Tonabersat Significantly Reduces Disease Progression in an Experimental Mouse Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease marked by chronic neuroinflammation thought to be mediated by the inflammasome pathway. Connexin 43 (Cx43) hemichannels contribute to the activation of the inflammasome through the release of adenosine triphosphate (ATP) inflammasome activation signals. The objective of the study was to evaluate if the Cx43 hemichannel blocker, tonabersat, is effective in modulating the inflammatory response and reducing disability in the myelin oligodendrocyte glycoprotein 35-55-induced experimental autoimmune encephalomyelitis (MOG35-55 EAE) model of MS. Here, we show that the Cx43 hemichannel blocking drug, tonabersat, significantly reduced expression of neuroinflammatory markers for microglial activation (ionized calcium-binding adapter molecule 1 (Iba1)) and astrogliosis (glial fibrillary acidic protein (GFAP)) while preserving myelin basic protein (MBP) expression levels in the corpus callosum, motor cortex, and striatum regions of the brain in MOG35-55 EAE mice. Reduced NOD-like receptor protein 3 (NLRP3) inflammasome complex assembly and Caspase-1 activation confirmed the drug's mode of action. MOG35-55 EAE mice showed clinical signs of MS, but MOG35-55 EAE mice treated with tonabersat retained behavior closer to normal. These data suggest that clinical trial phase IIb-ready tonabersat may merit further investigation as a promising candidate for MS treatment.

Influence of Harvest Time on the Chemical Profile of Pereskia aculeate Mill. Using Paper Spray Mass Spectrometry.

This study evaluated the physicochemical characteristics and the production of bioactive compounds of Pereskia aculeata Mill. at different harvest times. Here, we performed a qualitative evaluation of the chemical profile by paper spray mass spectrometry (PSMS), the phenolic acid and flavonoid profile by high-performance liquid chromatography (HPLC), antioxidant activity, total carotenoids, total phenolic compounds, total flavonoids, total anthocyanins, color characteristics, total soluble solids (TSS), total solids (TS), pH, and total titratable acidity (TTA). The chemical profile was not affected, with the exception of 4,5-dimethyl-2,6-octadiene and azelaic acid, which was only identified in the leaves harvested during the winter. The content of four phenolic acids and three flavonoids were analyzed; out of these, no significant amounts of ellagic acid and quercetin were detected. There was no difference in production of bioactive compounds between seasons, reflecting the antioxidant activity, which also did not differ. Brightness, chroma, and leaf pH were the only physicochemical characteristics that did not vary between seasons.

Environmentally Safe Photodynamic Control of Aedes aegypti Using Sunlight-Activated Synthetic Curcumin: Photodegradation, Aquatic Ecotoxicity, and Field Trial.

This study reports curcumin as an efficient photolarvicide against Aedes aegypti larvae under natural light illumination. Larval mortality and pupal formation were monitored daily for 21 days under simulated field conditions. In a sucrose-containing formulation, a lethal time 50 (LT50) of 3 days was found using curcumin at 4.6 mg L-1. This formulation promoted no larval toxicity in the absence of illumination, and sucrose alone did not induce larval phototoxicity. The photodegradation byproducts (intermediates) of curcumin were determined and the photodegradation mechanisms proposed. Intermediates with m/z 194, 278, and 370 were found and characterized using LC-MS. The ecotoxicity of the byproducts on non-target organisms (Daphnia, fish, and green algae) indicates that the intermediates do not exhibit any destructive potential for aquatic organisms. The results of photodegradation and ecotoxicity suggest that curcumin is environmentally safe for non-target organisms and, therefore, can be considered for population control of Ae. aegypti.

First Report of Meloidogyne Morocciensis Infecting Hops (Humulus Lupulus).

