved in higher rates of cellular toxicity, and we measured the cellular stress caused by such aggregates by using a fluorogenic intracellular biothiol sensor. Stress provoked by the peptide is evident by N2a cells generating high levels of biothiols as a defense mechanism. In our study, we demonstrate that Aβ aggregates act as seeds for aggregate growth upon interacting with the cellular membrane, which results in cell permeability and damage and induces lysis. In parallel, these damaged cells undergo a significant increase in intracellular biothiol levels.Spanish Ministerio de Ciencia, Innovacion y Universidades CTQ2014-56370-R CTQ2017-86568-R CTQ2017-86125-PSpanish Agencia Estatal de InvestigacionEuropean Union (EU

Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis

Citation: Herrera C, Macêdo JKA, Feoli A, Escalante T, Rucavado A, Gutiérrez JM, et al. (2016) Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis. PLoS Negl Trop Dis 10(4): e0004599. doi:10.1371/journal. pntd.0004599The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM) and other extracellular matrix (ECM) proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs) or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.Universidad de Costa Rica/[741-B4-660]/UCR/Costa RicaUniversidad de Costa Rica/[741-B6-125]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Effects of climate and atmospheric nitrogen deposition on early to mid-term stage litter decomposition across biomes

Litter decomposition is a key process for carbon and nutrient cycling in terrestrial ecosystems and is mainly controlled by environmental conditions, substrate quantity and quality as well as microbial community abundance and composition. In particular, the effects of climate and atmospheric nitrogen (N) deposition on litter decomposition and its temporal dynamics are of significant importance, since their effects might change over the course of the decomposition process. Within the TeaComposition initiative, we incubated Green and Rooibos teas at 524 sites across nine biomes. We assessed how macroclimate and atmospheric inorganic N deposition under current and predicted scenarios (RCP 2.6, RCP 8.5) might affect litter mass loss measured after 3 and 12 months. Our study shows that the early to mid-term mass loss at the global scale was affected predominantly by litter quality (explaining 73% and 62% of the total variance after 3 and 12 months, respectively) followed by climate and N deposition. The effects of climate were not litter-specific and became increasingly significant as decomposition progressed, with MAP explaining 2% and MAT 4% of the variation after 12 months of incubation. The effect of N deposition was litter-specific, and significant only for 12-month decomposition of Rooibos tea at the global scale. However, in the temperate biome where atmospheric N deposition rates are relatively high, the 12-month mass loss of Green and Rooibos teas decreased significantly with increasing N deposition, explaining 9.5% and 1.1% of the variance, respectively. The expected changes in macroclimate and N deposition at the global scale by the end of this century are estimated to increase the 12-month mass loss of easily decomposable litter by 1.1-3.5% and of the more stable substrates by 3.8-10.6%, relative to current mass loss. In contrast, expected changes in atmospheric N deposition will decrease the mid-term mass loss of high-quality litter by 1.4-2.2% and that of low-quality litter by 0.9-1.5% in the temperate biome. Our results suggest that projected increases in N deposition may have the capacity to dampen the climate-driven increases in litter decomposition depending on the biome and decomposition stage of substrate

Attitudes and burden in relatives of patients with schizophrenia in a middle income country

BACKGROUND: Most studies of family attitudes and burden have been conducted in developed countries. Thus it is important to test the generalizability of this research in other contexts where social conditions and extended family involvement may be different. The aim of this study was to assess the relationship between the attitudes of caregivers and the burden they experience in such a context, namely Arica, a town located in the northernmost region of Chile, close to the border with Peru and Bolivia. METHODS: We assessed attitudes towards schizophrenia (including affective, cognitive and behavioural components) and burden (including subjective distress, rejection and competence) in 41 main caregivers of patients with schizophrenia, all of whom were users of Public Mental Health Services in Arica. RESULTS: Attitude measures differed significantly according to socio-demographic variables, with parents (mainly mothers) exhibiting a more negative attitude towards the environment than the rest of the family (t = 4.04; p = 0.000).This was also the case for caregivers with a low educational level (t = 3.27; p < 0.003), for the oldest caregivers (r = 0.546; p = 0.000) and for those who had spent more time with the patient (r = 0.377; p = 0.015). Although attitudes had significant association with burden, their explanatory power was modest (R2 = .104, F = 4,55; p = .039). CONCLUSIONS: Similar to finding developed countries, the current study revealed a positive and significant relationship between the attitudes of caregivers and their burden. These findings emphasize the need to support the families of patients with schizophrenia in this social context

