Lyotropic Aqueous 2-Picolinium Ionic Liquid Crystals and Their Shear-Induced Foams.

1-Dodecyl-2-methylpyridinium bromide ([C12-2-Pic][Br]) and 1-hexadecyl-2-methylpyridinium bromide ([C16-2-Pic][Br]) are two ionic liquid crystals presenting thermotropic smectic phases above 80 °C. Aiming to take advantage of the liquid crystalline properties at lower temperatures, lyotropic aqueous systems were prepared from these two organic salts. Both systems were characterized by polarized optical microscopy (POM), X-ray powder diffraction (XRD), and fast field cycling nuclear magnetic resonance (FFC-NMR) relaxometry to assess their texture, phase structure, and molecular dynamics, respectively. The mesomorphic behavior was induced at room temperature. Moreover, the lyotropic [C12-2-Pic][Br]aq revealed a smectic phase with higher separation between layers, different from the lamellar phases found in the thermotropic system (S1 and SA), which is thermally stable up to 50 °C. Furthermore, the surfactant nature of the ionic liquids diluted solutions investigated in this work allowed the formation of foams. It was found that the precursor solutions of the lyotropic dilutions with the longest alkyl chain ([C16-2-Pic][Br]aq) originated liquid foams with more stable structures than those of [C12-2-Pic][Br]aq.

Comparative Chemical Profiling and Antimicrobial/Anticancer Evaluation of Extracts from Farmed versus Wild Agelas oroides and Sarcotragus foetidus Sponges.

Marine sponges are highly efficient in removing organic pollutants and their cultivation, adjacent to fish farms, is increasingly considered as a strategy for improving seawater quality. Moreover, these invertebrates produce a plethora of bioactive metabolites, which could translate into an extra profit for the aquaculture sector. Here, we investigated the chemical profile and bioactivity of two Mediterranean species (i.e., Agelas oroides and Sarcotragus foetidus) and we assessed whether cultivated sponges differed substantially from their wild counterparts. Metabolomic analysis of crude sponge extracts revealed species-specific chemical patterns, with A. oroides and S. foetidus dominated by alkaloids and lipids, respectively. More importantly, farmed and wild explants of each species demonstrated similar chemical fingerprints, with the majority of the metabolites showing modest differences on a sponge mass-normalized basis. Furthermore, farmed sponge extracts presented similar or slightly lower antibacterial activity against methicillin-resistant Staphylococcus aureus, compared to the extracts resulting from wild sponges. Anticancer assays against human colorectal carcinoma cells (HCT-116) revealed marginally active extracts from both wild and farmed S. foetidus populations. Our study highlights that, besides mitigating organic pollution in fish aquaculture, sponge farming can serve as a valuable resource of biomolecules, with promising potential in pharmaceutical and biomedical applications.

Molecular Interactions between Ionic Liquid Lubricants and Silica Surfaces: An MD Simulation Study.

The unique physicochemical properties of ionic liquids (ILs) attracted interest in their application as lubricants of micro/nano-electromechanical systems. This work evaluates the feasibility of using the protic ionic liquids [4-picH][HSO4], [4-picH][CH3SO3], [MIMH][HSO4], and [MIMH][CH3SO3] and the aprotic ILs [C6mim][HSO4] and [C6mim][CH3SO3] as additives to model lubricant poly(ethylene glycol) (PEG200) to lubricate silicon surfaces. Additives based on the cation [4-picH]+ exhibited the best tribological performance, with the optimal value for 2% [4-picH][HSO4] in PEG200 (w/w). Molecular dynamics (MD) simulations of the first stages of adsorption of the ILs at the glass surface were performed to portray the molecular behavior of the ILs added to PEG200 and their interaction with the silica substrate. For the pure ILs at the solid substrates, the MD results indicated that weak specific interactions of the cation with the glass interface are lost to accommodate the larger anion in the first contact layer. For the PEG200 + 2% [4-picH][HSO4] system, the formation of a more compact protective film adsorbed at the glass surface is revealed by a larger trans population of the dihedral angle -O(R)-C-C-O(R)- in PEG200, in comparison to the same distribution for the pure model lubricant. Our findings suggest that the enhanced lubrication performance of PEG200 with [4-picH][HSO4] arises from synergistic interactions between the protic IL and PEG200 at the adsorbed layer.