Humulus lupulus (Cannabaceae) is a climbing herbaceous plant with perennial production, intended mainly for the brewing industry. H. lupulus is widely cultivated in temperate regions; hop cultivars have shown good adaptation in regions of Brazil. In a hop-growing area in São Mateus, the state of Espírito Santo, leaf wilting and galling of the root system was observed. Soil and root samples were taken to the laboratory and processed, and the nematodes extracted from the Meloidogyne genus were identified by morphology, morphometry, and biochemical analysis. According to the results, the species identified in the hop roots was Meloidogyne morocciensis. This is the first report of H. lupulus as host of M. morocciensis.

Does the ultrasonic activation of sealer hinder the root canal retreatment?

OBJECTIVES: To evaluate if the ultrasonic activation of sealer hinders the root canal retreatment. MATERIALS AND METHODS: Thirty mandibular premolars were prepared using the ProTaper Universal system (Dentsply) until the instrument F3 (0.30/0.09). The canals were distributed into 2 groups (n = 15), according to the filling technique: NUact group - sealer without ultrasonic activation + gutta-percha cones and Uact group - sealer with ultrasonic activation + gutta-percha cones. The canals were re-instrumented with Largo burs, followed by the instrument R50 (0.50/0.05) of the Reciproc system. The time required to perform re-instrumentation was recorded (s). The roots were longitudinally cleaved, and the total area of root canal and remaining filling material were quantified (%). The ANOVA test was applied to the data and complemented by Student's t test (P < 0.05). RESULTS: Uact group had higher percentage of remaining filling material than NUact group (P < 0.05). When the root thirds were considered, there was statistically significant difference only for Uact group at the apical third (P < 0.05). There was no difference between groups regarding the time required to perform re-instrumentation (P > 0.05). CONCLUSIONS: Ultrasonic activation of sealer leads to a higher percentage of remaining filling material attached to the root canal walls. However, it did not affect the retreatment time. CLINICAL SIGNIFICANCE: Ultrasonic activation increases sealer penetration into dentinal tubules, improving its resistance to dislodgement. However, there is no scientific evidence to prove if ultrasonic activation of sealer hinders its removal when root canal retreatment is necessary.

A low-cost brewery waste as a carbon source in bio-surfactant production.

This work aims to produce bio-surfactant using a brewery waste (trub) as a strategy to reduce production costs related to the substrate, as well as to provide an eco-friendly destination for this residue. Trub is obtained during the boiling of the wort, being mainly composed of proteins and reducing sugars. To evaluate important process parameters on bio-surfactant production, a full factorial design (24) was elaborated, having agitation rate and concentrations of trub, yeast extract, and peptone as independent variables. The highest bio-surfactant concentration achieved was 100.76 mg L-1, where FTIR and Maldi-ToF-MS confirmed functional groups characteristic of peptides and isomers of surfactin in the bio-surfactant extract. Trub, agitation and yeast extract showed statistically significant effects on the response variable (surface tension), where an increase in the agitation rate and in the concentration of yeast extract demonstrated a positive impact on the production of bio-surfactant.

Biodegradation of azo dye-containing wastewater by activated sludge: a critical review.

The effluent from the textile industry is a complex mixture of recalcitrant molecules that can harm the environment and human health. Biological treatments are usually applied for this wastewater, particularly activated sludge, due to its high efficiency, and low implementation and operation costs. However, the activated sludge microbiome is rarely well-known. In general, activated sludges are composed of Acidobacteria, Bacillus, Clostridium, Pseudomonas, Proteobacteria, and Streptococcus, in which Bacillus and Pseudomonas are highlighted for bacterial dye degradation. Consequently, the process is not carried out under optimum conditions (treatment yield). Therefore, this review aims to contextualize the potential environmental impacts of azo dye-containing wastewater from the textile industry, including toxicity, activated sludge microbiome identification, in particular using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a novel, rapid and accurate strategy for the identification of activated sludge microbiome (potential to enhance treatment yield).

Lymphatic vessels in human adipose tissue.