A transcriptomic analysis of gene expression in the venom gland of the snake Bothrops alternatus (urutu)

<p>Abstract</p> <p>Background</p> <p>The genus <it>Bothrops </it>is widespread throughout Central and South America and is the principal cause of snakebite in these regions. Transcriptomic and proteomic studies have examined the venom composition of several species in this genus, but many others remain to be studied. In this work, we used a transcriptomic approach to examine the venom gland genes of <it>Bothrops alternatus</it>, a clinically important species found in southeastern and southern Brazil, Uruguay, northern Argentina and eastern Paraguay.</p> <p>Results</p> <p>A cDNA library of 5,350 expressed sequence tags (ESTs) was produced and assembled into 838 contigs and 4512 singletons. BLAST searches of relevant databases showed 30% hits and 70% no-hits, with toxin-related transcripts accounting for 23% and 78% of the total transcripts and hits, respectively. Gene ontology analysis identified non-toxin genes related to general metabolism, transcription and translation, processing and sorting, (polypeptide) degradation, structural functions and cell regulation. The major groups of toxin transcripts identified were metalloproteinases (81%), bradykinin-potentiating peptides/C-type natriuretic peptides (8.8%), phospholipases A₂(5.6%), serine proteinases (1.9%) and C-type lectins (1.5%). Metalloproteinases were almost exclusively type PIII proteins, with few type PII and no type PI proteins. Phospholipases A₂were essentially acidic; no basic PLA₂were detected. Minor toxin transcripts were related to L-amino acid oxidase, cysteine-rich secretory proteins, dipeptidylpeptidase IV, hyaluronidase, three-finger toxins and ohanin. Two non-toxic proteins, thioredoxin and double-specificity phosphatase Dusp6, showed high sequence identity to similar proteins from other snakes. In addition to the above features, single-nucleotide polymorphisms, microsatellites, transposable elements and inverted repeats that could contribute to toxin diversity were observed.</p> <p>Conclusions</p> <p><it>Bothrops alternatus </it>venom gland contains the major toxin classes described for other <it>Bothrops </it>venoms based on trancriptomic and proteomic studies. The predominance of type PIII metalloproteinases agrees with the well-known hemorrhagic activity of this venom, whereas the lower content of serine proteases and C-type lectins could contribute to less marked coagulopathy following envenoming by this species. The lack of basic PLA₂agrees with the lower myotoxicity of this venom compared to other <it>Bothrops </it>species with these toxins. Together, these results contribute to our understanding of the physiopathology of envenoming by this species.</p

Cross-recognition of a pit viper (Crotalinae) polyspecific antivenom explored through high-density peptide microarray epitope mapping