Monoclonal antibody therapy protects nonhuman primates against mucosal exposure to Lassa virus.

Lassa fever (LF) is an acute viral illness that causes thousands of deaths annually in West Africa. There are currently no Lassa virus (LASV) vaccines or antivirals approved for human use. Recently, we showed that combinations of broadly neutralizing human monoclonal antibodies (BNhuMAbs) known as Arevirumab-2 or Arevirumab-3 protected up to 100% of cynomolgus macaques against challenge with diverse lineages of LASV when treatment was initiated at advanced stages of disease. This previous work assessed efficacy against parenteral exposure. However, transmission of LASV to humans occurs primarily by mucosal exposure to virus shed from Mastomys rodents. Here, we describe the development of a lethal intranasal exposure macaque model of LF. This model is employed to show that Arevirumab cocktails rescue 100% of macaques from lethal LASV infection when treatment is initiated 8 days after LASV exposure. Our work demonstrates BNhuMAbs have utility in treating LASV infection acquired through mucosal exposure.

Monoclonal antibody therapy demonstrates increased virulence of a lineage VII strain of Lassa virus in nonhuman primates.

Lassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) based on the lineage IV Josiah strain protected 100% of cynomolgus macaques against heterologous challenge with lineage II and III strains of LASV when therapy was initiated beginning at day 8 after challenge. LASV strains from Benin and Togo represent a new lineage VII that are more genetically diverse from lineage IV than strains from lineages II and III. Here, we tested the ability of Arevirumab-3 to protect macaques against a LASV lineage VII Togo isolate when treatment was administered beginning 8 days after exposure. Unexpectedly, only 40% of treated animals survived challenge. In a subsequent study we showed that Arevirumab-3 protected 100% of macaques from lethal challenge when treatment was initiated 7 days after LASV Togo exposure. Based on our transcriptomics data, successful Arevirumab-3 treatment correlated with diminished neutrophil signatures and the predicted development of T cell responses. As the in vitro antiviral activity of Arevirumab-3 against LASV Togo was equivalent to lineage II and III strains, the reduced protection in macaques against Togo likely reflects the faster disease course of LASV Togo in macaques than other strains. This data causes concern regarding the ability of heterologous vaccines and treatments to provide cross protection against lineage VII LASV isolates.

Cross-sectional and longitudinal analysis of conditioned pain modulation and pain in fibromyalgia: CPM as an effect modifier of pain changes over time.

Background and purpose: Fibromyalgia (FM) is associated with altered descending pain modulatory pathways, which can be assessed through Conditioned Pain Modulation (CPM). In this study, we aimed to explore the relationship between CPM and self-reported baseline characteristics in patients with fibromyalgia. We also performed a longitudinal analysis exploring CPM as a potential predictor of clinical improvement over time in individuals with FM. Methods: We performed cross-sectional univariable and multivariable analyses of the relationship between CPM and other variables in 41 FM patients. We then performed longitudinal analyses, building linear mixed effects models with pain in the Visual Analogue Scale (VAS) as the dependent variable, and testing for the interaction between time and CPM. We also tested the interaction between CPM and time in models using other outcomes, such as the revised Fibromyalgia Impact Questionnaire (FIQR) and Quality of Life Scale (QOLs). Results: We found no association between CPM and other demographic and clinical variables in the univariable analysis. We found a statistically significant association in the multivariable linear regression model between CPM and the QOLs at baseline, after controlling for age, sex, and duration of symptoms. In the longitudinal analyses, we found that CPM is an effect modifier for clinical improvement over time for the pain VAS, QOLs and FIQR: individuals with low-efficient CPM at baseline have a different (improved) pattern of response over time when compared to those with high-efficient CPM. Conclusions: Our findings suggest that CPM is not a reliable biomarker of clinical manifestations in chronic pain patients during cross-sectional assessments. However, our results are consistent with previous findings that CPM can be used to predict the evolution of clinical pain over time. We expect that our findings will help in the selection of patients with the best profile to respond to specific interventions and assist clinicians in tailoring pain treatments.

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.