Despite being considered present in most vascularised tissues, lymphatic vessels have not been properly shown in human adipose tissue (AT). Our goal in this study is to investigate an unanswered question in AT biology, regarding lymphatic network presence in tissue parenchyma. Using human subcutaneous (S-) and visceral (V-) AT samples with whole mount staining for lymphatic specific markers and three-dimensional imaging, we showed lymphatic capillaries and larger lymphatic vessels in the human VAT. Conversely, in the human SAT, microcirculatory lymphatic vascular structures were rarely detected and no initial lymphatics were found.

Integration of Fenton's reaction based processes and cation exchange processes in textile wastewater treatment as a strategy for water reuse.

The remediation of a real textile wastewater aiming its reuse in the textile industry was carried out by integrating two processes: (i) a chemical or electrochemical advanced oxidation process (AOP or EAOP) based on Fenton's reaction for organics degradation, and (ii) a cation exchange process using marine macroalgae for removal of the iron acting in the Fenton's reaction based processes. Four AOPs/EAOPs at acidic pH 2.8 were tested: Fenton, photo-Fenton with ultraviolet A (UVA) radiation (PF/UVA), electro-Fenton (EF) and photoelectro-Fenton with UVA radiation (PEF/UVA). These processes provided very high color removals. After a running time of 45 min, the color removals were 68-95% for the Fenton process, 76-94% for the EF process, 80-98% for the PF/UVA process and 85-100% for the PEF/UVA process. In contrast, the mineralization was negligible for all the processes, indicating the generation/presence of persistent colorless compounds. The PF process was selected as first treatment stage due to its ability for color removal and related lower costs. A set of six marine macroalgae (Gracilaria caudata, Gracilaria cervicornis, Ascophyllum nodosum, Fucus spiralis, Laminaria hyperborea and Pelvetia canaliculata) were tested for iron uptake. Laminaria hyperborea showed the highest ion exchange capacity and affinity for iron species. Its application allowed the removal of all the iron acting in the PF process (3.4 mg/L). The textile wastewater resulting from the application of PF process followed by cation exchange with Laminaria hyperborea was successfully reused in scouring, bleaching and dyeing processes.

Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16+, CCR5+ and TLR8+ monocytes.

Macrophage infiltration into adipose tissue (AT) is a hallmark of the chronic inflammatory response in obesity and is supported by an intense monocyte migration towards AT. Although it has been detected an increased proportion of circulating CD16+ monocyte subsets in obese subjects, the mechanisms underlying this effect and the contribution of these cells to the inflamed profile of obese AT are still poorly understood. We investigated whether factors secreted by human obese omental AT could polarize monocytes to CD16+ enriched phenotype, and how these changes could modify their migratory capacity towards adipose tissue itself. We show that explants of human obese omental AT, obtained during bariatric surgery, released higher levels of MIP1-α, TNFα, leptin and also VEGF, together with increasing amounts of microparticles (MP), when compared to explants of lean subcutaneous AT. A higher content of circulating MP derived from preadipocytes and leukocytes was also detected in plasma of obese subjects. Conditioned media or MP released from obese omental AT increased CD16 and CCR5 expression on CD14+CD16- monocytes and augmented their migratory capacity towards the conditioned media from obese omental AT, itself. This effect was inhibited when MIP1-α was neutralized. Additionally, we demonstrate that MP derived from obese omental AT carry and transfer TLR8 to monocytes, thus triggering an increase in CD16 expression in those cells. Our data shows a positive feedback loop between blood monocytes and obese omental AT, which releases chemotactic mediators and TLR8-enriched MP, thus inducing an up-regulation of CD16+ monocytes, favoring leukocyte infiltration in the obese omental AT.

Pedicled Sensate Composite Calcaneal Flap in Children With Congenital Tibial Pseudoarthrosis.