Snakebite antivenom is a 120 years old invention based on polyclonal mixtures of antibodies purified from the blood of hyper-immunized animals. Knowledge on antibody recognition sites (epitopes) on snake venom proteins is limited, but may be used to provide molecular level explanations for antivenom cross-reactivity. In turn, this may help guide antivenom development by elucidating immunological biases in existing antivenoms. In this study, we have identified and characterized linear elements of B-cell epitopes from 870 pit viper venom protein sequences by employing a high-throughput methodology based on custom designed high-density peptide microarrays. By combining data on antibody-peptide interactions with multiple sequence alignments of homologous toxin sequences and protein modelling, we have determined linear elements of antibody binding sites for snake venom metalloproteases (SVMPs), phospholipases A2s (PLA2s), and snake venom serine proteases (SVSPs). The studied antivenom antibodies were found to recognize linear elements in each of the three enzymatic toxin families. In contrast to a similar study of elapid (non-enzymatic) neurotoxins, these enzymatic toxins were generally not recognized at the catalytic active site responsible for toxicity, but instead at other sites, of which some are known for allosteric inhibition or for interaction with the tissue target. Antibody recognition was found to be preserved for several minor variations in the protein sequences, although the antibody-toxin interactions could often be eliminated completely by substitution of a single residue. This finding is likely to have large implications for the cross-reactivity of the antivenom and indicate that multiple different antibodies are likely to be needed for targeting an entire group of toxins in these recognized sites.Novo Nordisk Foundation/[NNF13OC0005613]/NNF/DinamarcaNovo Nordisk Foundation/[NNF16OC0019248]/NNF/DinamarcaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Mitigación con Sistemas Silvopastoriles en Latinoamérica: Aportes para la incorporación en los sistemas de Medición Reporte y Verificación bajo la CMNUCC

En Latinoamérica el 46% de las emisiones de GEI proviene del cambio de usos de la tierra y el 20% de la agricultura, en donde el 58% y el 70% de las emisiones son debidas a la ganadería. El continuo crecimiento de este sector (+32% previsto al 2050) ha impulsado la expansión de la frontera agropecuaria en los bosques, generando múltiples impactos ambientales entre los cuales se encuentra la emisión de Gases Efecto Invernadero (GEI). Sin embargo, el sector tiene un alto potencial de mitigación reconocido por políticas, estrategias y programas de mitigación nacionales como las Contribuciones Nacionalmente Determinadas (NDC) y de desarrollo sectorial como las Acciones de Mitigación nacionalmente Apropiadas (NAMA). Entre estas acciones se incluye la implementación de sistemas silvopastoriles, cuya medición monitoreo y reporte a escala nacional presenta un estado de avance muy limitado, dejando su aporte a la mitigación invisible. A través de un Grupo Técnico de Trabajo ad hoc se han analizado el avance de los países de la región en la incorporación de los sistemas silvopastoriles en los sistemas nacionales de Medición/Monitoreo, Reporte y Verificación (MRV) de los Inventarios Nacionales de Gases Efecto Invernadero, y los requerimientos a cumplir para esto, generando una hoja de ruta a corto-medio plazo así como unas orientaciones técnicas para reducir la brecha existente

Mitigación con Sistemas Silvopastoriles en Latinoamérica: Aportes para la incorporación en los sistemas de Medición Reporte y Verificación bajo la CMNUCC

En Latinoamérica el 46% de las emisiones de GEI proviene del cambio de usos de la tierra y el 20% de la agricultura, en donde el 58% y el 70% de las emisiones son debidas a la ganadería. El continuo crecimiento de este sector (+32% previsto al 2050) ha impulsado la expansión de la frontera agropecuaria en los bosques, generando múltiples impactos ambientales entre los cuales se encuentra la emisión de Gases Efecto Invernadero (GEI). Sin embargo, el sector tiene un alto potencial de mitigación reconocido por políticas, estrategias y programas de mitigación nacionales como las Contribuciones Nacionalmente Determinadas (NDC) y de desarrollo sectorial como las Acciones de Mitigación nacionalmente Apropiadas (NAMA). Entre estas acciones se incluye la implementación de sistemas silvopastoriles, cuya medición monitoreo y reporte a escala nacional presenta un estado de avance muy limitado, dejando su aporte a la mitigación invisible. A través de un Grupo Técnico de Trabajo ad hoc se han analizado el avance de los países de la región en la incorporación de los sistemas silvopastoriles en los sistemas nacionales de Medición/Monitoreo, Reporte y Verificación (MRV) de los Inventarios Nacionales de Gases Efecto Invernadero, y los requerimientos a cumplir para esto, generando una hoja de ruta a corto-medio plazo así como unas orientaciones técnicas para reducir la brecha existente