Anti-Ebola virus mAb 3A6 with unprecedented potency protects highly viremic animals from fatal outcome and physically lifts its glycoprotein target from the virion membrane.

Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP1,2) are the standard of care for Ebola virus disease (EVD). Anti-GP1,2 mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro. However, their neutralization mechanism is poorly understood because they target a GP1,2 epitope that has evaded structural characterization. Moreover, their in vivo efficacy has only been evaluated in the mouse model of EVD. Using x-ray crystallography and cryo-electron tomography of 3A6 complexed with its stalk- GP1,2 MPER epitope we reveal a novel mechanism in which 3A6 elevates the stalk or stabilizes a conformation of GP1,2 that is lifted from the virion membrane. In domestic guinea pig and rhesus monkey EVD models, 3A6 provides therapeutic benefit at high viremia levels, advanced disease stages, and at the lowest dose yet demonstrated for any anti-EBOV mAb-based monotherapy. These findings can guide design of next-generation, highly potent anti-EBOV mAbs.

Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

Prevalence of nutritional deficiencies and morbidity by infectious diseases in children 0-5 years of age in Iñapari in the Peruvian Amazon

Introduction: Iñapari is a town located in Peru, on the border of Brazil, between the Amazonian states of Acre and Amazonas. The local Peruvian children under five years of age present moderate anemia while the percentage of chronic child malnutrition is a major public health problem in the country as a whole. Goals: The purpose of this study was to identify the prevalence of major childhood morbidities caused by anemia, malnutrition, intestinal parasites, toxocariasis, and hepatitis A, and identify connections with the socioeconomic and environmental conditions found in Iñapari. Methods: Interviews with questionnaires; anthropometric measurements, collection of feces and venous blood samples. Results: A 20% prevalence of anemia and 8.5% prevalence of chronic malnutrition (height for age deficiency) was found. A pathogenic intestinal parasite was noted in 24.5% of the samples, where Giardia intestinalis (14.7%) was the most frequent. The seroprevalence of toxocariasis was 33.8% and hepatitis A was 21.2%. Conclusion: There is a connection between the results found and the poor living and sanitary conditions of the population. The low income noted is also linked to the malnutrition and anemia detected

True branched nostocalean cyanobacteria from tropical aerophytic habitats and molecular assessment of two species from field samples

Aerophytic cyanobacteria are commonly found growing on rocks, tree trunks and soil, but the diversity of these organisms is still poorly known. This complex group is very problematic considering the taxonomic arrangement and species circumscription, especially when taking into account tropical populations. In this work, 20 samples of aerophytic cyanobacteria from 15 distinct sampling sites were collected along a tropical rainforest area at the São Paulo State (Brazil). Samples were dried at room temperature after the collection, and once in the laboratory, they were rehydrated and analyzed. The taxonomic study resulted in the record and description of nine species of true-branched cyanobacteria pertaining to the genera Spelaeopogon (one specie), Hapalosiphon (two species) and Stigonema (six species). The similarity of the flora found when compared to surveys conducted in other geographical regions was relatively low. These differences could be addressed to ecological conditions of the habitats, to the extension of the area surveyed or even to taxonomic misinterpretations. The molecular assessment of 16S rDNA on the basis of field material was successful for two morphospecies, Hapalosiphon sp. and Stigonema ocellatum; however, their relationships with other populations and species revealed to be uncertain. The results of the floristic survey and of the molecular approach evidenced the fragile delimitation of some genera and species in the true branched group of cyanobacteria.

Las bacterias aerofíticas crecen comúnmente en las rocas, troncos de árboles y el suelo, pero la diversidad de estos organismos todavía es poco conocida. Este complejo grupo es muy problématico considerando la disposición taxónomica y la circunscripción de las especies, especialmente cuando se toman en cuenta las poblaciones tropicales. En esta investigación, 20 muestras de cianobacterias aerofíticas de 15 distintos sitios de muestro fueron recolectadas a lo largo de un área de selva tropical en el estado de São Paulo (Brasil). Las muestras fueron secadas a temperatura ambiente después de su recolecta, y una vez en el laboratorio, se hidrataron y analizaron. El estudio taxónomico resultó en un registro y descripción de nueve especies de cianobacterias con ramificaciones verdaderas pertenecientes al género Spelaeopogon (una especie), Hapalosiphon (dos especies) y Stigonema (seis especies). La similutud de la flora encontrada en comparación con las encuestas realizadas en otras regiones geográficas fue relativamente baja. Estas diferencias podrían deberse a las condiciones ecológicas de los hábitats, a la extensión de la zona de estudio o incluso a malas interpretaciones taxonómicas. La evaluación molecular del 16S rDNA del material de campo fue un éxito para dos morfoespecies, Hapalosiphon sp. y Stigonema ocellatum, sin embargo, sus relaciones con otras poblaciones y especies revelan que son inciertas. Los resultados del estudio florístico y de la aproximación molecular evidencian la débil delimitación de algunos géneros y especies en el grupo de cianobacterias con ramificaciones verdaderas.