BACKGROUND: The preservation and functionality of a limb affected by a malformation (such as congenital pseudoarthrosis of the tibia) or a severely mangled lower limb in children, despite modern reconstructive techniques, remains challenging, often eventually requiring amputation to achieve a better outcome. The classical Syme and Boyd procedures are functionally better than transtibial (TT) amputation, but are not feasible for congenital tibial pseudoarthrosis. TT amputation delivers an excellent, effective, and functional stump that usually leads, after prosthetization, to a functional gait. Unfortunately, in some situations, particularly when amputation is performed conventionally, the stump is also associated with complications. Future surgical revisions are often needed, particularly in children, because of stump overgrowth. METHODS: Between 2008 and 2010, three patients diagnosed with congenital pseudoarthrosis of the tibia associated with neurofibromatosis who were indicated for TT amputation with calcaneal flap after failure of all previous surgical reconstructive procedures were selected. The chosen method for osteosynthesis was an external fixator of Ilizarov. RESULTS: At 12 weeks of follow-up, the stump had healed in all three patients, and tibiocalcaneal fusion was achieved without complications. All patients were prosthetized and had an asymptomatic gait. After a minimum follow-up of 6 years, all three cases with the pedicled sensate composite calcaneal flap still had a strong, full weight-bearing surface and have adapted easily to the conventional prosthesis, providing a painless stump with excellent functionality. CONCLUSION: With a 0 rate of needed revisions, all 3 cases with the pedicled sensate composite calcaneal flap preserving the hind foot still have a strong, full weight-bearing surface and have easily adapted to the conventional prosthesis, providing a painless and excellent functional stump that could last a lifetime. LEVEL OF EVIDENCE: Level IV.

Fetal Infection by Zika Virus in the Third Trimester: Report of 2 Cases.

Zika virus (ZIKV) infection acquired during pregnancy is associated with congenital microcephaly. We describe 2 cases of ZIKV infection in women in their 36th week of pregnancy whose fetuses had preserved head circumference at birth and findings of subependymal cysts and lenticulostriate vasculopathy in postnatal imaging. These represent the first signs of congenital brain injury acquired due to ZIKV in the third trimester.

The application of textile sludge adsorbents for the removal of Reactive Red 2 dye.

Sludge from the textile industry was used as a low-cost adsorbent to remove the dye Reactive Red 2 from an aqueous solution. Adsorbents were prepared through the thermal and chemical treatment of sludge originating from physical-chemical (PC) and biological (BIO) effluent treatment processes. The adsorbent characterization was carried out through physical-chemical analysis, X-ray fluorescence (XRF) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, pHPZC determination, Boehm titration method, Brunauer-Emmett-Teller (BET) surface area analysis and scanning electron microscopy (SEM). Batch kinetic experiments and adsorption isotherm modeling were conducted under different pH and temperature conditions. The results for the kinetic studies indicate that the adsorption processes associated with these systems can be described by a pseudo-second-order model and for the equilibrium data the Langmuir model provided the best fit. The adsorption was strongly dependent on the pH but not on the temperature within the ranges studied. The maxima adsorption capacities were 159.3 mg g(-1) for the BIO adsorbent and 213.9 mg g(-1) for PC adsorbent at pH of 2 and 25 °C.

Prevalence of Eimeria spp. in Broilers by Multiplex PCR in the Southern Region of Brazil on Two Hundred and Fifty Farms.

Parasitic infections caused by Eimeria species are responsible for most economic losses in poultry production. Prevalence studies can adequately assist the design of prophylaxis strategies for disease control. Therefore, stool samples from 251 flocks of broilers from 28 to 48 days old were collected in 21 municipalities in the state of Santa Catarina, Brazil, to detect and examine the prevalence of Eimeria acervulina, Eimeria maxima, Eimeria tenella, Eimeria mitis, Eimeria praecox, Eimeria necatrix, and Eimeria brunetti. The oocysts were recovered and quantified, and the species were identified by a multiplex PCR technique. Amplicons of seven Eimeria species originating from the PCR-positive samples were cloned. Microscopy studies demonstrated that 96% of the farms were positive for the Eimeria. Seven species were identified, as follows: E. maxima (63.7%) and E. acervulina (63.3%) were the most prevalent species, followed by E. tenella (54.6%), E. mitis (38.6%), E. praecox (25.1%), E. necatrix (24.3%), and E. brunetti (13.1%). The average number of species detected per farm was 2.96, and the most common were E. acervulina, E. maxima, and E. tenella (9.16%). The sequencing of the clones confirmed the specificity and effectiveness of multiplex PCR for the identification of seven species of Eimeria, so this tool can be useful in studying circulating species in poultry farms, thereby assisting prophylactic measures against coccidiosis.

Biodegradation kinetics of benzene, toluene and xylene compounds: microbial growth and evaluation of models.

The biodegradation kinetics of BTX compounds (benzene, toluene, and xylene) individually and as mixtures was studied using models with different levels of sophistication. To compare the performance of the unstructured models applied in this work we used experimental data obtained here and some results published in the literature. The system description was based on the material balances of key components for batch operations, where the Monod and Andrews models were applied to predict the biodegradation of individual substrates. To simulate the biodegradation kinetics of substrate mixtures, models of substrate inhibition were applied along with the Sum Kinetics with Interaction Parameters (SKIP) models, where for two-component association toluene-xylene SKIP model presented better performance and for tri-component association benzene-toluene-xylene, the uncompetitive inhibition model was better. The kinetic parameters were estimated via a global search method known as Particle Swarm Optimization (PSO). The main result of this study is that the sophisticated biodegradation kinetics of BTX mixtures can be successfully described by applying the SKIP model, with the main advantage being the consideration of the substrate interactions.

Nature of electrogenerated intermediates in nitro-substituted nor-ß-lapachones: the structure of radical species during successive electron transfer in multiredox centers.

Electrochemical, spectroelectrochemical, and theoretical studies of the reduction reactions in nor-ß-lapachone derivatives including a nitro redox center showed that reduction of the compounds involves the formation of several radical intermediates, including a biradical dianion resultant from the separate reduction of the quinone and nitro groups in the molecules. Theoretical descriptions of the corresponding Fukui functions f(αα)⁺ and f(ßß)⁺(r) and LUMO densities considering finite differences and frozen core approximations for describing the changes in electron and spin densities of the system allowed us to confirm these results. A description of the potential relationship with the obtained results and biological activity selectivity indexes suggests that both the formation of stable biradical dianion species and the stability of the semiquinone intermediates during further reduction are determining factors in the description of their biological activity.

Unlocking the effect of Li and Ce ions on the thermoluminescence and optically stimulated luminescence signals of the MgB4O7 compound.

Magnesium tetraborate (MgB4O7) is an example of a material that has attracted the attention of researchers in the field of ionising radiation dosimetry. Several challenges are present in order to achieve considerable advances in luminescence dosimetry. The incorporation of efficient dopants in the host matrix has been an experimentally useful but limited strategy. The lack of specific information about the introduced defects as well as their connection with the trapping and recombination processes associated with light emission may be quoted as challenging examples. Here, we demonstrate the influence of lithium incorporation on Optically Stimulated Luminescence (OSL)/Thermoluminescence (TL) signal modification/suppression of MgB4O7 by combining experimental and computational procedures. Li substitution into the Mg site leads to a signal suppression due to the probable quenching of the Fs and Fs+ centres in MgO and the formation of O''i, drastically reducing the possibility of MgO anti-Schottky defect formation in MgB4O7. When using Li-co-doped MgB4O7:Ce3+, the Li ions act as a charge balancer, facilitating the entry of Ce ions into the interstitial pores and making possible a positive synergistic effect on the luminescence and dosimetric properties. These findings provide new insights into designing more efficient dosimeters by tuning dopants.

Carbon gain is coordinated with enhanced stomatal conductance and hydraulic architecture in coffee plants acclimated to elevated [CO2]: The interplay with irradiance supply.