Lista de Cyanobacteria do Estado de São Paulo / Checklist of Cyanobacteria from São Paulo State, Brazil

Com base no levantamento bibliográfico realizado sobre as cianobactérias citadas para o Brasil e para o Estado de São Paulo em particular, além de consulta à lista de espécies da flora brasileira e aos bancos de dados de coleções paulistas, encontramos um total de 460 espécies citadas para o Brasil e 378 para o estado de São Paulo. Considerando que o grupo tem ao redor de 2800 espécies, estes números representam bem menos de 20% das espécies conhecidas. Assim, frente a diversidade de ambientes e habitats existentes nos biomas tropicais/subtropicais, o reduzido número de espécies já conhecidas indica que certamente essa biodiversidade está subestimada e deve ser muito maior do que identificamos até agora.

Based on the literature about the cyanobacteria from Brazil and particularly from São Paulo State, the list of Brazilian flora and the data bank of herbaria collections, a total of 460 species were referred to Brazil and 378 to São Paulo State. Taking into account that the group of cyanobacteria presents around 2800 species, these numbers represent much less than 20% of the known species. Considering the diversity of environments and habitats in the tropical/subtropical biomes compared to the reduced number of known species, this biodiversity is certainly underestimated and should be much larger.

Quantitative radiographic evaluation of periapical bone resorption in dog's teeth contaminated with bacterial endotoxin (LPS) associated or not with calcium hydroxide

The aim of this study was to quantify radiographically the periapical bone resorption in dogs' teeth contaminated with bacterial endotoxin (LPS), associated or not with calcium hydroxide. After pulp tissue removal, 60 premolars were randomly assigned to 4 groups and were either filled with LPS (group 1), filled with LPS plus calcium hydroxide (group 2) or filled with saline (group 3) for a period of 30 days. In group 4, periapical lesion formation was induced with no canal treatment. Standardized radiographs were taken at the beginning of the treatment and after 30 days and the Image J Program was used for measurement of periapical lesion size. Periapical lesions were observed in groups 1 (average of 8.44 mm2) and 4 (average of 3.02 mm2). The lamina dura was intact and there were no areas of periapical bone resorption in groups 2 and 3. It may be concluded that calcium hydroxide was effective in inactivating LPS, as demonstrated by the absence of apical periodontitis in the roots that were filled with bacterial endotoxin plus calcium hydroxide.

O objetivo deste estudo foi quantificar radiograficamente a reabsorção óssea periapical em dentes de cães contaminados com endotoxina bacteriana (LPS), associadas ou não ao hidróxido de cálcio. Sessenta pré-molares foram divididos em 4 grupos e preenchidos com LPS (grupo 1), LPS e hidróxido de cálcio (grupo 2), solução salina (grupo 3), ou lesões periapicais foram induzidas sem tratamento (grupo 4), por um período de 30 dias e o Programa Image J foi empregado para mensuração das lesões, em mm2. Radiografias foram realizadas no início do tratamento e após 30 dias. Lesões periapicais foram observadas no grupo 1 (média de 8,44 mm2) e 4 (média de 3,02 mm2). A lâmina dura estava intacta e não foram observadas áreas de reabsorção óssea periapical nos grupos 2 e 3. Concluindo, a avaliação radiográfica quantitativa do efeito do LPS associado ao hidróxido de cálcio demonstrou que quando juntos a endotoxina bacteriana é inativada, uma vez que não foram observadas lesões periapicais nas raízes deste grupo experimental.