We recently demonstrated that, under elevated [CO2] (eCa), coffee (Coffea arabica L.) plants grown at high light (HL), but not at low light (LL), display higher stomatal conductance (gs) than at ambient [CO2] (aCa). We then hypothesized that the enhanced gs at eCa/HL, if sustained at the long-term, would lead to adjustments in hydraulic architecture. To test this hypothesis, potted plants of coffee were grown in open-top chambers for 12 months under HL or LL (ca. 9 or 1 mol photons m-2 day-1, respectively); these light treatments were combined with two [CO2] levels (ca. 437 or 705 µmol mol-1, respectively). Under eCa/HL, increased gs was closely accompanied by increases in branch and leaf hydraulic conductances, suggesting a coordinated response between liquid- and vapor-phase water flows throughout the plant. Still under HL, eCa also resulted in increased Huber value (sapwood area-to-total leaf area), sapwood area-to-stem diameter, and root mass-to-total leaf area, thus further improving the water supply to the leaves. Our results demonstrate that Ca is a central player in coffee physiology increasing carbon gain through a close association between stomatal function and an improved hydraulic architecture under HL conditions.

Growth and Leaf Gas Exchange Upregulation by Elevated [CO2] Is Light Dependent in Coffee Plants.

Coffee (Coffea arabica L.) plants have been assorted as highly suitable to growth at elevated [CO2] (eCa), although such suitability is hypothesized to decrease under severe shade. We herein examined how the combination of eCa and contrasting irradiance affects growth and photosynthetic performance. Coffee plants were grown in open-top chambers under relatively high light (HL) or low light (LL) (9 or 1 mol photons m-2 day-1, respectively), and aCa or eCa (437 or 705 µmol mol-1, respectively). Most traits were affected by light and CO2, and by their interaction. Relative to aCa, our main findings were (i) a greater stomatal conductance (gs) (only at HL) with decreased diffusive limitations to photosynthesis, (ii) greater gs during HL-to-LL transitions, whereas gs was unresponsive to the LL-to-HL transitions irrespective of [CO2], (iii) greater leaf nitrogen pools (only at HL) and higher photosynthetic nitrogen-use efficiency irrespective of light, (iv) lack of photosynthetic acclimation, and (v) greater biomass partitioning to roots and earlier branching. In summary, eCa improved plant growth and photosynthetic performance. Our novel and timely findings suggest that coffee plants are highly suited for a changing climate characterized by a progressive elevation of [CO2], especially if the light is nonlimiting.

Antibacterial activity and anxiolytic-like effect of Ziziphus joazeiro Mart. leaves in adult zebrafish (Danio rerio).

Ziziphus joazeiro Mart. is an endemic plant of the Caatinga that presents a great socioeconomic importance for the Northeast and Semiarid Region of Brazil. In view of this, this study aimed to evaluate the antibacterial activity and anxiolytic-like effects of Ziziphus joazeiro Mart leaves in adult zebrafish (Danio rerio). The characterization of the main classes of metabolites was performed through chemical reactions. The antibacterial and antibiotic potentiating activity was evaluated by broth microdilution assays. The 96 h acute toxicity, open field test and anxiety models test was evaluated in vivo on adult zebrafish. The results obtained in the phytochemical prospection evidenced the presence of flobabenic tannins, leucoanthocyanidins, flavonois, flavonones, catechins, alkaloids, steroids, and triterpenoids. EEFZJ did not show antibacterial activity for all microorganism tested (MIC ≥ 1024 µg/mL), but reduced the concentration required for bacterial growth inhibition in combination with gentamicin and norfloxacin against multidrug-resistant strains of S. aureus (SA10) and E. coli (EC06), exhibiting synergistic effect with these antibiotics (p<0.0001). In the tests in vivo, EEFZJ was found to be nontoxic, performing reduced locomotor activity and demonstrated an anxiolytic-like effect in adult zebrafish via GABAergic and Serotoninergic systems (5-HT1, 5-HT2A/2C and 5-HT3A/3B).